Biomedical subjects
A Moore
Publications and source records attributed to A Moore.
Platelet number and platelet function: their importance in hemostasis.
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Spinal fluid kinetics of morphine and heroin.
Nine patients undergoing cardiopulmonary bypass surgery were given either 2 mg diamorphine or 2.5 mg morphine by intrathecal injection. Spinal fluid (sf) samples were collected over 25 min and drug concentrations measured by HPLC. Concentrations in sf were about 4000 times as great as after 1 mg/kg IV morphine. The kinetic properties of morphine and heroin in sf differed; diamorphine was removed from sf much more rapidly than morphine. Lipophilic opiates may be safer for intrathecal use because of the shorter life of substantial drug concentrations in the mobile sf phase.
Morphine kinetics during and after renal transplantation.
Plasma concentrations after intravenous morphine were measured by a specific radioimmunoassay method in patients undergoing renal transplantation and in control subjects. In both transplant patients and controls, plasma morphine fell in the first 10 min, but there was no significant further fall in the transplant patients until between 3 and 5 hr, when there was an abrupt reversion to the same elimination t1/2 as the controls. This coincided with recovery of renal function after the period of cold ischemia. In the transplant patients the AUC over 24 hr was higher and the plasma clearance was lower than in controls. The role of the kidney in morphine elimination is discussed.
Studies on the clearance of calcium pyrophosphate crystals from facsimile synovium.
Calcium pyrophosphate dihydrate crystals have been injected into the air pouch model of facsimile synovium. At various time intervals after crystal injection both infiltrating exudate cells and lining tissue were examined for the presence of crystalline material. The results show that the crystals are initially engulfed by mononuclear cells and to a lesser extent by polymorphonuclear cells in the exudate. Later, crystals became embedded in the lining tissue either within mononuclear cells or as crystal masses confined within granulomas. These studies suggest that the mesenchymal cells ( facsimile synovium) lining rat air pouches can clear calcium pyrophosphate dihydrate crystals from the air pouch cavity. It is therefore inferred that crystals found in the lining of human joint synovium may be incorporated therein by a similar mechanism.
Prolactin in hirsute women: possible roles for androgens in suppressing basal levels, and for oestrogens in enhancing TRH-induced responses.
Hyperprolactinaemic patients occasionally demonstrate hirsutism and elevated levels of DHA-S, a weak androgen of adrenal origin. Abnormal adrenal function is frequently observed in hirsute patients. These observations prompted speculation that prolactin may modulate normal adrenal secretion and that derangements of adrenal androgen secretion may be due to abnormalities in prolactin. In this study we examined the possibility that elevated prolactin levels may be involved in the pathogenesis of hyperandrogenaemia in hirsute patients. However, basal prolactin levels in hirsute women, with or without menstrual disturbances, 201 +/- 24.3 mU/l (mean +/- SE) and 192 +/- 24.3 mU/l respectively, were significantly suppressed below levels in normal women, 289 +/- 12.2 mU/l. The prolactin responses to stimulation with TRH and to suppression with L-dopa were also studied in hirsute patients. The prolactin response to TRH (maximum increment or integrated response) was exaggerated significantly in hirsute women with menstrual disturbances when compared to normal women, to hirsute women with normal menses or to normal men. This abnormal response may have been due to elevated oestrone levels present in patients with oligomenorrhoea (318 +/- 49.5 pmol/l compared to 191 +/- 12.1 pmol/l in normal women and 161 +/- 15.5 pmol/l in hirsute women with normal menses, P less than 0.05). There were no abnormalities detected in the suppression of prolactin in response to L-dopa in any of these groups. These findings do not support a role for prolactin in the pathogenesis of hyperandrogenaemia in hirsute patients. However, elevated androgen levels in women may bring about suppression of basal prolactin levels to values seen in normal men. (ABSTRACT TRUNCATED AT 250 WORDS)
Risks with danazol in the acquired immunodeficiency syndrome.
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Plasma morphine concentrations and analgesic effects of lumbar extradural morphine and heroin.
Patients undergoing lumbar laminectomy were given extradural narcotic, either 5 mg morphine sulphate or 5.5 mg heroin (diamorphine hydrochloride); the extradural catheter had been positioned adjacent to the dura under direct vision. Plasma morphine concentrations measured by specific radioimmunoassay showed that peak concentrations occurred significantly earlier with heroin (4.7 +/- 0.6 min, mean +/- SEM) than with morphine (7.6 +/- 0.9 min) and that peak concentrations were significantly higher after heroin 5-10 min after extradural injection. The fraction of extradural heroin crossing the dura was estimated to be 55% of the fraction of morphine crossing the dura. Postoperative fentanyl requirements using demand analgesia were the same with extradural morphine as with extradural heroin (mean, 6.6 micrograms/hr). Clinically significant slowing of respiratory rate occurred only after extradural heroin (three patients).
Nursing care study: Zellweger's syndrome.
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The effect on cost of medical care for patients treated with an automated clinical audit system.
An automated clinical medical record and audit system was developed to evaluate the effect of modifying physician behavior at the control points in the ambulatory care process and to determine if this change was reflected in patient care cost outcomes. This study compared clinical and cost results of patients in an experimental group, who had the automated record and audit system, to a control group, who had a traditional clinic record without chart audit. Physicians responded to the automated audit suggestions at a rate of 50.25 in the experimental group and 37.3 in the control group. No major differences were observed in clinical outcomes, with the exception of the number of days of hospitalizations and, consequently, the cost of hospitalizations. The experimental group cost for hospitalizations was one-third of the control group and accounted for a majority of the differences in the total annual cost for the two groups.
