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Biomedical subjects

P Thomas

Publications and source records attributed to P Thomas.

At least 235 records · Page 13Linked to original sources

Effects of estrogens and xenoestrogens on androgen production by Atlantic croaker testes in vitro: evidence for a nongenomic action mediated by an estrogen membrane receptor.

The short-term effects of estrogens and xenoestrogens on testicular androgen production were investigated in an in vitro incubation bioassay system using testicular tissue from the Atlantic croaker (Micropogonias undulatus). Incubation of testicular tissue fragments with estradiol over the concentration range of 37 nM to 37 microM caused concentration-dependent decreases in gonadotropin-stimulated 11-ketotestosterone (11-KT) production. The effect was specific for estrogens; progesterone, cortisol, and the synthetic androgen mibolerone did not significantly alter 11-KT production at similar concentrations. Diethylstilbestrol, the antiestrogen ICI 182,780, and several xenoestrogens including Kepone (chlordecone), 4-nonylphenol, and a hydroxylated polychlorinated biphenyl metabolite also significantly decreased gonadotropin-stimulated 11-KT production. The action of estradiol was rapid (<5 min) and was not blocked by actinomycin D and cycloheximide, inhibitors of transcription and translation, respectively. Moreover, estradiol conjugated to BSA, which cannot pass through the cell membrane, also caused a decrease in 11-KT production. In addition, an estrogen-binding moiety was identified in testicular membrane preparations that had a single class of high-affinity (K(d) 1.6 nM), saturable (1.2 nM), displaceable, finite (B(max) 0.03 nM, 26 fmol/g testis) binding sites specific for estrogens and exhibited rapid association (t(1/2) = 5 min), characteristics typical of steroid membrane receptors. Overall the relative binding affinities of estrogens, other steroids, antiestrogens, and xenoestrogens for the membrane preparation correlated with their activities in the androgen production bioassay, thereby satisfying the final criteria for the designation of this estrogen-binding moiety as a steroid membrane receptor. The results demonstrate that estrogens and also probably xenoestrogens can act on the cell surface via a nongenomic mechanism to alter testicular androgen production in this vertebrate species.

Androgens↗

Developing child abuse prevention, identification, and treatment systems in Eastern Europe.

Although the dissolution of the Soviet Union in 1989 brought a welcome end to the Cold War, the subsequent reestablishment of independent Eastern European countries revealed a host of problems. Among these was frequent child abuse and neglect, although lack of epidemiological data precluded any accurate estimate of prevalence. In an effort to address the problem of child abuse within this rapidly changing sociopolitical environment, the Children's Mental Health Alliance and the Soros Foundation organized the Eastern European Child Abuse and Child Mental Health Project in 1995. The authors describe the development of this multidisciplinary initiative involving collaboration with professionals from 17 countries in Eastern Europe. They highlight the goals, principles, and major phases of the project, as well as some of the challenges involved in its implementation.

Child↗

Human immunodeficiency virus-infected adolescents: a descriptive study of older children in New York City, Los Angeles County, Massachusetts and Washington, DC.

BACKGROUND: Children infected with HIV are entering adolescence with challenging and changing medical and social needs. Through chart review we describe certain medical and social characteristics of adolescents who acquired HIV as children. METHODS: HIV-infected children 12 years of age and older in 1995 were monitored through the Pediatric Spectrum of HIV Disease study from four US sites. In addition to standard 6-month medical chart reviews, a special chart abstraction in 1997 collected available psychosocial and sexual history information. RESULTS: A total of 131 adolescents HIV-infected as children were studied: 52 infected perinatally; 44 infected through a contaminated blood transfusion; 30 through receipt of contaminated blood products for hemophilia; and 5 with unknown transmission mode. Mean age at last medical contact was 15.5 years, 67% were Hispanic or African-American, 12% were employed, 66% attended regular school, 66% knew their HIV status and 48% (8% for the perinatally infected) lived with their biologic mother. Information on sexual activity showed that 18% had sexual relations, 28% did not and for 53% sexual activity was not recorded in the medical chart. Four percent used illicit drugs, which along with sexual activity showed a positive association with age. Forty-two percent had an AIDS-defining opportunistic infection, and 56% had a recent CD4+ lymphocyte count <200 cells/microl. CONCLUSIONS: Adolescents in this study represent a heterogeneous group of surviving HIV-infected children some of whom are sexually active and potential sources of HIV transmission. Clinicians who treat HIV-infected and high risk adolescents face the challenges of providing care and prevention services appropriate to adolescent development.

