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Biomedical subjects

F Gilbert

Publications and source records attributed to F Gilbert.

At least 73 records · Page 4Linked to original sources
PubMed1992

The multidisciplinary management of a family with epithelial ovarian cancer.

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.

Adult↗
PubMed1992

Activation of 5-HT1A receptor subtype in the paraventricular nuclei of the hypothalamus induces CRH and ACTH release in the rat.

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.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1992

Elbow fat pad sign: implications for clinical management.

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.

Adolescent↗
PubMed1990

The use of biomarkers in the prediction of survival in patients with pulmonary carcinoma.

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.

Adenocarcinoma↗
PubMed1990

Mesomelic dysplasia with absence of fibulae and hexadactyly: Nievergelt syndrome or new syndrome?

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.

Abnormalities, Multiple↗
PubMed1990

Bone density changes in osteoporosis-prone women exposed to pulsed electromagnetic fields (PEMFs).

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.

Aged↗
PubMed1990

Cytogenetic results of chorionic villus sampling: high success rate and diagnostic accuracy in the United States collaborative study.

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.

Amniocentesis↗
PubMed1989

Urinary levels of immunoreactive NH2-terminal of pro-opiomelanocortin in patients with malignant pulmonary disease.

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)

Adult↗
PubMed1989

Value of plasma NH2-terminal fragment of pro-opiomelanocortin in marking human lung cancer in various clinical settings.

Plasma concentration of amino-terminal segment of pro-opiomelanocortin (N-POMC) was measured by radioimmunoassay (RIA) in 144 patients with various forms of lung cancer during pneumonectomy, at different times of the day after being newly diagnosed and serially, throughout their treatment (surgery or chemotherapy) in order to assess its value as a biomarker in this disease. Normal volunteers, coal miners smoking but without known lung diseases, and the patients with diverse pulmonary disorders served as comparison groups. A significant transtumoral gradient of N-POMC was found at surgery in 15 of 57 (26%) patients. Subjects without lung afflictions had significantly lower N-POMC levels than patients with pulmonary diseases (benign or malignant) only when the blood was drawn before breakfast. Furthermore, fasting levels in all subgroups of patients were higher at any time of the day than nonfasting ones. Finally, N-POMC levels did not decrease significantly after successful treatment of lung cancer (by surgery or chemotherapy) but were markedly higher after relapse. These results suggest that N-POMC, despite the fact that it cannot be used to discriminate lung cancer patients from controls, is a biomarker which may predict relapse in patients successfully treated by chemotherapy for their pulmonary neoplasm.

Adult↗
PubMed1988

N-myc oncogene RNA expression in neuroblastoma.

Tumor specimens from 33 patients with neuroblastoma were assayed for amplification of the N-myc oncogene and RNA expression to determine whether N-myc RNA expression levels correlated with N-myc gene amplification and clinical outcome. N-myc gene amplification was detected in one stage II tumor, one stage IV-S tumor, and seven stage III or IV tumors. In each case, N-myc RNA expression roughly paralleled N-myc gene amplification. However, enhanced N-myc RNA expression was not confined to tumors with N-myc gene amplification: all of the early (stage I and II) tumors, five stage IV-S tumors, and 12 advanced (stage III and IV) tumors had levels of N-myc RNA that were elevated up to 50-fold. While N-myc gene amplification correlated with prognosis, there was no such correlation with levels of N-myc RNA expression. The precise role of the N-myc gene in the pathogenesis of neuroblastoma remains unclear.

Adolescent↗
PubMed1988

Membrane excitability expressed in human neuroblastoma cell hybrids.

The voltage-sensitive Na+ channel is responsible for the action potential of membrane electrical excitability in neuronal tissue. Three methods were used to demonstrate the presence of neurotoxin-responsive Na+ channels in two hybrid cell lines resulting from the fusion of excitable human neuroblastoma cells with mouse fibroblasts. Only one of the two electrically active hybrid cell lines maintained the sensitivity of the neuroblastoma parent to tetrodotoxin (TTX). The other hybrid, although electrically active, was not responsive to TTX or scorpion venom. Comparisons of the patterns of expression of membrane excitability and of chromosome complements in these human neuroblastoma cell hybrids suggest that the phenotype of membrane excitability is composed of genetically distinct elements.

Action Potentials↗
PubMed1988

Activation of the 5-HT1A receptor subtype increases rat plasma ACTH concentration.

