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Biomedical subjects

R Clark

Publications and source records attributed to R Clark.

At least 145 records · Page 8Linked to original sources
PubMed1996

Modulation of sexual behaviour in the rat by a potent and selective alpha 2-adrenoceptor antagonist, delequamine (RS-15385-197).

1. The contributions of alpha 2-adrenoceptors and 5-HT1A receptors to sexual behaviour in the rat have been re-evaluated by use of a highly potent and selective alpha 2-adrenoceptor antagonist, delequamine (RS-15385-197), yohimbine, idazoxan and the partial agonist at 5-HT1A receptors, 8-hydroxy-2(di-n-propylamino)-tetralin (8-OH-DPAT). 2. In a model where naive male rats were introduced to oestrogen-progesterone primed, sexually receptive female rats, delequamine (0.4-6.4 mg kg-1, p.o.) dose-relatedly increased the sexual behaviour score over the entire dose-range whereas yohimbine was effective at only one dose, 2 mg kg-1, p.o.. Idazoxan was active only at 2.5 and 5 mg kg-1, p.o. Yohimbine, but neither delequamine nor idazoxan, decreased ejaculation latency. 8-OH-DPAT (0.1 and 0.25 mg kg-1, s.c.) reduced the time, and the number of intromissions to ejaculation without affecting other parameters. A combination of delequamine (0.4 mg kg-1, p.o.) and 8-OH-DPAT (0.1 mg kg-1 s.c.) increased the percentage of rats mounting, intromitting and ejaculating, and reduced ejaculation latency and the number of intromissions. 3. In orchidectomized, sexually experienced rats exposed to sexually receptive females, delequamine, idazoxan and yohimbine increased the number of rats mounting, and there was a tendency to increase the number of animals intromitting, but no effect on ejaculatory behaviour. 4. In ovariectomized female rats brought to low level receptivity by priming with low dose injections of oestradiol benzoate and progesterone, delequamine, at 1.6 and 6.4 mg kg-1 p.o., increased lordosis, while yohimbine, at 2, 4 and 8 mg kg-1 p.o., reduced lordotic responses to sexually experienced males in a dose-dependent manner. 8-OH-DPAT at 0.1, 0.25 mg kg-1, s.c. reduced lordosis in a dose-dependent manner. 5. These findings may be explained on the basis that yohimbine is an alpha 2-adrenoceptor antagonist with affinity for 5-HT1A receptors and that the effects of 5-HT1A receptors may modulate the sexual behaviour responses to alpha 2-receptor antagonism in some models. Thus, in contrast to yohimbine, the highly-selective alpha 2-adrenoceptor antagonist, delequamine, was very effective in increasing the behavioural score in male and female rats over a wide dose-range.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1996

AIDS survival and progression in black Africans living in south London, 1986-1994.

OBJECTIVES: To describe the rate of progression to AIDS and survival following AIDS diagnosis in HIV-infected Africans living in London. To identify factors influencing progression and outcome of disease. DESIGN: Retrospectively constructed prevalent cohort. SETTING: Outpatient clinic population, London. SUBJECTS: HIV-infected individuals of African origin presenting between January 1986 and October 1994. MAIN OUTCOME MEASURES: AIDS indicator illness; cumulative survival probabilities to AIDS diagnosis and from AIDS diagnosis to death; rate of progression to AIDS. RESULTS: Ninety six patients (57 women) provided 166 person years of follow up. Median CD4 lymphocyte count at presentation was 205 (90% range 20-577) x 10(6)/l. Kaplan-Meier estimates of the proportion (95% confidence interval) of patients developing AIDS from the time of enrollment were 18 (9 to 27)% at 12 months and 44 (30 to 58)% at 36 months. Only CD4 count at HIV diagnosis was independently associated with a faster rate of progression to AIDS (adjusted relative hazard 9.18%, 95% confidence interval 2.84 to 29.67, p < 0.001). The proportion (95% confidence interval) surviving following AIDS diagnosis was estimated to be 73 (55 to 91)% at 12 months and 25 (0 to 52)% at 36 months. CONCLUSIONS: HIV-infected people of sub-Saharan African origin living in London present with advanced disease. When compared with published studies, their survival experience is comparable to that observed in HIV-infected individuals born in developed countries.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Sublingual testosterone replacement improves muscle mass and strength, decreases bone resorption, and increases bone formation markers in hypogonadal men--a clinical research center study.

