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Biomedical subjects

S M Webb

Publications and source records attributed to S M Webb.

At least 37 records · Page 2Linked to original sources
PubMed1999

Biochemical liver abnormalities in Turner's syndrome.

BACKGROUND: Turner's syndrome is a chromosomal abnormality (45X0) which may be associated with various autoimmune disorders and disease conditions; however, association with liver pathology has rarely been reported. OBJECTIVES: The aim of this work was to assess liver function abnormalities in a group of adult patients with Turner's syndrome. DESIGN AND METHODS: Liver function tests were performed in 16 women with Turner's syndrome all of whom had been previously treated with oestrogens. Patients with liver abnormalities were further studied with hepatic ultrasonography, serological markers of viral hepatitis and autoantibody determinations. RESULTS: Seven women (43.7%) presented with asymptomatic liver cholestasis; these patients were older than those with normal biochemical values (33.4+/-5.2 vs 24.7+/-5.7 years, P<0.05). Liver function abnormalities appeared 7.8+/-4.9 years after starting oestrogen therapy; however, no improvement of liver function was observed 20+/-17.7 months after stopping treatment. All of these women were anti-HCV and HBsAg negative, and autoimmune hepatitis was ruled out in all cases. Liver ultrasound only disclosed homogeneous liver enlargement in one case and cholelithiasis without bile duct abnormalities in another. Four patients underwent a percutaneous liver biopsy of which two were normal and two showed minimal non-specific changes. CONCLUSIONS: The incidence of biochemical liver cholestasis in this group of patients with Turner's syndrome is high. Oestrogen therapy and autoimmune disorders do not seem to be the responsible causes. It appears that this is a benign condition which does not seem to reflect any substantial liver dysfunction. The aetiology remains uncertain.

Adult↗
PubMed1999

Recovery of hypopituitarism after neurosurgical treatment of pituitary adenomas.

Surgery is the treatment of choice for many pituitary tumors; pituitary function may suffer after operation, but relief of pressure on the normal pituitary may also favor postoperative recovery of hypopituitarism. The aim of this study was to investigate the frequency of new appearance and recovery of hypopituitarism after neurosurgery and try to identify features associated with it. Pre- and postoperative anterior pituitary functions were investigated in 234 patients with pituitary adenomas (56 nonfunctioning, 71 PRL-secreting, 66 GH-secreting, 39 ACTH-secreting, 1 LH/FSH-secreting, and 1 TSH-secreting tumors). Eighty-eight new postoperative pituitary hypofunctions appeared in 52 patients (12 NF, 14 PRL-secreting, 15 GH-secreting, 10 ACTH-secreting, and 1 LH/FSH-secreting adenomas). They corresponded to 27% ACTH deficiencies (in 29 of the 107 patients with normal preoperative ACTH in whom postoperative evaluation was complete), 14.5% (15 of 103) new GH deficiencies, 10.5% (15 of 143; P < 0.0005, significantly less than ACTH deficiency) new TSH deficiencies, 16.5% (20 of 121) new gonadotropin deficiencies, and 13% (9 of 71) new PRL deficiencies. Preoperatively, 93 were deficient in at least 1 pituitary hormone; after surgery, 45 (48%) recovered between 1 and 3 hormones. The 2 patients with LH/FSH- and TSH-secreting macroadenomas did not recover pituitary function. Factors associated with a higher probability of postoperative pituitary function recovery were: no tumor rests on postoperative pituitary imaging (P = 0.001) and no neurosurgical (P = 0.001) or pathological evidence (P = 0.049) of an invasive nature. Tumor size did not differ significantly between those who did and those who did not recover pituitary function after surgery. Even if clear hypofunction is observed at initial work-up, patients should be reassessed after surgery without substitution therapy, because practically half the preoperative pituitary hormone deficiencies recover postoperatively, eliminating the need for life-long substitution therapy.

Adenoma↗
PubMed1999

Observational study in adult hypopituitary patients with untreated growth hormone deficiency (ODA study). Socio-economic impact and health status. Collaborative ODA (Observational GH Deficiency in Adults) Group.

