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Biomedical subjects

J Sherman

Publications and source records attributed to J Sherman.

At least 19 recordsLinked to original sources

Colour vision defects in asymptomatic carriers of the Leber's hereditary optic neuropathy (LHON) mtDNA 11778 mutation from a large Brazilian LHON pedigree: a case-control study.

AIMS: To determine if asymptomatic carriers from a previously identified large pedigree of the Leber's hereditary optic neuropathy (LHON) 11778 mtDNA mutation have colour vision deficits. METHODS: As part of a comprehensive analysis of over 200 members of a large Brazilian LHON pedigree spanning seven generations, colour vision tests were obtained from 91 members. Colour vision was tested one eye at a time using the Farnsworth-Munsell 100 (FM-100) hue colour vision test. The test was administered under uniform conditions, taking into account: ambient light levels, daylight colour temperature of 6700 kelvin, and neutral uniform background. Tests were scored using the FM-100 MS-Excel computer scoring program. Defects were determined and categorised as tritan, deutan, or protan. Categorisation of each dyschromatopsia was based on review of demonstrated axis computer generated plots and age adjusted error scores which coincided with Verriest 95% confidence intervals. Only the axis with the greatest magnitude error score was used to classify the defect. 55 of the 91 test subjects were LHON mtDNA 11778 J haplotype mutation carriers, proved by mtDNA analysis. The remaining 36 subjects were age matched non-blood relatives (off pedigree), who served as controls. RESULTS: 27 of 55 carriers (49.10%) were shown to have colour vision defects in one or both eyes. 13 of the 27 (48%) abnormal tests in the carrier group were tritan defects and the remaining 14 (52%) were deutan defects. Nine of the 27 (33%) abnormals in the carrier group were identified as having bilateral defects. Six of these were deutan, and the remaining three were tritan dyschromatopsias. Only six of the 36 (16.66%) age matched controls were found to have any type of dyschromatopsia. Five (83.3%) of these were deutan defects. The remaining one was a tritan defect. The difference between the two groups using a chi(2) test with one degree of freedom was statistically significant with a p value less that 0.001. CONCLUSIONS: Until now, LHON has always been characterised by a sudden, devastating vision loss. Asymptomatic carriers, those without vision loss, were considered unaffected by the disease. It now appears that asymptomatic carriers of the LHON mutation are affected by colour vision defects and may manifest other subtle, yet chronic, changes.

Brazil↗

Comprehension and awareness of symptoms in women with dyspepsia.

BACKGROUND: Overlapping symptoms of gastro-oesophageal reflux disease and dyspepsia are a problem for physicians and patients. AIM: This study explored comprehension of dyspepsia symptoms and associated medical terminology among women with symptoms of dyspepsia. METHODS: The US women aged > or = 18 years with dyspepsia (defined by Rome II criteria) were recruited in two phases, via direct mail, the Internet, clinical investigators and/or gastroenterologists. In phase I, subjects took part in an hour-long telephonic interview comprising open-ended questions relating to symptom frequency/duration, triggers/patterns and severity. During phase II, subjects took part in a 45-min telephonic interview, which explored their understanding of dyspepsia symptoms and their predominant or most bothersome symptom. RESULTS: Subjects with 'pure' dyspepsia (without overlapping symptoms of gastro-oesophageal reflux disease or irritable bowel syndrome) were sought, but of 777 subjects screened, most were excluded because of gastrointestinal comorbidities (irritable bowel syndrome, gastro-oesophageal reflux disease). Only 85 (11%) subjects had 'pure' dyspepsia of whom 11 withdrew. Of the 74 subjects interviewed, 70% were unfamiliar with the term 'dyspepsia'. Subjects reported several symptoms, including bloating (65%), gas (50%), nausea (41%) and discomfort (36%). Most subjects could distinguish between symptom bothersomeness and severity, and between pain and discomfort. Terms such as 'satisfactory relief', 'central upper abdominal discomfort', 'early satiety' and 'postmeal fullness' were often misunderstood. CONCLUSIONS: Subjects with 'pure' dyspepsia are rare, because of comorbidities. Dyspepsia-related terminology is often misunderstood by subjects.

