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1.  Intravesical instillation of pentosan polysulfate encapsulated in a liposome nanocarrier for interstitial cystitis 
We determined the effect of intravesical instillation of pentosan polysulfate encapsulated in liposomes for refractory interstitial cystitis patients. This was an open label uncontrolled study. Subjects were recruited from a private urology practice. Inclusion criteria included patients who met NIDDK criteria for Interstitial Cystitis (IC) and who were responding poorly to conventional treatments. Exclusion criteria included evidence of a urinary tract infection, bladder cancer, or other forms of chronic cystitis. Patients received 400 mg of Pentosan Polysulfate (PP) encapsulated into liposomes as an intravesical instillation performed every 2 weeks for 3 months. Baseline and post treatment outcome measures were obtained that included the O’Leary-Sant Interstitial Cystitis Symptom and Problem Questionnaire and the Pelvic Pain and Urgency/Frequency Patient symptom Scale tests. A total of 37 instillations were used and no adverse events occurred. Clinically significant decreases in symptom scores greater than 50% were seen in virtually all outcome measures at 3 month follow up. All subjects reported remarkable subjective improvement in pain symptoms marked by decreased use of narcotics and increased enjoyment of daily activities. No patients developed systemic symptoms or poor tolerance of the instillations. Intravesical Pentosan Polysulfate encapsulated into liposomes can significantly decrease frequency, urgency, pain and improve quality of life for two months after deployment. Additional studies are needed to determine cellular effects of glycosaminoglycan restoration, ideal doses, dosing intervals, safety and cost-effectiveness of this therapy.
PMCID: PMC4219302  PMID: 25374916
Interstitial cystitis; pentosan polysulfate; liposome; glycosaminoglycan; urothelium; nanospheres
2.  Hyperbaric oxygen therapy for late radiation tissue injury in gynecologic malignancies 
Current Oncology  2011;18(5):220-227.
Background
Late radiation tissue injury is a serious complication of radiotherapy for patients with gynecologic malignancies. Strategies for managing pain and other clinical features have limited efficacy; however, hyperbaric oxygen therapy (HBO2) may be an effective option for some patients.
Methods
In a systematic review of the literature, the Ovid medline, embase, Cochrane Library, National Guidelines Clearinghouse, and Canadian Medical Association Infobase databases were searched to June 2009 for clinical practice guidelines, systematic reviews, randomized controlled trials, or other relevant evidence. Studies that did not evaluate soft tissue necrosis, cystitis, proctitis, bone necrosis, and other complications were excluded.
Results
Two randomized trials, eleven nonrandomized studies, and five supporting documents comprise the evidence base. In addition, information on the harms and safety of treatment with HBO2 were reported in three additional sources. There is modest direct evidence and emerging indirect evidence that the use of HBO2 is broadly effective for late radiation tissue injury of the pelvis in women treated for gynecologic malignancies.
Conclusions
Based on the evidence and expert consensus opinion, HBO2 is likely effective for late radiation tissue injury of the pelvis, with demonstrated efficacy specifically for radiation damage to the anus and rectum;the main indication for HBO2 therapy in gynecologic oncology is in the management of otherwise refractory chronic radiation injury;HBO2 may provide symptomatic benefit in certain clinical settings (for example, cystitis, soft-tissue necrosis, and osteonecrosis); andHBO2 may reduce the complications of gynecologic surgery in patients undergoing surgical removal of necrosis.
PMCID: PMC3185899  PMID: 21980249
Hyperbaric oxygen therapy; HBO2; late radiation tissue injury; lrti; radiotherapy; gynecologic cancers; adverse effects; cancer pain; clinical practice guideline; systematic review
3.  Effects of hyperbaric oxygen on intestinal mucosa apoptosis caused by ischemia-reperfusion injury in rats 
BACKGROUND:
Hyperbaric oxygen (HBO) is an effective adjuvant therapy for ischemia- reperfusion (I/R) injury of the brain, small intestine and testis in addition to crushing injury. Studies have shown that HBO increases the activity of villi of the ileum 30 minutes after I/R injury. The present study aimed to observe the effect of HBO on apoptosis of epithelial cells in the small intestine during different periods of I/R and to elucidate the potential mechanisms.
METHODS:
Rats were subjected to 60-minute ischemia by clamping the superior mesenteric artery and 60-minute reperfusion by removal of clamping. The rats were randomly divided into four groups: I/R group, HBO precondition or HBO treatment before ischemia (HBO-P), HBO treatment during ischemia period (HBO-I), and HBO treatment during reperfusion (HBO-R). After 60-minute reperfusion, samples of the small intestine were prepared to measure the level of ATP by using the colorimetric method and immunochemical expression of caspase-3. The levels of TNF-α in intestinal tissue were measured using the enzyme-linked immunosorbent assay method (Elisa).
RESULTS:
TNF-α levels were significantly lower in the HBO-I group than in the HBO-P (P<0.05), HBO-R and I/R groups; there was no significant difference between the HBO-R and I/R groups (P>0.05). The expression of caspas-3 was significantly lower in the HBO-I group than in the HBO-P group (P<0.05); it was also significantly lower in the HBO-P group than in the I/R and HBO-R groups (P<0.05). ATP level was significantly lower in the HBO-I group than in the HBO-P group (P<0.05), and also it was significantly lower in the HBO-P group than in the I/R and HBO-R groups (P<0.05).
CONCLUSIONS:
There is an association between HBO, small intestinal I/R injury, and mucosa apoptosis. HBO maintains ATP and aerobic metabolism, inhibites TNF-α production, and thus prevents intestinal mucosa from apoptosis. Best results can be obtained when HBO is administered to patients in the period of ischemia, and no side effects are produced when HBO is given during the period of reperfusion.
doi:10.5847/wjem.j.issn.1920-8642.2012.02.010
PMCID: PMC4129796  PMID: 25215052
Hyperbaric oxygen; Ischemia-reperfusion injury; Apoptosis
4.  Hyperbaric Oxygen Treatment Induces a Two-Phase Antinociceptive Response of Unusually Long Duration in Mice 
Hyperbaric oxygen (HBO2) therapy is approved by the FDA for limited clinical indications but is reported to produce pain relief in several chronic pain conditions. However, there have been no studies to explain this apparent analgesic effect of HBO2. Research conducted in our laboratory demonstrates that four daily 60-min HBO2 treatments at 3.5 ATA induced an unparalleled antinociceptive response that consists of 1) an early phase that lasted at least six hours after the HBO2 treatment before dissipating; and 2) a late phase that emerged about 18 hours after the early phase and lasted for up to three weeks. The early phase was sensitive to antagonism by acutely intracerebroventricular (i.c.v.)-administered opioid antagonist naltrexone and the nitric oxide synthase (NOS)-inhibitor L-NAME. The late phase was inhibited by treatment with i.c.v. naltrexone or L-NAME during the four HBO2 treatments but was not antagonized by either naltrexone or L-NAME following acute pretreatment two weeks after HBO2 treatment. These experimental results implicate a novel mechanism that is activated by HBO2, resulting in an antinociceptive response of unusually long duration that is of potential interest in the clinical management of pain.
