Migraine patients who do not respond to conventional therapy, develop unacceptable side-effects, or are reluctant to take medicines resort to complementary and alternative medicines (CAM). Globally, patients have been seeking various non-conventional modes of therapy for the management of their headaches. An Ayurvedic Treatment Protocol (AyTP) comprising five Ayurvedic medicines, namely Narikel Lavan, Sootshekhar Rasa, Sitopaladi Churna, Rason Vati and Godanti Mishran along with regulated diet and lifestyle modifications such as minimum 8 h sleep, 30-60 min morning or evening walk and abstention from smoking/drinking, was tried for migraine treatment. The duration of the therapy was 90 days. Out of 406 migraine patients who were offered this AyTP, 204 patients completed 90 days of treatment. Complete disappearance of headache and associated symptoms at completion of AyTP was observed in 72 (35.2%); mild episode of headache without need of any conventional medicines in 72 (35.2%); low intensity of pain along with conventional medicines in 50 (24.5%); no improvement in seven (3.4%) and worst pain was noted in three (1.4%) patients, respectively. In 144 (70.5%) of patients marked reduction of migraine frequency and pain intensity observed may be because of the AyTP. Though the uncontrolled open-label design of this study does not allow us to draw a definite conclusion, from this observational study we can make a preliminary assessment regarding the effectiveness of this ayurvedic treatment protocol.
Alternative therapy; Ayurveda; CAM; migraine
Regression of cancer has been an interiguiny factor for medicinal science. This article is bringing out some interesting data on this issue with a view to generate in the Ayurvedic researchers to see the possibilities of Ayurveda in induced regression of cancer.
Determining the composition of protein complexes is an essential step towards understanding the cell as an integrated system. Using co-affinity purification coupled to mass spectrometry analysis, we examined protein associations involving nearly five thousand individual, FLAG-HA epitope-tagged Drosophila proteins. Stringent analysis of these data, based on a novel statistical framework to define individual protein-protein interactions, led to the generation of a Drosophila
Protein interaction Map (DPiM) encompassing 556 protein complexes. The high quality of DPiM and its usefulness as a paradigm for metazoan proteomes is apparent from the recovery of many known complexes, significant enrichment for shared functional attributes and validation in human cells. DPiM defines potential novel members for several important protein complexes and assigns functional links to 586 protein-coding genes lacking previous experimental annotation. DPiM represents, to our knowledge, the largest metazoan protein complex map and provides a valuable resource for analysis of protein complex evolution.
Drosophila; proteome; protein complex map; interactome
Spontaneous gas gangrene is necrosis of muscles in the absence of trauma, causing an acutely painful and potentially fatal condition. However, the occurrence of this condition in Crohn’s disease has been very rarely documented.
In this extremely rare case we describe an occurrence of spontaneous gas gangrene, in a known case of Crohn’s disease. The patient presented with fever and pain in the left arm and abdomen. After admission and initial management with antibiotics, the patient developed crepitus in the arm and myonecrosis necessitating a fasciotomy and later an emergency amputation of his left upper limb.
The pathogenesis of gas gangrene in inflammatory bowel disease is not fully understood. Management includes aggressive antibiotic administration followed by amputation of the non-salvageable limb.
A high index of suspicion of such rare complications is a must and surgical intervention is life saving; however, the efficacy of anti-gas gangrene serum is controversial. We recommend use of a multipronged approach in such cases with high mortality rates.
spontaneous gas gangrene; Crohns disease; fasciotomy
A health demographic surveillance system (HDSS) provides longitudinal data regarding health and demography in countries with coverage error and poor quality data on vital registration systems due to lack of public awareness, inadequate legal basis and limited use of data in health planning. The health system in Nepal, a low-income country, does not focus primarily on health registration, and does not conduct regular health data collection. This study aimed to initiate and establish the first HDSS in Nepal.
