Cystic fibrosis carrier screening: comparability of data and uniformity of testing.
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Biomedical subjects
Publications and source records attributed to F Gilbert.
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Both food intake and pituitary ACTH release respond to activation of serotonergic 5-HT1a receptors. However, the effects of the 5-HT1a agonist 8-OH-DPAT on these two paradigms are probably mediated by different mechanisms. Ten micrograms of 8-OH-DPAT were microinjected into the rat paraventricular nuclei (PVN) of the hypothalamus and elicited an elevation of plasma ACTH concentration, but did not change food consumption when compared with controls. On the other hand, microinjection of the same dose of 8-OH-DPAT into the rat dorsal raphé nucleus increased food intake, but failed to alter plasma ACTH levels. This suggests that, among its various possible mechanisms of action, 8-OH-DPAT induces an increase of food intake in rats by activating presynaptic 5-HT1a autoreceptors in the raphé nuclei, where most serotonergic fibers originate, while its effect on plasma ACTH concentration occurs through activation of postsynaptic 5-HT1a receptors in the PVN, where some serotonergic fibers terminate.
The results of a 5 year study of helminth parasites of Mus spretus, are reported. Six nematode and 5 cestode species were identified but no helminth showed 100% prevalence in M. spretus, the most commonly encountered nematode and cestode species being Syphacia obvelata (46.6%) and Taenia taeniaeformis (22.4%). Among the more unusual helminth species identified was Eucoleus bacillatus, a capillariid nematode inhabiting the stomach musculature. This species was identified in 3 of the 5 years of the study. The results are discussed in the broader context of previous studies and the epidemiology of rodent helminth infections in general.
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We describe a mother and daughter with a distinct phenotype that is different from previous reports. This is likely to constitute a new syndrome for which we propose the mnemonic GMS for G goniodysgenesis, M mental deficiency, and S short stature. The pattern of occurrence is compatible with either autosomal dominant or X-linked inheritance.
A system is described for determination of LC50 or IC50 by an iterative process based on data obtained from a plate reader using a marine unicellular alga as a target species. The esterase activity of Tetraselmis suesica on fluorescein diacetate as a substrate was measured using a fluorescence titerplate. Simultaneous analysis of results was performed using an iterative process adopting the sigmoid function Y = y/1 (dose of toxicant/IC50)slope for dose-response relationships. IC50 (+/- SEM) was estimated (P less than 0.05). An application with phosalone as a toxicant is presented.
Protocols are presented for preparation of banded metaphases for cytogenetic analysis from short-term and long-term cultures of ovarian cancer. For short-term cultures (less than 24 hours of culture of freshly dissociated tumor material), prolonged exposure (16-18 hours) to mitotic inhibitors was required for metaphase isolation; shorter exposures to mitotic inhibitors (3-6 hours) were generally sufficient for ovarian cancer cells in culture for days to weeks (long-term cultures).
OBJECTIVE: To describe the management of a family with an inherited predisposition to ovarian and breast cancer. Particular attention is paid to the problems of contraception, screening, prophylactic surgery and hormone replacement therapy. SETTING: The multidisciplinary Grampian Familial Epithelial Ovarian Cancer Study Group. SUBJECTS: 162 members of a family extending over five generations. In the third generation, five of the 10 women died with epithelial ovarian cancer. Three women in generation IV have developed pre-menopausal breast cancer. There are now 78 family members in the fifth generation aged between 2 and 22 years. INTERVENTIONS: Counselling of female family members is started at the age of 18 years. The combined oral contraceptive pill is advocated to suppress ovulation. Gynaecological follow-up after the age of 28 includes yearly pelvic examination, transvaginal ultrasonography and serum CA125 estimation. Laparoscopy with peritoneal cytology is indicated if any part of this yearly assessment is abnormal. Prophylactic oophorectomy is advised between the ages of 35 and 40 years after the family is complete. In generation IV, 20 of the 29 women have undergone prophylactic oophorectomy. Oestrogen hormone replacement therapy with a cyclical progestogen is recommended after prophylactic oophorectomy. Breast cancer screening starts at the age of 25 and involves annual clinical breast examination augmented by mammography and breast ultrasound. CONCLUSIONS: Only by the careful questioning and recording of family history, including at least third degree relatives (cousins), will similar groups with familial ovarian/breast cancer be identified. When predisposing genes are characterized it will be possible to identify carriers within the family and concentrate clinical effort on them while offering appropriate reassurance to those with decreased risk.
Previous studies have shown that activation of the 5-HT1A receptor subtype enhances rat plasma ACTH concentration. Such receptors have been suggested to be located on CRH neuronal cell bodies in the paraventricular nuclei of the hypothalamus (PVN). In this report, microinjection of 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), a selective 5-HT1A agonist, into the PVN increased rat plasma ACTH concentration in a dose-related manner. Similar responses were observed when two other 5-HT1A agonists, busipirone and gepirone, were used. (+/-)-Pindolol, known to have 5-HT1A antagonist properties, blocked the effect induced by an optimal dose of 8-OH-DPAT after injection into the PVN. This same dose of 8-OH-DPAT also induced a decrease of hypothalamic CRH concentration, which was completely antagonized as well by pretreatment injection of (+/-)-pindolol into the PVN. A significant inverse correlation was found between hypothalamic CRH and plasma ACTH levels. These results confirm that elevation of the plasma ACTH concentration induced by 5-HT1A receptor subtype activation is mediated by the release of CRH from the paraventricular nuclei of the hypothalamus in rats, but do not exclude other mechanisms.