OBJECTIVE: The aim of the present study was to assess the socio-economic impact at baseline and after one year of follow-up of clinical and health status characteristics and laboratory tests of adult-onset GH deficiency (AGHD), a well-known clinical entity, in a large group of Spanish hypopituitary patients with untreated AGHD. DESIGN AND METHODS: A total of 926 eligible patients with GHD (GH </= 5 ng/ml after stimulation) and at least one further pituitary hormone deficiency were retrospectively studied; 356 of these were followed for one year. Complete physical examination, IGF-I, lipid and routine biochemistry measurements and health-related quality of life (HRQoL) with the specific QoL-Assessment of Growth Hormone Deficiency in Adults (AGHDA) questionnaire were assessed at baseline and at 12 months in the prospective study. Health status and health-economic evaluation were measured by a specific questionnaire and a patient diary and compared with Spanish population study results. RESULTS: Clinical characteristics and laboratory tests of AGHD showed a higher incidence of cardiovascular risk factors and mortality compared with the general population (hypercholesterolaemia in 29% vs 18% and hypertension in 22.1% vs 14. 9%). QoL-AGHDA scores for patients were significantly worse (P<0.01) and direct health costs were higher than in the general population. CONCLUSIONS: Hypopituitary GHD adults had more cardiovascular risk factors, higher mortality, worse HRQoL and higher absolute health costs than the general population in Spain.

Adult↗
PubMed1998

Reversible endocrine dysfunction and pituitary stalk enlargement.

We report 4 patients (3 of which were children) with diabetes insipidus and different degrees of hypopituitarism in whom a pituitary stalk enlargement was disclosed on imaging techniques, and in whom radiological and functional recovery was observed during follow-up. Pituitary substitution therapy with desmopressin, thyroxine, hydrocortisone, growth hormone and/or oral contraceptives was prescribed. During follow-up, regression of the stalk lesion was seen which was spontaneous in 2 cases, following a short course of corticosteroids in another and an empirical trial of tuberculostatic drugs in the fourth. A partial recovery of pituitary function was also observed. These cases illustrate that pituitary stalk enlargement and associated hypopituitarism may be reversible; however, this morphological and functional recovery has rarely been described in adults and has not been previously reported in children.

Adolescent↗
PubMed1998

Study of glucose tolerance in consecutive patients harbouring incidental adrenal tumours. Study Group of Incidental Adrenal Adenoma.

OBJECTIVE: Clinically silent cortisol hypersecretion has been frequently observed in recent series of adrenal 'incidentalomas'. A significant body of data indicates that a spectrum of cortisol excess exists. Up to 90% of patients with cortisol hypersecretion are glucose intolerant. The aim of this study was (1) to assess glucose tolerance in consecutive patients with 'nonfunctioning' adrenal adenomas, and (2) to study the influence of the status of the hypothalamo-pituitary-adrenal axis (HPAA) on carbohydrate tolerance. PATIENTS AND METHODS: Sixty-four consecutive patients with nonfunctioning adrenal adenomas (non-hypersecretory) diagnosed between September 1995 and July 1996 in five hospitals were included in the study. The prevalence of glucose intolerance or diabetes mellitus was determined with an oral glucose tolerance test (oGTT) according to the recommendations of the National Diabetes Data Group. Twenty-three consecutive unselected patients diagnosed with 'nonfunctioning' adrenal adenoma were enrolled in a study to determine the influence of HPAA status on carbohydrate tolerance. In these patients, in addition to basal and post-dexamethasone serum and urinary free cortisol concentrations, assessment of peripheral sensitivity to insulin (estimated during the oGTT according to a previously validated method) and adrenal sensitivity to ACTH (calculated from the CRH test) were performed. RESULTS: Twenty-five patients were considered to have normal glucose tolerance (95% confidence interval (95% CI) for the mean of 2 h glucose, 5.5-6.5 mmol/l); 17 showed glucose intolerance (95% CI 8.5-9.3 mmol/l); and 22 were classified as having diabetes mellitus (95% CI 12.1-14.6 mmol/l), including six patients with previously known diabetes mellitus. These three groups were comparable in age, sex, body mass index, waist-hip ratio and concomitant diseases. Thus, the prevalence of disturbed glucose tolerance was 39/64 (61%), well above the prevalence of NIDDM described in a population of similar age in our area. Among the 23 patients included in the study of HPAA status, the size of the tumour correlated with serum cortisol after dexamethasone (DXM) (r = 0.52, P < 0.01) and 24-h urinary free cortisol (UFC) after DXM (r = 0.55, P < 0.01), and negatively with DHEAs (r = -0.42, P = 0.04). The area under the curve for ACTH after hCRH (AUCacth) correlated negatively with both UFC (r = -0.40, P = 0.04) and serum cortisol after dexamethasone (r = -0.47, P = 0.02). The degree of peripheral sensitivity to insulin (SI) positively correlated with adrenal sensitivity (r = 0.56, P = 0.005). CONCLUSIONS: A high prevalence (61%) of disturbed glucose tolerance was found among consecutive patients harbouring incidental 'nonfunctional' adrenal adenomas. Therefore, patients with incidental adrenal tumours should be tested for glucose tolerance. The positive correlation between insulin sensitivity and adrenal sensitivity to ACTH suggests that, in these patients, insulin resistance hampers ACTH action at the level of the adrenal.