Adult↗

Allelic variation at the VRN-1 promoter region in polyploid wheat.

Vernalization, the requirement of a long exposure to low temperatures to induce flowering, is an essential adaptation of plants to cold winters. We have shown recently that the vernalization gene VRN-1 from diploid wheat Triticum monococcum is the meristem identity gene APETALA1, and that deletions in its promoter were associated with spring growth habit. In this study, we characterized the allelic variation at the VRN-1 promoter region in polyploid wheat. The Vrn-A1a allele has a duplication including the promoter region. Each copy has similar foldback elements inserted at the same location and is flanked by identical host direct duplications (HDD). This allele was found in more than half of the hexaploid varieties but not among the tetraploid lines analyzed here. The Vrn-A1b allele has two mutations in the HDD region and a 20-bp deletion in the 5' UTR compared with the winter allele. The Vrn-A1b allele was found in both tetraploid and hexaploid accessions but at a relatively low frequency. Among the tetraploid wheat accessions, we found two additional alleles with 32 bp and 54 bp deletions that included the HDD region. We found no size polymorphisms in the promoter region among the winter wheat varieties. The dominant Vrn-A1 allele from two spring varieties from Afghanistan and Egypt ( Vrn-A1c allele) and all the dominant Vrn-B1 and Vrn-D1 alleles included in this study showed no differences from their respective recessive alleles in promoter sequences. Based on these results, we concluded that the VRN-1 genes should have additional regulatory sites outside the promoter region studied here.

Alleles↗

A randomised, double blind, placebo controlled study of celecoxib, a selective cyclooxygenase 2 inhibitor, on duodenal polyposis in familial adenomatous polyposis.

BACKGROUND: Non-selective cyclooxygenase (COX) inhibitors (non-steroidal anti-inflammatory drugs) inhibit large bowel carcinogenesis in patients with familial adenomatous polyposis (FAP). Their role in the duodenum of these patients is less certain. The disease modifying activity of specific COX-2 inhibitors has not been explored in humans. PATIENTS AND METHODS: This was a randomised, double blind, placebo controlled study of celecoxib (100 mg twice daily (n=34) or 400 mg twice daily (n=32)) versus placebo (n=17), given orally twice daily for six months to patients with FAP. Efficacy was assessed qualitatively by blinded review of shuffled endoscopy videotapes comparing the extent of duodenal polyposis at entry and at six months and quantitatively by measurement of the percentage change in duodenal area covered by discrete and plaque-like adenomas from photographs of high and low density polyposis. RESULTS: Shuffled and blinded video review showed a statistically significant effect of 400 mg twice daily celecoxib compared with placebo treatment (p=0.033) with all five independent observers scoring a beneficial effect. Overall, patients taking celecoxib 400 mg twice daily showed a 14.5% reduction in involved areas compared with a 1.4% for placebo (p=0.436). However, patients with clinically significant disease at baseline (greater than 5% covered by polyps) showed a 31% reduction in involved areas with celecoxib 400 mg twice daily compared with 8% on placebo (p=0.049). CONCLUSIONS: A panel of five endoscopists found a significant reduction in duodenal polyposis after six months of treatment with celecoxib 400 mg twice daily. COX-2 inhibition may help this otherwise untreatable condition.

Adenomatous Polyposis Coli↗

Is stealing a gateway crime?

Stealing behaviors are common among youth and adolescents and often begin in early ages due to a variety of developmental, behavioral, and social factors. This study explores the prevalence of stealing behaviors in a South Texas juvenile detention facility. Researchers discovered stealing was the most frequently reported offense followed by the lack of supervision. Youth arrested for stealing were also more likely to be arrested prior to their twelfth birthday, have subsequent charges that may include assault, and have multiple charges. Results with implications for interventions are provided.

