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Biomedical subjects

B Cook

Publications and source records attributed to B Cook.

At least 55 records · Page 3Linked to original sources

The relationship of panic disorder and its treatment outcome to 24-hour urinary MHPG levels.

Levels of 24-hour urinary 3-methoxy-4-hydroxyphenylglycol (MHPG) were not markedly elevated in a group of 35 panic disorder patients when compared to healthy controls (mean = 2,430 micrograms/day vs. 2,130 micrograms/day). There was a weak association between elevated pretreatment levels of MHPG and a positive treatment response to alprazolam or diazepam. Alprazolam and diazepam may differ in their effects on MHPG.

Adolescent

Luteinizing hormone response to an oestradiol challenge in 5 intersex pigs possessing ovotestes.

After challenge with oestradiol benzoate, the mean maximum LH concentration in 5 XX intersex pigs possessing ovarian and testicular tissue, or only testicular tissue, was 2.10 (+/- 0.41) ng/ml compared with 8.9 ng/ml in mature domestic gilts. These results indicate that exposure of the pig brain to testosterone before Day 30 of gestation is important, or that early testicular secretions other than testosterone are involved in the determination of brain gender. The observation that some intersex pigs show normal oestrous cycles implies that the response to these prenatal factors is primarily quantitative rather than qualitative.

Animals

The testicular response to hemicastration in the male rat cannot be maintained in vitro.

The testicular response to hemicastration (in which testicular vein testosterone from the remaining testis doubles in concentration) was studied in vitro in order to establish whether the response is maintained after testicular tissue is removed from the animal. Decapsulated testes and collagenase-dispersed cells from decapsulated testes of rats were incubated for 24 h after hemicastration and testosterone production was compared with that in tissue collected at the time of surgery. Testosterone concentration in the remaining testis 24 h after hemicastration was significantly (P less than 0.05) higher than in the testis removed at the time of hemicastration, but testosterone production in vitro was similar in both tissues. Apparently the single testis remaining in a hemicastrated rat requires extratesticular support in order to maintain its stimulated state.

Animals

Testes are asymmetric in the testicular hemicastration response of the male rat.

An enquiry was made into variability in the testicular hemicastration response of the mature rat (doubling of testicular vein testosterone concentration from the remaining testis 24 h after hemicastration). The response was shown to be asymmetric, being more reliable and more robust when the left testis was removed first. Apparently the testicular hemicastration response, which has been shown to be neurally controlled, shares the asymmetry which has been reported recently in the neural regulation of unilateral ovariectomy.

Animals

A 125I-radioimmunoassay for measuring androstenedione in serum and in blood-spot samples from neonates.

We developed a radioimmunoassay with a gamma-emitting radioligand to measure androstenedione in human serum and in dried blood-spot samples from newborns. Antisera were raised in rabbits against androstenedione linked to bovine serum albumin at positions 3, 6, or 11 on the steroid nucleus. Radioligands were prepared by linking [125I]iodohistamine at positions 3, 6, or 11. Linkages were through either carboxymethyloxime or hemisuccinate bridges. All label and antibody combinations were examined, and the most sensitive and specific combination (antiserum raised against androstenedione-3-carboxymethyloxime-bovine serum albumin with an androstenedione-carboxymethyloxime-[125I]iodohistamine label) was selected for full evaluation. We report the performance of these selected reagents in an immunoassay for androstenedione in both serum and dried blood-spot samples from neonates. We measured concentrations of androstenedione in serum under normal and pathological conditions such as congenital adrenal hyperplasia and polycystic ovarian disease. Diurnal variation in normal men was observed. Androstenedione was measured in blood spots from neonates born at term or prematurely, with respiratory distress syndrome, or with congenital adrenal hyperplasia.

Adrenal Hyperplasia, Congenital

Identification and screening of women at high risk of breast cancer.

First- and second-order female relatives of newly treated breast cancer patients who received their care by private practice surgeons were contacted to determine the feasibility of identifying an at-risk population, to ascertain screening practices, and to promote breast cancer screening. Utilizing the breast cancer patient as the primary contact, 42% of relatives participated. Only 32% of relatives reported ever having had a mammogram (40% of those 50 years of age and over), and 52% practiced monthly breast self-examination (BSE). Screening practices correlated with race, with having been taught BSE, and with income; 73% of relatives planned to be screened subsequent to contact. The results of this study indicate a low use of established screening modalities such as BSE and mammography.

Adult

Alteration of regional cerebral glucose metabolic rate in non-Korsakoff chronic alcoholism.

