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Biomedical subjects

J H Smith

Publications and source records attributed to J H Smith.

At least 37 records · Page 2Linked to original sources
PubMed2000

Effects of di-isononyl phthalate, di-2-ethylhexyl phthalate, and clofibrate in cynomolgus monkeys.

The effects of the peroxisome proliferators di-isononyl phthalate (DINP) and di-2-ethylhexyl phthalate (DEHP) were evaluated in young adult male cynomolgus monkeys after 14 days of treatment, with emphasis on detecting hepatic and other effects seen in rats and mice after treatment with high doses of phthalates. Groups of 4 monkeys received DINP (500 mg/kg/day), DEHP (500 mg/kg/day), or vehicle (0.5% methyl cellulose, 10 ml/kg) by intragastric intubation for 14 consecutive days. Clofibrate (250 mg/kg/day), a hypolipidemic drug used for cholesterol reduction in human patients was used as a reference substance. None of the test substances had any effect on body weight or liver weights. Histopathological examination of tissues from these animals revealed no distinctive treatment-related effects in the liver, kidney, or testes. There were also no changes in any of the hepatic markers for peroxisomal proliferation, including peroxisomal beta-oxidation (PBOX) or replicative DNA synthesis. Additionally, in situ dye transfer studies using fresh liver slices revealed that DINP, DEHP, and clofibrate had no effect on gap junctional intercellular communication (GJIC). None of the test substances produced any toxicologically important changes in urinalysis, hematology, or clinical chemistry; however, clofibrate produced some emesis, small increases in serum triglyceride, decreased calcium, and decreased weights of testes/epididymides and thyroid/parathyroid. The toxicological significance of these small changes is questionable. The absence of observable hepatic effects in monkeys at doses that produce hepatic effects in rodents suggests that DINP, DEHP, and clofibrate would also not elicit in primates other effects such as liver cancer. These data, along with results from in vitro hepatocyte studies, indicate that rodents are not good animal models for predicting the hepatic effects of phthalates in primates, including humans.

Administration, Oral↗
PubMed2000

Effects of Di-2-ethylhexyl phthalate (DEHP) on gap-junctional intercellular communication (GJIC), DNA synthesis, and peroxisomal beta oxidation (PBOX) in rat, mouse, and hamster liver.

The present study evaluated the effect of di-2-ethylhexyl phthalate (DEHP) on gap-junctional intercellular communication (GJIC), peroxisomal beta-oxidation (PBOX) activity, and replicative DNA synthesis in several rodent species with differing susceptibilities to peroxisome proliferator-induced hepatic tumorigenesis. A low (non-tumorigenic) and high (tumorigenic) dietary concentration of DEHP was administered to male F344 rats for 1, 2, 4, and 6 weeks. Additionally, a previously non-tumorigenic dose (1000 ppm) and tumorigenic dose of DEHP (12,000 ppm), as determined by chronic bioassay data, were examined following 2 weeks dietary administration. Male B6C3F1 mice were fed the non-tumorigenic concentration, 500 ppm, and the tumorigenic concentration, 6000 ppm, of DEHP for two and four weeks. The hepatic effects of low and high concentrations of DEHP, 1000 and 6000 ppm, were also examined in male Syrian Golden hamsters (refractory to peroxisome proliferator-induced tumorigenicity). In rat and mouse liver, a concentration-dependent increase in the relative liver weight, PBOX activity, and replicative DNA synthesis was observed at the earliest time point examined. Concurrent to these observations was an inhibition of GJIC. In hamster liver, a slight increase in the relative liver weight, PBOX activity, and replicative DNA synthesis was observed. However, these effects were not of the same magnitude or consistency as those observed in rats or mice. Furthermore, DEHP had no effect on GJIC in hamster liver at any of the time points examined (2 and 4 weeks). HPLC analysis of DEHP and its primary metabolites, mono-2-ethylhexyl phthalate (MEHP), and phthalate acid (PA), indicated a time- and concentration-dependent increase in the hepatic concentration of MEHP. At equivalent dietary concentrations and time points, the presence of MEHP, the primary metabolite responsible for the hepatic effects of DEHP, demonstrated a species-specific response. The largest increase in the hepatic concentration of MEHP was observed in mice, which was greater than the concentration observed in rats. The hepatic concentration of MEHP was lowest in hamsters. Hepatic concentrations of DEHP and phthalic acid were minimal and did not correlate with concentration and time. Collectively, these data demonstrate the inhibition of hepatic GJIC and increased replicative DNA synthesis correlated with the observed dose- and species-specific tumorigenicity of DEHP and may be predictive indicators of the nongenotoxic carcinogenic potential of phthalate esters.

