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Biomedical subjects

B J Carroll

Publications and source records attributed to B J Carroll.

At least 19 recordsLinked to original sources

Preliminary studies of 6 beta-hydroxydexamethasone and its importance in the DST.

The role of the metabolites of dexamethasone (DEX) in the dexamethasone suppression test (DST) has never been fully elucidated. We report here our preliminary studies of 6 beta-hydroxydexamethasone (6 OH-Dex), a known metabolite of DEX, on the hypothalamic-pituitary-adrenal (HPA) axis of the rat; its activity in the most commonly used radioimmunoassay for plasma DEX; and its plasma concentrations in a normal human subject during the standard 1.0 mg DST. Six OH-Dex administered subcutaneously to rats at a dose of 1 mg/kg was able to completely suppress corticosterone production for at least 3 hr. In the IgG Corp. radioimmunoassay for plasma DEX, 6 OH-Dex was moderately cross-reactive yielding a 50% cross-reactivity of 10%. Gas chromatographic coupled mass spectroscopic analysis of human plasma samples, obtained 12 to 20 hr after the oral ingestion of 1.0 mg DEX, demonstrated similar plasma concentrations for both the parent compound and the 6-hydroxyl metabolite. The relevance of these findings, particularly to pharmacokinetic studies of the DST, is discussed.

Animals

RU486 in depression.

RU486 is a synthetic glucocorticoid antagonist. The authors used RU486 to examine the hypothesis that the elevated plasma cortisol and ACTH in patients is due to suprahypophyseal stimulation of the anterior pituitary. Seven patients and matched controls were studied before and after the administration of RU486. RU486 produced an increase in HPA activity in depressed patients. Thus providing support for the hypothesis that there is increased suprahypophyseal stimulation of the anterior pituitary.

Adrenocorticotropic Hormone

Laparoscopic choledochoscopy: an effective approach to the common duct.

With increasing acceptance of routine cholangiography during laparoscopic cholecystectomy (for confirmation of anatomy) there has been increased identification of common duct calculi. A technique of laparoscopic transcystic common duct stone extraction is described and early clinical results are presented. Successful stone extraction was accomplished in 39 out of 41 consecutive attempts by one surgical team. Two cases required choledochotomy. There were four complications including hyperamylasemia (2), minor wound infection (1), and incidental pneumothorax (1). Recommendations regarding safety and indications are presented. Initial evaluation suggests laparoscopic transcystic stone extraction is safe and effective.

Adolescent

Laparoscopic-guided biopsy for diagnosis of hepatic candidiasis.

Histopathological evaluation of infected tissue is critical in the diagnosis of hepatic candidiasis since cultures are unreliable. Percutaneous techniques are inaccurate because lesions often are small and multifocal, and open biopsy is not always well-tolerated in acutely ill patients. The authors investigated the feasibility of laparoscopically guided biopsy in patients suspected of having hepatic candidiasis. Preliminary results suggest that laparoscopically guided biopsy is highly accurate and less invasive than open biopsy.

Adult

Laparoscopic colectomy.

Fifty-one laparoscopic colectomies were attempted at two institutions. The clinical results and methods are presented. Seven cases (14%) were converted to facilitated procedures, and four cases (8%) were converted to "open." Cases of cancer, diverticulitis, endometriosis, regional enteritis, villous adenomas, and sessile polyps were operated. Right, transverse, left, low anterior, and abdominoperineal colectomies were performed. Colotomies and wedge resections were also performed. Laparoscopic suturing was required in five cases of incomplete anastomosis by circular stapler (18%). Suturing was required in all right, transverse colectomies and colotomies. Operative time averaged 2.3 hours. Hospitalization averaged 4.6 days. Four patients had complications (8%), and one 95-year-old died of pneumonia (2%). Laparoscopic colectomies can be performed safely, but require two-handed laparoscopic coordination, as well as suturing and knot-tying skills.

Adult

Laparoscopic cholecystectomy in acute cholecystitis.

