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Biomedical subjects

L Turner

Publications and source records attributed to L Turner.

At least 91 records · Page 5Linked to original sources

Unusual presentation of a tuberculous peritonitis in a patient with concomitant AIDS and liver cirrhosis.

We report a case of tuberculous peritonitis in a patient with concomitant HIV infection and liver cirrhosis. A 50-year-old man with viral B and delta liver cirrhosis and AIDS was diagnosed with spontaneous Escherichia coli peritonitis and successfully treated with beta-lactamins. Three months later, ascites reappeared and Mycobacterium tuberculosis was identified in peritoneal fluid cultures. The triple antituberculosis regimen was adjusted to his level of liver failure but the patient died of hepatic encephalopathy. Concomitant HIV infection and liver cirrhosis favour tuberculous peritonitis but they also make its diagnosis extremely difficult. Considering the poor prognosis of this infection when untreated, tuberculous peritonitis should be systematically suspected in such patients.

Acquired Immunodeficiency Syndrome↗

Microbiological findings about pulmonary cryptosporidiosis in two AIDS patients.

There is no known treatment for pulmonary cryptosporidiosis, a rare complication of intestinal cryptosporidiosis in AIDS patients. We report two cases of cryptosporidiosis which were unusual because (i) extracellular invasive forms of the parasite were found in the bronchoalveolar lavage and (ii) the outcome was favorable in one patient after treatment with azithromycin.

AIDS-Related Opportunistic Infections↗

Establishing the minimum effective dose and additive effects of depot progestin in suppression of human spermatogenesis by a testosterone depot.

Hormonally induced azoospermia induced by weekly im injections of testosterone enanthate provides effective and reversible male contraception, but more practical regimens are needed. Given our previous findings that six 200-mg pellets implanted subdermally produced more stable, physiological T levels and reduced the delivered T dose by more than 50% while maintaining equally effective suppression of sperm output with fewer metabolic side-effects than weekly 200-mg testosterone enanthate injections, we sought in this study to determine 1) whether further dose-sparing could be achieved by lower testosterone doses while maintaining efficacy and 2) the efficacy of adding a depot progestin to a suboptimally suppressive depot testosterone dose as a model depot progestin/androgen combination male contraceptive. Healthy volunteers were randomized into groups (n = 10) who received either of two lower T doses (two or four 200-mg T pellets) or four 200-mg T pellets plus a single im injection of 300 mg depot medroxyprogesterone acetate (DMPA). Two T pellets (400 mg, 3 mg/day) had a negligible effect on sperm output. Four T pellets (800 mg, 6 mg/day) suppressed sperm output between the second to fourth postimplant months; output returned to normal by the seventh postimplant month, although only 4 of 10 men became azoospermic or severely oligozoospermic (< 3 mol/L/mL). The addition of a depot progestin markedly increased the extent, but not the rate, of sperm output suppression, with 9 of 10 becoming azoospermic and 10 of 10 becoming severely oligozoospermic. There were no serious adverse effects during the study. Plasma total and free testosterone levels remained within the eugonadal range at all times with each treatment. Plasma epitestosterone was suppressed by all 3 regimens, consistent with a dose-dependent inhibition of endogenous Leydig cell steroidogenesis. Plasma LH and FSH measured by a two-site immunoassay were suppressed in a dose-dependent fashion by T and further suppressed by the addition of DMPA. Sex hormone-binding globulin levels were decreased by DMPA, but not by either T dose. Prostate-specific antigen and lipids (total, low or high density lipoprotein cholesterol, and triglycerides) were not significantly changed in any group. Thus, a depot testosterone preparation with zero order release must be delivered at between 6-9 mg/day to provide optimal (but not uniform) efficacy at inducing azoospermia. The addition of a single depot dose of a progestin to a suboptimal testosterone dose (6 mg/day) markedly enhances the extent, but not the rate, of spermatogenic suppression, with negligible biochemical androgenic side-effects. These findings provide a basis for the use of a progestin/androgen combination depot for hormonal male contraception.

Adult↗

The effects of chronic high dose androgen or estrogen treatment on the human prostate [corrected].

