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Biomedical subjects

J Sherman

Publications and source records attributed to J Sherman.

At least 19 recordsLinked to original sources
PubMed1999

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↗
PubMed1999

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1997

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↗
PubMed1997

Reliability of the Medtrac MDI Chronolog.

BACKGROUND: The Medtrac MDI Chronolog is an electronic device for monitoring adherence to metered-dose inhalers. It replaces previous models of the Nebulizer Chronolog and uses a different mechanism of recording actuations. OBJECTIVE: This study was carried out to determine whether the new model can accurately record and report the date, time, and number of metered-dose inhaler actuations. METHODS: Four canisters of beclomethasone (Beclovent) were discharged through four Chronologs with fresh batteries at a rate of 1, 2, 4, or 8 times twice daily for 7 days. Four additional canisters were used as controls and discharged simultaneously through the standard actuator. The weight of all canisters and Chronolog battery voltage were measured before and at the end of the 7-day experiment. The data retrieved from the Chronologs were compared with the information recorded manually during each discharge. RESULTS: The loss in canister weight was consistent for the number of puffs discharged from all four Chronolog units and controls. However, the accuracy of the Chronologs in recording the number of actuations varied between 50% and 100%. The largest amount of data loss occurred with the unit used to discharge 8 puffs and was associated with a dead battery at the end of the 7-day trial. For actuations that were retrievable, the Chronologs accurately recorded the date and time. CONCLUSIONS: Unexpected battery voltage drain and other mechanical problems that we encountered may cause data loss and the false appearance of missed doses. Thus the units that we tested were not sufficiently reliable to monitor patient adherence.

Anti-Asthmatic Agents↗
PubMed1997

Breast cancer and pesticides in Hawaii: the need for further study.

Only 30% of all breast cancer can be explained by known risk factors. Increases in breast cancer incidence rates in Hawaii over the past few decades cannot be attributed solely to improvements in screening and detection. Avoidable environmental factors may contribute to a proportion of the unexplained cases. Emerging evidence on endocrine disruption suggests that environmental chemicals may play a role in the development of breast cancer. Agricultural chemicals, including endocrine disruptors, have been used intensively in Hawaii's island ecosystem over the past 40 years leaching into groundwater, and leading to unusually widespread occupational and general population exposures. This paper discusses breast cancer patterns in Hawaii in the context of documented episodes of exposure to two endocrine-disrupting chemicals, chlordane/heptachlor and 1,2-dibromo-3-chloropropane (DBCP), at levels that sometimes exceeded federal standards by several orders of magnitude. In light of this history, detailed geographic-based studies should be undertaken in Hawaii to elucidate the potential role of environmental factors in the development of breast cancer and other diseases.

Adult↗
PubMed1997

Methadone maintenance and hepatitis C virus infection among injecting drug users.

Harm reduction strategies for the prevention of transmission of human immunodeficiency virus (HIV) transmission among injecting drug users (IDUs) have been widely implemented in Australia and are seen to have been effective in preventing the spread of HIV. A major strategy has been increasing the availability of and accessibility to methadone maintenance therapy (MMT) programmes. We have reviewed the experience of a major MMT general practice with hepatitis C virus (HCV) infection from 1991 to 1995. Of 1741 individuals tested for HCV antibodies at least once 66.7% were positive. Of 73 IDUs who were initially seronegative and were retested at least once, 19 were subsequently seropositive. Seroconverters to HCV were younger than non-seroconverters, and were more likely to have evidence of previous hepatitis B infection. The overall HCV incidence rate was 22 cases per 100 person-years, and this did not differ between those on MMT programs (continuous or interrupted) between HCV tests and those not on MMT. These findings suggest that the role of MMT in the control of the spread of HCV infection among IDUs needs further assessment, and that control of the current epidemic of HCV infection among IDUs in Australia will be very difficult.

Adult↗
PubMed1996

Gait training efficacy using a home-based practice model in chronic hemiplegia.

OBJECTIVE: The efficacy of a home practice model for gait training was evaluated in 18 hemiplegic subjects 2.3 years (range, 1 to 5) after stroke. DESIGN: Uncontrolled case series. SETTING: Referral center. SUBJECTS: Patients at least 1 year poststroke referred to an outpatient rehabilitation program. INTERVENTION: Patients were taught home programs in two or more 2- to 5-day blocks averaging 35 physical therapy (PT) contact hours (range, 9.5 to 62.5); training extended over a mean of 22 months (range, 10 to 65). Training emphasized weight bearing, balance, segmental control, stretching, and bracing. MAIN OUTCOME MEASURES: Gait changes were measured using the newly developed Wisconsin Gait Scale (WGS). The patient-rated Falls Efficacy Scale (FES) was administered before and after training to 8 subjects, and the Health Status Questionnaire (HSQ) was retrospectively administered to all subjects to appraise subjective pretraining to posttraining changes and current psychological status. RESULTS: The average WGS score significantly improved (p < .05). Patients perceived that gait training increased the quality of their functional activities (p < .05). In a subset of patients, the FES showed that fear of falling was decreased (p < .05). Perception of well-being was comparable to a normative nonstroke reference population except for physical functioning. Compared to the only other published series (using traditional outpatient programming), the current model was of comparable cost. CONCLUSION: Despite the literature indicating a plateau in mobility function by 6 months after stroke, postacute training of gait in hemiplegic subjects using a home-based training model results in improved gait and the perception of improved function. Additionally, we provide validation for the newly developed Wisconsin Gait Scale, an instrument of gait measurement that may assist in comparing outcomes.

