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1.  Phase I and pharmacokinetic study of mitomycin C and celecoxib as potential modulators of tumor resistance to irinotecan in patients with solid malignancies 
Cancer chemotherapy and pharmacology  2008;63(6):1073-1082.
Purpose
Based on the preclinical evidence of topoisomerase I (Topo-1) upregulation by mitomycin C(MMC) and decreased NF-κB activation by celecoxib, we evaluated combinations of irinotecan/MMC and irinotecan/MMC/celecoxib in patients with advanced solid malignancies.
Patients–methods
Initially, patients received MMC on day 1 and irinotecan on days 2, 8, 15 and 22, every 6 weeks. MMC dose was fixed at 6 mg/m2 and cumulative doses of >36 mg/m2 were not permitted. Irinotecan was escalated in 25 mg/m2 increments. Due to late-onset diarrhea, the schedule was subsequently shortened to 4 weeks, omitting irinotecan on days 15 and 22. In the second part of the study, celecoxib 400 mg orally twice daily was added to irinotecan/MMC regimen. Potential pharmacokinetic interactions and Topo-1 and DT-diaphorase (NQ01) gene expressions in peripheral-mononuclear cells were evaluated.
Results
Forty-five patients were enrolled. Irinotecan 125 mg/m2 on days 2 and 8 in combination with MMC 6 mg/m2 on day 1 every 4 weeks is recommended for future studies; myelosuppression and diarrhea are dose-limiting. The addition of celecoxib resulted in unacceptable toxicities despite reductions on irinotecan’s dose. No relevant pharmacokinetic interactions occurred between irinotecan and MMC, and mean increases in Topo-1, were observed. Sixteen of 36 patients evaluable for response-assessment had discernable anti-tumor activity, including 1 complete, 4 partial, 10 minor and 1 tumor marker response. Four patients had prolonged (>4 months) disease-stability (stable disease, not included in CR or PR). Patients experiencing complete and partial responses had higher increments in Topo-1 expression.
Conclusions
Modulation of irinotecan by MMC is feasible, devoid of pharmacological interactions and active in solid malignancies. The lack of improvement in therapeutic index does not support the addition of celecoxib.
doi:10.1007/s00280-008-0826-3
PMCID: PMC3933356  PMID: 18795290
Phase I; Pharmacokinetic; Mitomycin C; Irinotecan; Celecoxib; Modulation
2.  High STOP-Bang score indicates a high probability of obstructive sleep apnoea 
BJA: British Journal of Anaesthesia  2012;108(5):768-775.
Background
The STOP-Bang questionnaire is used to screen patients for obstructive sleep apnoea (OSA). We evaluated the association between STOP-Bang scores and the probability of OSA.
Methods
After Institutional Review Board approval, patients who visited the preoperative clinics for a scheduled inpatient surgery were approached for informed consent. Patients answered STOP questionnaire and underwent either laboratory or portable polysomnography (PSG). PSG recordings were scored manually. The BMI, age, neck circumference, and gender (Bang) were documented. Over 4 yr, 6369 patients were approached and 1312 (20.6%) consented. Of them, 930 completed PSG, and 746 patients with complete data on PSG and STOP-Bang questionnaire were included for data analysis.
Results
The median age of 746 patients was 60 yr, 49% males, BMI 30 kg m−2, and neck circumference 39 cm. OSA was present in 68.4% with 29.9% mild, 20.5% moderate, and 18.0% severe OSA. For a STOP-Bang score of 5, the odds ratio (OR) for moderate/severe and severe OSA was 4.8 and 10.4, respectively. For STOP-Bang 6, the OR for moderate/severe and severe OSA was 6.3 and 11.6, respectively. For STOP-Bang 7 and 8, the OR for moderate/severe and severe OSA was 6.9 and 14.9, respectively. The predicted probabilities for moderate/severe OSA increased from 0.36 to 0.60 as the STOP-Bang score increased from 3 to 7 and 8.