Perspective
Hyperbaric oxygen treatment of mice can induce a two-phase antinociceptive response of unusually long duration. Nitric oxide and opioid receptors appear to initiate or mediate both phases of the antinociceptive response. Further elucidation of the underlying mechanism may potentially identify molecular targets that cause long-lasting activation of endogenous analgesic systems.
doi:10.1016/j.jpain.2009.12.004
PMCID: PMC2910818  PMID: 20418186
Hyperbaric oxygen; antinociception; nitric oxide; opioid receptors; mice
5.  Effects of hyperbaric oxygen on aggressive periodontitis and subgingival anaerobes in Chinese patients 
Objective:
To investigate the effects of hyperbaric oxygen (HBO2) on aggressive periodontitis (AgP), and subgingival obligate anaerobes in Chinese patients.
Materials and Methods:
Sixty cases of Chinese patients with AgP were randomly divided into two groups –the HBO2 group (30 cases) and the control group (30 cases). Study teeth were divided into four groups –: the HBO2 therapy, the HBO2 + scaling scaling group, the scaling group and the control group. Subgingival anaerobic organisms were measured with anaerobic culture, and number of obligate anaerobes and facultative anaerobes and Bacteroides melaninogenicus was counted. Comparisons of changes in the clinical indices, and subgingival anaerobes were made between the groups.
Results:
Highly significant differences in gingival index (GI), probing depth (PD), attachment loss (AL), and Plaque index (PLI), and tooth odontoseisis (TO) were seen in the HBO2, the HBO2 + scaling and the scaling groups when compared with the control group (P<0.01). The number of subgingival anaerobes as well as the types of obligate anaerobes and facultative anaerobes and the number of Bacteroides melaninogenicus were reduced markedly in these three treatment groups. Highly statistical differences in clinical indices, subgingival anaerobe number and types of obligate anaerobes and facultative anaerobes and Bacteroides melaninogenicus were found when comparisons were made between the HBO2 + scaling and the HBO2 groups, as well as between the HBO2 + scaling and the scaling groups. Clinical follow-ups indicated that the GI, PD, AL, TO, PLI and subgingival anaerobes number of the three therapeutic groups were reduced more severely than the control group.
Conclusions:
HBO2 had good therapeutic effects on Chinese patients with AgP. HBO2 therapy combined with scaling and root planing was the most beneficial in the treatment of AgP. The therapeutic effect of HBO2 on AgP is most likely through inhibition of the growth of subgingival anaerobes. Clinical follow-ups suggest that the effect could last more than 2 years.
doi:10.4103/0972-124X.106880
PMCID: PMC3590714  PMID: 23493978
Aggressive periodontitis; Chinese; hyperbaric oxygen; subgingival anaerobes
6.  Therapeutic effect of hyperbaric oxygen in psoriasis vulgaris: two case reports and a review of the literature 
Introduction
Psoriasis is an inflammatory and immunological cutaneous disease. The high morbidity in patients with psoriasis results from severe clinical manifestations and/or adverse effects of treatment. The Undersea and Hyperbaric Medical Society and Federal Medicare and Medicaid Services have approved the use of hyperbaric oxygen (HBO2) for more than 15 indications, including wound healing, infections and late effects of radiation, which are largely unresponsive to conventional treatments. Accumulated data show that HBO2 has anti-inflammatory effects and other positive influences on the immune system, making it a rational treatment in the management of psoriasis plaques and arthritis.
Case presentation
We present the cases of two patients with long histories of psoriasis vulgarus who exhibited marked improvement with use of HBO2. The first patient was 40 years old and had pustular psoriasis and psoriatic arthritis. He was treated with six sessions of HBO2 (at 2.8 atmospheres of pressure for 60 minutes), which successfully controlled his symptoms. At the 18-month post-treatment follow up, the patient exhibited complete remission of psoriasis and marked improvement in psoriatic arthritis without medication. The second patient was 55 years old with extensive psoriatic lesions, and exhibited marked improvement within 15 sessions of HBO2. No adverse effects of HBO2 were identified.
Conclusions
HBO2 may possess potential therapeutic efficacy in the management of psoriasis. We outline the pathogenesis of psoriasis and the selective anti-inflammatory and immunosuppressive effects of HBO2. We hope that this will provide a basis for elucidating the mechanisms of action and consequently pave the way for further controlled studies.
doi:10.1186/1752-1947-0003-0000007023
PMCID: PMC2737769  PMID: 19830133
7.  Oxybiotest project: microorganisms under pressure. Hyperbaric oxygen (HBO) and simple pressure interaction on selected bacteria 
Medical Gas Research  2012;2:24.
Background
HyperBaric Oxygen (HBO) therapy involves exposure to pure oxygen in a pressurized room, and it is an already well-established treatment for various conditions, including those originated by serious infections. Starting from the observation of an increased number of patients who were accessing our HBO units for diseases supported from concomitant multidrug-resistant microorganisms, as well as considering the evident clinical benefit and laboratory final outcome of those patients at the end of the treatment, aim of our study was to measure, or better define at least, if there was any interaction between a hyperbaric environment and some selected microorganisms and if those positive results were due to the increased oxygen partial pressure (pO2) value or just to the increased pressure, regardless of the fraction of inspired oxygen (FiO2) applied (21÷100%).
Design and methods
We applied various increased pO2 values in a hyperbaric environment. Our study design was tailored in four steps to answer four specific questions, ordered in a progressive process: OxyBioTest (OBT)-1,2,3, and 4. Specifically, we chose to investigate possible changes in the Minimum Inhibitory Concentration (MIC) and in the Minimum Bactericidal Concentration (MBC) of multi-resistant microorganisms after a single session of hyperbaric therapy.
Results
OBT-1 and OBT-2 provide a semi-quantitative confirmation of the bacterio-cidal and cytostatic effects of HBO. HBO is cidal only if the total exposure pressure is elevated, and cidal or cytostatic effect are not always dependent on the pO2 applied.
OBT-4 has shown the adjuvant effect of HBO and antimicrobial drug against some selected bacteria.
Discussion
We seem allowed to hypothesize that only in case of a good approach to a lesion, permitting smaller bacterial loads thanks to surgical debridement and/or eventual antibiotic therapy for example, You can observe the clear effectiveness of the HyperBaric Oxygen (HBO) exposure as a valid adjuvant therapy, even when that lesion is substained from multidrug-resistant micro-organisms. On the contrary when the bacterial load is very high we observe an unchanged situation or a just a slightly diminishing in the number of cfu/ml.