Activities of Daily Living↗
PubMed1996

Longitudinal study of a heteroplasmic 3460 Leber hereditary optic neuropathy family by multiplexed primer-extension analysis and nucleotide sequencing.

Nucleotide-sequencing and multiplexed primer-extension assays have been used to quantitate the mutant-allele frequency in 14 maternal relatives, spanning three generations, from a family that is heteroplasmic for the primary Leber hereditary optic neuropathy (LHON) mutation at nucleotide 3460 of the mitochondrial genome. There was excellent agreement between the values that were obtained with the two different methods. The longitudinal study shows that the mutant-allele frequency was constant within individual family members over a sampling period of 3.5 years. Second, although there was an overall increase in the mutant-allele frequency in successive generations, segregation in the direction of the mutant allele was not invariant, and there was one instance in which there was a significant decrease in the frequency from parent to offspring. From these two sets of results, and from previous studies of heteroplasmic LHON families, we conclude that there is no evidence for a marked selective pressure that determines the replication, segregation, or transmission of primary LHON mutations to white blood cells and platelets. Instead, the mtDNA molecules are most likely to replicate and segregate under conditions of random drift at the cellular level. Finally, the pattern of transmission in this maternal lineage is compatible with a developmental bottleneck model in which the number of mitochondrial units of segregation in the female germ line is relatively small in relation to the number of mtDNA molecules within a cell. However, this is not an invariant pattern for humans, and simple models of mitochondrial gene transmission are inappropriate at the present time.

Alleles↗
PubMed1996

Circumcision: successful glanular reconstruction and survival following traumatic amputation.

PURPOSE: Circumcision remains the most common operation performed on male individuals in the United States. Unfortunately various complications may occur during circumcision ranging from trivial to tragic. We report 7 cases of traumatic amputation of the glans penis and/or urethra during circumcision. In addition, errors in circumcision technique as probable mechanisms of injury, principles of repair and limits of tissue viability are discussed. MATERIALS AND METHODS: The medical records of 7 patients who underwent traumatic circumcision amputation of the glans penis and/or urethra were reviewed. Glanular amputation occurred in 6, 8-day-old neonates during ritual circumcision and in 1, 5-month-old infant circumcised by a physician. RESULTS: Excised glanular tissue remained viable up to 8 hours after injury. Followup ranged from 8.5 to 108 months. All patients had an acceptable cosmetic result. No long-term complications developed in the 8-day-old group but a distal urethral fistula formed in the 5-month-old patient. CONCLUSIONS: Careful selection of technique and device as well as strict attention to detail at circumcision should eliminate most injuries. On the basis of our results we recommend reanastomosis of the glans and/or urethra following distal amputation even when there is a delay in surgical repair of up to 8 hours.

Amputation, Traumatic↗
PubMed1996

Characterization of a derivative chromosome 17 by fish-technique.

We report a case with derivative chromosome 17 which could not be characterized by routine G-banding, since the additional material on 17q overlapped with chromosome bands 2q35 -->qter, 3p25-->pter, 4p15-->pter, 5q33-->qter, 7p15-->pter, 12p11.2-->pter, 14q24-->qter and 16q22-->qter. Therefore, whole chromosome paint and region specific probes were used to identify the abnormality by FISH-technique which revealed a 46,XY, der (17) t (4;17) (p15.2;q25) karyotype. The proband was partially trisomic for 4p15.2-->pter and monosomic for the distal 17q25-->qter regions. The major clinical features included: anti-mongoloid slanted palpebrae, coloboma of right iris, depressed nasal bridge, high arched palate, protruding tongue, micrognathia and small penis. The MRI of the brain revealed midly hypoplastic cerebellar vermis, and a normal septum pellucidum. The infant responded to therapy for hypoglycemia and was discharged under stable condition. Prior to cytogenetic evaluation the infant was not recognized as either "trisomy 4p syndrome" or "monosomy 17q syndrome".

Abnormalities, Multiple↗
PubMed1996

Leber's hereditary optic neuropathy: historical and contemporary considerations.

Leber's hereditary optic neuropathy (LHON) is a distinct form of optic atrophy with a unique pattern of inheritance. The clinical reports of this disorder remain consistent with the original classic description made by Theodor Leber in 1871. Recent advances in the field of molecular genetics, however, have yielded insights into the etiological determinants underlying the clinical expression of LHON. Disease presentation, both ophthalmoscopically and clinically, are reviewed. Classic and atypical presentations are discussed with genetic testing as the definitive diagnostic measurement. Clinical and histopathological findings have led to the investigation of promising preclinical indicators of LHON symptomatology. Evidence of a multifactorial etiology has implicated a broad spectrum of potential intervention protocols. Teaming of the clinician and laboratory geneticist to identify those at risk is critical, not only for future clinical protocols, but to allow for immediate intervention when an effective therapy becomes available.

Diagnosis, Differential↗