Conclusions
In the surgical population, a STOP-Bang score of 5–8 identified patients with high probability of moderate/severe OSA. The STOP-Bang score can help the healthcare team to stratify patients for unrecognized OSA, practice perioperative precautions, or triage patients for diagnosis and treatment.
doi:10.1093/bja/aes022
PMCID: PMC3325050  PMID: 22401881
mass screening; obstructive/ep (epidemiology); polysomnography; prospective studies; questionnaires; sleep apnoea; snoring/di (diagnosis); snoring/ep (epidemiology)
3.  Do cell surface trafficking impairments account for variable cell surface sodium iodide symporter levels in breast cancer? 
The Na+/I- symporter (NIS) is a transmembrane glycoprotein that mediates iodide uptake into thyroid follicular cells and serves as the molecular basis of radioiodine imaging and therapy for thyroid cancer patients. The finding that NIS protein is present in 80-90% of breast tumors suggests that breast cancer patients may also benefit from NIS-mediated radionuclide imaging and targeted therapy. However, only 17-25% of NIS-positive breast tumors have detectable radionuclide uptake activity. The discrepancy between NIS expression and radionuclide uptake activity is most likely contributed by variable cell surface NIS protein levels. Apart from the prevalent view that NIS cell surface trafficking impairments account for the variability, our current study proposes that differential levels of NIS expression may also account for variable cell surface NIS levels among breast tumors. We address the need to confirm the identity of intracellular NIS staining to reveal the mechanisms underlying variable cell surface NIS levels. In addition, we warrant a quantitative correlation between cell surface NIS levels and radionuclide uptake activity in patients such that the cell surface NIS levels required for radionuclide imaging can be defined and the defects impairing NIS activity can be recognized.
doi:10.1007/s10549-008-0059-5
PMCID: PMC2697904  PMID: 18500672
Breast cancer; glycoprotein; iodide uptake; radionuclide imaging and therapy; sodium iodide symporter (NIS)
4.  Preliminary randomized double-blind placebo-controlled trial of tryptophan combined with fluoxetine to treat major depressive disorder: antidepressant and hypnotic effects. 
OBJECTIVE: Because the initial phase of treatment of depression with a selective serotonin reuptake inhibitor is often complicated by a delayed onset of action of the antidepressant or severe insomnia or both, we investigated whether tryptophan, an amino acid with both antidepressant-augmenting and hypnotic effects, would benefit patients with depression at the beginning of treatment with fluoxetine. DESIGN: Randomized, double-blind, placebo-controlled trial. PATIENTS: Thirty individuals with major depressive disorder. INTERVENTIONS: Treatment over 8 weeks with 20 mg of fluoxetine per day and either tryptophan (2 to 4 g per day) or placebo. OUTCOME MEASURES: Mood was assessed using the 29-item Hamilton Depression Rating Scale (HDRS-29) and the Beck Depression Inventory (BDI). Laboratory sleep studies were done at baseline and after 4 and 8 weeks of treatment using standard procedures. RESULTS: During the first week of treatment, there was a significantly greater decrease in HDRS-29 depression scores, and a similar trend in BDI scores, in the tryptophan/fluoxetine group than in the placebo/fluoxetine group. No significant differences were noted at later time points. With respect to sleep measures, there was a significant group-by-time interaction for slow-wave sleep at week 4. Further analysis revealed a significant decrease in slow-wave sleep after 4 weeks of treatment in the placebo/fluoxetine group, but not in the tryptophan/fluoxetine group. No cases of serotonin syndrome occurred, and the combination was well tolerated, although the 4 g per day dosage of tryptophan produced daytime drowsiness. CONCLUSIONS: Combining 20 mg of fluoxetine with 2 g of tryptophan daily at the outset of treatment for major depressive disorder appears to be a safe protocol that may have both a rapid antidepressant effect and a protective effect on slow-wave sleep. Further large-scale studies are needed to confirm these initial findings.
PMCID: PMC1407729  PMID: 11022398
5.  Food-related illness and death in the United States. 
Emerging Infectious Diseases  1999;5(5):607-625.
To better quantify the impact of foodborne diseases on health in the United States, we compiled and analyzed information from multiple surveillance systems and other sources. We estimate that foodborne diseases cause approximately 76 million illnesses, 325,000 hospitalizations, and 5,000 deaths in the United States each year. Known pathogens account for an estimated 14 million illnesses, 60, 000 hospitalizations, and 1,800 deaths. Three pathogens, Salmonella, Listeria, and Toxoplasma, are responsible for 1,500 deaths each year, more than 75% of those caused by known pathogens, while unknown agents account for the remaining 62 million illnesses, 265,000 hospitalizations, and 3,200 deaths. Overall, foodborne diseases appear to cause more illnesses but fewer deaths than previously estimated.
PMCID: PMC2627714  PMID: 10511517
6.  Pseudo-narcolepsy: case report. 
This report describes the case of a 44-year-old woman presenting to a Sleep and Alertness clinic with symptoms of narcolepsy. The patient had clinical and polysomnographic features of narcolepsy, which disappeared after disclosure of severe psychological stress. Following a discussion of the differential diagnosis of narcolepsy, alternative diagnoses are considered. The authors suggest that the patient had a hysterical conversion disorder, or "pseudo-narcolepsy." Careful inquiry into psychological factors in unusual cases of narcolepsy may be warranted.
PMCID: PMC1189038  PMID: 10516803
7.  An outbreak of hepatitis A associated with an infected foodhandler. 
Public Health Reports  1999;114(2):157-164.
OBJECTIVE: The recommended criteria for public notification of a hepatitis A virus (HAV)-infected foodhandler include assessment of the foodhandler's hygiene and symptoms. In October 1994, a Kentucky health department received a report of a catering company foodhandler with hepatitis A. Patrons were not offered immune globulin because the foodhandler's hygiene was assessed to be good and he denied having diarrhea. During early November, 29 cases of hepatitis A were reported among people who had attended an event catered by this company. Two local health departments and the Centers for Disease Control and Prevention, in collaboration with two state health departments, undertook an investigation to determine the extent of the outbreak, to identify the foods and event characteristics associated with illness, and to investigate the apparent failure of the criteria for determining when immune globulin (IG) should be offered to exposed members of the public. METHODS: Cases were IgM anti-HAV-positive people with onset of symptoms during October or November who had eaten foods prepared by the catering company. To determine the outbreak's extent and factors associated with illness, the authors interviewed all case patients and the infected foodhandler and collected information on menus and other event characteristics. To investigate characteristics of events associated with transmission, the authors conducted a retrospective analysis comparing the risk of illness by selected event characteristics. To evaluate what foods were associated with illness, they conducted a retrospective cohort study of attendees of four events with high attack rates. RESULTS: A total of 91 cases were identified. At least one case was reported from 21 (51%) of the 41 catered events. The overall attack rate was 7% among the 1318 people who attended these events (range 0 to 75% per event). Attending an event at which there was no on-site sink (relative risk [RR] = 2.3, 95% confidence interval [CI] 1.4, 3.8) or no on-site kitchen (RR = 1.9, 95% Cl 1.1, 2.9) was associated with illness. For three events with high attack rates, eating at least one of several uncooked foods was associated with illness, with RRs ranging from 8 to undefined. CONCLUSION: A large hepatitis A outbreak resulted from an infected foodhandler with apparent good hygiene and no reported diarrhea who prepared many uncooked foods served at catered events. Assessing hygiene and symptoms s subjective, and may be difficult to accomplish. The effectiveness of the recommended criteria for determining when IG should be provided to exposed members of the public needs to be evaluated.
PMCID: PMC1308455  PMID: 10199718
8.  Preventing hepatitis B in people in close contact with hepatocellular carcinoma patients. 
Public Health Reports  1997;112(1):63-65.