Adenoma↗
PubMed1998

Somatostatin and somatostatin receptor subtype gene expression in medullary thyroid carcinoma.

The possible existence of an autocrine/paracrine role for SRIF in normal and neoplastic thyroid parafollicular C cells has supported the use of SRIF analogues in the treatment of patients with medullary thyroid carcinoma (MTC). In this study, we have investigated the expression of SRIF by immunohistochemistry and RT-PCR, and the expression of SRIF receptor (SSTR) subtypes by RT-PCR, in a series of 14 MTCs. SRIF messenger RNA was detected in all cases, although immunoreactive cells were only identified in 8. SSTR messenger RNA was present in 12 out of the 14 tumors. Expression of more than 1 SSTR subtype was detected in 10 tumors. SSTR2, the subtype that preferentially binds to the SRIF analogue octreotide, was the subtype most frequently detected, whereas SSTR4 was not detected in any case. These results confirm the frequent expression of both SRIF and its receptors in MTC. The presence of different combinations of SSTR subtypes in a given patient may explain the variable clinical response to SRIF analogues and may promote the search for more selective drugs with different affinities to the various receptor subtypes.

Adolescent↗
PubMed1997

Myocardial damage does not occur in untreated hyperthyroidism unless associated with congestive heart failure.

Even in the absence of underlying cardiac disease, hyperthyroidism has seldom been reported to be associated with left ventricular dysfunction and congestive heart failure. The left ventricular function invariably improves with achievement of euthyroid status. Anecdotal autopsy reports have suggested that myocardial necrosis associated with hyperthyroidism may be responsible for congestive heart failure. This study prospectively evaluates the role of myocardial necrosis in untreated hyperthyroidism by imaging with Indium-111 antimyosin antibody. Thirteen consecutive patients (7 men and 6 women, mean age 36 +/- 11 years) with hyperthyroidism and Graves' disease (10 patients), subacute thyroiditis (2 patients), or multinodular goiter (1 patient) formed the basis of the study. The T4 levels ranged from 33 to 183 pmol/L (mean 103 +/- 47 pmol/L) and cardiac output from 5.47 to 11.0 L/min (mean 7.17 +/- 1.75 L/min). Two patients had clinical congestive heart failure and mildly depressed left ventricular ejection fraction. Both patients had scintigraphic evidence of myocardial damage with abnormal antimyosin scans. In the remaining 11 patients with normal left ventricular ejection fraction, no antimyosin uptake was observed. The reevaluation of two patients with abnormal initial scans 6 to 8 months after treatment revealed euthyroid status, resolution of antimyosin uptake, and normalization of left ventricular function. This study indicates that myocardial necrosis may be detected in a small proportion of patients with hyperthyroidism, which could contribute to left ventricular systolic dysfunction.

Adult↗
PubMed1997

Circannual somatostatin gene and somatostatin receptor gene expression in the early post-natal rat pineal gland.

The origin of somatostatin in the pineal gland is controversial as a double origin - neural in pinealopetal nerve fibers and parenchymal corresponding to locally synthesized peptide - is suggested. We have investigated the ontogeny and possible circadian and circannual variations of somatostatin and somatostatin receptor gene expression in the rat pineal gland using RT-PCR. Somatostatin gene expression was observed in the pineal of animals up to 15 days of postnatal life in autumn and winter, but not in prepubertal or adult rats; no transcript was detected during spring and summer at any age and a circadian rhythm was only detected in 15-day-old rats. In situ hybridization confirmed these results. The transcript of the somatostatin receptor gene (SSTR2) was detected at all ages studied with no seasonal variations in its expression, indicating separate regulatory mechanisms. In conclusion, somatostatin and somatostatin receptor mRNAs are expressed in the neonatal rat pineal with circadian and seasonal variations.