Adolescent↗

Maggot débridement therapy in outpatients.

OBJECTIVE: To identify the benefits, risks, and problems associated with outpatient maggot therapy. DESIGN: Descriptive case series, with survey. SETTING: Urban and rural clinics and homes. PARTICIPANTS: Seven caregivers with varying levels of formal health care training and 21 ambulatory patients (15 men, 6 women; average age, 63 yr) with nonhealing wounds. INTERVENTION: Maggot therapy. MAIN OUTCOME MEASURE: Therapists' opinions concerning clinical outcomes and the disadvantages of therapy. RESULTS: More than 95% of the therapists and 90% of their patients were satisfied with their outpatient maggot débridement therapy. Of the 8 patients who were advised to undergo amputation or major surgical débridement as an alternative to maggot débridement, only 3 required surgical resection (amputation) after maggot therapy. Maggot therapy completely or significantly débrided 18 (86%) of the wounds; 11 healed without any additional surgical procedures. There was anxiety about maggots escaping, but actual escapes were rare. Pain, reported by several patients, was controlled with oral analgesics. CONCLUSIONS: Outpatient maggot débridement is safe, effective, and acceptable to most patients, even when administered by nonphysicians. Maggot débridement is a valuable and rational treatment option for many ambulatory, home-bound, and extended care patients who have nonhealing wounds.

Adult↗

Adherence to oral montelukast and inhaled fluticasone in children with persistent asthma.

STUDY OBJECTIVE: To evaluate adherence to oral montelukast and inhaled fluticasone in children with persistent asthma and to determine if age, monotherapy, and duration of therapy affect adherence. DESIGN: Retrospective analysis. SETTING: Pediatric pulmonary clinic. PATIENTS: One hundred seventy-one children with asthma who required continuous treatment with a controller agent year-round and in whom montelukast and/or fluticasone had been prescribed for at least 90 days. INTERVENTION: Montelukast monotherapy had been prescribed for 54 patients, fluticasone monotherapy for 48 patients, and combination therapy for 69 patients. MEASUREMENTS AND MAIN RESULTS: Prescription refill histories were obtained from pharmacies identified by the parents or from Medicaid pharmacy reimbursement records. The maximum possible adherence was calculated as [(no. of doses refilled)/(no. of doses prescribed)] x 100, for a mean observation period of 203 days (range 84-365 days) for montelukast and 314 days (range 97-365 days) for fluticasone. Median adherence rates were 59% (95% confidence interval [CI] 48-65%) for montelukast and 44% (90% CI 35-50%) for fluticasone. Adherence did not significantly correlate with age, length of observation period, or whether the patient was receiving monotherapy or combination therapy. The odds ratio for very poor adherence (< 50%) was 2.0 (95% CI 1.3-3.2) for fluticasone relative to montelukast. CONCLUSIONS: Adherence to both drugs was suboptimal. However, these data indicate that our patients were likely to take montelukast more consistently than fluticasone. Whether this translates into better asthma control requires further study.

Acetates↗

Four-year follow-up results of lumbar spine arthrodesis using the Bagby and Kuslich lumbar fusion cage.