To study the effects of androgen replacement therapy on muscle mass and strength and bone turnover markers in hypogonadal men, we administered sublingual testosterone (T) cyclodextrin (SLT; 5 mg, three times daily) to 67 hypogonadal men (baseline serum T, < 8.4 nmol/L) recruited from 4 centers in the U.S.: Torrance (n = 34), Durham (n = 12), New York (n = 9), and Salem (n = 12). Subjects who had received prior T therapy were withdrawn from injections for at least 6 weeks and from oral therapy for 4 weeks. Body composition, muscle strength, and serum and urinary bone turnover markers were measured before and after 6 months of SLT. We have shown previously that this regimen for 60 days will maintain adequate serum T levels and restore sexual function. Total body (P = 0.0104) and lean body mass (P = 0.007) increased with SLT treatment in the 34 subjects in whom body composition was assessed. There was no significant change in total body fat or percent fat. The increase in lean body mass was mainly in the legs; the right leg lean mass increased from 8.9 +/- 0.3 kg at 0 months to 9.2 +/- 0.3 kg at 6 months (P = 0.0008). This increase in leg lean mass was associated with increased leg muscle strength, assessed by leg press (0 months, 139.0 +/- 4.0 kg; 6 months, 147.7 +/- 4.2 kg; P = 0.0038). SLT replacement in hypogonadal men led to small, but significant, decreases in serum Ca (P = 0.0029) and the urinary calcium/creatinine ratio (P = 0.0066), which were associated with increases in serum PTH (P = 0.0001). At baseline, the urinary type I collagen-cross linked N-telopeptides/creatinine ratio [75.6 +/- 7.9 nmol bone collagen equivalents (BCE/mmol] was twice the normal adult male mean (41.0 +/- 3.6 nmol BCE/mmol) and was significantly decreased in response to SLT treatment at 6 months (68.2 +/- 7.7 nmol BCE/mmol; P = 0.0304) without significant changes in urinary creatinine. Serum skeletal alkaline phosphatase did not change. In addition, SLT replacement caused significant increases in serum osteocalcin (P = 0.0001) and type I procollagen (P = 0.0012). Bone mineral density did not change during the 6 months of SLT treatment. We conclude that SLT replacement therapy resulted in increases in lean muscle mass and muscle strength. Like estrogen replacement in hypogonadal postmenopausal females, androgen replacement therapy led to decreased bone resorption and urinary calcium excretion. Moreover, androgen replacement therapy may have the additional benefit of increasing bone formation. A longer term study for several years duration would be necessary to demonstrate whether these changes in bone turnover marker levels will result in increased bone mineral density decreased fracture risks, and reduced frailty in hypogonadal men.

Administration, Sublingual↗
PubMed1996

Disaster preparedness of poison control centers in the United States.

OBJECTIVE: To assess the state of disaster readiness of poison control centers, a survey questionnaire was sent to all 96 institutional poison control center members of the American Association of Poison Control Centers in the US, both certified and noncertified programs. DESIGN: The data reported are the results and responses from 76 of 96 (79.2%) poison control centers. RESULTS: Fifty-four percent of responding centers have written disaster plans, with 25% having drills to practice the plans. Of the centers that do not have a written plan, the majority have policies and procedures in place to address physical plant damage, increased phone traffic, loss of phone systems and malfunction of computers. Eighty-six percent of respondents have a back up generator, and 82% have an uninterruptable power supply in place. Fifty-four percent have a back up phone system and 33% have cellular phone capacity. Forty-six percent of responding centers have arrangements with other agencies in the event of a disaster. Only half of the managing directors of the responding centers believe their center can meet the public's needs in the event of a disaster.

Disaster Planning↗
PubMed1996

Clinical value of radiologists' interpretations of perioperative radiographs of orthopedic patients.

The content and accuracy of radiographic interpretations by radiologists was assessed to determine the reports' ability to provide sufficient information necessary to make clinical treatment decisions. A retrospective review was performed of 371 radiographic studies (211 consecutive patients) and their reports which had been generated by three Board-certified radiologists. Data were collected regarding fracture assessment and description as well as the description and assessment of orthopedic implants. These descriptions were categorized by their ability to be used clinically (precise) or not (general). Fracture descriptions were considered complete for 85% of reports, while their assessment of alignment and displacement (necessary to determine fracture care) was complete on only 9%. Orthopedic implants were described precisely on 12% of reports with 7% of the descriptions in error. The effect and position of orthopedic implants were described precisely for only 27% and 25% of cases, respectively, while implant stability was assessed precisely in only 4% of cases. For 61% of preoperative studies, the radiologist's report was not available until after the surgical procedure had already been performed. For all variables considered, an average of 3% of descriptions contained an error. Radiologists' reports of radiographs of these patients undergoing orthopedic procedures did not contain sufficient descriptive information to be used clinically, were not promptly available, and contained an error for 3% of variables studied. The attending orthopedic surgeon has traditionally interpreted such radiographs and should continue to do so to provide patients with more immediate and complete clinical evaluation and management.

