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Biomedical subjects

C Morgan

Publications and source records attributed to C Morgan.

At least 37 records · Page 2Linked to original sources

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

The effects of dopexamine hydrochloride on cardiopulmonary haemodynamics following cardiopulmonary bypass surgery.

We studied the effects of dopexamine hydrochloride in 14 patients following cardiopulmonary bypass for coronary revascularisation (12 patients) or valve replacement (2 patients). The drug was administered by intravenous infusion at rates of 1, 2, 4 and 6 micrograms/kilogram/minute for a period of 10 minutes at each dose. Measurements of heart rate, blood pressure, right atrial pressure, pulmonary arterial pressure, pulmonary arterial wedge pressure and cardiac output (thermodilution method) were made at the end of each period. There were significant increases in heart rate (P less than 0.05), cardiac index (P less than 0.05) and systolic blood pressure (P less than 0.05). There were significant falls in systemic vascular resistance (P less than 0.05) and pulmonary vascular resistance (P less than 0.05). There were no significant changes in pulmonary arterial or wedge pressure. No serious adverse effects were observed. Dopexamine hydrochloride appears to be a useful supportive agent in patients following cardiopulmonary bypass, although further trials need to be carried out in order to establish precise therapeutic indications for its use.

Adrenergic Agonists

The chick chorioallantoic membrane assay: an improved technique for the study of angiogenic activity.

The chick chorioallantoic membrane assay has been used for many years as an in vivo assay of angiogenic activity. However it has been plagued with the problem of a high incidence of false positive angiogenic responses. In this study the conventional chick chorioallantoic membrane assay was compared with a modification of this technique in a series of batches using a total of 100 eggs. False positive reactions were recorded in 32 out of 50 (64%) using the conventional method and only 11 out of 50 (22%) with the modified method (chi 2 = 17.992; p less than 0.001).

Amnion

The role of immunotherapy in cockroach asthma.

To evaluate the preventive role of immunotherapy in severe perennial asthma, we investigated cockroach asthma as a model. Twenty-eight subjects with bronchial asthma due to cockroach hypersensitivity (BACR) were divided into two groups in alternating order: 15 were started with cockroach antigen immunotherapy (CRa-IT) and 13 were given control immunotherapy. Eleven in the former group and two in the latter group completed the study after 5 years. The changes in symptoms and medication scores were assessed; blocking antibody factor in the paired pre- and postimmune serum of the two groups was measured and compared. Cellular sensitivity (HR50) was measured using the basophil-rich leukocytes (BRLs) obtained from the two treated asthma groups, and the result was compared with that of the untreated cockroach asthmatic cells. The average symptom score changed from 7.2 +/- 2.7 to 1.2 +/- 0.4 in the CRa-IT group. The control-IT group showed no change. The medication score changed from 11.4 +/- 1.6 to 5.2 +/- 1.4 in the CRa-IT group only (p less than 0.01). The mean blocking antibody factor in the immune serum of the CRa-IT group showed a 2.5 x 10(2)-fold increase [1.3 +/- 0.3 x 10(-1) in postimmune serum/5.2 +/- 2.0 +/- 10(-4) in preimmune serum (p less than 0.001)]. No difference was noted in the HR50 of the BRLs in the post- and preimmune serum of the control-IT group. Antihuman IgG absorption of the post-CRa-IT serum reduced the blocking antibody to 1/1000-fold; no difference in the HR50 of the BRLs was noted between the post-control-IT and the pre-CRa-IT serum (p greater than 0.2). The BRLs of the CRa-IT asthmatics, however, showed blunted sensitivity not affected by the serum factor (5.8 +/- 1.5 x 10(-2) micrograms/ml in post-CRa-IT serum and 5.6 +/- 1.3 x 10(-2) micrograms/ml in pre-CRa-IT serum) (p greater than 0.2). The BRLs of the control-IT group retained their cell sensitivity as well as the blocking effect of the CRa-immune serum. This study thus demonstrated that CRa-IT reduces symptom and medication scores clinically in cockroach-asthmatic subjects, and the CRa-IT produces the CRa-specific blocking antibody of the IgG type. It also reduces anaphylactic leukocyte sensitivity, which is not affected by humoral factor.

Anaphylaxis

Medical management of malignant pericardial effusion by tetracycline sclerosis.

Fifty-eight patients with malignant pericardial effusion were seen from 1979 to 1986. A Kifa catheter was inserted into the pericardial sac and allowed to drain for 12 to 24 hours during electrocardiographic monitoring. Lidocaine hydrochloride, 100 mg, was instilled intrapericardially, followed by tetracycline hydrochloride, 500 to 1,000 mg, in 20 ml of normal saline solution. The catheter was clamped for 1 to 2 hours and then reopened. This procedure was repeated daily until the net drainage was less than 25 ml/24 hours. There were 22 male and 36 female patients (median age 58 years). The primary malignancy included lung (27 patients), breast (16 patients), stomach (3 patients), adenocarcinoma of unknown primary (7 patients), mesothelioma (2 patients) and chronic granulocytic leukemia, ovary and lymphoma (1 patient each). Fifty-six patients received 1 to 5 tetracycline instillations. In 1 patient, the catheter could not be inserted and in another, clotting occurred within the catheter before injection of tetracycline. Complications included transient atrial arrhythmias (5 patients), pain after injection (9 patients) and temperature higher than 37.5 degrees C (5 patients). One patient had a cardiac arrest during pericardiocentesis. Forty-three patients (74%) had control of their effusions for longer than 30 days (median survival 168 days, range 30 to 1,149+), and 5 patients (9%) died before 30 days without effusion. Eight patients (14%) did not achieve control. One declined further therapy after 1 instillation, and 3 died within 6 days with progressive malignancy. One patient had persistent drainage after 3 instillations, and 3 had reaccumulation of fluid 2, 6 and 27 days after catheter removal.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult