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Biomedical subjects

C Morgan

Publications and source records attributed to C Morgan.

At least 127 records · Page 7Linked to original sources

Hypoxemic stimulation of heart glycogen synthase and synthesis. Effects of insulin and diabetes mellitus.

With radiotracer and 13C nuclear magnetic resonance (13C-NMR) methods, we studied the time course of glycogen resynthesis after three 90-s episodes of hypoxemia in both control and diabetic rats in vivo. Glycogen synthesis was measured in the presence and absence of infused insulin and compared with the changes in glycogen synthase (GS) and phosphorylase activities. We observed in 13C-NMR spectra the expected mobilization of glycogen during hypoxia in vivo. In control rats with or without exogenous insulin, this was followed by a rapid resynthesis of glycogen during a 40-min recovery period. A marked activation of GS was observed by 10 min (glucose-6-phosphate-independent form of GS [GSl] = 0.65 mumol.min-1.g-1 or 92% of total GS), and activation persisted up to 40 min in both groups. Glycogen synthesis during the recovery period averaged 0.51 and 0.45 mumol.min-1.g-1 in the saline- and insulin-treated rats, respectively. In the diabetic rats by 10 min after hypoxemia, GSl increased only modestly in both saline-treated (0.16 mumol.min-1.g-1) and insulin-treated (0.21 mumol.min-1.g-1) rats, and activation persisted up to 40 min only with insulin treatment. Glycogen synthesis was slower in the diabetic rats given insulin (0.28 mumol.min-1.g-1) and essentially absent in the saline-treated rats (0.03 mumol.min-1.g-1) compared with controls. We conclude that recovery from hypoxemia is accompanied by a marked activation of GSl and rapid rates of glycogen synthesis in nondiabetic rats, and diabetes markedly blunts this response. Acute insulin infusion only partially overcomes this block.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Treatment of heroin addicts using buprenorphine.

Thirty-nine opioid-dependent outpatients were treated with the partial agonist buprenorphine at 2 to 6 mg/day for 1 month. Treatment retention was good (72%), and illicit opioid use decreased from 50% overall to 17% for those who remained in treatment. Precipitated withdrawal symptoms were mild and related to dose of buprenorphine. At the end of this month, 28 subjects were abruptly discontinued from buprenorphine and given the antagonist naltrexone. Withdrawal symptoms from buprenorphine were quite mild, and naltrexone was initiated in 20 patients (51% of total or 71% of those 28 completing 30 days on buprenorphine), but only 4 patients (10% overall) were successfully maintained on naltrexone for at least 2 weeks.

Adult↗

Dipyridamole-thallium myocardial scanning in the preoperative assessment of patients undergoing abdominal aortic aneurysmectomy.

Dipyridamole thallium scanning (DTS) is an imaging technique with good sensitivity for coronary artery disease (CAD). The purpose of this study was to compare the haemodynamic courses and the correlation between pulmonary capillary wedge pressure (PCWP) and central venous pressure (CVP) in patients with normal DTS (Group 1: n = 12) with those whose scans demonstrated CAD (Group 2: n = 11). Haemodynamic profiles were obtained prior to anaesthesia and at several times during surgery. The haemodynamic courses in both groups were similar with significant decreases in cardiac index, stroke index, and left ventricular stroke work index during aortic cross-clamping compared with values prior to anaesthesia. There were no significant changes in PCWP and CVP throughout the study. The correlations between PCWP and CVP were significant in both groups as were the correlations between the changes in PCWP and the changes in CVP observed at the time of cross-clamping. These correlations all had large standard errors of the estimate, however, making it impossible to predict the PCWP from the CVP with precision. It is concluded that, in a limited study population, an abnormal DTS did not identify patients in whom the PCWP and CVP correlated poorly during abdominal aortic aneurysmectomy.

Aged↗

Sensitive non-radioisotopic in situ hybridization histochemistry: demonstration of tyrosine hydroxylase gene expression in rat brain and adrenal.