STUDY DESIGN: This was a prospective multicenter clinical trial of a lumbar interbody fusion cage with a minimum of 4 years' follow-up. OBJECTIVES: To determine whether the early positive clinical results in fusions with lumbar cages, such as the Bagby and Kuslich (BAK) cage, are maintained beyond 2 years. SUMMARY OF BACKGROUND DATA: Threaded cages have been used increasingly for the treatment of symptomatic degenerative intervertebral disc disease. Concerns about the long-term clinical outcomes of this procedure have been posed, particularly regarding bony fusion viability, revision rates, potential adjacent level disease, and late complications. METHODS: The study cohort was a 196-patient subset from a prospective investigational device exemption. In addition to early postoperative examinations, these patients were examined biannually with a minimum of 4 years' follow-up. Patient outcome was assessed by a 6-point scale that evaluated pain relief, and functional improvement was determined by changes in activities of daily living. Fusion rates and return to work were determined. Complications and secondary operations were reported and categorized as non-device related or device related. RESULTS: The patient cohort with 4-year follow-up represented 25.6% of the original study population eligible at that time. Overall, the largest percentage of pain relief and functional improvements occurred by 3 months, and these improvements were maintained at each follow-up. Overall fusion rate was 91.7% and 95. 1% at 2 and 4 years, respectively. In this cohort, 39.5% of patients were working or were able to work within 3 months of surgery. After 4 years, 62.7% of patients were gainfully employed or able to work. The late-occurring complication rate in this cohort was 13.8% (27/196). Complications necessitating a second operation occurred in 8.7% (17/196), whereas reoperations that were deemed device related were performed in 3.1% (6/196). CONCLUSIONS: This study indicates that the early positive benefits of interbody fusion cage procedures are maintained through 4 years with acceptably low morbidity.

Cohort Studies↗

Telephoning the patient's pharmacy to assess adherence with asthma medications by measuring refill rate for prescriptions.

OBJECTIVE: To determine whether a prescription refill history obtained by telephoning patients' pharmacies identifies poor adherence with asthma medications more frequently than physician assessment. METHODS: The study population consisted of 116 children with persistent asthma who were Medicaid recipients; patients who received medication samples were excluded. During a clinic visit pulmonologists interviewed patients, caretakers, or both and estimated adherence on a checklist. A nurse asked the caretakers where they obtained medications and telephoned 66 identified pharmacies for refill histories. The maximum possible adherence was calculated as the number of doses refilled/number of doses prescribed x 100 for a mean duration of 163 days (range, 63 to 365 days). The accuracy of the refill information was determined from Medicaid reimbursement records. RESULTS: Information provided by pharmacies was 92% accurate. The mean (95% CI) of maximum potential adherence was 72% (65%,77%) for theophylline, 61% (55%,68%) for inhaled corticosteroids, and 38% (23%,53%) for cromolyn; only cromolyn and theophylline were significantly different. Physicians were able to identify 21 (49%) of 43 patients who refilled </=50% of prescribed doses of long-term symptom controllers and only 3 (27%) of 11 patients who used albuterol excessively. CONCLUSIONS: Physicians often were unable to identify patients with very poor adherence. Checking prescription refills is an accurate and practical method of identifying such patients.

Anti-Asthmatic Agents↗

Intrapartum and neonatal single-dose nevirapine compared with zidovudine for prevention of mother-to-child transmission of HIV-1 in Kampala, Uganda: HIVNET 012 randomised trial.

BACKGROUND: The AIDS Clinical Trials Group protocol 076 zidovudine prophylaxis regimen for HIV-1-infected pregnant women and their babies has been associated with a significant decrease in vertical HIV-1 transmission in non-breastfeeding women in developed countries. We compared the safety and efficacy of short-course nevirapine or zidovudine during labour and the first week of life. METHODS: From November, 1997, to April, 1999, we enrolled 626 HIV-1-infected pregnant women at Mulago Hospital in Kampala, Uganda. We randomly assigned mothers nevirapine 200 mg orally at onset of labour and 2 mg/kg to babies within 72 h of birth, or zidovudine 600 mg orally to the mother at onset of labour and 300 mg every 3 h until delivery, and 4 mg/kg orally twice daily to babies for 7 days after birth. We tested babies for HIV-1 infection at birth, 6-8 weeks, and 14-16 weeks by HIV-1 RNA PCR. We assessed HIV-1 transmission and HIV-1-free survival with Kaplan-Meier analysis. FINDINGS: Nearly all babies (98.8%) were breastfed, and 95.6% were still breastfeeding at age 14-16 weeks. The estimated risks of HIV-1 transmission in the zidovudine and nevirapine groups were: 10.4% and 8.2% at birth (p=0.354); 21.3% and 11.9% by age 6-8 weeks (p=0.0027); and 25.1% and 13.1% by age 14-16 weeks (p=0.0006). The efficacy of nevirapine compared with zidovudine was 47% (95% CI 20-64) up to age 14-16 weeks. The two regimens were well tolerated and adverse events were similar in the two groups. INTERPRETATION: Nevirapine lowered the risk of HIV-1 transmission during the first 14-16 weeks of life by nearly 50% in a breastfeeding population. This simple and inexpensive regimen could decrease mother-to-child HIV-1 transmission in less-developed countries.