Fractures, Bone↗
PubMed1996

Resuscitation from severe brain trauma.

Severe traumatic brain injuries are extremely heterogeneous. At least seven of the secondary derangements in the brain that have been identified as occurring after most traumatic brain injuries also occur after cardiac arrest. These secondary derangements include posttraumatic brain ischemia. In addition, traumatic brain injury causes insults not present after cardiac arrest, i.e., mechanical tissue injury (including axonal injury and hemorrhages), followed by inflammation, brain swelling, and brain herniation. Brain herniation, in the absence of a mass lesion, is due to a still-to-be-clarified mix of edema and increased cerebral blood flow and blood volume. Glutamate release immediately after traumatic brain injury is proven. Late excitotoxicity needs exploration. Inflammation is a trigger for repair mechanisms. In the 1950s and 1960s, traumatic brain injury with coma was treated empirically with prolonged moderate hypothermia and intracranial pressure monitoring and control. Moderate hypothermia (30 degrees to 32 degrees C), but not mild hypothermia, can help prevent increases in intracranial pressure. How to achieve optimized hypothermia and rewarming without delayed brain herniation remains a challenge for research. Deoxyribonucleic acid (DNA) damage and triggering of programmed cell death (apoptosis) by trauma deserve exploration. Rodent models of cortical contusion are being used effectively to clarify the molecular and cellular responses of brain tissue to trauma and to study axonal and dendritic injury. However, in order to optimize therapeutic manipulations of posttraumatic intracranial dynamics and solve the problem of brain herniation, it may be necessary to use traumatic brain injury models in large animals (e.g., the dog), with long-term intensive care. Stepwise measures to prevent lethal brain swelling after traumatic brain injury need experimental exploration, based on the multifactorial mechanisms of brain swelling. Novel treatments have so far influenced primarily healthy tissue; future explorations should benefit damaged tissue in the penumbra zones and in remote brain regions. The prehospital arena is unexplored territory for traumatic brain injury research.

Animals↗
PubMed1996

Medical-legal pitfalls for the breast surgeon: incomplete mammographic localization of suspicious lesions and the correlation between palpable and mammographic abnormalities.

In approximately 5 per cent of mammographically detected lesions, the mammographic abnormality is present in only one view, either craniocaudal or mediolateral. In such a scenario, the physician has been left with the option of closely following the lesion, hoping it will eventually become apparent in two views, or guessing the approximate location of the lesion for subsequent open biopsy. However, with today's advances in technology, CT scan and its production of a three-dimensional image can compensate for mammography's two-dimensional limitation. With diminished need for identification on two mammographic views, localization in these instances falls more within the realm of possibility. This paper highlights Moffitt Cancer Center's experience with CT-directed breast biopsy as an alternative to close follow-up or blind-biopsy. In addition, because palpable breast abnormalities may not be the same as mammographic abnormalities, the report details the accuracy of CT-directed biopsy in allowing the surgeon to perform precise open biopsy, thus avoiding medical-legal exposure.

Biopsy↗
PubMed1996

Insulin-induced tyrosine phosphorylation of a M(r) 70,000 protein revealed by association with the Src homology 2 (SH2) and SH3 domains of p120GAP and Grb2.

We have used two approaches to identify possible substrates of the insulin receptor (IR) tyrosine kinase. First, we used a potent tyrosine phosphatase inhibitor, phenylarsine oxide (PAO), which is reported to be specific for the insulin-induced signal transduction route, to augment tyrosine phosphorylation. Second, we used src homology 2 (SH2) domains fused to glutathione S-transferase as high affinity binding agents for tyrosine-phosphorylated proteins. Using the SH2 domain-containing region of p120 GTPase-activating protein and growth factor-bound protein 2, we observed a tyrosine-phosphorylated M(r) 70,000 protein in insulin- plus PAO-treated NIH3T3 cells overexpressing the IR. This M(r) 70,000 protein, which migrated as a doublet on SDS-polyacrylamide gels, efficiently bound to polyuridylic acid-Sepharose but is distinct from similar-size RNA-binding proteins such as p62 (sam68) and heterogeneous nuclear ribonucleoproteins I, K, L, and M. In addition, it differs from other M(r) 70,000 tyrosine-phosphorylated proteins, such as SH2-containing tyrosine phosphatase, raf1, and paxillin. Tyrosine phosphorylation of this protein was hardly observed after epidermal growth factor treatment. This suggests that the M(r) 70,000 protein is a novel and specific substrate for the IR kinase or an insulin-induced tyrosine kinase. The requirement for PAO to identify this tyrosine phosphorylation indicates a high turnover rate of the tyrosine phosphate.

3T3 Cells↗
PubMed1995

Growth hormone improves cardiac performance in experimental heart failure.

BACKGROUND: Growth hormone has been shown to increase maximum isometric active force of the left ventricular papillary muscle of rats in vitro. Administration of growth hormone causes an increase in myocardial contractility in normal humans. Our preliminary study suggests that treatment with growth hormone results in increased ventricular contractility in rats with left ventricular dysfunction. In the present study, the effects of growth hormone on cardiac function, including cardiac output, stroke volume, and peripheral vascular resistance, were determined in a rat model of heart failure. METHODS AND RESULTS: Ligation of the left coronary artery or sham operation was performed; 4 weeks after surgery, recombinant human growth hormone (2 mg/kg per day SC) or vehicle then was administered for 15 days. The animals were catheterized after 13 days of the treatment. Cardiac output, measured by a thermodilution method, and other hemodynamic parameters were measured in the conscious animals 2 days after catheterization. The infarct sizes induced by left coronary ligation were comparable between growth hormone-treated and vehicle-treated rats. Six weeks after ligation, rats treated with vehicle exhibited significant decreases in cardiac index, stroke volume index, and left ventricular maximum dP/dt and increases in left ventricular end-diastolic pressure compared with sham rats. In the ligated rats, treatment with growth hormone increased cardiac index, stroke volume index, and left ventricular maximum dP/dt (P < .05) and reduced left ventricular end-diastolic pressure and systemic vascular resistance (P < .05). In sham rats, growth hormone slightly reduced arterial pressure but did not significantly alter cardiac performance. There was no significant difference in heart rate between the experimental groups. CONCLUSIONS: These results suggest that growth hormone treatment may improve cardiac function by both increased myocardial contractility and decreased peripheral vascular resistance in heart failure.

Animals↗
PubMed1995

Comparison of multiple drug therapy regimens for HIV-related disseminated Mycobacterium avium complex disease.

In June 1993, the United States Public Health Service (USPHS) made recommendations for treatment of disseminated Mycobacterium avium complex (MAC) in patients infected with the human immunodeficiency syndrome (HIV). It was suggested that every treatment regimen include either azithromycin or clarithromycin plus one or more of the following drugs: ethambutol, clofazimine, rifabutin, rifampin, ciprofloxacin, or amikacin. This study compares the effect of multiple drug therapy regimens on the survival of patients of the HIV outpatient department of the Medical Center of New Orleans, Louisiana. A retrospective chart review of 122 confirmed cases of MAC was conducted. Three treatment groups were considered: no/monotreatment (n = 40), multitreatment without clarithromycin (n = 32), and multitreatment with clarithromycin (n = 50). Azithromycin, amikacin, and rifabutin were not used in this clinic during the study period. Both multitreatment without clarithromycin (p < 0.03) and multitreatment with clarithromycin (p < 0.005) were significantly protective for survival after adjusting for CD4 cell count at time of diagnosis, nonadherence to treatment, number of concomitant opportunistic infections at diagnosis, and weight loss > 10%. Neither of the groups that received multidrug therapy were significantly less likely to have MAC-related symptoms than the no/mono group at 3 and 6 months postdiagnosis. These findings support the USPHS recommendation for multiple drug treatment either with or without clarithromycin. Prospective controlled clinical trials will clarify the optimal regimen for disseminated MAC disease.

AIDS-Related Opportunistic Infections↗
PubMed1995

Remote monitoring of health status of the elderly at home. A multidisciplinary project on aging at the University of New South Wales.

This paper discusses the design and implementation of a multidisciplinary research project and associated field trials to test the hypothesis that functional health status amongst the elderly can be accurately determined remotely by continuously monitoring relatively simple parameters that measure the interaction between participants and their environment. In this study we propose that changes in such simple measures as mobility, sleep patterns, and utilisation of cooking, washing and toilet facilities, can identify changes in functional health status. One of the primary end goals of the project will be to automatically prompt appropriate, timely and cost-effective intervention of medical and community based services to help reduce morbidity and maintain an independent high quality of life for the elderly. Targeted intervention will diminish the demand for high cost medical services. This will have large potential economic implications in helping to contain and reduce the increasing cost of providing health care services to the aged.

Activities of Daily Living↗