Conclusions
Even if confined in this ‘in vitro’ environment and in a single treatment, just knowing the microorganism strain responsible of the lesion we seem allowed to both weight the possible related effectiveness using HBO Therapy (HBOT) and derive the best pO2 to treat the case. A further possible development of the study highlights a comparison between Acinetobacter baumannii (ACBA) and Pseudomonas aeruginosa (PSAE), and Escherichia coli (ESCO) and Klebsiella pneumoniae (KLPN).
doi:10.1186/2045-9912-2-24
PMCID: PMC3517458  PMID: 22963601
Hyperbaric; Oxygen; Microorganism; Bacteria
8.  Hyperbaric oxygen improves engraftment of ex-vivo expanded and gene transduced human CD34+ cells in a murine model of umbilical cord blood transplantation 
Delayed engraftment and graft failure represent major obstacles to successful umbilical cord blood (UCB) transplantation. Herein, we evaluated the use of hyperbaric oxygen (HBO) therapy as an intervention to improve human UCB stem/progenitor cell engraftment in an immune deficient mouse model. Six-to eight-week old NSG mice were sublethally irradiated 24 hours prior to CD34+ UCB cell transplant. Irradiated mice were separated into a non-HBO group (where mice remained under normoxic conditions) and the HBO group (where mice received two hours of HBO therapy; 100% oxygen at 2.5 atmospheres absolute). Four hours after completing HBO therapy, both groups intravenously received CD34+ UCB cells that were transduced with a lentivirus carrying luciferase gene and expanded for in vivo imaging. Mice were imaged and then sacrificed at one of 10 times up to 4.5 months post-transplant. HBO treated mice demonstrated significantly improved bone marrow, peripheral blood , and spleen (p=0.0293) retention and subsequent engraftment. In addition, HBO significantly improved peripheral, spleen and bone marrow engraftment of human myeloid and B-cell subsets. In vivo imaging demonstrated that HBO mice had significantly higher ventral and dorsal bioluminescence values. These studies suggest that HBO treatment of NSG mice prior to UCB CD34+ cell infusion significantly improves engraftment.
doi:10.1016/j.bcmd.2013.07.013
PMCID: PMC4075130  PMID: 23953010
Umbilical cord blood; CD34+; engraftment; hyperbaric oxygen
9.  Hyperbaric Hyperoxia Accelerates Fracture Healing in Mice 
PLoS ONE  2013;8(8):e72603.
Increased oxygen tension influences bone metabolism. This study comprised two main experiments: one aimed to determine the bone mineral apposition and bone formation rates in vivo under hyperbaric hyperoxia (HBO), and the other aimed to evaluate the effects of exposure to HBO on fracture healing. In experiment 1, male mice were exposed to HBO [90 min/day at 90% O2 at 2 atmospheres absolute (ATA) for 5 days]. In experiment 2, an open femur fracture model was created in mice, followed by exposure to HBO 5 times/week (90 min/day at 90% O2 at 2 ATA) for 6 weeks after surgery. In experiment 1, HBO treatment significantly increased the mineral apposition and bone formation rates in the lumbar vertebra and femur and type 1 collagen alpha 1 and alkaline phosphatase mRNA expression in the lumbar vertebra. In experiment 2, at 2 weeks after fracture, the fracture callus was significantly larger in the HBO group than in the non-HBO group. Furthermore, at 4 and 6 weeks after fracture, radiographic findings showed accelerated fracture healing in the HBO group. At 6 weeks after fracture, femur stiffness and maximum load were significantly higher in the HBO group than in the non-HBO group. Urinary 8-hydroxy-2′-deoxyguanosine and plasma calcium concentrations were not significantly different between groups. These results suggest that exposure to HBO enhances bone anabolism and accelerates fracture healing without causing oxidative DNA damage or disruption of plasma calcium homeostasis.
doi:10.1371/journal.pone.0072603
PMCID: PMC3743787  PMID: 23967323
10.  Influence of Adjuvant Hyperbaric Oxygen Therapy on Short-term Complications During Surgical Reconstruction of Upper and Lower Extremity War Injuries: Retrospective Cohort Study 
Croatian medical journal  2008;49(2):224-232.
Aim
To determine the effects of hyperbaric oxygen (HBO) therapy on short-term complications of complex war wounds to the upper and lower extremities in patients who were and those who were not treated according to North Atlantic Treaty Organization (NATO) emergency war surgery recommendations.
Method
We retrospectively analyzed data of 388 male patients undergoing reconstructive surgery for Gustilo type III A, B, and C war wounds to the extremities at the Department of Reconstructive Surgery, Split University Hospital Center, between 1991 and 1995. The occurrence of main wound complications (deep infection, osteomyelitis, skin grafts lyses, and flap necrosis) during hospitalization and time from wounding to granulation formation were analyzed with respect to the use of HBO therapy as a risk factor. Odds ratio (OR) with 95% confidence intervals (CI) was calculated for the occurrence of wound complications with respect to HBO therapy and adjusted for NATO surgical strategy by logistic regression.
Results
Of 388 patients, 310 (80%) were initially treated according to the NATO surgical strategy and 99 (25%) received HBO therapy. Deep soft-tissue infection developed in 196 (68%) patients who did not receive HBO therapy and in 35 (35%) who received it (P<0.001). Osteomyelitis developed in 214 (74%) patients who did not receive HBO therapy and in 62 (63%) who received it (P = 0.030). Skin graft lysis occurred in 151 (52%) patients who did not receive HBO therapy and in 23 (23%) who received it (P<0.001, χ2 test). Flap necrosis occurred in 147 (51%) patients who did not receive HBO therapy and in 15 (15%) who received it (P<0.001). Median time to granulation formation was 9 (5-57) days in patients who received HBO therapy, and 12 (1-12) days in those who did not (P<0.001, Mann-Whitney test). These results were consistent over the groups of patients stratified according to the wound severity and remained unaltered after the adjustment for NATO surgical strategy. The effect of HBO therapy was greater in non-NATO than in NATO treated patients in case of deep soft-tissue infection (OR, 10.7 vs OR, 3.8; P = 0.031 for interaction).
Conclusion
HBO therapy reduced the frequency of wound complications in patients with Gustilo type III wounds and shortened the time to granulation formation. HBO therapy was more effective in non-NATO than in NATO treated patients for the prevention of deep soft-tissue infection but not flap necrosis.
doi:10.3325/cmj.2008.2.224
PMCID: PMC2359875  PMID: 18461678
11.  Interstitial Cystitis in Persistent Posthysterectomy Chronic Pelvic Pain 
Objectives:
Hysterectomies may be performed unnecessarily in women with chronic pelvic pain if the diagnosis of interstitial cystitis is not considered. The objectives of this study were to investigate the prevalence of interstitial cystitis in patients with posthysterectomy chronic pelvic pain and to evaluate the efficacy of various therapies for interstitial cystitis.
