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Biomedical subjects

M A Thomas

Publications and source records attributed to M A Thomas.

At least 19 recordsLinked to original sources

Sleep deprivation and impaired cognition. Possible role of brain catecholamines.

To assess the role of brain catecholamines in cognitive decline associated with sleep deprivation, 40 healthy male volunteers were randomized to conditions of total sleep deprivation or 40.5 h of rest. Within each sleep condition, subjects were further randomized to treatment with a 2-day regimen of placebo or alpha-methyl-para-tyrosine (AMPT), a catecholamine synthesis inhibitor. Cognitive performance was measured repeatedly over time using a computerized performance assessment battery. Treatment with AMPT or treatment with sleep deprivation increased sleepiness without producing marked or consistent deterioration in performance. By contrast, subjects who received both treatments reported greater sleepiness than those receiving either treatment alone, and developed severe cognitive impairment on a variety of tasks. These findings, along with previous evidence that catecholamine-enhancing drugs improve performance in sleep-deprived individuals, support the view that decline in cognitive performance during sleep deprivation may be mediated by brain catecholamines.

Adult

Surgical management of subfoveal choroidal neovascularization.

BACKGROUND: Subfoveal choroidal neovascularization (CNV) usually is associated with a poor visual prognosis. Laser photocoagulation of certain subfoveal membranes secondary to age-related macular degeneration (ARMD) appears preferable to observation based on recent Macular Photocoagulation Study (MPS) findings but is associated with decreased vision. The authors explored the use of vitreoretinal surgical techniques as an alternative method of eradicating subfoveal CNV. METHODS: After vitrectomy, a small retinotomy technique was used to extract or disconnect from the choroidal circulation subfoveal CNV in 58 eyes. There were 33 eyes with ARMD, 20 eyes with presumed ocular histoplasmosis, and 5 eyes with miscellaneous etiologies. Five eyes also received subfoveal RPE patches. RESULTS: With limited follow-up, significant improvement in vision (defined as 2 Snellen lines) was achieved in 7 of 22 eyes with ARMD CNV removal (1 eye 20/20), 0 of 4 eyes with ARMD CNV removal and RPE patches, and 1 of 7 eyes with ARMD CNV disconnection. Significant improvement was achieved in 6 of 16 eyes with presumed ocular histoplasmosis removal and 0 of 4 eyes with presumed ocular histoplasmosis CNV disconnection. In 5 eyes with miscellaneous CNV, 2 improved (20/20 and 20/40). CNV recurred in 29%. CONCLUSIONS: Some patients with subfoveal CNV appear to benefit from surgical removal. Only rarely do eyes with ARMD improve. Longer-term follow-up and refined case selection are required before this approach can be widely recommended.

Aged

Membrane properties of the sarcolemma and sarcoplasmic reticulum of pigs susceptible to malignant hyperthermia. Action of halothane.

The role of sarcolemma and sarcoplasmic reticulum in malignant hyperthermia was studied by the esr technique using the trapezius muscle membrane of both normal and genetically susceptible pigs. Normal and malignant hyperthermia membranes from sarcolemma as well as from sarcoplasmic reticulum did not show significant differences near the polar heads of the phospholipidic bilayer. In contrast, the fluidity and activation energy of normal membranes differed from those in malignant hyperthermia; in both sarcolemma and sarcoplasmic reticulum the mobility of the label was greater than the controls. The presence of halothane was examined, by inducing this disease anesthetically. The drug effect confirmed the above results, i.e. the disease affects mainly the hydrophobic core of the lipid bilayer of both sarcolemma and sarcoplasmic reticulum membranes.

Animals

Surgical removal of subfoveal neovascularization in the presumed ocular histoplasmosis syndrome.

We treated two patients with presumed ocular histoplasmosis, subfoveal neovascular membranes, and progressive visual acuity loss to 20/400. Vitreoretinal surgical techniques were used to remove the subfoveal membranes. Visual acuity returned to 20/20 with seven months of follow-up in one patient (Case 1) and to 20/40 with three months of follow-up in the other patient (Case 2). No evidence of persistent or current subretinal neovascular membranes in either patient have been noted. These preliminary results suggest that vitreoretinal surgical techniques may be successful in mechanically removing subfoveal neovascular membranes with preservation of overlying neurosensory retina and thus preservation of central visual acuity.

Adult

Endogenous Pseudallescheria boydii endophthalmitis. Clinicopathologic findings in two cases.

Two cases of endogenous Pseudallescheria boydii endophthalmitis are presented. One patient had severe pulmonary fibrosis but no history of ocular trauma and no clinical or laboratory evidence of immunocompromise. Despite therapy with repeated intravitreal miconazole nitrate injections and systemic fluconazole, enucleation of the globe was required, and the patient eventually died with disseminated pseudallescheriasis. The other patient was an immunosuppressed cardiac transplant recipient who also received systemic fluconazole therapy. The infected eye eventually required evisceration, but there was no evidence of disseminated pseudallescheriasis before his death of unrelated causes.