Serotonergic (5-HT) neuronal pathways regulate the release of adrenocorticotropin hormone (ACTH) from the pituitary gland probably through the action of hypothalamic corticotropin-releasing hormone (CRH). 8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), a selective 5-HT1A receptor agonist, dose dependently (0.016-3 mg/kg s.c.) increased rat plasma ACTH concentration. This response was blocked stereoselectively by (-)-pindolol, known to have 5-HT1 antagonist properties, but not by (+)-pindolol, beta 1-, beta 2- or alpha 1-adrenoceptor, dopamine, muscarinic, 5-HT2 or 5-HT3 receptor antagonists. Similar increases of plasma ACTH were induced by other 5-HT1A receptor ligands (buspirone, ipsapirone and gepirone). These results suggest that activation of the 5-HT1A receptor induces the secretion of ACTH from the rat pituitary gland.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1988

The 5-HT1A agonist 8-OH-DPAT increases consumption of palatable wet mash and liquid diets in the rat.

The 5-HT1A agonist 8-OH-DPAT, at a dose of 30 micrograms/kg, enhanced the consumption of sweetened wet mash and sweetened milk in non-deprived rats. In partially satiated rats, sensitivity to the hyperphagic effect of 8-OH-DPAT on wet mash intake was substantially increased, so that the minimally effective dose was reduced to 3 micrograms/kg. Similarly, 8-OH-DPAT was more efficacious in increasing milk intake in satiated rats. Thus, 30 and 40 micrograms/kg 8-OH-DPAT produced a 4-fold increase of milk intake in completely satiated rats compared to a 2-fold increase in partially satiated animals at a dose of 30 micrograms/kg. The increased intake of liquid and wet mash diets observed after treatment with low doses of 8-OH-DPAT argues against the involvement of non-specific gnawing in the increased consumption of solid food produced by the drug. Rather, the data suggest that 8-OH-DPAT may specifically stimulate appetite by counteracting a tonic serotonergic inhibition of feeding. The present experiments also showed that 8-OH-DPAT attenuates fenfluramine-induced anorexia which is thought to depend on increased serotonergic neurotransmission.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1988

Prenatal diagnostic options in cystic fibrosis.

There are currently two diagnostic options in cystic fibrosis. These involve assays for certain microvillar enzyme activities in amniotic fluid and recombinant deoxyribonucleic acid studies of markers linked to the cystic fibrosis gene on chromosome 7. The former are reduced in cystic fibrosis homozygotes; the latter make it possible to determine the particular pattern of chromosome 7 markers predictive of a cystic fibrosis homozygote in a specific family. However, neither test is appropriate for, applicable to, or informative in all families. The problems and potential of each approach are discussed.

Adult↗
PubMed1988

Relationship of increased food intake and plasma ACTH levels to 5-HT1A receptor activation in rats.

Various putative agonists of the 5-HT1A receptor subtype induce feeding in rats, probably by activating raphé somatodendritic 5-HT autoreceptors. These drugs also produce a marked increase in plasma concentrations of corticotropin (ACTH). In the present experiment we attempted to localize the site of action of 5-HT1A agonists on the secretion of ACTH and examined the relationship between 5-HT1A agonist-induced feeding and ACTH secretion. Rats were injected with either the high affinity 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) (0.016-1.0 mg/kg, s.c.) or the novel anxiolytics buspirone, gepirone or ipsapirone (2.0-16.0 mg/kg, s.c.), and either had their food intake measured 2 hr post injection or were sacrificed 30-40 min post injection for measurement of plasma ACTH. Plasma ACTH also was measured in rats pretreated with the serotonin synthesis inhibitor, para-chlorophenylalanine (PCPA) for three days (150 mg/kg, i.p. per day) and subsequently injected with 8-OH-DPAT (0.3 mg/kg, s.c.). As previously reported, the 5-HT1A agonists increased both food agonists increased both food intake and plasma ACTH concentrations. After 8-OH-DPAT, ipsapirone and gepirone the amount of food consumed was positively correlated with the concentration of plasma ACTH. No such correlation was evident following buspirone. PCPA pretreatment resulted in near total depletion of brain 5-HT content but had no effect on the ACTH rise induced by 8-OH-DPAT. Therefore, in contrast to the presynaptic site previously proposed for 5-HT1A agonist-induced feeding, the present results suggest a agonist-induced feeding, the present results suggest a postsynaptic location for the 5-HT1A receptor mediating ACTH release.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1988

Unilateral microscopic gonadoblastoma in a prepubertal Turner mosaic with Y chromosome material identified by restriction fragment analysis.

A high incidence of gonadal tumors has been demonstrated in patients with gonadal dysgenesis in the presence of Y chromosome material. A unilateral, microscopic gonadoblastoma was found in the dysgenetic gonad of a ten-year-old, phenotypic female, with Turner stigmata and chromosome mosaicisms of three cell populations 45,X/46,X,+mar,/47,X,+mar,+mar. It is often impossible to determine by cytogenetic analysis if the marker chromosome has derived from the X or Y chromosome. The origin of these marker chromosomes was elucidated by the use of DNA probe (pDP34) for male-specific sequences of the Y chromosome. The presence of Y-specific fragments in the patient's DNA led to surgical exploration and the detection of a gonadoblastoma.

Child↗