Methods:
A study was performed of 111 patients with chronic pelvic pain whose pain persisted after hysterectomy. Patients were screened with the Pelvic Pain and Urgency/Frequency symptom scale, and underwent Potassium Sensitivity Testing. Patients were treated with dietary changes alone or in combination with cystoscopic hydrodistention or oral pentosan polysulfate, or both of these, for 3 to 6 months.
Results:
Of the 111 patients enrolled, 79% (n=88) were diagnosed with bladder dysfunction consistent with interstitial cystitis. For patients treated with dietary modification alone (n=33), the mean score on the Pelvic Pain and Urgency/Frequency questionnaire improved 15.4%, from 13.18 at baseline to 11.15 at follow-up. For patients treated with pentosan polysulfate or cystoscopic hydrodistention, or both, plus diet changes (n=78), Pelvic Pain and Urgency/Frequency scores improved 34.2%, from 15.01 to 9.87.
Conclusion:
In this study, nonsurgical treatment for interstitial cystitis resulted in a marked improvement in symptoms that had not improved with surgery. Without determining the origin of bladder pain, gynecologists should not proceed to hysterectomy in patients with chronic pelvic pain.
PMCID: PMC3016837  PMID: 15554275
Chronic pelvic pain; Posthysterectomy pain; Bladder-origin pain; Interstitial cystitis; Potassium Sensitivity Test; Pelvic Pain and Urgency/Frequency questionnaire
12.  Synergistic Inhibitory Effect of Hyperbaric Oxygen Combined with Sorafenib on Hepatoma Cells 
PLoS ONE  2014;9(6):e100814.
Objectives
Hypoxia is a common phenomenon in solid tumors, associated with chemotherapy and radiotherapy resistance, recurrence and metastasis. Hyperbaric oxygen (HBO) therapy can increase tissue oxygen pressure and content to prevent the resistance, recurrence and metastasis of cancer. Presently, Sorafenib is a first-line drug, targeted for hepatocellular carcinoma (HCC) but effective in only a small portion of patients and can induce hypoxia. The purpose of this study is to investigate the effect of HBO in combination with sorafenib on hepatoma cells.
Methods
Hepatoma cell lines (BEL-7402 and SK-Hep1) were treated with HBO at 2 atmosphere absolute pressure for 80 min per day or combined with sorafenib or cisplatin. At different time points, cells were tested for cell growth, colony formation, apoptosis, cell cycle and migration. Finally, miRNA from the hepatoma cells was detected by microRNA array and validated by qRT-PCR.
Results
Although HBO, sorafenib or cisplatin alone could inhibit growth of hepatoma cells, HBO combined with sorafenib or cisplatin resulted in much greater synergistic growth inhibition (cell proliferation and colony formation) in hepatoma cells. Similarly, the synergistic effect of HBO and sorafenib on induction of apoptosis was also observed in hepatoma cells. HBO induced G1 arrest in SK-Hep1 not in BEL-7402 cells, but enhanced cell cycle arrest induced by sorafenib in BEL-7402 treated cells. However, HBO had no obvious effect on the migration of hepatoma cells, and microRNA array analysis showed that hepatoma cells with HBO treatment had significantly different microRNA expression profiles from those with blank control.
Conclusions
We show for the first time that HBO combined with sorafenib results in synergistic growth inhibition and apoptosis in hepatoma cells, suggesting a potential application of HBO combined with sorafenib in HCC patients. Additionally, we also show that HBO significantly altered microRNA expression in hepatoma cells.
doi:10.1371/journal.pone.0100814
PMCID: PMC4067386  PMID: 24956259
13.  Hyperbaric Oxygen Exposures at 3 and 4 Atmospheres Absolute Pressure for Experimental Gas Gangrene: Succinate Protection Against Oxygen Toxicity 
The concurrent effect of succinate administration to protect against oxygen toxicity and of hyperbaric oxygen (HBO) exposures to treat model gas gangrene in mice was tested to determine whether succinate would interfere with the therapeutic efficacy of HBO. HBO (seven 90-min exposures) at 3 atmospheres absolute pressure (ATA) had been shown to reduce significantly the mortality of mice injected with Clostridium perfringens suspended in 10 μg of Adrenalin. When succinate was tested with this system, mortality of HBO-exposed infected animals was again significantly reduced (79% control mortality versus 17% HBO-exposed mortality), indicating that succinate does not interfere with the action of HBO. Exposures to 4 ATA of O2 were evaluated in the same model clostridial infection with succinate used to prevent oxygen toxicity. Five 30-min exposures at 4 ATA reduced the mortality of infected animals (62% control versus 6% HBO-exposed mortality). Intraperitoneal succinate injections (10 mmoles/kg) were given 20 to 25 min prior to four of the seven 3-ATA exposures and before three of the five 4-ATA exposures. The intermittent succinate injections gave significant protection against the development of oxygen toxicity in infected and noninfected mice at both O2 pressures. These studies support the potential clinical use of succinate or other oxygen-protective agents (i) to shorten HBO exposure times by using higher pressures to deliver the necessary O2 dose, (ii) to increase the O2 dose for difficult clinical situations by using maximal exposures at 4 ATA or more prolonged exposures at 2 to 3 ATA, and (iii) to continue HBO exposures in patients who require treatment but develop symptoms of oxygen toxicity.
PMCID: PMC444324  PMID: 4670508
14.  Involvement of brain opioid receptors in the anti-allodynic effect of hyperbaric oxygen in rats with sciatic nerve crush-induced neuropathic pain 
Brain research  2013;1537:10.1016/j.brainres.2013.08.050.
Earlier research has demonstrated that hyperbaric oxygen (HBO2) can produce an antinociceptive effect in models of acute pain. Recent studies have revealed that HBO2 can produce pain relief in animal models of chronic pain as well. The purpose of the present investigation was to ascertain whether HBO2 treatment might suppress allodynia in rats with neuropathic pain and whether this effect might be blocked by the opioid antagonist naltrexone (NTX). Male Sprague Dawley rats were subjected to a sciatic nerve crush under anesthesia and mechanical thresholds were assessed using an electronic von Frey anesthesiometer. The time course of the HBO2-induced anti-allodynic effect in different treatment groups was plotted, and the area-under-the-curve (AUC) was determined for each group. Seven days after the nerve crush procedure, rats were treated with HBO2 at 3.5 atmospheres absolute (ATA) for 60 min and exhibited an anti-allodynic effect, compared to nerve crush-only control rats. Twenty-four hours before HBO2 treatment, another group of rats was implanted with Alzet® osmotic minipumps that continuously released NTX into the lateral cerebral ventricle for 7 days. These NTX-infused, HBO2-treated rats exhibited an allodynic response comparable to that exhibited by rats receiving nerve crush only. Analysis of the AUC data showed that HBO2 significantly reduced the nerve crush-induced allodynia; this anti-allodynic effect of HBO2 was reversed by NTX. These results implicate opioid receptors in the pain relief induced by HBO2.
doi:10.1016/j.brainres.2013.08.050
PMCID: PMC3827781  PMID: 23998986
Hyperbaric oxygen; anti-allodynia; naltrexone; opioid receptors; neuropathic pain; sciatic nerve crush; rat
15.  Long Course Hyperbaric Oxygen Stimulates Neurogenesis and Attenuates Inflammation after Ischemic Stroke 
Mediators of Inflammation  2013;2013:512978.