We conducted a baseline survey in Jhaukhel and Duwakot, two villages in Bhaktapur district. The study surveyed 2,712 households comprising a total population of 13,669. The sex ratio in the study area was 101 males per 100 females and the average household size was 5. The crude birth and death rates were 9.7 and 3.9/1,000 population/year, respectively. About 11% of births occurred at home, and we found no mortality in infants and children less than 5 years of age. Various health problems were found commonly and some of them include respiratory problems (41.9%); headache, vertigo and dizziness (16.7%); bone and joint pain (14.4%); gastrointestinal problems (13.9%); heart disease, including hypertension (8.8%); accidents and injuries (2.9%); and diabetes mellitus (2.6%). The prevalence of non-communicable disease (NCD) was 4.3% (95% CI: 3.83; 4.86) among individuals older than 30 years. Age-adjusted odds ratios showed that risk factors, such as sex, ethnic group, occupation and education, associated with NCD.
Our baseline survey demonstrated that it is possible to collect accurate and reliable data in a village setting in Nepal, and this study successfully established an HDSS site. We determined that both maternal and child health are better in the surveillance site compared to the entire country. Risk factors associated with NCDs dominated morbidity and mortality patterns.
Ashwagandha (Withania somnifera) (WS), a “rasayana” drug, is recommended for balavardhan and mamsavardhan. The study was intended to evaluate dose-related tolerability, safety, and activity of WS formulation in normal individuals. The design was prospective, open-labeled, variable doses in volunteers. Eighteen apparently healthy volunteers (12M:6F, age:18-30 years, and BMI: 19-30) were enrolled. After baseline investigations, they received WS capsules (Rx) (aqueous extract, 8:1) daily in two divided doses with increase in daily dosage every 10 days for 30 days (750 mg/day ×10 days, 1 000 mg/day × 10 days, 1 250 mg/day × 10 days). Volunteers were assessed for symptoms/signs, vital functions, hematological and biochemical organ function tests. Muscle activity was measured by hand grip strength, quadriceps strength, and back extensor force. Exercise tolerance was determined using cycle ergometry. Lean body weight and fat% were computed from skin fold thickness measurement. Adverse events were recorded, as volunteered by the subjects. Repeated measures ANOVA, McNemar's test, and paired t test were employed. All but one volunteer tolerated WS without any adverse event. One volunteer showed increased appetite, libido, and hallucinogenic effects with vertigo at the lowest dose and was withdrawn from study. In six subjects, improvement in quality of sleep was found. Organ function tests were in normal range before and after the intervention. Reduction in total- and LDL- cholesterol and increase of strength in muscle activity was significant. Total body fat percentage showed a reduction trend. WS, in escalated dose, was tolerated well. The formulation appeared safe and strengthened muscle activity. In view of its traditional Rasayana use, further studies are planned to evaluate potential of this drug in patients of sarcopenia.
Ayurvedic plant drug; exercise tolerance; muscle activity; muscle strength; Rasayana drug; Withania somnifera
As a major organ of intermediary metabolism, the liver is exposed to a variety of metabolic insults due to diseases and xenobiotics viz., insulin resistance (IR) drugs, toxins, microbial products, etc. One of the consequences of these metabolic insults including obesity and type 2 diabetes mellitus is the development of non-alcoholic fatty liver disease (NAFLD). The recent alarming increase in the prevalence of NAFLD compels the need to develop an appropriate animal model of the disease so as to evolve effective interventions. In this study, we have developed, in the rat, a new model of NAFLD showing several key features akin to the disease in humans. Male Wistar rats were challenged with 30% high fat diet (HFD) – butter, for 2 weeks to induce NAFLD. A hydroalcoholic extract of Picrorhiza kurroa was administered to study the possible reversal of fatty changes in the liver. The extract was given in two doses viz., 200mg/kg and 400 mg/kg b.i.d., p.o. for a period of 4 weeks. There were three control groups (n = 6/group) – vehicle with a regular diet, vehicle with HFD, and HFD with silymarin – a known hepatoprotective.
