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Biomedical subjects

M E Thompson

Publications and source records attributed to M E Thompson.

At least 19 recordsLinked to original sources
PubMed1992

Hyperuricemia and gout among heart transplant recipients receiving cyclosporine.

PURPOSE: To determine the frequency and characteristics of hyperuricemia and gouty arthritis among cyclosporine-treated heart transplant recipients. PATIENTS AND METHODS: One hundred ninety-six surviving adult heart or heart/lung transplant recipients were evaluated. Medical records were reviewed to determine peak serum uric acid levels after transplantation, and to evaluate potential risk factors for hyperuricemia. Patients were surveyed by postal questionnaire for a history of gouty arthritis, with positive responses evaluated by telephone interview and/or examination of the patient. RESULTS: Hyperuricemia occurred in 72% of male and 81% of female patients and was not correlated with cyclosporine level, presence of hypertension, or degree of renal insufficiency. Eleven (6%) patients had gout prior to transplantation; 14 (8%) had onset of definite gout and seven (4%) had probable gout a mean of 17 months after transplantation. Polyarticular arthritis and/or tophi developed in six (43%) of the posttransplant-onset definite gout group within a mean of 31 months. CONCLUSION: Both hyperuricemia and gouty arthritis occur with increased frequency among cyclosporine-treated heart or heart/lung transplant recipients. The clinical course of gout in these patients is often accelerated, with management complicated by the patients' renal insufficiency and interaction with transplant-related medications.

Arthritis, Gouty↗
PubMed1992

Differential regulation of chromogranin B/secretogranin I and secretogranin II by forskolin in PC12 cells.

The factors which regulate the expression of the granin family of secretory proteins have yet to be completely described. The present study investigated the effects of forskolin (FSK), an activator of adenylate cyclase, on the regulation of chromogranin B/secretogranin I (CgB) and secretogranin II (SgII) mRNA levels in rat PC12 cells. PC12 cells were treated with 10 microM FSK for time points up to 48 h and were harvested for cAMP determination, RNA isolation and Northern blot analysis, or fixed in 4% paraformaldehyde for immunocytochemistry. Cellular cAMP levels peaked after two h of FSK treatment and remained elevated for 48 h. Chromogranin B mRNA increased with FSK treatment, reaching a maximum of 7-fold above control after 24 h, while the level of SgII mRNA decreased to a level of 65 +/- 10% of control after 48 h. The effects of FSK on CgB mRNA appear to be mediated by cAMP, as 8-bromo-cAMP (500 microM) resulted in a 2.8-fold increase in CgB mRNA, and H-89 (30 microM), a selective inhibitor of cAMP-dependent protein kinase, reduced the FSK-mediated response. The level of CgB was also increased in FSK-treated cells, as evidenced by immunofluorescent analysis which showed a more intense staining in PC12 cells treated with FSK for 48 h than in untreated cells. The intensity of SgII staining was diminished by FSK treatment, most likely a result of a decreased rate of synthesis as well as an increase in the release of SgII. This study demonstrated that the mRNA and protein levels of CgB and SgII are differentially regulated by cAMP in PC12 cells.

Amino Acid Isomerases↗
PubMed1992

Prolactin granulogenesis is associated with increased secretogranin expression and aggregation in the Golgi apparatus of GH4C1 cells.