Antifungal Agents

Multiple therapies for vaginal bleeding secondary to large uterine myomas.

Acute vaginal bleeding secondary to uterine myomas can be a devastating event. We report the use of a combined therapeutic approach in a patient who presented with protracted bleeding of a myomatous uterus that was equivalent in size to a 38 week gestation. This patient's course was further complicated by her refusal of blood or blood products.

Acute Disease

Vitrectomy for premacular fibroplasia. Prognostic factors, long-term follow-up, and time course of visual improvement.

Two hundred seventy eyes with premacular fibroplasia consecutively treated by pars plana vitrectomy and membrane peeling were reviewed. This study is among the largest series with long-term follow-up reported to date. Visual improvement of two or more lines was achieved in 43% of eyes at 6 to 12 months, in 54% at 1 to 2 years, in 60% at 2 to 3 years, and in 58% at 3 to 5 years. Overall, complications occurred in 34 eyes (13%). Cataract progression after vitrectomy was noted in 106 (57%) of phakic eyes at 3 to 5 years, and 43 of these eyes underwent subsequent cataract extraction. Mean time to best visual acuity after vitrectomy was slightly less than 1 year for all eyes unless they had cataract worsening with subsequent cataract extraction (1.9 years). Significant factors affecting visual outcome were: preoperative lens status, visual acuity before vitrectomy, duration of preoperative symptoms of distortion and/or blurred vision, and the occurrence of intraoperative complications.

Adolescent

Malacoplakia of the uterine cervix and endometrium.

A rare case of malacoplakia involving the female genital tract is presented. The characteristic granular histiocytes with intracytoplasmic Michaelis-Gutmann bodies were identified in a cervical smear. The cytological preparation also showed prominent capillary vessels and differed from biopsy material in that cytoplasmic bacteria were easily identified.

Cervix Uteri

High-affinity androgen binding and androgenic regulation of alpha 1(I)-procollagen and transforming growth factor-beta steady state messenger ribonucleic acid levels in human osteoblast-like osteosarcoma cells.

Clinical observations have demonstrated a positive effect of estrogens and androgens on the maintenance of structural bone integrity. This study examines the direct effects of androgenic hormones on the osteoblast-like human osteosarcoma cell line, HOS TE85. Employing radiolabeled dihydrotestosterone (DHT), 2800 saturable, high-affinity (dissociation constant = 0.66 nM) androgen binding sites were detected per HOS TE85 cell. Androgen binding was specific in that DHT and testosterone (T) displayed significantly greater competition than the progestins, progesterone and medroxyprogesterone. The expression of androgen receptors in HOS TE85 cells was further substantiated by Northern analysis. A human androgen receptor complementary DNA probe revealed a 9.5 kilobase transcript which corresponds to the predominant human androgen receptor transcript detected in human male reproductive tissues. Androgens were also found to elicit biological responses in HOS TE85 cells. Physiological concentrations of DHT and T decreased HOS TE85 cell proliferation as assessed by cell count. This finding suggests that DHT may also play a role in osteoblast differentiation. In support of this hypothesis, treatment with T (24 h, 10 nM) enhanced the abundance of both alpha 1(I)-procollagen messenger RNA (mRNA) (5-fold) and transforming growth factor-beta mRNA (2.2 fold). The nonaromatizable androgen DHT (24 h, 10 nM) elicited an increase in the steady state concentration of alpha 1(I)-procollagen mRNA similar to the increase observed with T treatment. Thus, in addition to the recent discovery of estradiol receptors and estrogenic regulation of HOS TE85 cells, it is now evident that these osteoblast-like osteosarcoma cells also express high affinity androgen binding sites and can respond biologically to androgens.

Androgens

Dose-response effects of exogenous pulsatile human corticotropin-releasing hormone on adrenocorticotropin, cortisol, and gonadotropin concentrations in agonadal women.