Animals↗
PubMed1996

Expression of the somatostatin gene and receptors in the rat harderian gland.

Somatostatin is one of the numerous peptides described in the Harderian gland of different animals. With the aim of trying to elucidate its physiological role, we investigated whether this peptide is expressed in OFA rat Harderian gland at different ages and seasons and, if so, studied the regulatory proteins involved in the activation of the somatostatin gene, and also whether it contains any somatostatin receptors. Nursing (4-15-day-old), prepubertal (21-30-day-old), and adult (54-day-old) OFA rats were sacrificed by decapitation throughout the year, and the Harderian glands were excised and immediately frozen in liquid N2. The expression of somatostatin and its receptors was investigated using RT-PCR techniques; additionally, the existence of proteins which bind to cAMP responsive elements (CRE) was investigated using a band-shift technique. The somatostatin gene was expressed in the Harderian gland of rats aged 4-30 days in autumn and winter but not in spring and summer or in older animals. However, the somatostatin receptor was expressed throughout the year at all the ages studied. In the autumn, nuclear proteins binding to CRE (CREB) were present in 8-10-day-old rats but not in younger 4-day-old animals. We conclude that rat Harderian gland cells transcribe the somatostatin gene depending on the season and age of the animals, while its receptor is always present at all the ages studied; the CREB found produces the same retardation complex as ICER (inducible cAMP early repressor), an isoform of CREM (cAMP responsive element modulator), which in the pineal has been shown to be under adrenergic control. Since somatostatin expression is regulated by cAMP mechanisms, it is feasible that the existence of this repressor ICER could explain why somatostatin expression disappears in adult animals once maturation is complete.

Aging↗
PubMed1996

Bronchial carcinoid tumor presenting as a thyroid nodule: an unusual clinical manifestation.

Although rare, carcinoid tumors may present as thyroid metastatic nodules. We describe two patients with an undiagnosed bronchial carcinoid tumor, who presented as a thyroid nodule. Pathological examination of these nodules was diagnostic. Chemotherapy was indicated despite the dissemination of the tumors. The patients have an excellent quality of life. They are asymptomatic and alive, 18 and 24 months after diagnosis, respectively. In one case, chemotherapy obtained an important reduction in the size of the tumoral lesions but the other case showed no regression. Octreotide (SMS 201-995) was used in the case with carcinoid syndrome, with an excellent response.

Adult↗
PubMed1996

Cushing's disease and pregnancy: report of six cases.

We describe six pregnancies in five patients with Cushing's disease --four had undergone transsphenoidal surgery, with improvement but no cure of their hypercortisolism; the other woman became pregnant during initial work up. At conception, none of the patients were receiving specific treatment for hypercortisolism. Mean free urinary cortisol (FUC) prior to pregnancy was 430 nmol/24 h (normal range: 51-280). In two patients, FUC throughout pregnancy increased significantly, but no clinical progression was observed. FUC measured in 20 healthy pregnant women was found to rise above the normal non-pregnant range ( < 280 nmol/24 h) in the second (mean +/- 2 S.D. = 463 +/- 256 nmol/24 h; P < 0.01) and third trimester (424 +/- 210 nmol/24 h; P < 0.05). However, in the Cushing patients values were higher. Two pregnancies ended in spontaneous abortions, one resulted in an ectopic pregnancy, and the remaining three were followed to term of which one developed third trimester gestational diabetes, and her baby developed neonatal sepsis which resolved uneventfully. We conclude that despite high abortion and ectopic pregnancy rates, a remarkably uneventful and uncomplicated outcome with no clinical progression of cushingoid symptoms, was observed in two of the three pregnancies followed to term, despite significant increases in FUC.

Adrenocorticotropic Hormone↗
PubMed1996

Thirty years of human pineal research: do we know its clinical relevance?