The GH4C1 pituitary tumor cell line (GH cells) serves as a model system to study the role of the granins in the packaging of PRL into secretory granules. The number of secretory granules containing PRL and two members of the granin family, chromogranin-B (CgB) and secretogranin-II (SgII), can be hormonally manipulated. In the present study we have investigated whether 1) granulogenesis in GH cells is preceded by condensation of the granins and PRL in the Golgi; 2) granulogenesis is preceded by an increase in granin expression in GH cells; and 3) PRL and the granins aggregate in vitro under high calcium, low pH conditions. GH cells were treated for up to 3 days with 17 beta-estradiol (1 nM), insulin (300 nM), and epidermal growth factor (10 nM) and were fixed in 4% paraformaldehyde for immunocytochemistry or harvested for RNA isolation and Northern blot analysis. After 1 day of hormone treatment, there was a significant increase in staining for PRL and the granins in the Golgi apparatus, which was identified using an antibody to MG-160. After 3 days of hormone treatment, PRL and granin staining was also found in a perinuclear region that was not stained with anti-MG-160 antibody, most likely representing secretory granules. An increase in PRL and granin expression contributed to increased Golgi staining, as the steady state levels of CgB, SgII, and PRL mRNA increased 186 +/- 14%, 203 +/- 7%, and 337 +/- 5% above control levels, respectively, within 6 h after hormone treatment. An in vitro aggregation system was used to determine whether PRL and the granins coprecipitate under high calcium, low pH conditions, which are thought to be characteristic of the trans-Golgi and secretory granules. Aggregation of the granins CgB and SgII was negligible during overnight dialysis against a buffer containing 150 mM NaCl and 10 mM 2[N-morpholino]ethanesulfonic acid-NaOH (pH 5.5) in the absence of calcium. There was significant aggregation of PRL under these conditions. When dialysis was performed in the presence of 10 mM CaCl2, PRL, CgB, and SgII coaggregated. This study indicates that increased expression and aggregation of the granins is associated with PRL granulogenesis in hormone-treated GH cells. However, the role of the granins may not be obligatory, as some cells can store PRL in the absence of detectable levels of CgB and SgII, and PRL has the capacity to self-aggregate.

Animals↗
PubMed1992

Indices of hearing in patients with central auditory pathology. II. Choice response time.

The response times of three groups of subjects with pathology of the auditory pathway, localized either to the eighth nerve or to the right or left temporal cortex, were compared on three psychoacoustic tasks. These tasks included detection, frequency discrimination and duration discrimination. Measurements were made at two stimulus frequencies, 500 and 2000 Hz, in combination with two durations, 50 and 300 ms. The results were compared to those obtained for normal hospitalized and non-hospitalized control subjects. All subjects, except those with acoustic neuroma, had age-corrected normal hearing. Statistically significant group differences were apparent in discrimination but not detection, indicating the importance of task demands for response time measures, especially in patients with cortical pathology. The outcomes were not related to neuropsychological measures of speed or accuracy, supporting the conclusion that the time for decision-making rather than motor function had been affected.

Auditory Cortex↗
PubMed1992

Indices of hearing in patients with central auditory pathology. I. Detection and discrimination.

This paper describes the effect of site of lesion on auditory detection, discrimination and speech processing. Three groups of ten patients with confirmed pathology of the eighth nerve and right and left temporal cortex and two normal-hearing control groups, differing with respect to hospitalization, participated. In each of the fifty subjects, measurements were made of detection thresholds, and difference limens for frequency and duration for 50 and 300 ms pure tones of 500 Hz and 2000 Hz. Consonant discrimination was assessed using the Four Alternative Auditory Feature Test (Foster & Haggard, 1979), presented in quiet. Subjects with left temporal pathology had the largest frequency and duration difference limens. Those with either left temporal or eighth nerve pathology had significantly lower speech intelligibility scores that were correlated with the duration difference limen for short stimuli and detection thresholds, respectively. These findings challenge traditional views of cortical processing and highlight differences between peripheral and central mediators of speech processing.

Adult↗
PubMed1991

Treatment and career attitudes of prehospital care providers associated with potential exposure to HIV/AIDS.

Career and treatment attitudes related to potential human immunodeficiency virus and acquired immunodeficiency syndrome (HIV/AIDS) exposure are reported based on a survey of 1,228 Maryland career and volunteer prehospital care providers trained to provide basic (BLS) and advanced (ALS) life support. Sixty-five percent stated potential exposure to HIV/AIDS was a major occupational stressor. Ninety-two percent stated they would treat HIV/AIDS patients if protected. Given a choice, 38% would avoid providing treatment to HIV/AIDS patients. Eighteen percent considered resigning from emergency medical services (EMS) work. An attitudinal scale (AIDSTRESS) was developed to evaluate overall treatment and career reactions. Respondents with significantly higher (more negative reactions) AIDSTRESS scores were: BLS providers, men, paid providers, personnel with more than 3 years of field experience, those working in urban areas, personnel with no formal education beyond high school, and those who stated that their HIV/AIDS training was inadequate. Implications of the findings for quality of care, career decision making, and inservice education are discussed.