Animals↗
PubMed1999

Spontaneous regression of orbital Langerhans cell granulomatosis in a three-year-old girl.

PURPOSE: To report a case of spontaneous regression of orbital Langerhans cell granulomatosis. METHOD: Case report. A 3-year-old girl was initially examined with a 5-week history of slowly progressive blepharoptosis and periorbital swelling of the left eye. RESULTS: Computed tomographic scan showed a mass in the left orbit eroding into the left frontal bone; fine-needle aspiration confirmed diagnosis of Langerhans cell granulomatosis. After initial biopsy, the patient was treated by close observation alone. Six months after initial examination, the monostotic lesion had completely resolved. CONCLUSIONS: In some cases of monostotic Langerhans cell granulomatosis, initial biopsy followed by observation alone may allow for the spontaneous regression of the lesion. This conservative approach to treatment is an important therapeutic option that may spare the patient the adverse effects of surgical resection, radiation, or chemotherapy.

Blepharoptosis↗
PubMed1999

Outcome after surgical resection for high-grade anal intraepithelial neoplasia (Bowen's disease).

BACKGROUND: High-grade anal intraepithelial neoplasia (Bowen's disease) may predispose to anal carcinoma. Treatment options include surgical resection but effectiveness remains uncertain. This paper reports long-term follow-up of patients with high-grade anal intraepithelial neoplasia treated by surgical resection. METHODS: Between 1989 and 1996, 46 patients were identified with high-grade anal intraepithelial neoplasia. Thirty-four underwent local excision of all macroscopically abnormal disease and the resulting defect was left open, closed primarily or skin grafted. Regular follow-up subsequently included anoscopy and biopsy of any suspicious lesions. RESULTS: Median follow-up was 41 (range 12-104) months. Total excision was difficult; 19 patients had histological evidence of incomplete excision at the time of initial resection. Some 12 of 19 had histo-logically proven recurrent high-grade intraepithelial neoplasia within 1 year. Even with microscopically complete excision two of 15 patients subsequently developed recurrent high-grade intraepithelial neoplasia at 6 and 32 months after operation. No patient developed carcinoma but five had complica-tions of anal stenosis or faecal incontinence. CONCLUSION: Although no definite recommendations can be made for the treatment of high-grade anal intraepithelial neoplasia, these results illustrate some potential drawbacks of surgical excision with a high potential for incomplete excision and persistent disease, even after complete excision in some patients, and a high morbidity rate.

Anus Neoplasms↗
PubMed1999

Ocular manifestations of systemic malignancies.

Ocular manifestations of systemic malignancy are important for both the ophthalmologist and the internist to recognize because they may precede the diagnosis of cancer. This review of the current literature discusses the clinical manifestations, etiology, and potential therapeutic interventions for a group of visual paraneoplastic syndromes, including carcinoma-associated retinopathy and melanoma-associated retinopathy. These conditions are characterized by elevated serum levels of autoantibodies directed against tumor antigen that cross-react with retinal proteins, resulting in rod and cone dysfunction. The clinical presentation, site of origin, frequency, and intraocular distribution of tumors metastatic to the eye are also reviewed.

Diagnosis, Differential↗
PubMed1999

Identification of Porphyromonas gingivalis strains by heteroduplex analysis and detection of multiple strains.

Heteroduplex analysis has been used extensively to identify allelic variation among mammalian genes. It provides a rapid and reliable method for determining and cataloging minor differences between two closely related DNA sequences. We have adapted this technique to distinguish among strains or clonal types of Porphyromonas gingivalis. The ribosomal intergenic spacer region (ISR) was amplified directly from a subgingival plaque sample by PCR with species-specific primers, avoiding the need for culturing the bacteria. The PCR products were then directly compared by heteroduplex analysis with known strains of P. gingivalis for identification. We identified 22 distinct but closely related heteroduplex types of P. gingivalis in 1,183 clinical samples. Multiple strains were found in 34% of the samples in which P. gingivalis was detected. Heteroduplex types were identified from these multistrain samples without separating them by culturing or molecular cloning. PCR with species-specific primers and heteroduplex analysis makes it possible to reliably and sensitively detect and identify strains of P. gingivalis in large numbers of samples.

