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Biomedical subjects

C Morgan

Publications and source records attributed to C Morgan.

At least 19 recordsLinked to original sources

Beta endorphin levels during heroin, methadone, buprenorphine, and naloxone challenges: preliminary findings.

Beta endorphin (BE) is a polypeptide agonist for the brain's endogenous opioid system. Levels of BE are elevated by opioid antagonists such as naloxone and depressed by short-acting agonists such as heroin and morphine; they become normalized during steady-state methadone. Buprenorphine (BUP) is a partial opioid agonist whose effects on BE levels were examined in six former heroin addicts and 14 methadone-maintained patients before and after being switched to sublingual BUP 2 mg daily for 1 month. In six former methadone-treated subjects BE levels also were measured after stopping BUP and after naloxone challenge. Levels of BE were not significantly lower in subjects started on BUP after stopping heroin (n = 6) (8.0 versus 8.1 ng/ml) or in subjects started on BUP after stopping methadone (n = 14) (11.6 vs 15.6 ng/ml). However, BE levels were lower on BUP than after naloxone challenge (n = 6) (7.0 versus 34.9 ng/ml). Levels of BE did not significantly change between the first 2 weeks ("early") and "later," although BE levels on methadone significantly correlated with BE levels on BUP in the "early" but not the "later" phase. The BE levels on BUP also did not differ from BE levels of unmedicated normals.

Adult

Identification and localization of multiple forms of serine hydroxymethyltransferase in pea (Pisum sativum) and characterization of a cDNA encoding a mitochondrial isoform.

Serine hydroxymethyltransferase (SHMT) has been purified from the mitochondria of green pea leaves. Activity can be fractionated into two distinct peaks by ion exchange chromatography. While these two forms of the enzyme are immunologically indistinguishable, immunoinhibition experiments show the presence of a distinct non-mitochondrial third form of the enzyme to also be present in green pea leaves. While this mitochondrial form of SHMT is abundant in leaves it is absent from roots, although the two tissues have comparable SHMT activity. An antibody raised to purified mitochondrial SHMT was used to screen a cDNA expression library. The sequence of one of the isolated positive clones contained an open reading frame, which encoded a sequence that matched the amino acid sequence determined from the N terminus of the mature protein. The open reading frame encodes a mature protein of 487 amino acids with a M(r) of 54,000, together with a 27-31 amino acid serine-rich leader sequence, presumably required for mitochondrial targeting. The cDNA hybridizes to a small multigene family of 2-3 genes, which appear to be expressed predominantly in leaves. Comparison of the deduced amino acid sequence with the amino acid sequences of the rabbit mitochondrial and cytoplasmic SHMT, show that pea mitochondrial SHMT is equally similar to both of these enzymes. In addition, the rabbit sequences are more like one another than they are to the pea sequence, suggesting an interesting evolutionary relationship for these proteins.

Amino Acid Sequence

Laparoscopic unroofing of a renal cyst.

Excision of a renal cyst via the flank approach results in a painful postoperative recovery requiring several days of hospitalization. We used laparoscopy in a selected patient to unroof a large complex renal cyst. The technique could optimally be used for simple cysts. The procedure was minimally traumatic, morbidity was negligible and the patient was discharged from the hospital the morning after the operation. After a 6-month followup, we believe that this laparoscopic technique is a significant advance in urological surgical management and may be better indicated for symptomatic, recurrent, simple renal cysts.

Female

Once a boring task always a boring task? Interest as a self-regulatory mechanism.

A process was proposed through which individuals regulate their motivation to perform necessary but uninteresting activities over time. If committed to continuing, individuals may engage in interest-enhancing strategies that can change the activity into something more positive to perform. In Study 1 Ss performed novel tasks and generated strategies to make regular performance interesting. In Study 2 Ss actually used these strategies primarily in conditions indicating a self-regulatory attempt: The task was currently boring, there was a perceived reason to continue (alleged health benefit), and a relevant strategy was available. Strategy use was associated with a change in activity definition and greater likelihood of subsequently performing the activity. In Study 3 Ss beliefs about how to maintain motivation to perform more everyday activities emphasized the importance of regulating interest relative to other self-regulatory strategies.