The significance of the radiological fat pad sign indicating elbow joint effusion after trauma when a fracture is not visible remains controversial. This retrospective analysis of 45 cases examines the need for routine repeat radiography at 2-week review. At follow-up, 29 had normal repeat radiographs, two had undisplaced radial head fractures, three had no radiographs but were clinically well and 11 failed to attend. The incidence of fracture in those having repeat radiography was 6%. We conclude that routine repeat radiography is unnecessary.
Data on ten variables and 16 biomarkers were obtained on 119 patients with newly diagnosed pulmonary cancer. The prognostic value of 16 biomarkers (alpha-1-antitrypsin [AAT], adrenocorticotropic hormone [ACTH], alpha-fetoprotein [AFP], carcinoembryonic antigen [CEA], human chorionic gonadotropin [HCG], immune complexes, immunoglobulins, N-terminal peptide of proopiomelanocortin [NTERM], and tumor-associated antibody [TAA]) was tested by adding these to the model of age, gender, stage, morphology, Feinstein's classification of symptoms, Karnofsky scale, leukocyte count, recent weight loss, and liver enzymes. Using Cox's regression method and a forward stepwise procedure, seven biomarkers (ACTH, AAT, AFP, calcitonin, HCG, TAA, and prolactin) entered the model. Elevated levels of cortisol and TAA were associated with longer survival. The selection of biomarkers by stepwise regression needs to be interpreted with caution, especially since the Z scores were found to be dependent on the particular variables included in the model. Furthermore, when dichotomized on maximum of the normal laboratory values, HCG and AFP were infrequently (2%) elevated. The lack of correlation among the biomarkers supports the hypothesis of random derepression of the genome of cancer cells. Further studies in improved modeling and the formulation of a biomarker index could enhance our understanding of the biology of cancer.
Mesomelic dysplasia is a form of short-limb dwarfism characterized by disproportionate shortness of the middle segment of all limbs. Included in this category of skeletal disorders is the Nievergelt syndrome, which typically manifests a rhomboidal shape of the tibiae and fibulae, an unusual foot deformity, radioulnar synostosis, and dysplasia of the elbow and knee joints. We describe a patient with mesomelic dysplasia with findings suggestive of the Nievergelt syndrome and with absence of fibulae and hexadactyly.
To determine the effect of a 72 Hz pulsating electromagnetic field (PEMF) on bone density of the radii of osteoporosis-prone women, the nondominant forearms of 20 subjects were exposed to PEMF 10 h daily for a period of 12 weeks. Bone density before, during, and after the exposure period was determined by use of a Norland-Cameron bone mineral analyzer. Bone mineral densities of the treated radii measured by single-photon densitometry increased significantly in the immediate area of the field during the exposure period and decreased during the following 36 weeks. A similar but weaker response occurred in the opposite arm, suggesting a "cross-talk" effect on the nontreated radii, from either possible arm proximity during sleep or very weak general field effects. The data suggest that properly applied PEMFs, if scaled for whole-body use, may have clinical application in the prevention and treatment of osteoporosis.
Cytogenetic results of first-trimester chorionic villus sampling are reported from seven U.S. medical centers. For 6033 patients who had a successful chorionic villus sampling procedure, the rate for obtaining a cytogenetic diagnosis was 99.6% with the direct method, long-term culture, or both. There were no incorrect sex predictions and no diagnostic errors involving trisomies 21, 18, or 13, sex chromosome aneuploidies, or structural abnormalities. There were no cases of normal cytogenetic diagnosis followed by birth of a cytogenetically abnormal infant. Three cases of unusual aneuploidies (tetraploidy, trisomy 16, and trisomy 22) detected by the direct method only were not confirmed by cytogenetic follow-up. Mosaic cytogenetic abnormalities were observed in 0.83% of all cases in which chorionic villus sampling was done but were confirmed by amniocentesis or in fetal tissues in only 7 of 30 cases (23.3%). Maternal cell contamination occurred in 1.9% of long-term cultures, although this did not present any cytogenetic diagnostic difficulties. Overall, a very high degree of laboratory success and diagnostic accuracy was observed with either cytogenetic method, although fewer predictive errors were observed with the long-term culture method and none were observed when both methods were used.
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Urinary levels of immunoreactive (IR) human NH2-terminal (hNT) of pro-opiomelanocortin were measured in 43 patients with various cell types of lung cancer (19 squamous cells, 12 oat cells, 2 large cells, and 10 adenocarcinoma), 32 patients with benign lung disease, two patients after hypophysectomy, and in 23 healthy volunteers. Lung cancer patients were divided into two subgroups according to the stage of the disease: 22 patients had "limited", and 21 patients "extensive" disease. Urinary and plasma levels were measured in 9 patients with lung cancer before and after radio- and chemotherapy or surgery. Urine samples were dialyzed and IR hNT material was extracted by Sep Pak C-18 cartridges using a propanol-2/TFA solvent system. The plasma and urinary IR hNT levels of the normal controls were 124 +/- 25 pg/ml and 47.8 +/- 14.5 pg/mg creatinine, respectively. The plasma levels of IR hNT were elevated (greater than mean + 2SD) in 65% of our patients with histologically proven lung cancer (422 +/- 775, mean +/- SD, pg/ml). The highest incidence of an elevated plasma level of IR hNT was found in oat cell carcinoma (83%). Elevated plasma IR hNT occurred in 66% of the patients with benign pulmonary disease (246 +/- 141 pg/ml, N.S.). In cancer patients with "limited" disease we found levels of 226 +/- 143 pg/ml and in patients with "extensive" disease 627 +/- 1074 pg/ml (N.S.). The urinary IR hNT level in lung cancer patients was 186 +/- 337 pg/mg creatinine and 81% of our patients had elevated levels.(ABSTRACT TRUNCATED AT 250 WORDS)