Adolescent↗

Tuberculosis in human immunodeficiency virus-infected and human immunodeficiency virus-exposed children in New York City. The New York City Pediatric Spectrum of HIV Disease Consortium.

BACKGROUND: Tuberculosis disease incidence increased sharply in New York City (NYC) in the late 1980s in children and adults. The relationship of tuberculosis disease in adults with the coincident epidemic of immunosuppression caused by HIV disease has been well-documented. This paper examines the relationship of tuberculosis and HIV in children in NYC. METHODS: Information on tuberculosis was collected by retrospective chart abstraction in a cohort of HIV-exposed and infected children enrolled in a longitudinal study of HIV. Tuberculosis cases were ascertained by chart review or by matching HIV-infected and -exposed children to NYC Tuberculosis Registry cases. NYC Tuberculosis Registry data on children reported from 1989 to 1995, and not reported as HIV-infected, were used for comparison. RESULTS: Tuberculosis disease was found in 45 (3%) of 1426 HIV-infected children (0.61 per 100 child years of observation) and in 5 (0.5%) of 1085 HIV-exposed uninfected children (0.2 per 100 child years). 30% of children were evaluated for HIV only after presenting with tuberculosis. Children with tuberculosis and HIV were more likely than other age-matched HIV-infected children to have decreased CD4+ T lymphocyte counts (66% vs. 37%, P = 0.02) and more likely than other NYC children with tuberculosis to have culture-confirmed and extrapulmonary tuberculosis. In this series 8 of 21 deaths in HIV-infected children with tuberculosis appeared to be related to tuberculosis. CONCLUSIONS: During a period of high tuberculosis incidence in NYC, 3% of HIV-infected children in our cohort had tuberculosis, higher than the rate in uninfected children born to HIV-positive mothers in the same cohort. Because of this association, HIV-infected children with pulmonary illness should be tested for tuberculosis; and all children with tuberculosis should be tested for HIV.

AIDS-Related Opportunistic Infections↗

Thermohalobacter berrensis gen. nov., sp. nov., a thermophilic, strictly halophilic bacterium from a solar saltern.

A new thermophilic, strictly halophilic, anaerobic, non-sporulating rod-shaped bacterium, measuring 0.5 x 3.0-8.0 microns and designated strain CTT3T, was isolated from a solar saltern. Strain CTT3T stained Gram-negative, was motile by means of laterally inserted flagella, had a genome G + C content of 33 mol% and grew optimally at 65 degrees C and pH 7.0 with 5% NaCl. The strain also grew readily at 70 degrees C in the presence of 15% NaCl. Strain CTT3T fermented cellobiose, fructose, glucose, maltose, mannitol, mannose, sucrose, glycerol, N-acetylglucosamine, starch, pyruvate and bio-Trypticase. It produced acetate, ethanol, H2 and presumably CO2 from glucose. 16S rRNA gene sequence analysis indicated that it is a member of cluster XII of the Clostridiales and related genera of the subphylum of the Gram-positive bacteria containing genomes of low G + C content. Its phenotypic and phylogenetic characteristics clearly differentiated it from all other members of this cluster. Based on the findings it is proposed that strain CTT3T be designated as a new species of a new genus, Thermohalobacter berrensis gen. nov., sp. nov. The type strain is CTT3T (= CNCM 105955T).

Base Composition↗

Thermoanaerobacter subterraneus sp. nov., a novel thermophile isolated from oilfield water.

A new thermophilic, anaerobic glucose-fermenting, Gram-positive, rod-shaped bacterium, designated strain SEBR 7858T, was isolated from an oilfield water sample. Under optimal conditions on a glucose-containing medium (3% NaCl, 65 degrees C and pH 7.5), the generation time was 2.5 h. No growth occurred at 35 or 80 degrees C, nor at pH 5..5 or 9.0. Strain SEBR 7858T possessed lateral flagella. Spores were undetected but heat-resistant forms were present. Strain SEBR 7858T fermented a range of carbohydrates to acetate, L-alanine, lactate, H2 and CO2. The isolate reduced thiosulfate and elemental sulfur, but not sulfate or sulfite to sulfide. In the presence of thiosulfate, the ratio of acetate produced per mole of glucose consumed increased, suggesting a shift in the use of electron acceptors during carbohydrate metabolism. The DNA G+C content was 41 mol%. Based on 16S rRNA gene sequence analysis, the strain was almost equidistantly related to all members of the genus Thermoanaerobacter (mean similarity 92%). Based on phenotypic, genomic and phylogenetic characteristics, strain SEBR 7858T was clearly different from all members of the genus Thermoanaerobacter and was therefore designated as a new species, Thermoanaerobacter subterraneus sp. nov. The type strain is SEBR 7858T (= CNCM 1-2383T, DSM 13054T).

