Fine-needle aspiration of the thyroid.
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Biomedical subjects
Publications and source records attributed to I Young.
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In the rat pineal gland, alpha 1-adrenergic agonists, which stimulate arachidonic acid release, also potentiate vasoactive intestinal peptide (VIP)- or beta-adrenergic-stimulated cyclic AMP (cAMP) and cyclic GMP (cGMP) accumulation. In this study, the possible involvement of the arachidonic acid pathway in the potentiation mechanism was examined in dispersed rat pinealocytes using two inhibitors of the arachidonic acid cascade, indomethacin and nordihydroguaiaretic acid. These two inhibitors appeared to have differential effects on the alpha 1-adrenergic potentiation of VIP- or beta-adrenergic-stimulated cAMP and cGMP responses. Whereas nordihydroguaiaretic acid was effective in suppressing both the alpha 1-adrenergic potentiation of VIP- or beta-adrenergic-stimulated cAMP and cGMP responses, indomethacin inhibited selectively the VIP-mediated cAMP and cGMP responses. The role of arachidonic acid metabolites was further determined using several prostaglandins--A2, I2, E2, and F2 alpha--and leukotrienes--B4, C4, and D4. Of the seven compounds tested, prostaglandins E2 and F2 alpha stimulated basal cAMP but not cGMP accumulation. The prostaglandin E2- and F2 alpha-stimulated cAMP responses were additive to those stimulated by VIP or beta-adrenergic receptors. The other five compounds had no effects on basal or VIP- or beta-adrenergic-stimulated cAMP or cGMP accumulation. Taken together, these findings indicate that the arachidonic acid cascade is likely involved in the alpha 1-adrenergic potentiation of VIP- or beta-adrenergic-stimulated cAMP and cGMP accumulation. However, the specific arachidonic acid metabolite involved in the potentiation mechanisms of VIP- versus beta-adrenergic-stimulated cyclic nucleotide responses may be different.
In rat pinealocytes, activation of alpha 1-adrenergic receptors leads to increases in intracellular pH (pHi). In this study, the role of pHi on adrenergic regulation of cyclic nucleotide accumulation was investigated using ammonium chloride, which increased pHi, and sodium propionate, which reduced pHi. Ammonium chloride significantly enhanced the norepinephrine-stimulated adenosine 3',5'-cyclic monophosphate (cAMP) and guanosine 3',5'-cyclic monophosphate (cGMP) responses, while it selectively potentiated the isoproterenol (ISO)-stimulated cGMP response. Reduction of pHi by sodium propionate reduced the norepinephrine-stimulated cGMP accumulation by 70%, and its effect on the ISO-stimulated cGMP response was stimulatory. Treatment with sodium propionate effectively neutralized the enhancing effects of ammonium chloride on the adrenergic-stimulated cAMP and cGMP responses. These effects of sodium propionate and ammonium chloride on cyclic nucleotides appeared to reflect altered rate of synthesis, and they were also in part secondary to changes in intracellular Ca2+. Our findings indicate that the receptor-mediated changes in pHi may play an integral part in the adrenergic regulation of cAMP and cGMP production in rat pinealocytes.
We present 2 cases of postoperative urinary retention associated with massive prostatic infarction after a complicated vascular operation. The pathophysiological principles involved in this entity are discussed.
The value of a new Home Detoxification service was assessed in a variety of ways employing data collected from 41 clients of the service, their family and GP's. By 60 days from the start of treatment, 11 clients were abstinent, two were controlling their drinking with relatively few problems, 13 had 'improved', 14 were not 'improved' and one had an unknown outcome. Subsequent involvement in treatment by both clients and their partners was high in comparison with other studies. Significant predictors of 'Good' outcome included attendance for after-care by client and by spouse/partner and a low Alcohol Problems Inventory score. High levels of satisfaction were expressed with the HD service by clients, their carers and GP's. The great majority of clients gave 'home' as their preferred place of treatment and nearly half claimed they would have been unwilling to accept hospital care. There was evidence of significant, though modest, shifts in GP's management practices towards less use of hospitals and greater use of the patient's home after 15 months of the programme.
This paper describes a 4-day module on health promotion which is part of the undergraduate programme for medical students at the University of Edinburgh. Early experience of the module from both the learner and teacher perspectives are reported. The module is part of a new 4-week course on community medicine for fourth- and fifth-year students and is a collaborative venture between people working in the field of health promotion in the University, the local health service and the national health education organization, the Scottish Health Education Group. The aims of the module, together with details about the content, teaching methods and form of assessment are described. Some of the formal evaluation results are presented. The module has proved highly popular with both students and teachers. The paper concludes with a discussion of the key factors that have been important in the successful development of the module.