That chronic alcoholism yields devastating effects to the central nervous systems of its victims is well known, but the actual physiologic mechanisms underlying that deterioration have yet to be completely identified. What is also known is that many chronic alcoholics seem to recover brain function after a protracted period of abstinence, but the actual mechanisms of that restoration are also not well understood. Using positron emission tomography with the tracer 11C-2-deoxy-D-glucose as a probe to measure regional cerebral metabolic rate of glucose (RCMRGlu), we compared the magnitudes of glucose consumption in 44 brain regions between a group of newly abstinent chronic alcoholics without Korsakoff's psychosis and a control group of normal nonalcoholic subjects whose range of age was that of the alcoholic group. We found that RCMRGlu measurements in the brains of alcoholics were significantly lower than in the brains of the control group, and that there were many fewer significant interregional correlations in the brains of the alcoholics than in the brains of the control group. We also found no significant correlation between age and global metabolic rate of glucose in either group. However, even though the number of alcoholic subjects was too few to allow a reliable statistical comparison, the measurements suggest that chronic alcoholics over the age of 50 years suffer a greater decrease of RCMRGlu values than do their counterparts under the age of 50 years. While resting in a bland environment, neither alcoholic nor control subjects were found to have significant differences in RCMRGlu values between their brain hemispheres. In contrast to this similarity, normal dextrous subjects responded to a nonverbal auditory stimulus by increasing the metabolic rate of glucose in their right hemispheres while eight of nine chronic alcoholics did not. The results of this pilot study point to arguments that the alcoholic brain metabolizes glucose at a lower rate than do normal brains, that there are fewer region-to-region functional relationships in the alcoholic brain than in the normal brain, and that alcoholics may be impaired in right hemispheric processing. In subsequent investigations, we will measure the metabolic changes that follow abstinence, if any, by tracking subjects throughout an interval of rehabilitation. Also, we intend to test the findings of this study by measuring greater numbers of alcoholic subjects to separate the consequences of measurement variability, age, and chance from the underlying biologic processes that seem to be affected by chronic alcoholism.

Adult

The ectodermal dysplasias.

In order to be considered an ectodermal dysplasia, a disorder should meet the following criteria: it must be congenital; it must be diffuse (not localized) and must involve the epidermis as well as at least one of its appendages; and it must not be progressive. Included is a discussion of some well-documented, as well as some newer, conditions about which there appears to exist enough information to make some decisions concerning their categorization.

Arthrogryposis

Neonatal screening for congenital adrenal hyperplasia: a programme based on a novel direct radioimmunoassay for 17-hydroxyprogesterone in blood spots.

We have assessed the feasibility of screening newborn babies for congenital adrenal hyperplasia (CAH) by the direct measurement of 17-hydroxyprogesterone (17-OHP) in blood spots collected on filter paper (Guthrie cards) for the phenylketonuria, hypothyroidism and galactosaemia screening programmes run in Scotland. The procedure described for CAH uses an iodinated 17-OHP tracer and a specific 17-OHP antiserum sheathed within semipermeable nylon microcapsules. The method does not require a solvent extraction step, is inexpensive, precise, efficient and, therefore, practical for large-scale use. With this system the value of a neonatal screening programme was assessed in a retrospective analysis and a prospective trial. The retrospective study of 15 paediatric cases of CAH illustrated that at least half were not diagnosed within 3 weeks of birth. Analysis of the original Guthrie card samples revealed increased levels of 17-OHP in all cases. The prevalence of CAH as calculated in the retrospective study was 1 in 20 907 with a range (within 95% confidence limits) of from 1 in 12 675 to 1 in 32 604 (n = 301 450). In the prospective trial a total of 92 051 consecutive samples was screened. Five cases of CAH were correctly identified with a current false positive rate of 0.042%. Analysis of urinary steroids confirmed defective adrenal 21-hydroxylase activity in all positive cases. In the prospective trial the prevalence was 1 in 18 401 with a range of from 1 in 7422 to 1 in 50 006. We conclude that mass screening for CAH is both feasible and desirable.

Adrenal Hyperplasia, Congenital

Intersexuality in five pigs, with particular reference to oestrous cycles, the ovotestis, steroid hormone secretion and potential fertility.