Histopathology showed that the P. kurroa extract brought about a reversal of the fatty infiltration of the liver (mg/g) and a lowering of the quantity of hepatic lipids (mg/g) compared to that in the HFD control group (38.33 ± 5.35 for 200mg/kg; 29.44 ± 8.49 for 400mg/kg of P. kurroa vs.130.07 ± 6.36mg/g of liver tissue in the HFD control group; P<0.001). Compared to the standard dose of the known hepatoprotective silymarin, P. kurroa reduced the lipid content (mg/g) of the liver more significantly at the dose of 400mg/kg (57.71 ± 12.45mg/kg vs. 29.44 ± 8.49 for the silymarin group vs. 400mg/kg of P. kurroa, P<0.001). In view of the increasing prevalence of metabolic syndrome and NAFLD, P. kurroa should be investigated by the reverse pharmacology path as a potential drug for the treatment of NAFLD, and essential safety studies and preformulation research for concentration of the putative actives should be carried out.
Hepatoprotective; high fat diet; insulin resistance; metabolic syndrome; non-alcoholic fatty liver; Picrorhiza kurroa reverse pharmacology
Mother and child care has been described in great detail in Ayurveda. All basic principles of Ayurveda need to be applied to deal with the problems of maternal and foetal mortality. Rules of Ahara (diet), Vihara (lifestyle), Sadavrutta (moral conduct), along with varied therapies are used in tackling the various problems. There is need to take an in depth view at causes. Major changes in lifestyle may be required. Uses of various Ayurvedic formulations like various ghrtas and tailas (ghees and oils) have given wonderful results. Ayurveda aims at producing “Supraja” or healthy progeny. Ayurveda provides answers to some of the most worrying problems facing doctors today.
Pulmonary hypertension is comprised of heterogeneous diagnoses with distinct hemodynamic pathophysiology. Identifying elevated pulmonary vascular resistance (PVR) is critical for appropriate treatment. We reviewed data for patients seen at referral PH clinics who underwent echocardiography and right heart catheterization within 1 year. We derived equations to estimate PVR based on the ratio of estimated pulmonary artery (PA) systolic pressure (PASPDoppler) to RVOT VTI. We validated these equations in a separate sample and compared them to a published model based on the ratio of transtricuspid flow velocity to RVOT VTI (Model 1, Abbas et al 2003). The derived models were:
(Model 2)PVR=1.2×PASPRVOT VTI
(Model 3)PVR=PASPRVOT VTI+3if notch present
The cohort included 217 patients with mean PA pressure=45.3±11.9mmHg, PVR=7.3±5.0WU and PA wedge pressure=14.8±8.1mmHg; just over 1/3rd had PA wedge pressure >15mmHg (35.5%) and 82.0% had PVR>3WU. Model 1 systematically underestimated PVR, especially with high PVR. The derived models demonstrated no systematic bias. Model 3 correlated best with PVR (r=0.80 vs. 0.73 and 0.77 for Models 1 and 2 respectively). Model 3 had superior discriminatory power for PVR>3WU (AUC=0.946) and PVR>5WU (AUC=0.924), though all models discriminated well. Model 3 estimated PVR>3 was 98.3% sensitive and 61.1% specific for PVR>3WU (PPV=93%; NPV=88%). In conclusion, we present an equation to estimate PVR, using the ratio of PASPDoppler to RVOT VTI and a constant designating presence of RVOT VTI mid-systolic notching, which provides superior agreement with PVR across a wide range of values.
pulmonary hypertension; hemodynamics; echocardiography
Mutations in the ABL kinase domain and SH3-SH2 domain of the BCR/ABL gene and amplification of the Philadelphia chromosome are the two important BCR/ABL dependent mechanisms of imatinib resistance. Here, we intended to study the role played by TKI, imatinib, in selection of gene mutations and development of chromosomal abnormalities in Indian CML patients.
Direct sequencing methodology was employed to detect mutations and conventional cytogenetics was done to identify Philadelphia duplication.