An alkaline phosphatase-labelled anti-sense oligonucleotide probe specific for tyrosine hydroxylase (TOH) mRNA has been used for visualisation of TOH mRNA in the rat brain and adrenal gland. Both ribonuclease pre-treatment and the use of excess non-labelled probe abolished the specific hybridization signal. Furthermore the TOH mRNA-positive signal was only found in cells known from earlier studies to react with anti-TOH antibodies. To determine if the alkaline phosphatase-labelled probe could be used in a semiquantitative manner for measurement of the density of TOH mRNA signal, we used reserpine pre-treatment which induces TOH mRNA expression. The results revealed a significant increase in TOH mRNA signal in locus coeruleus and substantia nigra neurons, and in adrenal medulla chromaffin cells. The increased signal in these areas agreed with the increase in TOH mRNA signal previously observed by Northern analysis and suggests that this type of alkaline phosphatase-labelled probe allows sensitive detection of changes in TOH gene expression.

Adrenal Glands↗

Comparative study of the effects of enoximone and dobutamine in patients with impaired left ventricular function undergoing cardiac surgery.

In the light of several incidences at Brompton Hospital in which enoximone brought about a striking improvement in cardiac index in patients with refractory left ventricular failure, a study was initiated to compare the effects of enoximone and dobutamine following cardiopulmonary bypass in patients with impaired left ventricular function (preoperative ejection fraction less than 0.5). In two groups of 10 patients, similar responses of haemodynamic variables were obtained with enoximone or dobutamine administration. In particular, mean cardiac index increased by 25% in the first 15 min and by 60% over the 24-hour study period after bypass. Mean systemic vascular resistance fell by approximately 10%. Mixed venous oxygen saturation increased marginally from a preoperative value of approximately 76% within 15 min of drug administration and then fell and stabilized at about 65% in the next 12 h during re-warming. Patients were weaned from enoximone, after 24 h, without event. Both drugs were shown to produce favourable haemodynamic profiles and to be well tolerated in this relatively high-risk cohort of patients.

Cardiac Surgical Procedures↗

Evidence for altered desipramine disposition in methadone-maintained patients treated for cocaine abuse.

Plasma concentrations of desipramine (DMI) and its 2-hydroxy metabolite (OHDMI) were compared among 72 patients being treated with desipramine for either depression (n = 39) or cocaine abuse (n = 33). Eleven cocaine abusers who were concurrently maintained on methadone had a significantly lower ratio of DMI dose to plasma concentration (0.9) than the depressives (2.2) or nonmethadone cocaine abusers (2.0). Their OHDMI/DMI ratios were significantly lower (0.19) than for either the other 22 cocaine abusers (0.39) or the depressed (0.50) patients. This difference was not due to DMI dosage. Although the underlying mechanism cannot be determined from these plasma studies, possible reduced hydroxylation of DMI in methadone patients suggests the need for DMI plasma monitoring.

Adult↗

Differentiating various abnormalities of thyroxin binding to serum proteins by radioelectrophoresis of thyroxin and immunoassay of binding proteins.

Using the simple method of protein analysis described here, we could identify thyroxin (T4)-binding-protein abnormalities in euthyroid patients with hyperthyroxinemia or hypothyroxinemia. Serum incubated with [125I]thyroxin was analyzed by agarose gel electrophoresis, with bromphenol blue staining of protein. The relative distribution of radioactive T4 was determined for each binding protein--thyroxin-binding globulin (TBG), transthyretin, albumin, and T4-binding immunoglobulin (when present)--and the mass of T4 bound to each was determined. We also used sensitive immunoassays to quantify TBG, transthyretin, and albumin concentrations, then calculated the mass of T4 (as determined by electrophoresis) bound per unit mass of the respective binding protein. When the concentration of binding proteins was altered (e.g., TBG excess or TBG deficiency), the T4 binding/mass ratio for each protein remained within the expected range; but when the functional affinity of a binding protein was altered--as in dysalbuminemic hyperthyroxinemia and in low-T4 nonthyroidal illness--this ratio was abnormal. This procedure can be used to help identify TBG excess, TBG deficiency, dysalbuminemic hyperthyroxinemia, prealbumin-associated hyperthyroxinemia, variant TBG with reduced affinity for T4, euthyroid sickness, and T4-binding autoantibodies.

Autoantibodies↗

Organization of afferent and efferent pathways in the pudendal nerve of the female cat.