Anaerobiosis↗

Hepatic colon cancer metastases in mice: dynamic in vivo correlation with hypoechoic rims visible at US.

PURPOSE: To use videomicroscopy of tumor-bearing livers of live mice to depict tumors directly to determine the exact nature of rims seen on corresponding ultrasonographic (US) scans. MATERIALS AND METHODS: Seventy-six hepatic colorectal cancer metastases were studied in exteriorized livers of 18 mice by using intravital microscopy, US, and histologic examination of the same tumors. RESULTS: Hypoechoic rims correlated with distended sinusoidal spaces in vivo. These spaces surrounded only locally invasive tumors (mean diameter, 0.85 mm) that had obstructed the supplying terminal portal venules. These spaces, containing adherent leukocytes and tumor cells, gave rise to new tumor vasculature. Results of histologic examination of rims (portal inflammation, congested or compressed sinusoids, cell atrophy) correlated with leukocyte endothelial adherence, occluded sinusoids, and new vessel formation in vivo. CONCLUSION: Unlike results from previous studies, dynamic in vivo observations of peritumoral rims demonstrated distended sinusoidal spaces giving rise to new tumor-penetrating vessels. These sinusoids arose around locally invasive tumors and were associated with more advanced intrahepatic disease. These dynamic observations provide a pathophysiologic explanation for previous histologic correlates of peritumoral rims.

Analysis of Variance↗

Early detection of airway involvement in obliterative bronchiolitis after lung transplantation. Functional and bronchoalveolar lavage cell findings.

As defined by the International Society for Heart and Lung Transplantation, the diagnosis of posttransplant obliterative bronchiolitis (OB) is based on histopathologic features and/or spirometric staging criteria, using FEV(1) to determine the extent of disease. However, this last parameter reflects an advanced bronchiolar process. The present study investigated whether physiologic parameters reflecting smaller airways dysfunction on one hand, and neutrophils in bronchoalveolar lavage fluid (BALF) on the other hand, could be useful for the earlier detection of bronchiolitis obliterans syndrome (BOS). We analyzed data obtained both from 765 pulmonary function test results and from 467 BALF specimens from 45 patients who survived at least 1 yr after surgery (n = 47, including two retransplantations). Of the transplant procedures, 22 were associated with BOS and 25 were not. The mean delay from transplantation to the diagnosis of BOS was 578 d (range: 122 to 2,619 d). The threshold values of the following parameters were studied: decline in the forced expiratory flow rate at 25% to 75% of FVC (FEF(25-75)) to </= 70% of the predicted value and of baseline values, increase in the slope of the nitrogen washout curve (DeltaN(2)) > 3%, and alveolar neutrophilia >/= 20% of the total BALF cell count. Agreement on the diagnosis of BOS (using the decline in FEV(1)) was equally good for each of the four markers (kappa coefficient > 0.65, p < 10(-)(5)). In the OB group, mean delays after the threshold was reached for each of these parameters were 110 d (p = 0.09), 173 d (p = 0.03), 150 d (p = 0.003), and 131 d (p = 0.1), respectively, before the FEV(1) criteria were fulfilled. At the chosen threshold values, the decline in FEF(25-75), increase in DeltaN(2), and development of a substantial alveolar neutrophilia all occurred significantly before a decline in FEV(1) in posttransplant OB.

Adult↗

Diagnostic accuracy of protected catheter sampling in ventilator-associated bacterial pneumonia.

The aim of this study was to assess the accuracy of protected telescoping catheter performed using: 1) protected distal aspiration, or 2) protected mini-bronchoalveolar lavage for the diagnosis of ventilator-associated bacterial pneumonia. Twenty-seven patients who died after receiving mechanical ventilation for at least 72 h were included in a comparative prospective post-mortem study. The two microbiological sampling procedures were performed immediately after death. Surgical pneumonectomies and biopsies were performed within 30 min of death at the bedside for histological examination. The results of the two techniques were compared with histological post-mortem lung examination or biopsies. Histological examination of the parenchyma showed signs of pneumonia in 14 cases. Lung tissue culture was positive in nine of these 14 cases. When ventilator-associated bacterial pneumonia was defined by the association of histological signs and positive lung tissue culture the sensitivity was 78% for both sampling techniques, specificity was 86% for mini-bronchoalveolar lavage and 100% for protected distal aspiration (at a threshold of 1 x 10(3) cfu x mL(-1)). Both techniques protected the distal aspiration and mini-bronchoalveolar lavage, and provided good specificity with an acceptable sensitivity for the diagnosis of ventilator-associated bacterial pneumonia.