Bacteroidaceae Infections↗
PubMed1999

Physiological determinants of performance on an indoor military obstacle course test.

Obstacle courses (OCs), physical challenge courses, and confidence courses are valuable in training and assessing military troops. However, OCs are not well characterized with regard to physical demands and requisite abilities. The purpose of this study was to evaluate the physical capabilities associated with success on an OC. Male subjects (N = 47) were assessed on an OC, skinfolds, upper and lower body aerobic and anaerobic power, muscular strength, and endurance. Faster performers were lighter (p < 0.003), leaner, and, relative to body weight, averaged greater arm anaerobic peak and mean power, leg aerobic power, one-repetition maximum leg press, and one-repetition maximum latissimus dorsi pull-down, than slower performers. There were significant correlations between OC time and weight (0.59), percent fat (0.54), anaerobic leg mean power (-0.43), arm anaerobic peak (-0.48) and mean power (-0.48), and arm (-0.51) and leg aerobic power (-0.53), all expressed relative to body weight. A three-variable regression model accounted for 35% of the variation in OC time. Good performers on this OC displayed many diverse physical capabilities.

Adult↗
PubMed1998

Cystoid macular edema associated with cytomegalovirus retinitis in patients with the acquired immunodeficiency syndrome.

PURPOSE: To describe the clinical and fluorescein angiographic appearance of cystoid macular edema associated with cytomegalovirus retinitis in patients with the acquired immunodeficiency syndrome (AIDS). METHODS: We retrospectively examined the clinical and photographic records of four patients with AIDS and cytomegalovirus retinitis who developed cystoid macular edema. RESULTS: Seven eyes of four patients with AIDS and cytomegalovirus retinitis experienced decreased vision associated with cystoid macular edema. Vitreous inflammation was mild in each patient. In all eyes, the retinitis involved zone 1, and in all but one eye, the cytomegalovirus retinitis was inactive. In one eye, the cystoid macular edema was worsened by formation of a dense juxtafoveal epiretinal membrane. CONCLUSIONS: Although infrequently recognized, cystoid macular edema can cause visual loss in patients with AIDS and cytomegalovirus retinitis. Fluorescein angiography should be considered in any patient with cytomegalovirus retinitis and unexplained visual loss.

AIDS-Related Opportunistic Infections↗
PubMed1998

Guidelines for anal cytology--to make cytological diagnosis and follow up much more reliable.

Anal intraepithelial neoplasia is a difficult diagnostic and management problem, particularly when it occurs in women with synchronous or metachronous genital intraepithelial neoplasia. Diagnosis and follow up by colposcopy is too specialized for widespread use, and although anal cytology has been used before it has been thought of as too inconsistent for practical application. This study standardized collection of specimens and investigated interobserver variation. The aim of the study was to determine whether observers could reliably distinguish high grade anal intraepithelial neoplasia from other conditions. Standardized collection of anal preparations was achieved in the host centre. A meeting of experienced cytopathologists was convened to agree guidelines for anal cytology. These guidelines were sent to the panel of six observers who were subsequently circulated with 30 cytopathological preparations in random order and asked to report them all. The results were collected and processed centrally. Four individuals were in complete agreement about those preparations which were inadequate for reporting, but two others had a lower threshold for rejecting preparations as inadequate. There was agreement between the observers in over 95% of cases in distinguishing high grade intraepithelial neoplasia from other cytological conditions. Kappa values range from 0.66 to 1.00. This study demonstrates that the provision of guidelines for the interpretation of anal cytopathological preparations can result in a high degree of interobserver agreement about the clinically important distinction between high grade anal intraepithelial neoplasia and other conditions. Anal cytology is a more useful technique for diagnosis and follow up of 'at risk' individuals than has previously been suggested, and should be utilized more widely in this group of patients.