Among the different mechanisms of imatinib resistance, kinase domain mutations (39%) of the BCR/ABL gene were seen to be more prevalent, followed by mutations in the SH3-SH2 domain (4%) and then BCR/ABL amplification with the least frequency (1%). The median duration of occurrence of mutation was significantly shorter for patients with front line imatinib than those pre-treated with hydroxyurea. Patients with high Sokal score (p = 0.003) showed significantly higher incidence of mutations, as compared to patients with low/intermediate score. Impact of mutations on the clinical outcome in AP and BC was observed to be insignificant. Of the 94 imatinib resistant patients, only 1 patient exhibited duplication of Philadelphia chromosome, suggesting a less frequent occurrence of this abnormality in Indian CML patients.
Close monitoring at regular intervals and proper analysis of the disease resistance would facilitate early detection of resistance and thus aid in the selection of the most appropriate therapy.
A heterogeneous gold catalyst with
remarkable activity for promoting
the electrophilic reactions of aryl vinyl ketones and aryl dienyl
ketones is described. The catalyst is easy to prepare, is robust,
and can be recycled. Low loadings are effective for different types
of cationic reactions, including Nazarov cyclizations, lactonizations,
and [1,2] shifts.
To determine the prevalence and incidence of epiretinal membranes (ERM) in eyes with inactive extramacular cytomegalovirus (CMV) retinitis in patients with acquired immune deficiency syndrome (AIDS).
A case–control report from a longitudinal multicenter observational study by the Studies of the Ocular Complications of AIDS (SOCA) Research Group. A total of 357 eyes of 270 patients with inactive CMV retinitis and 1084 eyes of 552 patients with no ocular opportunistic infection (OOI) were studied. Stereoscopic views of the posterior pole from fundus photographs were assessed at baseline and year 5 visits for the presence of macular ERM. Generalized estimating equations (GEE) logistic regression was used to compare the prevalence and 5-year incidence of ERM in eyes with and without CMV retinitis at enrollment. Crude and adjusted logistic regression was performed adjusting for possible confounders. Main outcome measures included the prevalence, incidence, estimated prevalence, and incidence odds ratios.
The prevalence of ERM at enrollment was 14.8% (53/357) in eyes with CMV retinitis versus 1.8% (19/1084) in eyes with no OOI. The incidence of ERM at 5 years was 18.6% (16/86) in eyes with CMV retinitis versus 2.4% (6/253) in eyes with no OOI. The crude odds ratio (OR) (95% confidence interval, CI) for prevalence was 9.8 (5.5–17.5) (P < 0.01). The crude OR (95% CI) for incidence was 9.4 (3.2–27.9) (P < 0.01).
A history of extramacular CMV retinitis is associated with increased prevalence and incidence of ERM formation compared to what is seen in eyes without ocular opportunistic infections in AIDS patients.
Eyes with inactive extramacular CMV retinitis have increased prevalence and incidence of ERM compared to eyes without ocular opportunistic infections in AIDS patients.
CMV retinitis; epiretinal membrane; prevalence; incidence; AIDS
The timing and developmental factors underlying the establishment of language dominance are poorly understood. We investigated the degree of lateralization of traditional fronto-temporal and modulatory prefrontal-cerebellar regions of the distributed language network in children (n=57) ages 4 to 12 – a critical period for language consolidation. We examined the relationship between the strength of language lateralization and neuropsychological measures and task performance. The fundamental language network is established by four with ongoing maturation of language functions as evidenced by strengthening of lateralization in the traditional frontotemporal language regions; temporal regions were strongly and consistently lateralized by seven, while frontal regions had greater variability and were less strongly lateralized through age ten. In contrast, the modulatory prefrontal-cerebellar regions were the least strongly lateralized and degree of lateralization was not associated with age. Stronger core language skills were significantly correlated with greater right lateralization in the cerebellum.