Adult

Guidelines for the use of fresh frozen plasma. British Committee for Standards in Haematology, Working Party of the Blood Transfusion Task Force.

Fresh frozen plasma should only be used to treat bleeding episodes or prepare patients for surgery in certain defined situations. Definite indications for the use of FFP: 1. Replacement of single coagulation factor deficiencies, where a specific or combined factor concentrate is unavailable. 2. Immediate reversal or warfarin effect. 3. Acute disseminated intravascular coagulation (DIC). 4. Thrombotic thrombocytopenic purpura (TTP). Conditional uses: FFP only indicated in the presence of bleeding and disturbed coagulation: 1. Massive transfusion. 2. Liver disease. 3. cardiopulmonary bypass surgery. 4. Special paediatric indications. No justification for the use of FFP: 1. Hypovolaemia. 2. Plasma exchange procedures. 3. 'Formula' replacement. 4. Nutritional support. 5. Treatment of immunodeficiency states.

Adult

Regression of liver metastases following treatment with yttrium-90 microspheres.

Selective internal radiation (SIR) therapy is a technique developed by our group for concentration of Yttrium-90 microspheres into liver metastases. The technique involves laparotomy, insertion of the catheter into the hepatic artery, redistribution of liver blood flow with vaso-active agents and incremental embolization of Yttrium-90 containing microspheres (SIR spheres) into the liver. Twenty-nine patients with non-resectable liver metastases from primary adenocarcinoma of the large bowel were treated by this technique and followed for a minimum of three months to assess evidence of tumour regression. Response to treatment was measured by serial estimations of carcino-embryonic antigen (CEA) and tumour volumes measured from serial computerized tomography (CT) scanning of the liver. There was a fall in the serum CEA level in all 26 patients in whom the serial estimations of CEA were performed following SIR therapy. The overall mean fall in CEA was 70% of pre-treatment levels with 88% of patients (23 of 26) experiencing more than a 50% fall in pre-treatment CEA levels. In 18 of 22 evaluable patients CT measured tumour volumes decreased following SIR therapy. In 48% of patients (10 of 22 patients) the decrease in tumour volume was more than 50%. SIR therapy results in a high rate of tumour regression in patients with liver metastases secondary to large bowel cancer.

Adenocarcinoma

The magnitude-of-reinforcement function in closed and open economies.

It has been hypothesized that the magnitude-of-reinforcement effect may differ in closed and open experimental economies. We determined the relationship between magnitude of reinforcement and response rate in three feeding conditions: a closed economy in which total intake was unrestricted, a closed economy in which total intake was restricted so as to maintain body weight at 85% of free-feeding weight, and a traditional open economy in which subjects received food outside the experimental session. In the closed economies, regardless of body weight, the rats responded faster for smaller pellets and when the fixed ratio for pellets was higher. In the open economy, there was no reliable effect of pellet size or pellet cost on response rate. It is concluded that although there are circumstances in which response rate is an immediate function of the parameters of reinforcement, rate is not necessarily a measure of response strength. Response rate may instead, or additionally, contribute to a strategy of reducing the costs associated with resource utilization.

Adult

Complement activation during bypass in acquired C1 esterase inhibitor deficiency.

Serial complement estimations during cardiopulmonary bypass are reported in a patient with acquired C1 esterase inhibitor deficiency. Although the extent of classic and alternative pathway activation appeared appropriate, exaggerated common pathway activation with massive increase in the C3d:C3 ratio occurred. A fatal hemostatic disorder, pulmonary edema, and circulatory collapse ensued despite prophylaxis and therapy.