Adult↗

Bronchoconstrictor additives in bronchodilator solutions.

Nebulized bronchodilator solutions are available in the United States as both nonsterile and sterile-filled products. Sulfites, benzalkonium chloride (BAC), or chlorobutanol are added to nonsterile products to prevent bacterial growth, but there have been reports of contaminated solutions containing preservatives. Ethylenediamine tetraacetic acid (EDTA) is added to some products to prevent discoloration of the solution. With the exception of chlorobutanol, all of these additives are capable of inducing bronchospasm in a concentration-dependent manner. However, it is rarely apparent to the patient or health care provider that the additive diminishes the bronchodilator effects. Older products (eg, isoproterenol and isoetharine) contain enough sulfites to produce bronchospasm in most patients with asthma, even in those without a prior history of sulfite sensitivity. Bronchoconstriction from inhaled BAC is cumulative, prolonged, and correlates directly with basal airway responsiveness. The multidose dropper bottle of albuterol contains 50 microg BAC/dose, which is below the threshold for bronchoconstriction whereas the screwcap unit-dose vial contains 300 microg/dose, which is above the threshold for many patients. If the screwcap product is used in the emergency department, a patient could receive as much as 1800 microg of BAC in the first hour. Three sterile-filled unit dose albuterol products contain no additives, whereas a fourth, (manufactured by Dey Laboratories) contains 300 microg of EDTA, which is also below the threshold dose for bronchoconstriction. Only additive-free sterile solutions should be used for hourly or continuous nebulization of albuterol. The multidose dropper bottle or the Dey product can be used when the interval between doses is longer, whereas the screwcap product should not be used for acute therapy. Ipratropium is available only as a sterile, additive-free unit-dose vial, as is levalbuterol.

Administration, Inhalation↗

Age specific prostate specific antigen reference ranges: population specific.

PURPOSE: We determined whether 60 to 79-year-old men with a negative digital rectal examination and a serum prostate specific antigen (PSA) within age specific PSA reference ranges could safely forgo prostate biopsy. MATERIALS AND METHODS: We reviewed the medical records of all 60 to 79-year-old men at the Brooklyn Veterans Administration Medical Center who had a PSA assay, digital rectal examination and subsequent prostate biopsy for an abnormal rectal examination and/or PSA greater than 4.0 ng./ml. from January 1991 through August 1995. We compared our results using the standard reference range of 0 to 4.0 ng./ml. with those obtained had we used any of 4 different age specific PSA reference ranges. RESULTS: We performed 1,280 prostate biopsies in 1,046 men with available PSA and digital rectal examination data. Using age specific PSA reference ranges 73 of 1,280 biopsies (5.7%) would have been avoided. Of those 73 avoided biopsies 15 (20.5%) had cancer that would have gone undetected and 9 of 15 (60%) undetected cancers had unfavorable histology. Results were not statistically significantly different among the 4 age specific PSA reference ranges. Regarding race, cancer detection rates were significantly higher for black compared with white men but there was no statistically significant difference for missed cancers or missed cancers with unfavorable histology. CONCLUSIONS: In contrast to previous reports of unfavorable histological characteristics in only 5% of missed cancers using age specific PSA reference ranges, 60% of missed cancers in our patients exhibited unfavorable histology. We conclude that age specific PSA reference ranges did not safely eliminate the need for prostate biopsy in our study population. In 60 to 79-year-old men with a negative digital rectal examination we continue to use PSA greater than 4.0 ng./ml. as an indication for prostate biopsy.

Age Factors↗

Solvent replacement for green processing.

The implementation of the Montreal Protocol, the Clean Air Act, and the Pollution Prevention Act of 1990 has resulted in increased awareness of organic solvent use in chemical processing. The advances made in the search to find "green" replacements for traditional solvents are reviewed, with reference to solvent alternatives for cleaning, coatings, and chemical reaction and separation processes. The development of solvent databases and computational methods that aid in the selection and/or design of feasible or optimal environmentally benign solvent alternatives for specific applications is also discussed.

Air Pollution↗

High dose combination radiotherapy for the treatment of localized prostate cancer.

PURPOSE: We evaluate the efficacy of high dose combination radiotherapy for the treatment of localized prostate cancer. MATERIALS AND METHODS: A total of 212 patients with localized prostate cancer (T1-T3) were treated with transperineal radioactive seed implantation followed by 45 Gy. external beam radiation therapy. Patients with Gleason scores of 2-5 were treated with 125iodine at a minimum peripheral dose of 120 Gy., while 103palladium at a minimum peripheral dose of 90 Gy. was used for those with Gleason scores of 7-10. Patients with Gleason 6 diploid tumors were treated with 125iodine and those with aneuploid tumors were treated with 103palladium. Biochemical failure was defined as inability to achieve a prostate specific antigen nadir value of 0.5 ng./ml. or less. No patient was treated with androgen deprivation therapy. RESULTS: The 212 patients have a minimum of 24 months of followup (mean 33 months). Prostate specific antigen 0.5 ng./ml. or less was reached by 72% of the patients (152 of 212) and positive biopsies were detected in 13.9% (20 of 144). Using life table survivorship analysis the probability of initial biochemical success at 5 years was 91% (95% confidence interval, 83 to 97). The probability of subsequent failure following an initial success was 11% (95% confidence interval, 6 to 20) at 24 months. The complications of combination therapy included proctitis in 21.4% (47 of 212 men), impotence in 38% (38 of 100), urinary retention in 1.5%, incontinence in 2.8%, rectoprostate fistula in 2.4%, rectal wall breakdown in 0.5% and urethral stricture in 0.5%. Six patients (2.8%) required colostomy and urinary diversion. CONCLUSIONS: Short-term responses to high dose combination radiotherapy for localized prostate cancer are promising. The morbidity is acceptable. Further long-term followup is warranted to assess this treatment.

Aged↗

Myositis induced by naked DNA immunization with the gene for histidyl-tRNA synthetase.

Polymyositis is regarded as an autoimmune inflammatory muscle disease. A major subgroup of patients have autoantibodies to cellular histidyl-transfer RNA synthetase (HRS). We have analyzed the role of the autoantigen HRS in the induction of murine myositis in a comparative study of inoculation of BALB/c mice with recombinant HRS protein versus naked DNA coding for HRS. Adult BALB/c mice produced antibodies to human HRS following inoculation with HRS protein and adjuvant, but myositis was not observed. Alternatively, expression plasmid DNA constructs encoding full-length and truncated human HRS were inoculated intramuscularly in gene transfer studies. DNA-inoculated mice produced relatively low anti-HRS antibody titers. However, in contrast to recombinant HRS protein-inoculated mice, HRS gene transfer induced pathology with evidence of cellular infiltration of perivascular and endomysial regions of the inoculated muscle. Multiple inoculations of a plasmid construct encoding a hybrid molecule consisting of HRS and the transferrin receptor cytoplasmic tail induced the highest levels of antibodies and persisting cellular infiltration. Unlike HRS, expression of influenza virus hemagglutinin (HA) following inoculation of an HA plasmid did not induce myositis. Transfer of naked DNA constructs expressing HRS is likely to provide valuable information on the autoimmune response to this protein and its role in the development of myositis.

Animals↗