Acute activation of the hypothalamic-pituitary axis with CRH has been reported to suppress gonadotropin secretion in women of reproductive age. In this study we specifically examined the effects of increasing doses of human CRH (hCRH) on circulating concentrations of ACTH, cortisol, and gonadotropins in five agonadal women, aged 46-65 (mean, 51.2) yr. The subjects had undergone either natural menopause or surgical removal of their ovaries at least 1 yr before study. Each woman was studied on four separate occasions and received either saline or hCRH at a dose of 0.5, 1.0, or 2.0 micrograms/kg BW through an indwelling iv catheter in a randomized, single blind fashion. During each experiment, five sequential iv injections of the same dose of hCRH or saline were administered at 90-min intervals over an 8-h period, followed by a 10-micrograms iv bolus of GnRH to test for pituitary gonadotropin responsiveness. Blood samples for measurement of LH, FSH, PRL, ACTH, and cortisol were obtained at 15-min intervals through an indwelling iv in the contralateral arm. Episodic pulses of LH secretion were analyzed using the Cluster computer program. Transverse mean LH, FSH, and PRL levels did not change with increasing hCRH doses. Mean (+/- SEM) LH pulse frequency [saline, 5.2 +/- 0.4/8 h; hCRH, (0.5 micrograms/kg), 4.8 +/- 0.2; hCRH (1 microgram/kg), 5.2 +/- 0.2; hCRH (2 micrograms/kg), 5.4 +/- 0.2] and amplitude [saline, 14.4 +/- 4.2 IU/L; hCRH (0.5 microgram/kg), 14.0 +/- 2.4; hCRH (1 microgram/kg), 15.8 +/- 2.5; hCRH (2 micrograms/kg), 17.2 +/- 2.9] did not differ among groups. Although the transverse mean levels of ACTH [saline, 8.7 +/- 0.2 pmol/L; hCRH (0.5 microgram/kg), 12.4 +/- 0.3; hCRH (1 microgram/kg), 11.5 +/- 0.4; hCRH (2 micrograms/kg), 12.8 +/- 0.4] did not change with increasing doses of hCRH, the duration of cortisol peaks after hCRH was longer and accounted for the increased transverse mean at each dose [saline, 152.8 +/- 4.1 nmol/L; hCRH (0.5 microgram/kg), 265.4 +/- 10.5; hCRH (1 microgram/kg), 329.7 +/- 14.3; hCRH (2 micrograms/kg), 348.2 +/- 12.1]. These findings suggest that ever larger doses of pulsatile hCRH continue to increase adrenal output of cortisol secondary to more sustained ACTH responses. However, hCRH-induced acute hypercortisolism does not alter gonadotropin secretion in agonadal women.

Adrenocorticotropic Hormone

Clinical and epizootiologic characteristics of dogs seropositive for Borrelia burgdorferi in Texas: 110 cases (1988).

Of 2,409 canine serum samples submitted to the Texas Veterinary Medical Diagnostic Laboratory between Jan 1, 1988 and Dec 31, 1988 and tested by immunofluorescent antibody technique for antibody to Borrelia borgdorferi, 132 (5.5%) had positive results. Clinical and epizootiologic characteristics of seropositive dogs from Texas (n = 110) were examined. Male dogs were more likely than female dogs to be seropositive for B burgdorferi. The most frequent clinical sign of disease described in seropositive dogs was lameness; neurologic, ophthalmologic, dermatologic, renal, and hepatic signs also were reported by referring veterinarians.

Age Factors

Abnormal fluidity state in membranes of malignant hyperthermia pig skeletal muscle.

The fluidity state was analyzed on sarcoplasmic reticulum membranes and phospholipid vesicles prepared from normal and malignant hyperthermia susceptible pig muscle. Electron spin resonance studies were performed to determine the fluidity state at the region near the polar headgroups and in the central core of the bilayer using 5-nitroxide (5-NS) and 16-nitroxide stearic acid (16-NS), respectively. With the 5-NS label, no differences were found between normal and malignant hyperthermia sarcoplasmic reticulum (MH SR) membranes whereas with the 16-NS label, a significant increase of the activation energy was shown with MH membranes. Lower values of fluorescence anisotropy observed with DPH-labeled MH membranes as compared with normal ones, confirmed the higher abnormal fluidity state of these membranes. The fluidizing effect of halothane, a triggering agent of malignant hyperthermia syndrome, was also studied in these membranes. We show that a relatively low concentration of the drug destabilized not only the diseased sarcoplasmic reticulum membranes but also the vesicles made of total phospholipids extracted from MH skeletal muscle. Together, these findings strongly suggest that an overall increase in membrane fluidity may be implied in the MH disease, improving the general membrane defect hypothesis for this syndrome.

Animals

Epizootiologic association between feline immunodeficiency virus infection and feline leukemia virus seropositivity.

Five hundred twenty-one feline serum samples submitted to the Texas Veterinary Medical Diagnostic Laboratory between Nov 1, 1988, and Jan 31, 1989 were tested for antibody to feline immunodeficiency virus (FIV) by use of an ELISA. The prevalence of FIV infection in this population was 11.3% (95% confidence interval: 8.6 to 14.0%). Serologic test results for FeLV were available for 156 of the 521 cats. A significant (P = 0.008) association between FIV infection and FeLV seropositivity was observed; FeLV-positive cats were nearly 4 times more likely to be seropositive for FIV than were FeLV-negative cats. The association remained statistically significant (P = 0.021) after adjusting for age and gender, using multiple-logistic regression analysis.

Age Factors