A role for melatonin in humans is becoming evident in an increasing number of clinical situations. Marked variations in the magnitude of the nocturnal melatonin peak are observed throughout the human lifespan. The highest levels occur in children and then fall during puberty and further during adulthood. A negative correlation between circulating melatonin and sex steroids has been observed in a number of instances, and appears to be independent of concomitant gonadotrophins. No clear melatonin pattern has been observed in pituitary tumors, but in large lesions that involve the hypothalamus, a reduced nocturnal rise has been reported. Reported effects of exogenously administered melatonin are variable, probably reflecting differences in dose and timing; a slight stimulation of prolactin, as well as a partial inhibition of gonadotrophins, has been reported, which explains its utility as an oral contraceptive, associated with a progestogen. A potential clinical use of melatonin as an oncostatic drug still awaits confirmation, although experimental data firmly support this possibility. The indole has also been used to hasten entrainment of subjects travelling across various time zones, and has been found to be specially useful in eastward travel. Finally, changes in the normal melatonin circadian pattern have been reported in psychiatric diseases and in sudden infant death syndrome.

Adult↗
PubMed1996

Flow cytometry analysis of pituitary adenomas.

UNLABELLED: Using flow cytometry, DNA content and index, and/or proliferative capacity (measuring proliferating cell nuclear antigen PCNA) in operated pituitary tumors, control pituitaries obtained at necropsy, and experimental pituitary hyperplasia induced in rats were analyzed. Simultaneous measurement of cell ploidy and proliferation differentiated normal pituitary (diploid DNA index and negative PCNA) from pituitary hyperplasia (diploid DNA index with intensely positive PCNA, between 30 and 72% of cells). In the tumors 83% (19/ 23) were positive for PCNA (between 3 and 84%) and 73% (17/23) aneuploid; only 1 tumor was diploid and negative for PCNA. CONCLUSIONS: Differentiation between normal and abnormal (neoplastic or hyperplastic) pituitary is possible by flow cytometry, but in the adenomas no correlation with postoperative clinical outcome was observed.

Adenoma↗
PubMed1995

A gonadotrophin dependent stromal luteoma: a rare cause of post-menopausal virilization.

A stromal luteoma is an uncommon ovarian tumour in post-menopausal women, which presents rarely with hyperandrogenism and virilization. We present the case of a 64-year-old woman referred for evaluation of virilization which had developed over 5 years. Testosterone, FSH and LH were markedly inhibited following the administration of a GnRH analogue, suggesting a gonadotrophin dependent, testosterone secreting ovarian tumour, which could not be localized with imaging techniques. Surgery revealed normal sized ovaries with no apparent lesions, but microscopic examination showed a small stromal luteoma in the right ovary and severe stromal hyperthecosis in the adjacent and contralateral ovarian stroma. We conclude that stromal luteoma is an uncommon cause of virilization in post-menopausal women. This case illustrates, to our knowledge for the first time, that a stromal luteoma is not autonomous but is gonadotrophin dependent.

Depression, Chemical↗
PubMed1995

In vivo and in vitro flow cytometry comparative analysis of somatostatin-positive cells in the pineal gland of the neonatal rat.

Flow cytometry was used for comparative in vivo and in vitro analysis of cell populations staining positively for somatostatin. Experiments were carried out with pineals obtained from neonatal, 8- and 15-day-old rats. Pineal cells were obtained by dispersion with collagenase and then processed in a flow cytometer or maintained in culture for 1 or 2 weeks. Identification of somatostatin-immunopositive cell populations was performed using a polyclonal somatostatin antibody and confirmed by indirect immunostaining of cytospun smears with the avidin-biotin-peroxidase method. In vivo, the percentage of somatostatin-positive cells was 60.6 +/- 4% in neonatal pineals and declined to 22.2 +/- 11% in 15-day-old animals (p < 0.04). The density of peptide immunostaining decreased in 8-day-old animals but recovered to the neonate levels in 15 day-old animals; homogeneity in the immunopositive population increased with age. Maintenance in culture for 1 week resulted in an increase in positive somatostatin staining in animals of 8 and 15 days with no changes in neonates; however, after 2 weeks of culture, the percent of immunopositive cells decreased from 53.3 +/- 6 to 12.2 +/- 4% in the older animals and remained unchanged in neonates. We conclude that somatostatin is found in pinealocytes and shows a declining pattern during the perinatal period; this probably implies that the peptide plays a paracrine role important for cell differentiation in these young animals, since maximal cellularity and a high mitotic index occur within the first 3 days of life, and pineal cell differentiation is completed before the end of the third week of extrauterine life.

Age Factors↗