Several studies have provided evidence with regard to the neuroprotection benefits of hyperbaric oxygen (HBO) therapy in cases of stroke, and HBO also promotes bone marrow stem cells (BMSCs) proliferation and mobilization. This study investigates the influence of HBO therapy on the migration of BMSCs, neurogenesis, gliosis, and inflammation after stroke. Rats that sustained transient middle cerebral artery occlusion (MCAO) were treated with HBO three weeks or two days. The results were examined using a behavior test (modified neurological severity score, mNSS) and immunostaining to evaluate the effects of HBO therapy on migration of BMSCs, neurogenesis, and gliosis, and expression of neurotrophic factors was also evaluated. There was a lower mNSS score in the three-week HBO group when compared with the two-day HBO group. Mobilization of BMSCs to an ischemic area was more improved in long course HBO treatments, suggesting the duration of therapy is crucial for promoting the homing of BMSCs to ischemic brain by HBO therapies. HBO also can stimulate expression of trophic factors and improve neurogenesis and gliosis. These effects may help in neuronal repair after ischemic stroke, and increasing the course of HBO therapy might enhance therapeutic effects on ischemic stroke.
doi:10.1155/2013/512978
PMCID: PMC3595722  PMID: 23533308
16.  Early Identification of Interstitial Cystitis May Avoid Unnecessary Hysterectomy 
Background:
Interstitial cystitis is a clinical syndrome characterized by symptoms of pelvic pain, urinary urgency and frequency, and nocturia. It can be difficult to accurately identify interstitial cystitis because the symptoms overlap many other common gynecologic and urologic conditions. Patients with undiagnosed interstitial cystitis may undergo unnecessary procedures, including hysterectomy.
Methods:
A PubMed literature search for articles dating back to 1990 was conducted on the topics of interstitial cystitis and hysterectomy. Further references were identified by cross-referencing the bibliographies in articles of interest.
Results:
The literature review found that hysterectomy is performed more often in patients with undiagnosed interstitial cystitis than in patients with a confirmed diagnosis. Interstitial cystitis often coexists with conditions like endometriosis, for which hysterectomy is indicated. Many patients subsequently diagnosed with interstitial cystitis continue to experience persistent pelvic pain despite having had a hysterectomy for chronic pelvic pain. Careful history and physical examination can identify the majority of interstitial cystitis cases.
Conclusion:
Interstitial cystitis should be considered prior to hysterectomy in women who present with pelvic pain or who experience pelvic pain after a hysterectomy. If interstitial cystitis is diagnosed, appropriate therapy may eliminate the need for hysterectomy.
PMCID: PMC3015962  PMID: 19793476
Interstitial cystitis; Hysterectomy; Pelvic pain; Pentosan polysulfate sodium
17.  Comparison of an Interstitial Cystitis/Bladder Pain Syndrome Clinical Cohort With Symptomatic Community Women From the RAND Interstitial Cystitis Epidemiology Study 
The Journal of urology  2011;187(2):508-512.
Purpose
The RAND Interstitial Cystitis Epidemiology survey estimated that 2.7% to 6.5% of United States women have urinary symptoms consistent with a diagnosis of interstitial cystitis/bladder pain syndrome. We describe the demographic and clinical characteristics of the symptomatic community based RAND Interstitial Cystitis Epidemiology cohort, and compare them with those of a clinically based interstitial cystitis/bladder pain syndrome cohort.
Materials and Methods
Subjects included 3,397 community women who met the criteria for the RAND Interstitial Cystitis Epidemiology high sensitivity case definition, and 277 women with an interstitial cystitis/bladder pain syndrome diagnosis recruited from specialist practices across the United States (clinical cohort). Questions focused on demographic information, symptom severity, quality of life indicators, concomitant diagnoses and treatment.
Results
Average symptom duration for both groups was approximately 14 years. Women in the clinical cohort reported worse baseline pain and maximum pain, although the absolute differences were small. Mean Interstitial Cystitis Symptom Index scores were approximately 11 for both groups, but mean Interstitial Cystitis Problem Index scores were 9.9 and 13.2 for the clinical cohort and the RAND Interstitial Cystitis Epidemiology cohort, respectively (p <0.001). The RAND Interstitial Cystitis Epidemiology subjects were more likely to be uninsured.
Conclusions
The RAND Interstitial Cystitis Epidemiology community cohort was remarkably similar to an interstitial cystitis/bladder pain syndrome clinical cohort with respect to demographics, symptoms and quality of life measures. In contrast to other chronic pain conditions for which clinical cohorts typically report worse symptoms and functional status than population based samples, our data suggest that many measures of symptom severity and functional impact are similar, and sometimes worse, in the RAND Interstitial Cystitis Epidemiology cohort. These findings suggest that interstitial cystitis/bladder pain syndrome is significantly burdensome, and likely to be underdiagnosed and undertreated in the United States.
doi:10.1016/j.juro.2011.10.040
PMCID: PMC3894739  PMID: 22177158
cystitis; interstitial; epidemiology; prevalence; questionnaires
18.  Effects of hyperbaric oxygen on pain-related behaviours and nitric oxide synthase expression in a rat model of neuropathic pain 
BACKGROUND:
Neuropathic pain is complex, and a satisfactory therapeutic method of treatment has yet to be developed; therefore, finding a new and effective therapeutic method is an important issue in the field of neuropathic pain.
OBJECTIVE:
To determine the effects of hyperbaric oxygen (HBO) on pain-related behaviours and nitric oxide synthase (NOS) expression in a rat model of neuropathic pain.
METHODS:
Forty male Sprague Dawley rats were randomly divided into five groups (eight rats per group) including control, sham operation, sciatic nerve with chronic constriction injury (CCI), HBO pretreatment (pre-HBO) and HBO post-treatment (post-HBO) groups. Pain-related behaviours and NOS expression in the spinal cord were compared among the five groups.