Between August 1989 and December 1990, twenty-five patients with a preoperative diagnosis of acute cholecystitis underwent laparoscopic cholecystectomy. Twenty-one patients (84%) had abdominal tenderness, 16 (64%) had leukocytosis, and 10 (40%) had fever. Eleven patients (44%) came to the hospital with only one of these previously mentioned clinical signs. Six patients (24%) had two clinical signs. Eight patients (32%) came to the physician with all three findings. The length of surgery correlated directly with the number of presenting clinical signs. The average operating time was 119 minutes. Intraoperative cholangiograms were routinely performed on all patients. Four patients (16%) had common bile duct stones. The average hospitalization was 3.8 days and patients returned to work or routine physical activity between 3 days and 2 weeks (average 8 days) after surgery. There were three wound infections and two cases of hyperamylasemia. One patient developed urinary retention and another had a CO2 embolus. There were no intra-abdominal abscesses and no mortality. Laparoscopic cholecystectomy in acute cholecystitis is technically difficult. The incidence of common bile duct stones is greater than in elective cases, and routine cholangiography is crucial. With sufficient experience and skill, laparoscopic cholecystectomy can be performed safely in patients with acute cholecystitis.

Academic Medical Centers

Fast feedback regulation of ACTH by cortisol.

1. Fast feedback regulation of ACTH by cortisol has not been well studied in humans. The authors studied the existence and characteristics of fast feedback regulation in normal humans. 2. Hydrocortisone hemisuccinate was infused at two different rates: 6 mg/hour and 12 mg/hour for two hours. 3. The studies did not demonstrate the existence of fast feedback regulation of basal ACTH concentration by cortisol in man. Further, the response was variable and the rate sensitive character was difficult to demonstrate.

Adrenocorticotropic Hormone

Nocturnal and early morning secretion of ACTH and cortisol in humans.

It is well established that the adrenocorticotropic hormone (ACTH) stimulates the synthesis and release of cortisol from the adrenal cortex, but the role of ACTH in the physiological regulation of basal cortisol secretion has received surprisingly little study. The authors studied the nocturnal and early morning secretory pulses of cortisol and ACTH in normal subjects. A pulse detection algorithm was developed. The relationship between ACTH and cortisol pulses in terms of temporal and proportional relationship is described. Pulse concomitance for ACTH with cortisol was 47% and for cortisol with ACTH pulses it was 60%. The first description of the relationship between concomitant ACTH and cortisol pulse magnitudes in humans is presented. A highly significant linear relationship between the magnitudes of ACTH and cortisol pulses is shown. Putative reasons for dissociated pulses and the potential implication of these findings are discussed.

Adrenocorticotropic Hormone

Plasma dexamethasone concentrations and the dexamethasone suppression test.

Altered bioavailability or altered pharmacokinetics of dexamethasone (dex) may contribute to a positive Dexamethasone Suppression Test (DST) in psychiatric patients. We measured plasma dex and plasma cortisol concentrations in 32 patients with primary major depressive disorder (MDD), 14 patients with other psychiatric disorders, and 16 normal controls. Cortisol was measured by the competitive protein binding (CPB) assay and dex by RIA (IgG Corp.). Additionally, cortisol was measured by a fluorescent polarization immunoassay (FPIA) available on the Abbott TDx analyzer in an attempt to validate this method for use in the DST. The agreement between FPIA and CPB cortisol results was excellent. Depressed nonsuppressors, by definition, had significantly higher mean plasma cortisol concentrations than depressed suppressors, psychiatric controls, and normal volunteers at 8:00 AM, 3:00 PM, and 10:00 PM postdex. When DST nonsuppressors and suppressors were compared regardless of diagnostic group, plasma dex concentrations were significantly lower (p less than 0.01) in the DST nonsuppressors. There was a significant negative correlation between plasma cortisol levels and plasma dex levels across all subjects at 8:00 AM (r = -0.365, n = 44, p less than 0.05). When the subjects were sorted by diagnostic category, there was a strong, but not statistically significant, trend toward lower plasma dex concentrations in the melancholic nonsuppressors versus the melancholic suppressors and between the psychiatric control non-suppressors and the corresponding suppressor group. These relationships disappeared when we restricted our analyses to an empirically derived middle range of plasma dex concentrations within which the DST results were considered to be valid. We conclude that bioavailability or pharmacokinetics of dex may significantly contribute to DST results. Further investigation is needed to determine whether or not the quantification of dex and its metabolites and their determination at which specific timepoints during the DST will enhance the predictive or interpretive value of the DST in psychiatric patients.

Adult

Comparison of early and delayed inpatient dexamethasone suppression tests.