Adolescent↗
PubMed1991

Reversible control of oestradiol-stimulated growth of MCF-7 tumours by tamoxifen in the athymic mouse.

We investigated the ability of high concentrations of oestradiol to reverse the growth inhibitory action of tamoxifen on MCF-7 breast cancer cells in vivo. Tamoxifen inhibits the oestradiol stimulated growth of MCF-7 cells in athymic mice. Using a sustained release preparation of tamoxifen we consistently achieved serum concentrations of the drug in the 40 to 50 ng ml-1 range and much higher levels in tissues. These serum levels are sufficient to inhibit the oestrogen stimulated growth of MCF-7 tumours exposed to physiologic (i.e. 300-600 pg ml-1 serum oestradiol concentrations). However, by administering dosages that increase serum oestradiol concentrations to 900-2000 pg ml-1, mimicking the increase often observed clinically in premenopausal women taking tamoxifen, we show that the growth inhibitory action of tamoxifen can be partially reversed. Serum tamoxifen levels were elevated to nearly 400 ng ml-1 by injecting 1 mg day-1 tamoxifen (IP 3 x weekly); this dosage was more effective at inhibiting oestradiol stimulated tumour growth than subcutaneous tamoxifen capsules alone. Our data suggest that at low serum levels tamoxifen may not act optimally. There may be a need to monitor tamoxifen levels in premenopausal patients to ensure that they are high enough not to be overcome by a tamoxifen induced increase in ovarian steroidogenesis.

Animals↗
PubMed1990

Cyclosporine nephrotoxicity in cardiac allograft patients--a seven-year follow-up.

Renal function was observed retrospectively in a population of 228 adults who underwent a cardiac allograft at the University of Pittsburgh from June 1980 through June 1987, survived a minimum of one year, and received cyclosporine. Renal function was determined by serial measurement of serum creatinine concentration. Serum creatinine rose from 1.2 +/- 0.0 mg/dl at time of hospital discharge to 2.0 +/- 0.0 mg/dl at two and four years and 3.3 +/- 0.1 mg/dl at seven years. The fall in renal function was biphasic, with a rapid decline (reciprocal creatinine slope -0.018 dl/mg-mo) through 24 months and a slower decline thereafter -0.0036 dl/mg/month). This occurred despite a progressive decrease in cyclosporine levels from 668 +/- 23 ng/ml (whole blood RIA) to 380 +/- 12 ng/ml at seven years. Three of 222 patients (1.6%) developed end-stage renal disease within 18 months of initiation of cyclosporine therapy. Only one additional patient of 26 followed through 54 months (3.8%) developed end-stage disease thereafter. The decline in renal function seen with cyclosporine is rapid in the first 18 months, with a slower but continuing decline seen with later follow up. At least in heart transplantation, the risk of end-stage renal disease is significant, but not prohibitive.

Adult↗
PubMed1990

Characterization of monoclonal antibodies against ovine prolactin: suitability for use in immunocytochemical analysis of rat prolactin.

The aim of this study was to identify a monoclonal antibody (MAb) suitable for use in the immunocytochemical localization of prolactin in rat tissues. We took advantage of the conservation of certain amino acid sequences in prolactin among species by examining the crossreactivity patterns of five MAb, originally generated to ovine prolactin, with rat prolactin by enzyme-linked immunoassay (ELISA), Western blot analysis, and immunocytochemistry. Two of five antibodies (17D9 and 6F11) showed reactivity with 100 ng of immobilized rat prolactin (NIH RP-3) by ELISA, 6F11 reacting more strongly than 17D9. Only 6F11 reacted with prolactin in lysates of GH4C1 rat pituitary tumor cells by Western blot analysis. When we examined the crossreactivity of the MAb with rat prolactin in monolayer cultures of GH4C1 cells by indirect immunofluorescence, we found that both 17D9 and 6F11 reacted strongly with the cultures. The distribution of staining with 17D9 or 6F11 was coincident with staining with a polyclonal antiserum to rat prolactin. Preabsorption of the antibodies with a 20-fold excess of purified rat prolactin abolished the staining of GH4C1 cell cultures with either antibody. Therefore, we have selected from a series of MAb raised to ovine prolactin two antibodies (17D9 and 6F11) that react specifically with rat prolactin in immunocytochemical studies, whereas 6F11 also reacts strongly with rat prolactin by ELISA and Western blot analysis.