Anal Canal↗
PubMed1998

An efficient, automatable template preparation for high throughput sequencing.

We have developed a 96-well format for DNA template isolation that can be readily automatable. The template isolation protocol involves simple alkaline lysis chemistry and reversible capture on a silica solid phase. After the cells are lysed, no centrifugation is necessary, as lysate purification, DNA binding, washing, and release occur in 96-well filter plates. Large numbers of templates prepared using the silica purification method have been sequenced and analyzed. The quality of sequence resulting from our method has been compared with that generated from several commercial plasmid preparation protocols. We found sequence quality of the silica bead preparations to be equivalent to or, in some cases, better than those prepared by other methods. This method offers many advantages over other protocols we have used. First, the silica purifications have allowed us to more than double overall laboratory throughput while decreasing our template isolation materials cost at least five-fold. Second, because we have eliminated all centrifugation steps in the protocol, automation has been much simpler. The protocol has also been adapted to purify PCR products for use as templates in subsequent sequencing reactions.

Automation↗
PubMed1997

Disability in US presidents report. Recommendations and commentaries by the Working Group. The Working Group on Presidential Disability.

If the president of the United States must decide within minutes how to respond to a dire emergency, its citizens expect him or her to be mentally competent and to act wisely. Because the presidency of the United States is now the world's most powerful office, should its incumbent become even temporarily unable to exercise good judgment, the consequences for the world could be unimaginably far-reaching.

Persons with Disabilities↗
PubMed1997

Outcomes of cataract surgery by residents at a public county hospital.

PURPOSE: To determine whether outcomes of extracapsular cataract surgery with intraocular lens implantation performed by residents at an urban county hospital are comparable to previously reported patient outcomes at Veterans Affairs and university hospitals. METHODS: We performed a retrospective analysis of all extracapsular cataract procedures with intraocular lens implantation, both by standard extracapsular cataract extractions and by phacoemulsification, performed by first-year, second-year, and third-year residents at San Francisco General Hospital from January 1, 1994, through June 30, 1995. RESULTS: Final best-corrected visual acuity of 20/40 or better was achieved in 183 (84%) of 218 eyes. When patients with preexisting eye disease limiting visual potential were excluded, 20/40 or better visual acuity was achieved in 159 (94%) of 169 eyes. Vitreous loss occurred in six (16%) of 37 eyes operated on by first-year residents, in six (10%) of 63 eyes operated on by second-year residents, and in seven (6%) of 118 eyes operated on by third-year residents. The mean change in vision was a gain of 6 lines of Snellen acuity. CONCLUSIONS: Patients undergoing cataract surgery performed by residents at an urban county hospital have visual outcomes equivalent to those of patients at Veterans Affairs and at university facilities.

Adult↗
PubMed1997

Liver function tests in pre-eclampsia: importance of comparison with a reference range derived for normal pregnancy.

OBJECTIVES: To determine reference ranges for liver function tests in uncomplicated pregnancy and to relate abnormal results by these criteria to outcome in pre-eclampsia. DESIGN: Prospective, cross-sectional study to establish the reference ranges. Prospective observational study of women with pre-eclampsia. SETTING: Antenatal clinics and obstetric unit of St Mary's Hospital, London. PARTICIPANTS: Four hundred and thirty women with uncomplicated pregnancies and 85 consecutive women with gestational hypertension. MAIN OUTCOME MEASURES: Aspartate transaminase (AST), alanine transaminase (ALT), bilirubin and gamma glutamyl transferase (GGT) were measured to determine their ranges in normal pregnancy. The severity of pre-eclampsia was determined by the maximum blood pressure, creatinine and 24 h urinary protein; minimum platelet count; maternal complications; mode of and gestation at delivery; and fetal outcome with centile weight adjusted for gestational age and sex. RESULTS: AST, ALT, bilirubin and GGT were each lower in uncomplicated pregnancy than the nonpregnant laboratory reference ranges. Of those cases with elevated liver function tests in the pre-eclampsia group, 37% were abnormal only by the new reference ranges. Using the new ranges, the prevalence of elevated liver function tests was significantly higher in the pre-eclampsia group (54%) than in those with pregnancy induced hypertension (14%) (P < 0.01). Amongst those with pre-eclampsia, abnormal liver function tests were associated with greater proteinuria (P < 0.05), lower platelet count (P < 0.001) and more maternal complications (P < 0.01) than normal liver function tests; there was no difference in the severity of hypertension between the groups. CONCLUSIONS: Liver function tests are lower in normal pregnancy than the reference ranges currently used. Our pregnancy-derived ranges allow more precise identification of abnormal liver function in women with pre-eclampsia than is possible using standard reference ranges derived from a nonpregnant population.