Ninety-five inpatients completed a dexamethasone suppression test (DST) within 72 hours after admission and again after at least 1 week of medication-free hospital care. The frequency of cortisol nonsuppression in patients with endogenous depression (ED) was high and not significantly different at both tests. In patients with diagnoses other than ED, the higher rate of cortisol nonsuppression at the first DST was associated with a significant decrease in test specificity. Change in postdexamethasone cortisol levels at repeat testing was associated with a decrease in depressive symptomatology, but was not related to weight change during hospitalization.

Adult

Plasma corticosterone in dexamethasone suppression test on depressed patients.

We retrospectively assayed plasma corticosterone (B) in 143 dexamethasone suppression tests (DST) given serially to 19 depressed patients during the course of their hospitalization. A total of 424 blood samples from these 19 patients were analyzed for both plasma cortisol (F) and B. Concentrations of plasma B were not distributed normally. To establish a cut-off point for a positive B value in the DST, we log transformed the values for B to approximate a normal distribution. Using this approach we determined that a value of 1.3 ng/ml is the most sensitive cut-off point for the plasma B-DST in our laboratory. The serial DST's were performed weekly during the patients' stay and plasma B values were compared with plasma F values. Severities were assessed by weekly Hamilton ratings (17 items). In general, the B values closely parallel the F values. The sensitivity of F-DST was 53% (20/38) and the sensitivity was 56% (20/36) for B-DST. During treatment, both B and F normalized in parallel and this correlated strongly with improvements in the patients' severity ratings. These data confirm the fact that plasma B is as good (but not better) a marker for depression as plasma F in the DST.

Adrenal Cortex Function Tests

Solubilization kinetics of a triglyceride/n-alkane mixture in a non-ionic surfactant solution.

The kinetics of solubilization in a non-ionic surfactant solution of pure n-hexadecane, pure triolein and a mixture of the two oils have been investigated. The rates were determined from observations of the dissolution of a single, microscopic droplet, using a drop-on-fibre technique. Conditions were such that negligible saturation of the micellar surfactant with solubilizate occurred. The rate of solubilization of each of the pure oils was found to be independent of time, hexadecane solubilization on a volume basis being about 8 times as rapid as that for triolein. The rate of solubilization of a mixture of the two oils, having a volume fraction 0.69 for triolein, was found to vary in the medium term, the rates apparently being steady both initially and (at a lower value) in the long term. These observations can be related quantitatively to the rates found for the pure oils.

Alkanes

Circadian rhythm of adrenergic regulation of adrenocorticotropin and cortisol secretion in man.

The effects of the alpha-adrenergic agonist methoxamine on the human hypothalamic-pituitary-adrenal axis was assessed by a placebo-controlled study in the morning and one in the evening. A 5-mg iv bolus dose of methoxamine in normal subjects caused a significant rise in plasma ACTH and cortisol concentrations in the morning study. However, no significant change in plasma cortisol or ACTH concentrations was noted during the evening study. These studies suggest the existence of a diurnal variation in alpha 1-adrenergic regulation of the hypothalamic-pituitary-adrenal axis.

Adrenocorticotropic Hormone

Lymphocyte numbers in endogenous depression.

The blood counts of 80 patients with depression were examined (50 unipolar, 30 bipolar). Many had reduced numbers of circulating lymphocytes. This abnormality was more common in the unipolar group (52%) than in the bipolar group (27%). When those patients with an abnormal dexamethasone suppression test response in both groups were compared, the relative and absolute lymphocyte counts were significantly lower in unipolars. Although cortisol hypersecretion may reduce lymphocyte numbers it is not yet clear whether the findings can be satisfactorily explained in this way.

Adult

Investigations of the solubilization kinetics of binary mixtures of non-polar oils by non-ionic surfactants.

An investigation of the solubilization kinetics of binary mixtures of non-polar oils by a non-ionic surfactant has been made using the drop-on-fibre technique. Variables studied were the oil composition, surfactant concentration and the temperature. Rates vary linearly with the surfactant concentration for all oil compositions. The observed rate during nearly total solubilization of each oil drop was constant, implying that in these systems solubilization is non-selective. The rates increase as the lower consolute (cloud) temperature of the surfactant is approached. Activation energies of the solubilization process are shown to be independent of the oil composition for the system studied. This suggests that the important stage of the process involves dissociation of the surfactant micelles.

Hydrocarbons