Animals↗
PubMed1990

Sensory integrative processing in delinquent-prone and non-delinquent-prone adolescents.

The purposes of this study were to obtain a preliminary description of the sensory integrative and practic abilities of 114 non-delinquent-prone adolescents aged 12 through 18 years and to compare their performances with those of 12 delinquent-prone adolescents with learning problems. Ten of the 17 subtests of the Sensory Integration and Praxis Tests (SIPT) (Ayres, 1989) as well as the Finger Posture Imitation Test (Druker, 1980) and the MacQuarrie Test for Mechanical Ability (MacQuarrie, 1925/1953) were administered to both groups. It was hypothesized that performance on some tests would correlate with age in the non-delinquent-prone adolescents. It was also hypothesized that some delinquent-prone adolescents with learning problems would perform significantly worse on the tests of sensory integrative and practic abilities than would the non-delinquent-prone adolescents. A data analysis indicated that performance on the praxis tests, Manual Form Perception, Graphesthesia, and Bilateral Motor Coordination showed a significant age correlation. The results of this study indicated a difference between the two groups, and it was concluded that the delinquent-prone group performed more poorly on all of the praxis-related tests and on the absolute values of the tests of Postrotary Nystagmus, Standing and Walking Balance, and Bilateral Motor Coordination. Some of the vestibular- and praxis-related tests, therefore, may still provide useful information on children older than 8 years of age.

Adolescent↗
PubMed1990

Hypertension, creatinine, and plasma renin activity in heart transplant recipients.

Development of de novo hypertension in a large proportion of orthotopic heart transplant recipients receiving cyclosporine has previously been reported. This hypertension is characterized by a persistence of increased peripheral resistance, sodium retention, and loss of nocturnal decline in BP. Vascular nephropathy with plasma renin activity (PRA) elevation from cyclosporine (CsA) may also be major factor in the progress of hypertension. To investigate this hypothesis, observations of BP, creatinine (Cr), and PRA were made in 144 heart transplant recipients followed for up to four and a half years. Median Cr was 133 mumol/l. Average diastolic BP and mean PRA values were significantly higher in patients with Cr greater than or equal to the median. Cr and PRA were significantly correlated (r = 0.4; P less than 0.001) in recipients with Cr greater than or equal to 133 mumols/l but not in those with Cr less than 133 mumols/l. In a selected subsample of heart transplant recipients with repeated Cr and PRA values, Cr and PRA appeared to increase longitudinally after transplant. These data are derived from a case series of patients managed on a variety of antihypertensive agents (excluding ACE inhibitors) needed to control the persistent hypertension.

Antihypertensive Agents↗
PubMed1990

Hypertension following orthotopic cardiac transplantation.

It seems established that hypertension, to some degree, is a frequent consequence of cardiac transplantation. The hypertension occurs de novo and is not related to whether hypertension was present in association with the heart disease that led to the need for transplantation. The etiology of this hypertension is multifactorial and varies depending on the time that has ensued after transplantation. Acutely, it is primarily a problem related to intravascular volume expansion and persistently increased systemic vascular resistance. Although it may be modest in severity, it seems to be particularly resistant to therapy with most antihypertensive drugs. Moreover, the total "hyperbaric impact" of the hypertension is rendered greater because the blood pressure and heart rate in these patients with denervated hearts fails to show the usual 10 to 15 percent fall when recumbent/asleep at night, which occurs in normotensive individuals and in most with hypertension of other etiologies. The major factor in the persistence of the hypertension through the later stages post-transplantation appears to be the cyclosporine that is used as an immunosuppressive. Although cyclosporine has been the major contributor to reduced rejection in these individuals, and to their increasingly prolonged survival, it inevitably produces slowly progressive impairment of renal function. The damage to the kidney is reflected both in tubular as well as glomerular and vascular damage, with a steady fall in glomerular filtration and a rise in creatinine. From our studies it appears that the renal alterations are associated with a gradual rise in plasma renin activity and angiotensin II, which perhaps further damages the kidney and causes persistence of the increased systemic vascular resistance. The use of lower doses of cyclosporine during the ischemic phase in the kidney that immediately follows surgery and of reduced doses over time, often with azathioprine added, seems to minimize the renal damage, or at least to stabilize it and to slow progression of the renal dysfunction and hypertension. Treatment of the hypertension with conventional drugs has definite but limited value. Diuretics and vasodilators have been the mainstay of our approach during the early phases of the hypertension but our recent data indicate that ACE inhibitors may become relatively specific in management during the later phases of the post-transplantation period as PRA levels rise in response to vascular damage by cyclosporine. ACE inhibitors have inherent dangers that require careful monitoring.(ABSTRACT TRUNCATED AT 400 WORDS)

Cyclosporins↗
PubMed1989

Responses of nucleus ambiguus neurons to arterial pressure manipulations.

Nearly 69% of nucleus ambiguus neurons in the anesthetized, artificially respired dog responded to nonpharmacological manipulations of arterial pressure (AP). All were active at resting AP, most responded robustly to increased AP, and of these, about half showed activity modulated by the respiratory cycle. Other AP-sensitive neurons fired only during the inspiratory or expiratory phase of the pump-driven respiratory cycle, and were inhibited by increased AP and excited by decreased AP.

Action Potentials↗
PubMed1989

Gout in the heart transplant recipient: physiologic puzzle and therapeutic challenge.

PURPOSE: Hyperuricemia and gouty arthritis have been associated with cyclosporine use in renal transplant recipients. Patients requiring heart or heart-lung transplantation may have additional risk factors for the development of gout, yet it has not previously been described in this population. We share herein our clinical experience with gouty arthritis in six heart transplant recipients. PATIENTS AND METHODS: During a one-year period, six hospitalized male heart transplant patients were seen in consultation for gouty arthritis. Five were subsequently followed for gout as outpatients; the sixth died within six months. Management included trials of nonsteroidal anti-inflammatory drugs (NSAIDs), colchicine, allopurinol, and intra-articular steroid injections, as well as attempts to minimize cyclosporine nephrotoxicity. RESULTS: Three patients had gout in remission at time of transplant surgery, and three others developed gout for the first time two to 45 months after transplantation. Following transplant surgery, both pre-existing and new-onset gout appeared to exhibit an accelerated course, with unusually rapid development of chronic polyarticular disease and tophi in four of the five patients followed for more than six months. Peak serum uric acid levels ranged from 11.0 mg/dL to 16.5 mg/dL. NSAIDs produced reversible renal insufficiency in four patients. Gout-related infections occurred in three patients, one of whom died. CONCLUSION: Acute gouty arthritis may occur in the heart transplant recipient despite concomitant use of immunosuppressive drugs. Cyclosporine, with its attendant hypertension and nephrotoxicity, appears to be the major risk factor for hyperuricemia in this setting, leading to the accelerated development of tophi and chronic polyarthritis. Management is complicated by the patients' renal insufficiency and propensity to infection, as well as by interaction with transplant-related medications. Prevention of hyperuricemia by minimizing cyclosporine nephrotoxicity appears to be the best management strategy, with judicious use of allopurinol for those patients in whom this preventive approach fails.

Adult↗
PubMed1989

Prehospital providers' AIDS knowledge and attitudes.

Of the 110 career and volunteer prehospital care providers surveyed from two Maryland counties, about 20 percent were concerned about dealing with AIDS patients, including 24 percent who have considered leaving EMS due to the risk of HIV infection.

Acquired Immunodeficiency Syndrome↗