OBJECTIVE: To determine the prevalence of testing for hepatitis B virus (HBV) infection in the clinical management of primary liver cancer (hepatocellular carcinoma). METHODS: The authors reviewed the records of 78 patients treated for hepatocellular carcinoma in hospitals in the Puget Sound area in 1988 and early 1989 and reviewed all 1990 U.S. death certificates on which primary liver cancer was listed. RESULTS: The records of 50 (64%) of 78 hepatocellular carcinoma patients contained no evidence that the patient's hepatitis B surface antigen (HBsAg) status had been determined. In addition, of 4353 people who died in 1990 for whom the diagnosis of primary liver cancer was listed on the death certificate, HBV infection was also listed for only 136 (3%), much less than expected based on case series. CONCLUSIONS: Many patients with hepatocellular carcinoma are not tested for HBV infection, suggesting that their close contacts are also not evaluated for HBV infection and the need for vaccination. Hepatitis B vaccination of close personal contacts of HBV-infected hepatocellular carcinoma patients is an important strategy for preventing HBV transmission.
PMCID: PMC1381841  PMID: 9018291
9.  Epidemiology of group C rotavirus infection in Western New York women of childbearing age. 
Journal of Clinical Microbiology  1997;35(2):486-488.
Umbilical cord serum samples (380), an average of 10 per month for 3 years (1990 to 1992), were tested by indirect immunofluorescence assay for group C rotavirus immunoglobulin G. Thirty percent were positive, suggesting that approximately one-third of women of childbearing age in western New York have experienced group C rotavirus infection.
PMCID: PMC229607  PMID: 9003623
11.  Morbidity in nocturnal asthma: sleep quality and daytime cognitive performance. 
Thorax  1991;46(8):569-573.
Most patients with asthma waken with nocturnal asthma from time to time. To assess morbidity in patients with nocturnal asthma nocturnal sleep quality, daytime sleepiness, and daytime cognitive performance were measured prospectively in 12 patients with nocturnal asthma (median age 43 years) and 12 age and intellect matched normal subjects. The median (range) percentage overnight fall in peak expiratory flow rate (PEF) was 22 (15 to 50) in the patients with nocturnal asthma and 4 (-4 to 7) in the normal subjects. The patients with asthma had poorer average scores for subjective sleep quality than the normal subjects (median paired difference 1.1 (95% confidence limits 0.1, 2.3)). Objective overnight sleep quality was also worse in the asthmatic patients, who spent more time awake at night (median difference 51 (95% CL 8.1, 74) minutes), had a longer sleep onset latency (12 (10, 30) minutes), and tended to have less stage 4 (deep) sleep (-33 (-58, 4) minutes). Daytime cognitive performance was worse in the patients with nocturnal asthma, who took a longer time to complete the trail making tests (median difference 62 (22, 75) seconds) and achieved a lower score on the paced serial addition tests (-10 (-24, -3)). Mean daytime sleep latency did not differ significantly between the two groups (2 (-3, 7) minutes). It is concluded that hospital outpatients with stable nocturnal asthma have impaired sleep quality and daytime cognitive performance even when having their usual maintenance asthma treatment.
PMCID: PMC463276  PMID: 1926025
12.  Hepatitis B virus precore mutation and fulminant hepatitis in the United States. A polymerase chain reaction-based assay for the detection of specific mutation. 
Journal of Clinical Investigation  1994;93(2):550-555.