Prostate development and disease are androgen dependent. However, the nature of hormonal effects on the prostate of healthy young men is not clear. We, therefore, measured prostate size in males chronically exposed to high doses of androgens (AS; habitual anabolic steroid abusers; n = 15) or estrogens (E; male to female transsexuals; n = 11) and compared the results with those in age-matched healthy eugonadal men without known prostate disorders. Prostate size was measured by planimetric ultrasound as cross-sectional areas and maximal dimensions in three orthogonal dimensions with a 7.5-megahertz B-mode sector scanner biplane in a transrectal transducer at 2.5 mm steps from the base to the apex of prostate. Total prostate volume (TPV) was reconstructed from planimetric sections, central prostate volume (CPV) was calculated by the ellipsoidal formula from the appropriate three maximum dimensions, and peripheral prostate volume was determined by the difference between TPV and CPV. Compared with age-matched controls, TPV was normal (-2%) in AS (P = 0.752) and reduced by 31% in E (P = 0.002), whereas CPV was increased by 20% in AS (P = 0.002) and reduced by 46% in E (P = 0.002), and the ratio of CPV/peripheral prostate volume was increased by 77% in AS (P < 0.001) and decreased by 33% in E (P = 0.047). Blood sex hormone-binding globulin was elevated by nearly 500% in E (P < 0.001), but was reduced by 47% in AS (P = 0.003). Prostate-specific antigen was normal (-6%) in AS (P = 0.799) and decreased by 86% in E (P = 0.002). Prostatic acid phosphatase was increased by 26% in AS (P = 0.007), but was unchanged (-28%) in E (P = 0.106). Total and free testosterone levels were reduced to castrate levels in E, whereas LH, FSH, and total testosterone levels were significantly reduced in AS. We conclude that in the human prostate of young men, CPV is more hormonally sensitive than TPV, and during high dose treatment, CPV is preferentially increased by chronic androgen treatment and decreased by chronic estrogen treatment. The reduction of TPV by estrogens was less than expected if solely attributable to inhibition of endogenous gonadotropin and testosterone secretion, suggesting that estrogens also have a positive effect on the normal human prostate. The reversibility and long term significance of androgen-induced stimulation of CPV and, in particular, its relationship to the onset and severity of benign prostatic hyperplasia remain to be clarified.

Adolescent↗

Association of depressive symptoms and school adolescents' smoking: a cross-lagged analysis.

This study examined the association of depressive symptoms of adolescents and their smoking behavior. A national cohort sample of school adolescents (N = 5,855) who participated in the 1989 and 1993 Teenage Attitudes and Practices Survey was obtained. The information from this survey included measures of smoking behavior and a series of factors related to depressive symptoms during a 3-yr. span. A cross-lagged analysis with Kendall tau b correlations was used. Judging from the magnitude of the cross-lagged correlations, the direction of causation cannot be ascertained. Rather, a reciprocal relationship between depression and smoking may be suggested.

Adolescent↗

[Increase of alpha-fetoprotein in pancreatic endocrine tumors with hepatic metastases. Apropos of 2 cases].

We report two cases of metastatic non-functioning pancreatic endocrine tumour with very elevated plasma levels of alpha-fetoprotein. In these two cases, serial plasma levels of alpha-fetoprotein, initially normal, correlated well with hepatic tumour progression and were associated with fatal outcome. These results suggest that elevated plasma concentration of alpha-fetoprotein may be caused by metastatic pancreatic endocrine tumour and than alpha-fetoprotein serial measurement may be useful in prognostic evaluation.

Antineoplastic Agents↗

RANTES-activated human T lymphocytes. A role for phosphoinositide 3-kinase.

RANTES (regulated on activation, normal T cell expressed and secreted), a member of the chemokine family, is a potent chemoattractant for CD4+/CD45RO human T lymphocytes, but the signal-transduction mechanisms utilized by RANTES are poorly defined. In freshly isolated human T lymphocytes loaded with fura-2 acetoxymethyl, the CD3 mAb, UCHT-1, but not RANTES, elicited elevation of intracellular calcium levels. However, RANTES produced a bell-shaped chemotactic response and an increase in polarization of the T lymphocytes. Immunoprecipitates of phosphoinositide (PI) 3-kinase, derived from T lymphocytes stimulated with RANTES, contained increased in vitro PI 3-kinase activity compared with that present in immunoprecipitates derived from vehicle-treated cells. RANTES induction of PI 3-kinase activity was maximal at 10 to 100 ng/ml. Furthermore, the fungal metabolite, wortmannin, which is a potent PI 3-kinase inhibitor, inhibited RANTES-induced T lymphocyte migration, polarization, and increased PI 3-kinase activity. Our results show that RANTES activation of T lymphocytes seems to be independent of detectable elevation of cytosolic-free calcium, but the functional effects of chemotaxis and polarization, induced by RANTES, seem to involve the putative PI 3-kinase signal-transduction pathway.

Androstadienes↗

Cells of Escherichia coli swim either end forward.

Chemotactic cells of the bacterium Escherichia coli were marked asymmetrically by growth on a rich medium containing tetrazolium red. When this dye is reduced, it tends to form a refractile granule near one end of the cell, readily visualized by dark-field microscopy. In smooth-swimming cells, the marker was found with equal probability in front or behind. In wild-type cells, tumbles changed the cell orientation nearly as often as not. Some cells formed flagellar bundles at one end more frequently than at the other, but the run-interval distributions were the same either way. We conclude that the sensory system does not favor one end of the cell over the other. Thus, chemoreceptors that appear in patches at only one pole do not serve as a nose.

Biomarkers↗

Inhibition of CD28-mediated T cell costimulation by the phosphoinositide 3-kinase inhibitor wortmannin.