Adolescent↗
PubMed1997

Detection of Mycobacterium tuberculosis directly from sputum by using a prototype automated Q-beta replicase assay.

We have adapted an assay for the direct detection of Mycobacterium tuberculosis using a prototype automated instrument platform in which probes are amplified with Q-beta replicase. The assay was based on amplification of specific detector probe following four cycles of background reduction (reversible target capture) in a closed disposable pack. The assay signal was the time required for fluorescence to exceed background levels (response time [RT]). RT was inversely related to the number of M. tuberculosis rRNA target molecules in the sample. Equivalent signals and noises were observed in assays containing either sputum or buffer. All mock samples containing > or = 10 CFU of M. tuberculosis responded in the assay (average RT, 13.91 min), while most (83%) samples containing as many as 10(7) CFU of Mycobacterium avium gave no response during a 25-min amplification reaction. The samples containing M. avium which did respond had an average RT of 17.04 min. Seventy-five percent (167 of 223) of samples containing no target gave no responses; the remaining 25% had an average RT of 15.53 min. Eighty-three frozen sputum samples were tested to develop a candidate cutoff RT for the assay prior to more extensive clinical testing. After resolution of discrepant results and with a 14-min RT cutoff, 30 of 38 M. tuberculosis-positive samples were positive by the assay; 1 of 45 negative samples responded within 14 min. Assay sensitivity, specificity, and positive and negatives predictive values in this pilot study were 79, 98, 97, and 85%, respectively.

DNA Probes↗
PubMed1997

Performance of an automated Q-beta replicase amplification assay for Mycobacterium tuberculosis in a clinical trial.

We present data from a clinical trial study in which an automated version (Galileo) of a previously described Q-Beta replicase-amplified probe assay (J. S. Shah et al., J. Clin. Microbiol. 33:1435-1441, 1995) was used for the direct detection of Mycobacterium tuberculosis complex in sputum. The assay was designed to target specific regions of 23S rRNA found in M. tuberculosis, Mycobacterium bovis, Mycobacterium africanum, and Mycobacterium microti and had a sensitivity ranging from approximately <10 to 300 CFU. The assay was tested for cross-hybridization by using large numbers (e.g., 10(5)to 10(10) CFU/assay) of 133 other organisms commonly found in respiratory tract samples, including non-M. tuberculosis Mycobacterium spp., other bacteria, fungi, and viruses. All of these competitors tested negative by the assay. Automated assay results for 780 respiratory tract samples (sputum or bronchoalveolar lavage specimens) collected and tested at three trial sites in the United States) were compared with the results of culture and acid-fast microscopy. Aliquots of conventionally digested and decontaminated sputum pellets were heated at 100 degrees C and mechanically disrupted prior to hybridization and background reduction, amplification, and detection in a closed disposable test pack. Pertinent elements of individual patient histories relating to tuberculosis exposure, previous active disease, antituberculosis therapy status, etc., were considered in the resolution of discrepant results for 48 (assay false-positive) samples. Seventy-one of 90 (78.9%) culture-positive samples were positive when tested in the Galileo assay, while 7% of culture-negative samples were assay positive, corresponding to a sensitivity of 79% and a specificity of 93%. Following resolution of discrepant results by chart review, the sensitivity and specificity for the Q-Beta replicase amplification assay with the Galileo analyzer were 84 and 97%, respectively. A total of 69.2% of smear-negative (culture positive) samples were detected by the assay. Ten test packs at a time were automatically processed by the Galileo analyzer without operator intervention following loading of samples. The first result was reported in approximately 3 h, and the last result was available in 6.5 h. To our knowledge, this is the first report of a clinical study with a fully automated amplification probe hybridization assay for the detection of pathogens directly from a clinical specimen.

Bronchoalveolar Lavage Fluid↗