Aged↗

The homeobox gene Hex is required in definitive endodermal tissues for normal forebrain, liver and thyroid formation.

The homeobox gene Hex is expressed in the anterior visceral endoderm (AVE) and rostral definitive endoderm of early mouse embryos. Later, Hex transcripts are detected in liver, thyroid and endothelial precursor cells. A null mutation was introduced into the Hex locus by homologous recombination in embryonic stem cells. Hex mutant embryos exhibit varying degrees of anterior truncation as well as liver and thyroid dysplasia. The liver diverticulum is formed but migration of hepatocytes into the septum transversum fails to occur. Development of the thyroid is arrested at the thyroid bud stage at 9.5 dpc. Brain defects are restricted to the rostral forebrain and have a caudal limit at the zona limitans intrathalamica, the boundary between dorsal and ventral thalamus. Analysis of Hex(-/-) mutants at early stages shows that the prospective forebrain ectoderm is correctly induced and patterned at 7.5 days post coitum (dpc), but subsequently fails to develop. AVE markers are expressed and correctly positioned but development of rostral definitive endoderm is greatly disturbed in Hex(-/-) embryos. Chimeric embryos composed of Hex(-/-) cells developing within a wild-type visceral endoderm show forebrain defects indicating that Hex is required in the definitive endoderm. All together, these results demonstrate that Hex function is essential in definitive endoderm for normal development of the forebrain, liver and thyroid gland.

Animals↗

Development of chick axial mesoderm: specification of prechordal mesoderm by anterior endoderm-derived TGFbeta family signalling.

Two populations of axial mesoderm cells can be recognised in the chick embryo, posterior notochord and anterior prechordal mesoderm. We have examined the cellular and molecular events that govern the specification of prechordal mesoderm. We report that notochord and prechordal mesoderm cells are intermingled and share expression of many markers as they initially extend out of Hensen's node. In vitro culture studies, together with in vivo grafting experiments, reveal that early extending axial mesoderm cells are labile and that their character may be defined subsequently through signals that derive from anterior endodermal tissues. Anterior endoderm elicits aspects of prechordal mesoderm identity in extending axial mesoderm by repressing notochord characteristics, briefly maintaining gsc expression and inducing BMP7 expression. Together these experiments suggest that, in vivo, signalling by anterior endoderm may determine the extent of prechordal mesoderm. The transforming growth factor (beta) (TGFbeta) superfamily members BMP2, BMP4, BMP7 and activin, all of which are transiently expressed in anterior endoderm mimic distinct aspects of its patterning actions. Together our results suggest that anterior endoderm-derived TGFbetas may specify prechordal mesoderm character in chick axial mesoderm.

Activins↗

A new look at intrauterine growth and the impact of race, altitude, and gender.

BACKGROUND: Growth curves described in the 1960s are used to classify neonate intrauterine growth as normal or abnormal. Our objective was to determine whether continued use of these curves is appropriate. METHODS: From 1996 to 1998, we collected birth weight, length, head circumference, estimated gestational age (EGA), gender, race, and place of birth (<4,000 feet or >/=4,000 feet) on 27 229 neonates to evaluate the effects of each on intrauterine growth and the diagnoses of small for gestational age (SGA) and large for gestational age (LGA). We compared the gestation-specific growth parameters derived from our sample with those reported in 1966 and 1969. RESULTS: Gestational age had the largest influence on each growth parameter. Race and gender both had effects on birth weight. Female neonates were smaller than male neonates, and black neonates were smaller than Hispanic and white neonates at each EGA. For neonates with an EGA <30 weeks, our data had a smaller variance and lower average weights, lengths, and head circumferences than those reported in 1966 and in 1969. For neonates >36 weeks, the variance was similar, but our curves showed that neonates in our sample were larger and heavier. Use of the older growth curves to classify neonates as SGA, LGA, and appropriate for gestational age (AGA) led to significantly different rates of each by gender and race. CONCLUSIONS: Intrauterine growth patterns previously described and commonly used to classify neonates as AGA are inaccurate for use in current populations and lead to gender- and race-specific diagnoses of SGA and LGA that are misleading. neonates, growth, race, gender.