Traumatic dislocations of the shoulder commonly present to emergency departments (EDs). Immediate closed reduction of both anterior and posterior glenohumeral dislocations is recommended and is frequently performed in the ED. Recurrence of dislocation is common, as anteroinferior labral tears (Bankart lesions) are present in many anterior shoulder dislocations.14,15,18,23 Immobilization of the shoulder following closed reduction is therefore recommended; previous studies support the use of immobilization with the shoulder in a position of external rotation, for both anterior and posterior shoulder dislocations.7–11,19 In this study, we present a technique for assembling a low-cost external rotation shoulder brace using materials found in most hospitals: cotton roll, stockinette, and shoulder immobilizers. This brace is particularly suited for the uninsured patient, who lacks the financial resources to pay for a pre-fabricated brace out of pocket. We also performed a cost analysis for our low-cost external rotation shoulder brace, and a cost comparison with pre-fabricated brand name braces. At our institution, the total materials cost for our brace was $19.15. The cost of a pre-fabricated shoulder brace at our institution is $150 with markup, which is reimbursed on average at $50.40 according to our hospital billing data. The low-cost external rotation shoulder brace is therefore a more affordable option for the uninsured patient presenting with acute shoulder dislocation.
The objective of this study is to valuate two biomarkers that may guide nutritional assessment during follow up after intestinal transplantation. We performed a retrospective study on prospectively collected data of insulin-like growth factor-1 (IGF-1) and effluent calprotectin in patients undergoing intestinal transplantation. Optimal nutritional status (ONS) was defined by using the Malnutrition Universal Screening Tool (MUST). IGF-1 and calprotectin were correlated with ONS by Pearson correlation. Eighteen cadaveric intestinal transplants were performed over 1,650 days (median follow up 425 days, range 29–1,650 days). Mean IGF-1 and calprotectin were significantly associated with independent nutrition. Seven patients became malnourished on one or more occasions. During malnutrition the mean IGF-1 was 22 ± 14 ng/ml and calprotectin 1,597 ± 1,055 mcg/g. Mean weight during episodes of malnutrition changed from 64.77 ± 8.76 kg to 59.05 ± 8.5 kg (–8.9 ± 1.25%). Both IGF-1 and calprotectin negatively correlated with ONS (Pearson’s r, –0.612, p = 0.014). Patients broadly aligned with three groups: nutritionally replete (normal IGF-1 and normal calprotectin), nutritionally equivocal (normal or low normal IGF-1 and high calprotectin), and malnourished (low IGF-1 and high calprotectin). Patients with low IGF-1 and high calprotectin may have a benign clinical presentation. However it is in their interests to have parenteral nutrition restarted pending further investigation.
IGF-1; calprotectin; intestinal transplantation; nutritional status
The quest for new antimalarial drugs, especially those with novel modes of action, is essential in the face of emerging drug-resistant parasites. Here we describe a new chemical class of molecules, pyrazoleamides, with potent activity against human malaria parasites and showing remarkably rapid parasite clearance in an in vivo model. Investigations involving pyrazoleamide-resistant parasites, whole-genome sequencing and gene transfers reveal that mutations in two proteins, a calcium-dependent protein kinase (PfCDPK5) and a P-type cation-ATPase (PfATP4), are necessary to impart full resistance to these compounds. A pyrazoleamide compound causes a rapid disruption of Na+ regulation in blood-stage Plasmodium falciparum parasites. Similar effect on Na+ homeostasis was recently reported for spiroindolones, which are antimalarials of a chemical class quite distinct from pyrazoleamides. Our results reveal that disruption of Na+ homeostasis in malaria parasites is a promising mode of antimalarial action mediated by at least two distinct chemical classes.
Novel antimalarial drugs are urgently needed to combat parasite drug resistance. Here, Vaidya et al. describe a new chemical class of potent antimalarial compounds that act by disrupting the parasite's sodium homeostasis.
The use of retrograde nailing for gunshot wound femur fractures is controversial due to concerns of knee sepsis after this procedure since the knee is entered to introduce the nail into the canal.
We compared retrograde and antegrade nailing for gunshot femur fractures to determine whether (1) knee sepsis or other adverse events were more likely to complicate procedures using retrograde nails, (2) there were differences in surgical time or blood loss, and (3) there were differences in radiographic union.