Thirty-one patients with advanced malignant mesothelioma, previously untreated or having received only one prior cytotoxic regimen, were treated in a prospective, single-arm phase II trial with carboplatin (NSC 241240) at a dose of 150 mg/m2 per day intravenously (IV) for 3 days (450 mg/m2/course). One complete remission and four partial remissions were achieved, yielding an overall objective response rate of 16% (95% confidence interval [CI], 5.4% to 34%). The median duration of remission was 8 months (range, 5 to 17). Nonhematological toxicity was mild (only 12% with World Health Organization [WHO] grade 3 vomiting); 16% suffered WHO grade 3 to 4 hematological toxicity, but there were no life-threatening episodes and no treatment-related deaths. Carboplatin has modest activity against malignant mesothelioma and, because of its low toxicity, has a role in the management of this disease.
In rat pinealocytes, alpha 1-adrenergic receptor activation increases intracellular pH (pHi) through Ca2+/protein kinase-C-dependent activation of the Na+/H+ antiporter. Using a series of amiloride analogs, norepinephrine stimulation of cGMP accumulation is also found to be pHi dependent. In this study, we examined the postreceptor mechanisms involved in the amiloride effects on cyclic nucleotide accumulation using agents that simulate alpha 1-adrenoceptor activation. Four amiloride analogs, with a 500-fold difference in their inhibitory potency of the Na+/H+ antiporter, were used. 5-(N,N-Hexamethylene)amiloride (HA), the most active inhibitor of the Na+/H+ antiporter, had a stimulatory effect on isoproterenol (ISO)-stimulated cAMP, while its effect on cGMP was inhibitory. The other three amiloride derivatives had no effect on the ISO-stimulated cAMP or cGMP responses. All four amilorides (at 10 microM) had no effect on the phenylephrine potentiation of cAMP responses in beta-adrenergically stimulated cells, while they inhibited the potentiation of cGMP accumulation according to their inhibitory potency on the Na+/H+ antiporter. Using depolarizing concentrations of K+, it was found that HA was additive to the submaximal potentiation by K+ on ISO-stimulated cAMP, while its effect on cGMP was inhibitory. Amiloride hydrochloride dihydrate, the amiloride that is least potent in its inhibitory action on the Na+/H+ antiporter, had no effect on the K+ potentiation of either cAMP or cGMP. Using 4 beta-phorbol 12-myristate 13-acetate in cells treated with 10 mM K+ and ISO, it was found that HA was additive to phorbol 12-myristate 13-acetate and K+ potentiation of the cAMP response, while its effect on the cGMP response was inhibitory. Amiloride hydrochloride had no effect on either the cAMP or cGMP response. It can be concluded from these studies that 1) HA has a stimulatory effect on the beta-adrenoceptor-Gs-adenylate cyclase pathway that is independent of inhibition of the Na+/H+ antiporter; 2) postreceptor mechanisms are involved in HA's effects on cAMP and cGMP accumulation; and 3) the action of HA on cGMP is likely to be related to its effect on the Na+/H+ antiporter.
Incompletely and even adequately clipped berry aneurysms are often reinforced with finely shredded gauze. In seven female patients this practice led to a series of events including headache, pyrexia, seizures, cranial nerve deficits, endocrinopathy, cerebrospinal fluid pleocytosis, and an enhancing mass demonstrated by computerized tomography at the aneurysm site. One patient with blindness, hydrocephalus, and panhypopituitarism died and was examined at autopsy. Three additional female patients have been identified in the literature with similar case histories. It is suggested that in these patients the gauze induced a foreign-body granuloma, accompanied by progressive occlusion of neighboring small arteries. It would seem prudent to reserve gauze reinforcement for aneurysms that cannot be securely obliterated surgically.
The murine serum amyloid A1 (SAA1), SAA2, and SAA3 genes are expressed in various tissues in response to acute inflammation. Prolonged expression may be accompanied by amyloid deposition in liver, spleen, and kidney. Shortly before and during deposition, an amyloid-enhancing factor (AEF) can be extracted from these tissues which accelerates amyloid formation when administered with an inflammatory agent. We have investigated the ability of liver AEF to alter expression of the three SAA genes in liver, spleen, and kidney when administered to normal mice or to mice in which inflammation was created with the injection of silver nitrate. In liver, both AEF and silver nitrate induce SAA1 and SAA2 mRNA accumulation. However, AEF elicits a more rapid response and also acts as a potent inducer of hepatic SAA3 mRNA. Silver nitrate does not induce any SAA mRNA species in kidney, whereas AEF induces all three species. In contrast, AEF induces only SAA3 mRNA in the spleen. We also show that the elevation in hepatic SAA mRNA levels induced by either AEF or silver nitrate is associated with a transient increase in the length of the poly(A) tail.