RESULTS:
Compared with the CCI group, the mechanical withdrawal threshold was significantly increased and thermal withdrawal latency was significantly extended in the pre-HBO and post-HBO groups (all P<0.05). After CCI, expression of spinal neuronal NOS and inducible NOS were increased. Expression of spinal neuronal NOS and inducible NOS were significantly decreased in the pre-HBO and post-HBO groups compared with the CCI group (all P<0.05). Spinal eNOS expression changed very little.
DISCUSSION:
HBO has been used as an effective and noninvasive method for the treatment of spinal cord injuries and high-altitude sickness, and in immunosuppression and stem-cell research; however, it has yet to be applied to the treatment of neuropathic pain. The present study indicated that HBO effectively increased mechanical withdrawal threshold and thermal withdrawal latency, demonstrating that HBO has therapeutic effects on neuropathic pain.
CONCLUSION:
HBO inhibits pain in rats with CCI through the regulation of spinal NOS expression.
PMCID: PMC3673931  PMID: 23748254
Hyperbaric oxygen; Neuropathic pain; Nitric oxide synthase
19.  Hyperbaric oxygen therapy as an adjunctive treatment for sternal infection and osteomyelitis after sternotomy and cardiothoracic surgery 
Purpose
A retrospective study to evaluate the effect of hyperbaric oxygen (HBO2) therapy on sternal infection and osteomyelitis following median sternotomy.
Materials and methods
A retrospective analysis of patients who received sternotomy and cardiothoracic surgery which developed sternal infection and osteomyelitis between 2002 and 2009. Twelve patients who received debridement and antibiotic treatment were selected, and six of them received additional HBO2 therapy. Demographic, clinical characteristics and outcome were compared between patients with and without HBO2 therapy.
Results
HBO2 therapy did not cause any treatment-related complication in patients receiving this additional treatment. Comparisons of the data between two study groups revealed that the length of stay in ICU (8.7 ± 2.7 days vs. 48.8 ± 10.5 days, p < 0.05), duration of invasive (4 ± 1.5 days vs. 34.8 ± 8.3 days, p < 0.05) and non-invasive (4 ± 1.9 days vs. 22.3 ± 6.2 days, p < 0.05) positive pressure ventilation were all significantly lower in patients with additional HBO2 therapy, as compared to patients without HBO2 therapy. Hospital mortality was also significantly lower in patients who received HBO2 therapy (0 case vs. 3 cases, p < 0.05), as compared to patients without the HBO2 therapy.
Conclusions
In addition to primary treatment with debridement and antibiotic use, HBO2 therapy may be used as an adjunctive and safe treatment to improve clinical outcomes in patients with sternal infection and osteomyelitis after sternotomy and cardiothoracic surgery.
doi:10.1186/1749-8090-6-141
PMCID: PMC3215992  PMID: 22004802
hyperbaric oxygen; sternal infection; osteomyelitis; sternotomy; Cardiothoracic surgery
20.  Sacral Nerve Stimulation For Urinary Urge Incontinence, Urgency-Frequency, Urinary Retention, and Fecal Incontinence 
Executive Summary
Objective
The aim of this review was to assess the effectiveness, safety, and cost of sacral nerve stimulation (SNS) to treat urinary urge incontinence, urgency-frequency, urinary retention, and fecal incontinence.
Background: Condition and Target Population
Urinary urge incontinence, urgency-frequency, urinary retention, and fecal incontinence are prevalent, yet rarely discussed, conditions. They are rarely discussed because patients may be uncomfortable disclosing their symptoms to a health professional or may be unaware that there are treatment options for these conditions. Briefly, urge incontinence is an involuntary loss of urine upon a sudden urge. Urgency-frequency is an uncontrollable urge to void, which results in frequent, small-volume voids. People with urgency-frequency may or may not also experience chronic pelvic pain. Urinary retention refers to the inability to void despite having the urge to void. It can be caused by a hypocontractile detrusor (weak or no bladder muscle contraction) or obstruction due to urethral overactivity. Fecal incontinence is a loss of voluntary bowel control.
The prevalence of urge incontinence, urgency-frequency, and urinary retention in the general population is 3.3% to 8.2%, and the prevalence of fecal incontinence is 1.4% to 1.9%. About three-quarters of these people will be successfully treated by behaviour and/or drug therapy. For those who do not respond to these therapies, the options for treatment are management with diapers or pads, or surgery. The surgical procedures are generally quite invasive, permanent, and are associated with complications. Pads and/or diapers are used throughout the course of treatment as different therapies are tried. Patients who respond successfully to treatment may still require pads or diapers, but to a lesser extent.
The Technology Being Reviewed: Sacral Nerve Stimulation
Sacral nerve stimulation is a procedure where a small device attached to an electrode is implanted in the abdomen or buttock to stimulate the sacral nerves in an attempt to manage urinary urge incontinence, urgency-frequency, urinary retention, and fecal incontinence. The device was originally developed to manage urinary urge incontinence; however, it has also been used in patients with urgency-frequency, urinary retention, and fecal incontinence. SNS is intended for patients who are refractory to behaviour, drug, and/or interventional therapy.
There are 2 phases in the SNS process: first, patients must undergo a test stimulation phase to determine if they respond to sacral nerve stimulation. If there is a 50% or greater improvement in voiding function, then the patient is considered a candidate for the next phase, implantation.
Review Strategy
The standard Medical Advisory Secretariat search strategy was used to locate international health technology assessments and English-language journal articles published from 2000 to November 2004. The Medical Advisory Secretariat also conducted Internet searches of Medscape (1) and the manufacturer’s website (2) to identify product information and recent reports on trials that were unpublished but that were presented at international conferences. In addition, the Web site Current Controlled Trials (3) was searched for ongoing randomized controlled trials (RCTs) investigating the role of sacral nerve stimulation in the management of voiding conditions.
Summary of Findings
Four health technology assessments were found that reviewed SNS in patients with urge incontinence, urgency-frequency, and/or urinary retention. One assessment was found that reviewed SNS in patients with fecal incontinence. The assessments consistently reported that SNS was an effective technology in managing these voiding conditions in patients who did not respond to drug or behaviour therapy. They also reported that there was a substantial complication profile associated with SNS. Complication rates ranged from 33% to 50%. However, none of the assessments reported that they found any incidences of permanent injury or death associated with the device.
The health technology assessments for urge incontinence, urgency-frequency, and urinary retention included (RCTs (level 2) as their primary source of evidence for their conclusions. The assessment of fecal incontinence based its conclusions on evidence from case series (level 4). Because there was level 2 data available for the use of SNS in patients with urinary conditions, the Medical Advisory Secretariat chose to review thoroughly the RCTs included in the assessments and search for publications since the assessments were released. However, for the health technology assessment for fecal incontinence, which contained only level 4 evidence, the Medical Advisory Secretariat searched for studies on SNS and fecal incontinence that were published since that assessment was released.