Adrenal abnormalities in idiopathic hirsutism.
The possibility that abnormal adrenal androgen production may be present in patients with idiopathic hirsutism was examined. Plasma testosterone, dihydrotestosterone and androstenedione levels were elevated in hirsute patients. In response to exogenous alpha 1-24 ACTH the increments in plasma androstenedione, dehydroepiandrosterone (DHA) and cortisol were significantly greater in hirsute patients than in normal subjects. The testosterone response was exaggerated following endogenous stimulation induced by metyrapone. Treatment with dexamethasone, 0.5 mg each night for 3 months, corrected both the androgen excess and the exaggerated androgen responses but not the excessive cortisol response to stimulation. These observations indicate adrenal abnormalities in idiopathic hirsutism. The dissociation of cortisol and adrenal androgen responsiveness following dexamethasone suggests that the abnormalities observed may be due to excessive adrenal androgen production stimulated by a dexamethasone-suppressible factor other than ACTH. Excess adrenal androgen production may be the primary disorder leading to the development of idiopathic hirsutism.
Amenorrhea with cryptic hyperandrogenemia.
It is current practice to assume that when menstrual disturbances are associated with androgen excess there will be additional clinical evidence of this. We have recently seen three women with secondary amenorrhea who did not have any other clinical features of androgen excess, i.e. hirsutism, acne, etc., but who had elevated plasma testosterone and androstenedione levels in addition to increased estrone values. Correction of hypertestosteronemia and elevated estrone levels was followed by ovulation, regular menstruation, and pregnancy. Variable tissue sensitivity to androgens probably accounts for these observations. If measurement of androgen levels is omitted in the evaluation of patients with amenorrhea without hirsutism, cryptic hyperandrogenemia will remain undetected. Plasma testosterone levels should be measured in all patients with amenorrhea of unknown etiology, and only if these are normal should a diagnosis of functional amenorrhea be assigned.
The sensitivity of isolated osteoclasts to morphological transformation by calcitonin.
We recently developed a technique for isolating osteoclasts from other bone cells which allows the direct effect of hormones on these cells to be assessed. We found that calcitonin (CT), which inhibits osteoclastic bone resorption, abolished cytoplasmic movement in these cells. In this paper we use the shape-change which accompanies immotility to define the sensitivity of osteoclasts to human and salmon CT. Concentrations of human CT above 62 pg/ml and salmon CT above 3 pg/ml regularly induced the shape-change in osteoclasts which corresponds to complete inhibition of cytoplasmic motility. Morphological transformation of osteoclasts by such low concentrations implies that CT may inhibit bone resorption by inhibiting the motility of the bone-resorptive cell. Even relatively high concentrations of other hormones had no effect on the sensitivity of osteoclasts to CT. This suggests that the response of isolated osteoclasts to CT is sufficiently specific and sensitive to be used as a bioassay, and we used the response to compare the biological potency of several samples of known immunoassayable CT content.
Normal cortisol response to corticotropin in patients with secondary adrenal failure.
A normal plasma cortisol response to exogenous corticotropin has been advanced as a reliable indication of adequate hypothalamic-pituitary-adrenal function in patients suspected of having secondary adrenal failure. We have examined the validity of this diagnostic strategy in five patients who had undergone hypophysectomy and 27 patients recently treated with glucocorticoids. Eleven of the patients had normal adrenal responses to cosyntropin but had subnormal responses when the entire hypothalamic-pituitary-adrenal axis was examined using metyrapone; no patient who responded normally to metyrapone failed to respond to cosyntropin. Inducing hypoglycemia with insulin yielded results concordant with the results induced by metyrapone in four patients tested. A normal cortisol response to corticotropin alone should not be relied on to exclude secondary adrenal insufficiency. To do this it is necessary to demonstrate normal activity of the entire hypothalamic-pituitary-adrenal axis, which can be conveniently examined using metyrapone.
Perineural injection of morphine fails to relieve postoperative pain in humans.
Ten patients scheduled for bilateral foot surgery were given general anesthesia plus ankle blocks. One side was blocked with 0.02% morphine and the other with 0.9% saline. A second group of 10 patients for bilateral foot surgery had one side blocked with 0.02% morphine and the other with 0.01% morphine. A within-patient blind comparison of postoperative analgesia between the two sides was performed by nurse observers, using categorical and visual analogue scales for both pain intensity and pain relief. Postoperative analgesia recorded by the nurse observer was not significantly different between morphine and saline. Similarly, there was no significant difference in postoperative analgesia between legs blocked with the higher or lower dose of morphine. Thus, perineural morphine does not relieve postoperative pain at doses equivalent to 2-4 mg in a 70-kg man.
Toxic-shock syndrome associated with post-partum staphylococcal endometritis.
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Scleredema adultorum: the surgical implications of a rare dermatologic disorder.
A case report of nonpitting induration of the skin, scleredema adultorum of Buschke, is presented. Although it may be a benign, self-limited disease, its complications may require drainage of abscesses or soft-tissue coverage, which may result in delayed wound healing. In the reconstruction of tissue defects, skin grafts are preferred, since the skin is unyielding.
Structural studies on the chromophore attachment site of rhodopsin following bleaching.
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