Application of horseradish peroxidase to the pudendal nerve in the female cat labelled lumbosacral afferent and efferent neurons and their processes. Afferent axons entered the spinal cord primarily at the S1 and S2 segments and traveled rostrocaudally in Lissauer's tract and the dorsal columns. A distinctive component of the dorsal column projection was located at the lamina I-dorsal column border as a densely labelled, compact bundle that distributed fibers to the dorsal horn at spinal levels near the segments of entry of the afferent axons. Afferent terminal labelling was located in the marginal zone, the intermediate gray matter, and the dorsal gray commissure in the lumbosacral and coccygeal spinal cord. A well-defined terminal field restricted to the S1 and rostral S2 segments was present in the medial third of the nucleus proprius and substantia gelatinosa. Labelled motoneurons in Onuf's nucleus (S1 and S2) exhibited longitudinal dendrites that extended rostrocaudally within the nucleus and three groups of transverse dendrites that emanated periodically from the nucleus and passed to the ventrolateral funiculus, the intermediate gray, and the dorsal gray commissure. Components of the pudendal nerve that innervate the anal and urethral sphincters were also labelled by injecting HRP into the respective sphincter muscles. Motoneurons innervating the anal and urethral sphincters were located in the dorsomedial and ventrolateral divisions, respectively, of Onuf's nucleus. Afferent projections from the two sphincters were similar; the most prominent terminations were present in the marginal zone, intermediate gray, and dorsal gray commissure. These results are discussed with respect to the physiological function of the pudendal nerve and its relationship with sacral autonomic pathways.

Afferent Pathways↗

The usefulness of various polymorphisms in paternity testing. Experience with three southern African populations.

Genetic studies have been carried out on 1,059 cases (involving 3,177 blood samples) of disputed paternity. Seventeen polymorphic systems, representing 21 loci, have been used on all the cases and an additional 11 system (12 loci) were used when an exclusion on only one of the system was obtained. The overall rate of exclusion was 34.0% and the data were analysed according to the population from which the case came (white, 'coloured' or black). HLA is the most informative system in all three populations, followed by PGM1, with the rhesus blood group the next most useful in the whites and 'coloured's, whereas ABO is the next most useful in the blacks. The probability of excluding a man falsely accused of paternity was 99.1% in the black, 99.4% in the white and 99.7% in the 'coloured' populations. The data were also used to calculate the probability of paternity in the cases in which an exclusion could not be demonstrated; values of over 98% were found in 98.5% of whites, 98.8% of 'coloureds' and 90% of blacks; a further 9.1% of blacks gave values of 95.1 - 98.0%. The range of genetic markers, representing red cell antigen, red cell enzyme, serum protein and HLA polymorphisms used in this study, meets the requirements of an efficient paternity testing service.

Black People↗

Desipramine facilitation of initial cocaine abstinence.

We conducted a double-blind, random assignment, six-week comparison of desipramine hydrochloride (n = 24), lithium carbonate (n = 24), and placebo (n = 24) treatments for cocaine dependence. Subjects were 72 outpatient cocaine abusers who met DSM-III-R dependence criteria for cocaine but not for other substance abuse. Subjects in each treatment group were similar in history of cocaine and other substance abuse, cocaine craving, sociodemographics, and other psychiatric comorbidity. Desipramine, compared with both other treatments, substantially decreased cocaine use. Lithium treatment outcome did not differ from that of placebo. Desipramine-treated subjects attained contiguous periods of abstinence substantially more frequently than subjects receiving lithium or placebo. Fifty-nine percent of the desipramine-treated subjects were abstinent for at least three to four consecutive weeks during the six-week study period, compared with 17% for placebo and 25% for lithium. Cocaine craving reductions were also substantially greater in the desipramine-treated subjects. Establishment of initial abstinence is the first stage in recovery from cocaine dependence. Our findings indicate that desipramine is an effective general treatment, for this first treatment stage, in actively cocaine-dependent outpatients.

Adult↗

Role of opioid antagonists in treating intravenous cocaine abuse.

Intravenous cocaine abuse is a major probel in opioid abusers including those treated in methadone maintenance. Studying 138 opioid addicts, we found that speedballing by combining opioid agonists with cocaine may be blocked by opioid antagonists such as naltrexone and by partial antagonists such as buprenorphine. With both these treatments cocaine abuse was five to eight times less than with methadone treatment.

Adult↗