We retrospectively reviewed our prospective trauma database from 1999 to 2012 for patients with a diagnosis of gunshot and femur fracture. We performed a detailed review of medical records and radiographs for those patients with OTA Classification Type 32 femur fractures secondary to gunshot injury treated with either retrograde or antegrade femoral nailing. Eighty-one patients were treated with intramedullary nailing (53 retrograde and 28 antegrade). We reviewed elements of the operative treatment (procedure, anesthesia time, operative time, and estimated blood loss) for all 81 patients. For clinical and radiographic review, followup was adequate for 43 and 25 patients with retrograde and antegrade nailing, respectively. Minimum followup was 3 months for both groups (retrograde: mean, 41 months; range, 3–148 months; antegrade: 26 months: range, 3–112 months).
No patients in either group developed knee sepsis. No significant differences were found between groups with regard to operative time, blood loss, or radiographic union.
With the numbers available, immediate retrograde nailing appears as safe and effective as antegrade nailing for gunshot femur fractures. Immediate retrograde nailing is as safe as antegrade nailing for gunshot femur fractures.
Level of Evidence
Level III, therapeutic study. See Instructions for Authors for a complete description of levels of evidence.
Implicit probabilistic sequence learning (IPSL) involves extracting statistical regularities from sequences of events without awareness, and is thought to underlie learning of language and behavioral repertoires of everyday life. We examined whether resting-state functional connectivity networks of the caudate predicted individual differences in IPSL performance measured on a separate day. Whole-brain connectivity maps of a bilateral dorsal caudate (DC) seed were created for each subject and examined for voxelwise correlations with sequence learning performance, as well as with overall response speed. Higher learning scores (but not overall response speed) were associated with stronger resting-state connectivity between the DC and right medial temporal lobe, as well as with lower resting-state connectivity between the DC and premotor regions involved in motor planning. Thus, how well one learns probabilistic regularities without awareness is predicted by the strength of a striato-cortical network in the resting brain.
caudate; fMRI; functional connectivity; implicit sequence learning; resting state
High resolution multi detector computed tomography (HRMDCT) is an excellent tool for evaluation of a variety of congenital and acquired conditions affecting the temporal bones. We describe our experience of HRMDCT of temporal bones of 145 patients in a tertiary care and teaching hospital of Armed Forces Medical Services of India over a period of three and half years. Hearing loss was the most frequent indication for HRMDCT and congenital bilateral profound sensorineural hearing loss for evaluation prior to possible cochlear implant formed the single largest group (62, 42%) among all indications for HRMDCT of temporal bones. Major vestibule-cochlear and semicircular canal anomalies were noted in 11 such cases. Seven patients of microtia were studied and all had positive CT scan findings. All patients of vertigo had normal HRCT study. Extent of temporal bone injuries and inflammatory conditions were clearly delineated in all cases. Thinner collimations allowing image reconstructions in planes of anatomical interest with near isotropic resolution has been a major advantage of HRMDCT of temporal bones.
Temporal bone; High resolution multi detector computed tomography; Multiplanar reconstruction
Acute Biliary Pancreatitis is one of the commonest forms of pancreatitis in Nepal. Controversies exist as to the most appropriate way of management of these cases. The present study was carried out to evaluate the management and outcome of Acute Biliary Pancreatitis cases in a tertiary level hospital of Nepal. A retrospective analysis of the patients managed with Acute Biliary Pancreatits was done. All patients admitted with the diagnosis of Acute Biliary Pancreatitis over a period of 2 years were included in the study. The variables measured were age, sex, clinical presentation, laboratory investigations, mode of treatment and outcome. A total of 45 cases had Acute Biliary Pancreatitis suggesting a prevalence of 28 %. The mean age was 45 ± 10 year. 39 patients (86.6 %) were treated with conservative management. 23 patients (54 %) had an uneventful recovery without any complications. 21 patients (46 %) developed some form of complications but recovered successfully. Mortality was seen in only one patient in the conservatively treated group. In a resource poor setting such as Nepal, definitive management is not always possible. Conservative management of Acute Biliary Pancreatitis has a favorable outcome in the majority of our patients with acceptable morbidity and mortality. Definitive management can be safely performed during index admission where possible.
Acute pancreatitis; Biliary; Conservative management; Outcome