Reproductive tissues, steroid hormone secretion, and sexual behaviour have been examined in five gilts, in each of which the right gonad was an ovotestis. Although from different females, these animals were sired by the same boar and each possessed an XX sex chromosome constitution as determined by karyotype analysis of blood cells. Despite variable amounts of testicular tissue in the ovotestis and unilateral development of a prominent epididymis, four of the animals had oestrous cycles of normal duration (20-22 days) and extended periods of standing oestrus (3-6 days). The fifth animal did not have detectable oestrous cycles but was extremely aggressive in the presence of a mature boar. Two of the gilts were mated, and there were small numbers of embryos in each uterine horn 23 and 26 days later. Removal of the ovary did not prompt compensatory hypertrophy in the ovarian portion of the ovotestis, nor did injection of pregnant mare serum gonadotrophin stimulate detectable follicular growth in ovarian tissue adjoining testicular tissue. Concerning the aetiology of this intersex condition, the unilateral appearance of an ovotestis precludes any simple involvement of a translocated portion of the Y chromosome or systemic effects of unusual titres of the putative H-Y antigen. However, bearing in mind a predisposition to gonadal asymmetry in eutherian mammals, a case is advanced for apposition or incorporation of adrenocortical tissue in the right embryonic ovary. The resultant virilization of neighbouring reproductive tissues would stem from adrenocortical androgen synthesis.

Animals

Alopecia areata treated with topical minoxidil.

A 1% minoxidil topical solution was used to treat 48 patients with alopecia areata, ie, 24 patients with patchy disease and 24 patients with alopecia totalis or alopecia universalis. Twenty-five patients had terminal hair regrowth; in 11 of the 25 patients, it was cosmetically acceptable. No clinical features of the disease seemed to indicate the likelihood of hair regrowth. Hair regrowth began approximately two months after the initiation of treatment and was not uniformly well maintained after the treatment was terminated. One patient had an allergic contact dermatitis reaction to the minoxidil solution; no systemic side effects were seen. No notable systemic absorption was found in 18 adult patients. Effects on cutaneous blood flow or the immune system or some direct effect on hair follicles are possible mechanisms by which minoxidil therapy might stimulate hair growth.

Administration, Topical

Regulation of oviduct function in pigs by local transfer of ovarian steroids and prostaglandins: a mechanism to influence sperm transport.

Blood was collected from a prominent ear vein and from the arterioles supplying the caudal portion of each oviduct in 5 estrous animals. Sampling was arranged at 4 preovulatory intervals, and just after ovulation in the fifth animal. Steroid hormones and prostaglandins were determined by radioimmunoassay of plasma. Whereas the concentration of cortisol did not differ between peripheral and oviduct blood samples, the overall values for progesterone, androstenedione and estradiol were significantly higher in oviduct samples (P less than 0.001) - frequently by 5- to 10-fold or more. The concentration of these three hormones in oviduct blood corresponded, in most instances, with the number of preovulatory follicles or recent ovulations in the adjacent ovary but suitable statistical correlations could not be performed. Prostaglandin F2 alpha was also present in higher concentrations in oviduct compared with peripheral plasma (P less than 0.005), although pulmonary clearance of prostaglandins would have influenced the peripheral values. Differences in the concentration of prostaglandin E2 were not significant. A local transfer of follicular hormones from the ovarian vein to the ovarian and utero-tubal arteries is proposed as a means of regulating oviduct function. Elevated concentrations of steroids and prostaglandins transferred in this way would permit incisive changes in the patency and contractile activity of the isthmus, thereby facilitating the periovulatory phase of sperm transport from the caudal portion of the oviduct to the site of fertilization.

Animals

Serial dexamethasone suppression test results during antidepressant therapy: relationship to diagnosis and clinical change.

Thirty-two outpatients with major depression of mild to moderate severity were given a 1 mg dexamethasone test (DST) after 1 week of placebo. Those who failed to show a response to placebo began a 6-week course of desipramine treatment. Severity ratings and the DST were repeated during biweekly visits. DST results robustly validated Winokur's familial subtyping and the primary/secondary distinction only when multiple results were considered. The use of multiple DSTs doubled the sensitivity of this test to primary depression and to familal pure depressive disorder without affecting specificity. Based on these data, a single abnormal DST result is considerably more meaningful than a single normal one. This finding may have particular importance to outpatients.

Depressive Disorder

The stability of amoxycillin sodium in intravenous infusion fluids.

The stability of amoxycillin sodium has been determined at 25 degrees C in water and in ten intravenous infusion fluids at concentrations of 1, 2 and 5% w/v. Little difference in stability was found between 1% and 2% amoxycillin solutions in the various vehicles, but the antibiotic was significantly less stable at 5%. Stabilities in sodium and potassium chloride solutions were similar to those in water and were markedly superior to those in dextrose or dextran fluids. Solutions in lactate or bicarbonate had intermediate stability. The antibiotic was, for practical purposes, unstable in 30% sorbitol solution. Guidelines are provided for intravenous infusion of amoxycillin in the solutions studied.

Amoxicillin