Aged

Impact of an ambulatory care clerkship on the attitudes of students from five classes (1985-1989) toward primary care.

This study was designed to evaluate the effects of a required ambulatory care clerkship during the fourth year of medical school on the students' knowledge of primary care medicine and their subsequent career choices. A questionnaire was mailed to the graduates of the Albert Einstein College of Medicine classes of 1985-1989. Fifty-six percent (408) of the questionnaires were returned. An average of 74% of the respondents answered yes to six items that asked whether the clerkship had successfully introduced them to basic concepts and practices of outpatient medicine (range from 58% to 93%, depending on the item). In addition, 90% reported that the clerkship had enhanced their understanding of primary care medicine, while 41% indicated that the rotation had wholly or partially influenced their career choices. The survey findings suggest that exposure to outpatient medicine during medical school plays an important role in facilitating students' knowledge of primary care medicine and influencing their career choices.

Ambulatory Care

Myocardial protein turnover in patients with coronary artery disease. Effect of branched chain amino acid infusion.

The regulation of protein metabolism in the human heart has not previously been studied. In 10 postabsorptive patients with coronary artery disease, heart protein synthesis and degradation were estimated simultaneously from the extraction of intravenously infused L-[ring-2,6-3H]phenylalanine (PHE) and the dilution of its specific activity across the heart at isotopic steady state. We subsequently examined the effect of branched chain amino acid (BCAA) infusion on heart protein turnover and on the myocardial balance of amino acids and branched chain ketoacids (BCKA) in these patients. In the postabsorptive state, there was a net release of phenylalanine (arterial-cardiac venous [PHE] = -1.71 +/- 0.32 nmol/ml, P less than 0.001; balance = -116 +/- 21 nmol PHE/min, P less than 0.001), reflecting protein degradation (142 +/- 40 nmol PHE/min) in excess of synthesis (24 +/- 42 nmol PHE/min) and net myocardial protein catabolism. During BCAA infusion, protein synthesis increased to equal the degradation rate (106 +/- 24 and 106 +/- 28 nmol PHE/min, respectively) and the phenylalanine balance shifted (P = 0.01) from negative to neutral (arterial-cardiac venous [PHE] = 0.07 +/- 0.36 nmol/ml; balance = 2 +/- 25 nmol PHE/min). BCAA infusion stimulated the myocardial uptake of both BCAA (P less than 0.005) and their ketoacid conjugates (P less than 0.001) in proportion to their circulating concentrations. Net uptake of the BCAA greatly exceeded that of other essential amino acids suggesting a role for BCAA and BCKA as metabolic fuels. Plasma insulin levels, cardiac double product, coronary blood flow, and myocardial oxygen consumption were unchanged. These results demonstrate that the myocardium of postabsorptive humans is in negative protein balance and indicate a primary anabolic effect of BCAA on the human heart.

Aged

Positive end-expiratory pressure vs T-piece. Extubation after mechanical ventilation.

Because T-piece breathing may impair oxygenation, the best airway pressure from which to extubate ventilated patients is controversial. We compared the effects of extubation after 1 h of either CPAP 5 and T-piece/ZEEP. Once weaned from mechanical ventilation and breathing spontaneously, 106 patients were randomized to 1 h CPAP or 1 h T-piece/ZEEP, following which patients were extubated and mask O2 administered. No significant difference existed between groups in age, sex, HR, BP, FIO2, PaCO2 or PaO2. However, P(A-a)O2 was significantly greater at 120 min in the CPAP group. Within the CPAP group, P(A-a)O2 was also significantly worse at 120 vs 0 min. Nineteen T-piece patients showed improved P(A-a)O2 at 120 min compared with only ten CPAP patients. Three CPAP and two T-piece patients subsequently required reintubation. This study demonstrates that use of a T-piece dose not impair arterial oxygenation and may in fact be superior to direct extubation from CPAP 5.

Humans

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