Urge Incontinence
Two RCTs were identified that compared SNS to no treatment in patients with refractory urge incontinence. Both RCTs reported significant improvements (> 50% improvement in voiding function) in the SNS group for number of incontinence episodes per day, number of pads used per day, and severity of incontinence episodes.
Urgency-Frequency (With or Without Chronic Pelvic Pain)
One RCT was identified that compared SNS to no treatment in patients with refractory urgency-frequency. The RCT reported significant improvements in urgency-frequency symptoms in the SNS group (average volume per void, detrusor pressure). In addition to the RCT, 1 retrospective review and 2 prospective case series were identified that measured pelvic pain associated with urgency-frequency in patients who underwent SNS. All 3 studies reported a significant decrease in pain at median follow-up.
Urinary Retention
One RCT was identified that compared SNS to no treatment in patients with refractory urinary retention. The RCT reported significant improvements in urinary retention in the SNS group compared to the control group for number of catheterizations required and number of voids per day. In addition to this RCT, 1 case series was also identified investigating SNS in women with urinary retention. This study also found that there were significant improvements in urinary retention after the women had received the SNS implants.
Fecal Incontinence
Three case series were identified that investigated the role of SNS in patients with fecal incontinence. All 3 reported significant improvements in fecal incontinence symptoms (number of incontinent episodes per week) after the patients received the SNS implants.
Long-Term Follow-up
None of the studies identified followed patients until the point of battery failure. Of the 6 studies identified describing the long-term follow-up of patients with SNS, follow-up periods ranged from 1.5 years to over 5 years. None of the long-term follow-up studies included patients with fecal incontinence. All of the studies reported that most of the patients who had SNS had at least a 50% improvement in voiding function (range 58%–77%). These studies also reported the number of patients who had their device explanted in the follow-up period. The rates of explantation ranged from 12% to 21%.
Safety, Complications, and Quality of Life
A 33% surgical revision rate was reported in an analysis of the safety of 3 RCTs comparing SNS to no treatment in patients with urge incontinence, urgency-frequency, or urinary retention. The most commonly reported adverse effects were pain at the implant site and lead migration. Despite the high rate of surgical revision, there were no reports of permanent injury or death in any of the studies or health technology assessments identified. Additionally, patients consistently said that they would recommend the procedure to a friend or family member.
Economic Analysis
One health technology assessment and 1 abstract were found that investigated the costing factors pertinent to SNS. The authors of this assessment did their own “indicative analysis” and found that SNS was not more cost-effective than using incontinence supplies. However, the assessment did not account for quality of life. Conversely, the authors of the abstract found that SNS was more cost-effective than incontinence supplies alone; however, they noted that in the first year after SNS, it is much more expensive than only incontinence supplies. This is owing to the cost of the procedure, and the adjustments required to make the device most effective. They also noted the positive effects that SNS had on quality of life.
Conclusions and Implications
In summary, there is level 2 evidence to support the effectiveness of SNS to treat people with urge incontinence, urgency-frequency, or urinary retention. There is level 4 evidence to support the effectiveness of SNS to treat people with fecal incontinence.
To qualify for SNS, people must meet the following criteria:
Be refractory to behaviour and/or drug therapy
Have had a successful test stimulation before implantation; successful test stimulation is defined by a 50% or greater improvement in voiding function based on the results of a voiding diary. Test stimulation periods range from 3 to 7 days for patients with urinary dysfunctions, and from 2 to 3 weeks for patients with fecal incontinence.
Be able to record voiding diary data, so that clinical results of the implantation can be evaluated.
Patients with stress incontinence, urinary retention due to obstruction and neurogenic conditions (such as diabetes with peripheral nerve involvement) are ineligible for sacral nerve stimulation.
Physicians will need to learn how to use the InterStim System for Urinary Control. Requirements for training include these:
Physicians must be experienced in the diagnosis and treatment of lower urinary tract disorders and should be trained in the implantation and use of the InterStim System for Urinary Control.
Training should include the following:
Participation in a seminar or workshop that includes instructional and laboratory training on SNS. This seminar should include a review of the evidence on SNS with emphasis on techniques to prevent adverse events.
Completion of proctoring by a physician experienced in SNS for the first 2 test stimulations and the first 2 implants
PMCID: PMC3382408  PMID: 23074472
21.  Effect of hyperbaric oxygen on mesenchymal stem cells for lumbar fusion in vivo 
Background
Hyperbaric oxygen (HBO) therapy has been proved in improving bone healing, but its effects on mesenchymal stem cells (MSCs) in vivo is not clear. The aims of this study are to clarify whether the HBO therapy has the same enhancing effect on MSCs with regard to bone formation and maturation and to ascertain whether the transplanted MSCs survive in the grafted area and contribute to new bone formation.
Methods
Twenty-three adult rabbits underwent posterolateral fusion at L4-L5 level. The animals were divided into three groups according to the material implanted and subsequent treatment: (1) Alginate carrier (n = 6); (2) Alginate-MSCs composite (n = 11); and (3) Alginate-MSCs composite with HBO therapy (n = 6). After 12 weeks, spine fusion was examined using radiographic examination, manual testing, and histological examination. Using a PKH fluorescence labeling system, whether the transplanted MSCs survived and contributed to new bone formation in the grafted area after HBO therapy was also examined.
Results
The bilateral fusion areas in each animal were evaluated independently. By radiographic examination and manual palpation, union for the Alginate, Alginate-MSCs, and Alginate-MSCs-HBO groups was 0 of 12, 10 of 22, and 6 of 12 respectively. The difference between the Alginate-MSCs and Alginate-MSCs-HBO groups was not significant (P = 0.7997). The fluorescence microscopy histological analysis indicated that the transplanted PKH67-labeled MSCs survived and partly contributed to new bone formation in the grafted area.
Conclusions
This study demonstrated that the preconditioned MSCs could survive and yield bone formation in the grafted area. HBO therapy did not enhance the osteogenic ability of MSCs and improve the success of spine fusion in the rabbit model. Although there was no significant effect of HBO therapy on MSCs for spine fusion, the study encourages us to research a more basic approach for determining the optimal oxygen tension and pressure that are required to maintain and enhance the osteogenic ability of preconditioned MSCs. Further controlled in vivo and in vitro studies are required for achieving a better understanding of the effect of HBO treatment on MSCs.