Hepatitis B virus (HBV) variants with precore mutation(s) resulting in the absence of HBeAg production have been associated with the occurrence of fulminant hepatitis in Japan, Israel, and southern Europe, where the prevalence of this HBV strain appears common. In areas such as United States, where HBV infection is not endemic, the role of this mutant virus in fulminant hepatitis is unknown. We developed an amplification refractory mutation detection system to detect specifically the presence of the G to A mutation at nucleotide position 1898, which is the most frequently observed mutation resulting in a precore stop codon. In addition, this method provided a quantitative measurement of the relative ratio of one strain to the other. Using this system, we tested HBV strains for the presence of the stop codon mutation in sera from 40 cases of fulminant hepatitis B occurring in the United States. Serum HBV DNAs from 28 patients were analyzed successfully. A mixture of wild-type and mutant strains in various ratios were observed in 15 patients, wild type exclusively in 11, and mutant exclusively in 2. Four of these patients had undergone liver transplantation for HBV-associated cirrhosis and developed fulminant HBV-associated hepatitis after transplantation. Pre- and posttransplant serum samples from one patient were analyzed: a mixture of wild-type and mutant HBV strains was detected in both samples. Our study demonstrated that both wild-type and mutant HBV strains are associated with fulminant hepatitis, and that in some patients in the United States, factors other than precore mutations contribute to the development of fulminant hepatitis.
Images
PMCID: PMC293877  PMID: 8113393
13.  Availability and use of hepatitis B vaccine in laboratory and nursing schools in the United States. 
Public Health Reports  1991;106(5):529-535.
Hepatitis B is a well-documented occupational hazard for health care workers, including both laboratory and nursing personnel. Since the development of effective hepatitis B vaccines, the Immunization Practices Advisory Committee (ACIP) has recommended that health care workers receive the vaccine. In this study, 78 laboratory training programs and 83 nursing training programs were surveyed regarding availability and usage of hepatitis B vaccine. The hepatitis B vaccine was made available to students in 81 percent of the laboratory programs and 23 percent of the nursing programs. In those programs making the vaccine available, only 59 percent of the laboratory programs and 5 percent of the nursing programs reported a high (greater than 75 percent) use by students. Concern about cost and payment for the vaccine was the most common reason (80 percent) noted by laboratory schools that did not have hepatitis B vaccination programs for students. Of the nursing schools that did not have vaccine programs, 58 percent had not yet considered a program. At laboratory schools with vaccination programs, who paid for the vaccine (hospital or school versus student) was among the most important determinants for vaccine usage by students. These findings point out that some laboratory schools and many nursing schools have not applied the ACIP recommendations to their own programs. Educational efforts and creative payment plans for the vaccine are needed to increase the availability and use of hepatitis B vaccine among laboratory and nursing students.
PMCID: PMC1580298  PMID: 1832779
17.  ABC of sleep disorders. Medical problems during sleep. 
BMJ : British Medical Journal  1993;306(6889):1403-1405.
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PMCID: PMC1677840  PMID: 8518611
18.  ABC of sleep disorders. Psychotropic drugs and sleep. 
BMJ : British Medical Journal  1993;306(6888):1331-1334.
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PMCID: PMC1677758  PMID: 8518577
20.  ABC of sleep disorders. Nocturnal asthma. 
BMJ : British Medical Journal  1993;306(6886):1189-1192.
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PMCID: PMC1677647  PMID: 8499828
21.  ABC of sleep disorders. Non-Psychotropic drugs and sleep. 
BMJ : British Medical Journal  1993;306(6885):1118-1121.
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PMCID: PMC1677534  PMID: 8495162
22.  ABC of sleep disorder. Dreams and medical illness. 
BMJ : British Medical Journal  1993;306(6883):993-995.
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PMCID: PMC1677442  PMID: 8490484
23.  ABC of sleep disorders. Parasomnias. 
BMJ : British Medical Journal  1993;306(6882):921-924.
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PMCID: PMC1677359  PMID: 8490425
24.  ABC of sleep disorders. "I don't get enough sleep, doctor". 
BMJ : British Medical Journal  1993;306(6881):843-846.
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PMCID: PMC1677269  PMID: 8490380
25.  ABC of sleep disorders. Sleep disorders in children. 
BMJ : British Medical Journal  1993;306(6878):640-643.
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PMCID: PMC1676915  PMID: 8461819

Results 1-25 (41)