Birth Weight↗

Articular diffusion of meloxicam after a single oral dose: relationship to cyclo-oxygenase inhibition in synovial cells.

OBJECTIVE: To investigate the distribution of meloxicam in the human knee joint and to compare it with the inhibition of cyclo-oxygenase (COX) activity in synovial cells. DESIGN: Prospective pharmacokinetic study and in vitro laboratory investigation. PATIENTS AND PARTICIPANTS: 42 male and female patients aged 26 to 85 years hospitalised for rheumatic disease and requiring a diagnostic and/or therapeutic knee puncture. METHODS: After a single oral dose of meloxicam 15mg, synovial fluid and blood samples were collected once per patient at various intervals after administration. Meloxicam concentrations were determined by a validated high performance liquid chromatography assay, protein binding by equilibrium dialysis, and pharmacokinetic parameters were calculated by noncompartmental analysis from the mean drug concentration-time profiles. The inhibitory effect of meloxicam on COX activity was investigated separately in unstimulated or interleukin-1beta-stimulated human synovial cells from osteoarthritic patients. RESULTS: Meloxicam was found in synovial fluid at the earliest sampling time (1 hour). Peak concentrations were reached approximately 6 hours postdose in both plasma (842 microg/L) and synovial fluid (320 microg/L). A plateau was observed after the distribution phase (6 hours), corresponding to a constant ratio of drug concentration between synovial fluid and plasma of about 0.47. This ratio was higher in patients with acute inflammation (0.58) than in those with no inflammation (0.38). Meloxicam was extensively bound to protein, mainly to serum albumin. The area under the drug concentration-time curve (AUC) in plasma was more than 2.5 times that in synovial fluid. The AUC for free meloxicam was similar in plasma and synovial fluid. The 50% inhibitory concentrations (IC50) for basal and stimulated COX activity in human synovial cells were 33.7 nmol/L (11.8 microg/L) and 2.0 nmol/L (0.70 microg/L), respectively. The free concentration of meloxicam in synovial fluid was higher than the IC50 for stimulated COX activity from 6 to 36 hours postdose. CONCLUSION: On the basis of free synovial concentrations and the IC50 for stimulated COX activity, meloxicam is expected to have a long duration of action. Inhibition of COX activity is expected to be more marked in inflamed synovium compared with non-inflamed synovium.

Administration, Oral↗

[Ambulatory skin grafting in leg ulcers: a feasibility study of 34 patients].

OBJECTIVES: Despite the advent of modern dressings, management of leg ulcers remains a long costly process, particularly if no etiological treatment is possible. Autologous skin grafting is more and more widely used in this indication. The aim of this open single center noncomparative study was to analyze the feasibility of ambulatory procedures for skin grafting and the incidence of ambulatory care in a medical nursing clinic as an alternative to traditional hospitalization on total cost in this pathological condition. PATIENTS AND METHODS: Thirty-nine grafts were performed in 34 consecutive patients. No selection was made for etiology or duration of the leg ulcers. Three grafting techniques were used after debridement-cleansing: flap grafts for medium sized ulcers (29 cases), mesh grafts for large ulcers (6 cases) and patch grafts for small ulcers or ulcers with irregular contours (4 cases). The dressing was opened on day 5, nursing care was provided every 2 days and daily in case of infection. Percentage of healing was evaluated clinically on days 5, 15 and 30 then at months 3, 6 and 12. Photographs were taken. RESULTS: Four patients were lost to follow-up and one died. Among the 34 grafts assessed at 6 months, we obtained total healing in 56 p. 100, 75 p. 100 healing in 6 p. 100, 50 p. 100 healing in 9 p. 100 and failure in 29 p. 100. Healing rates were those expected for arterial ulcers and necrotic angiodermas. For venous leg ulcers, the rate of total healing was only 30 p. 100 at 6 months and 43 p. 100 at 1 year. Outcome depended on duration of the lesion and not on the type of skin graft or patient age. DISCUSSION: This prospective study reports outcome of ambulatory skin grafting in a large representative sample of patients with leg ulcers of various etiologies. The less favorable outcome for venous ulcers can be explained by the duration of the ulcerations and infection in these often neglected lesions. The risk of graft displacement, contact eczema, and infection must be recognized for early treatment. There were no cases with general complications. This ambulatory technique has the enormous advantage of limiting the risk of hospital-related problems in this elderly population and of reducing overall cost of care for leg ulcers, and finally of limiting the risk of recurrence by regular post-graft follow-up in a specialized center and by treatment of the causal disease.

Aged↗