doi:10.1186/1471-2474-11-52
PMCID: PMC2850325  PMID: 20302633
22.  Hyperbaric oxygenation enhances transplanted cell graft and functional recovery in the infarct heart 
A major limitation to the application of stem-cell therapy to repair ischemic heart damage is the low survival of transplanted cells in the heart, possibly due to poor oxygenation. We hypothesized that hyperbaric oxygenation (HBO) can be used as an adjuvant treatment to augment stem-cell therapy. Therefore, the goal of this study was to evaluate the effect of HBO on the engraftment of rat bone-marrow-derived mesenchymal stem cells (MSCs) transplanted in infarct rat hearts. Myocardial infarction (MI) was induced in Fisher-344 rats by permanently ligating the left-anterior-descending coronary artery. MSCs, labeled with fluorescent superparamagnetic iron oxide (SPIO) particles, were transplanted in the infarct and peri-infarct regions of the MI hearts. HBO (100% oxygen at 2 ATA for 90 min) was administered daily for 2 weeks. Four MI groups were used: untreated (MI); HBO; MSC; MSC+HBO. Echocardiography, electro-vectorcardiography, and magnetic resonance imaging were used for functional evaluations. The engraftment of transplanted MSCs in the heart was confirmed by SPIO fluorescence and Prussian-blue staining. Immunohistochemical staining was used to identify key cellular and molecular markers including CD29, troponin-T, connexin-43, VEGF, α-smooth-muscle actin, and von-Willebrand factor in the tissue. Compared to MI and MSC groups, the MSC+HBO group showed a significantly increased recovery of cardiac function including left-ventricular (LV) ejection fraction, fraction-shortening, LV wall-thickness, and QRS vector. Further, HBO treatment significantly increased the engraftment of CD29-positive cells, expression of connexin-43, troponin-T and VEGF, and angiogenesis in the infarct tissue. Thus, HBO appears to be a potential and clinically-viable adjuvant treatment for myocardial stem-cell therapy.
doi:10.1016/j.yjmcc.2009.04.005
PMCID: PMC2703688  PMID: 19376124
Mesenchymal stem cell; hyperbaric oxygen; myocardial infarction; stem-cell therapy
23.  Hyperbaric Oxygen Prevents Early Death Caused by Experimental Cerebral Malaria 
PLoS ONE  2008;3(9):e3126.
Background
Cerebral malaria (CM) is a syndrome characterized by neurological signs, seizures and coma. Despite the fact that CM presents similarities with cerebral stroke, few studies have focused on new supportive therapies for the disease. Hyperbaric oxygen (HBO) therapy has been successfully used in patients with numerous brain disorders such as stroke, migraine and atherosclerosis.
Methodology/Principal Findings
C57BL/6 mice infected with Plasmodium berghei ANKA (PbA) were exposed to daily doses of HBO (100% O2, 3.0 ATA, 1–2 h per day) in conditions well-tolerated by humans and animals, before or after parasite establishment. Cumulative survival analyses demonstrated that HBO therapy protected 50% of PbA-infected mice and delayed CM-specific neurological signs when administrated after patent parasitemia. Pressurized oxygen therapy reduced peripheral parasitemia, expression of TNF-α, IFN-γ and IL-10 mRNA levels and percentage of γδ and αβ CD4+ and CD8+ T lymphocytes sequestered in mice brains, thus resulting in a reduction of blood-brain barrier (BBB) dysfunction and hypothermia.
Conclusions/Significance
The data presented here is the first indication that HBO treatment could be used as supportive therapy, perhaps in association with neuroprotective drugs, to prevent CM clinical outcomes, including death.
doi:10.1371/journal.pone.0003126
PMCID: PMC2518956  PMID: 18769544
24.  Assessing urgency in interstitial cystitis/painful bladder syndrome 
Urology  2007;69(2):210-214.
Objective
Interstitial cystitis/painful bladder syndrome (IC/PBS) at present is a symptom-based diagnosis. The Interstitial Cystitis Symptom Index (ICSI), also known as the O’Leary-Sant Symptom Index, is a widely used scale that assesses the 4 cardinal symptoms of IC/PBS, i.e. bladder pain, urgency, frequency, and nocturia, by asking how often each is experienced. In an ongoing case control study of recent onset IC/PBS, we compared the ICSI to questions that addressed severity of these symptoms.
Methods
Recruiting nationally, we enrolled women with IC/PBS symptoms of ≤12 months. We assessed severity of pain, frequency, and urgency by Likert and categorical scales, and how often these symptoms were experienced by the ICSI. We compared these scales by frequency distributions and inter-scale correlations.
Results
In 138 women with recent onset IC/PBS, scores for frequency were correlated and for pain appeared to be complementary. However for urgency, the ICSI question of “the strong need to urinate with little or no warning” consistently yielded lower scores than the severity question of “the compelling urge to urinate which is difficult to postpone”. Indeed, some patients denied urgency to the ICSI question yet reported intense urgency to the severity question.
Conclusions
Compared to the severity question, the ICSI underestimated the prevalence and degree of urgency. This observation is consistent with the views of others that sudden urgency does not define the sensation experienced by many IC/PBS patients. Clarifying this symptom description may assist in developing a usable case definition for IC/PBS.
doi:10.1016/j.urology.2006.09.053
PMCID: PMC1855150  PMID: 17275075
Interstitial cystitis; painful bladder syndrome; symptoms; urgency
25.  Bladder Pain Syndrome Treated with Triple Therapy with Gabapentin, Amitriptyline, and a Nonsteroidal Anti-Inflammatory Drug 
Purpose
Bladder pain syndrome is a chronic disease that manifests as bladder pain, frequency, nocturia, and urgency. Gabapentin, amitriptyline, and nonsteroidal anti-inflammatory drugs are efficacious treatments for bladder pain syndrome. Here, we assessed the effect of triple therapy with these drugs in women with bladder pain syndrome.
Methods
Between May 2007 and May 2010, we conducted a prospective nonrandomized study on 74 patients with bladder pain syndrome. Of these patients, 38 (11 men and 27 women; mean age, 55.9 years; range, 25 to 77 years; mean follow-up, 12.6 months) were administered the interstitial cystitis (IC) symptom scales (O'Leary-Sant Symptom Index) and visual analog scale (VAS) 1, 3, and 6 months after treatment to assess the efficacy of triple therapy.
Results
The pretreatment O'Leary-Sant IC symptom score was 11.7, and the post-treatment scores were 4.4, 3.8, and 4.0 at 1, 3, and 6 months, respectively; the pretreatment problem index score was 10.5, and the post-treatment scores were 3.7, 2.7, and 2.9 at 1, 3, and 6 months, respectively. The pretreatment VAS score was 6.7, and the post-treatment scores were 1.8, 1.5, and 1.7 at 1, 3, and 6 months, respectively. The O'Leary-Sant IC symptom index and problem index and VAS scores improved considerably 1 month after treatment (P<0.05). However, the results at 1, 3, and 6 months after treatment were not significantly different (P>0.05).
Conclusions
Triple therapy was sufficiently effective in patients with bladder pain syndrome and caused no significant adverse effects. However, large-scale studies should be performed to verify our findings.
doi:10.5213/inj.2010.14.4.256
PMCID: PMC3021818  PMID: 21253338
Bladder pain syndrome; Interstitial cystitis; Visual analog scale

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