T lymphocyte activation requires at least two signals, one via the antigen-specific T cell receptor and a second via the surface molecule CD28 which provides signals critical to interleukin-2 (IL-2) production and T cell proliferation. We have previously shown (Ward S. G., Westwick, J., Hall N. and Sansom D. M. Eur. J. Immunol. 1993. 23: 2572) that CD28 stimulates phosphoinositide (PI) 3-kinase activity, indicating that D-3 phosphoinositides may act as mediators of CD28-induced T cell costimulation. Here, we report that immunoprecipitation of CD28 molecules from Jurkat cells stimulated with the CD28-ligand B7, results in a ligand-dependent association of CD28 with PI 3-kinase. This association correlates with the appearance of PI 3-kinase enzymatic activity in CD28 immunoprecipitates and the formation of D-3 phosphoinositides. Consistent with the hypothesis that D-3 phosphoinositides are important mediators of CD28 signaling, treatment of T cells with the PI 3-kinase inhibitor wortmannin, inhibited both T cell proliferation and production of IL-2, but not the response of T cells to exogenous IL-2. Hence, abrogation of PI 3-kinase activity by wortmannin, appears sufficient to disrupt the costimulatory pathway utilized by CD28, indicating a central role for this enzyme in the CD28 signaling pathway.

Androstadienes↗

Mechanical limits of bacterial flagellar motors probed by electrorotation.

We used the technique of electrorotation to apply steadily increasing external torque to tethered cells of the bacterium Escherichia coli while continuously recording the speed of cell rotation. We found that the bacterial flagellar motor generates constant torque when rotating forward at low speeds and constant but considerably higher torque when rotating backward. At intermediate torques, the motor stalls. The torque-speed relationship is the same in both directional modes of switching motors. Motors forced backward usually break, either suddenly and irreversibly or progressively. Motors broken progressively rotate predominantly at integral multiples of a unitary speed during the course of both breaking and subsequent recovery, as expected if progressive breaking affects individual torque-generating units. Torque is reduced by the same factor at all speeds in partially broken motors, implying that the torque-speed relationship is a property of the individual torque-generating units.

Cell Movement↗

Pharmacokinetics of human follicle-stimulating hormone in gonadotropin-deficient men.

Gonadotropin treatment of hypogonadotropic infertile men usually requires regular im administration of human urinary FSH (uFSH); however, testicular function is rarely normalized despite years of treatment. As the pharmacokinetics of standard FSH doses (75 IU, two or three times weekly) in gonadotropin-deficient men are poorly characterized, we studied 10 gonadotropin-deficient men by measuring plasma FSH levels with an ultrasensitive fluoroimmunoassay (Delfia, Pharmacia) in single dose and multidose studies. The single dose studies involved blood samples taken 15 min before and 0, 1, 2, 4, 6, 8, 10, 12, 15, 18, 21, 24, 48, 72, and 96 h after the injection of 75 IU uFSH in 1 mL diluent, either sc under the abdominal wall skin or im into the deltoid muscle, in a random sequence, cross-over design (n = 7 men) and after the injection of 150 IU, sc, with additional blood sampling at 120 and 168 h (n = 7 men). The multidose studies used a fixed ascending dose sequence, with blood sampled at 24-h intervals posttreatment after at least 1 month of regular administration of either 75 or 150 IU uFSH, sc, at injection intervals of 72, 48, and 24 h (n = 6 men). From the single dose studies, pharmacokinetic variables were estimated from a one-compartment open model fitted by a weighted polyexponential curve fit of plasma FSH over time. The bioavailability of uFSH via the sc route was high (mean area under the curve, 90% for 75 IU and 143% for 150 IU vs. 75 IU, im). Peak plasma FSH levels were later (21.1 vs. 7.1 h; P < 0.001) and lower (2.0 vs. 2.7 IU/L; P < 0.001) after sc compared with im administration of 75 IU due to a slower absorption half-time (6.1 h vs. 1.4 h; P < 0.001), whereas mean residence times and clearance half-times were similar. The pharmacokinetic features of the 150- and 75-IU doses sc were essentially identical, apart from expected dose-dependent increases in peak plasma FSH level (2.8 vs. 2.0 IU/L; P < 0.001) and area under the curve (206 vs. 129 IU.h/L; P < 0.05). Multidose simulations based on the single dose pharmacokinetic models predicted that during chronic sc administration of standard FSH doses, plasma FSH levels would be in the lower half of the eugonadal range and fluctuate less than with im administration. The multidose study confirmed empirically these predictions. These studies form a pharmacological basis for a more flexible, cost-effective, and convenient self-administered sc regimen.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

[Dysphagia with fever revealing mediastinal lymph node tuberculosis. Apropos of 2 cases].

The oesophagus is a rare localization of extrapulmonary tuberculosis. We report 2 cases of tuberculous mediastinal lymph nodes revealed by dysphagia and fever in immunocompetent subjects. With the actual outbreak of tuberculosis, this localization is worth mentioning, as the precocity of the diagnosis and the therapeutic handling is an important prognostic factor.

Adult↗