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Using pilot-scale production of our present factor IX (II and X) concentrate, we have studied the effects of starting plasma source and processing parameter on two in-vitro indicators of product quality - yield and thrombogenic potential. Plasma source did not affect factor IX yield but had a marked effect on thrombogenic potential. Factor IX concentrates produced from plasma derived through centrifugation-based technology showed significantly higher thrombogenic potential than products derived from plasma derived through a filtration-based system. Removal of Cohn fraction I prior to ion-exchange chromatography resulted in a drop in factor IX yield and thrombogenic potential, as did heat treatment to 80 degrees C for 72 h. We conclude that a membrane-filtration-based plasmapheresis system may be the preferred method of plasma procurement for factor IX concentrate production.
Primary carcinoids of the kidney are very rare, only 10 cases having been reported in the literature. The authors report a case of primary renal carcinoid in a 50-year-old woman. A radical nephrectomy with lymphadenectomy was successfully performed and there was no residual or recurrent tumour at 2-year follow-up. A review of the reported cases revealed a variable, nonspecific presentation. Most laboratory tests were non-contributory except for urinalysis. When a renal carcinoid is diagnosed, a search should be made for a possible primary elsewhere. Primary renal carcinoid does exhibit malignant behaviour. It should be managed by radical nephrectomy with retroperitoneal lymphadenectomy.
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Two-hundred and fifty discrete lesions of the lung and mediastinum were sampled by a modified fine-needle aspiration biopsy (FNAB) technique. Aspirates were collected directly into 15 ml of Saccomanno's fixative, and all preparative work was carried out in the cytopathology laboratory. Only seven aspirates were "insufficient for diagnosis," giving a productivity rate of 97%. Five insufficient aspirates later proved to be neoplasms. Of the 243 cases with a primary FNAB diagnosis, 21 had insignificant disease, 29 had benign neoplasms or nonneoplastic disease, and 193 had malignant tumors. Most malignancies could be assigned to a specific histologic type by FNAB; those that proved difficult by FNAB were usually difficult on histopathologic examination. There were no false-positive diagnoses of malignancy and only eight false-negative results. Of 12 results interpreted as "suspicious," 10 proved to be malignant on follow-up. This modified method has proven to have a low complication rate and to be both highly productive and reliable in the diagnosis of malignant and nonmalignant disease.
To determine how starvation affects adrenal steroidogenesis we measured the activities of 3 adrenal enzymes involved in corticosterone biosynthesis in a group of adult female rats. The animals were either starved for 7 days or fed ad libitum for the same period. Relative adrenal weight and plasma corticosterone levels were increased in the experimental group of animals compared to the control group (40 +/- 2 vs 27 +/- 1 mg/100 g body weight, P less than 0.001, and 45 +/- 4 vs 30 +/- 5 ng/dl, P less than 0.05 respectively). There were no differences in plasma ACTH levels between the groups (34 +/- 5 vs 26 +/- 4 pg/ml). 11-Hydroxylase activity was increased in the starved group of animals (18 +/- 3 vs 8 +/- 2 nmol/mg protein/min, P less than 0.01). 3 beta-Hydroxysteroid dehydrogenase and 21-hydroxylase activities were not different between the groups (19 +/- 2 vs 16 +/- 1 nmol/mg protein/min, and 100 +/- 10 vs 110 +/- 10 pmol/mg protein/min respectively). These results suggest that acute starvation in rats produces an increase in adrenal 11-hydroxylase activity.
Sixty-five patients with small cell lung cancer were treated with VP16, vincristine, cyclophosphamide, and doxorubicin (VOCA) intravenously at three-week intervals. Patients with limited disease received four cycles with responders receiving radiation to the primary site and prophylactic cranial irradiation. Patients with extensive disease received chemotherapy only. Of 59 patients evaluable for chemotherapy response, eight (14%) achieved complete remission and 30 (51%) partial remission. Major side-effects included myelosuppression, alopecia, nausea, and vomiting. Reinduction with VOCA at relapse yielded objective or subjective response in four of seven patients. This regimen is active in small cell lung cancer and was well tolerated by patients. Reinduction of response was possible in a small number of patients retreated and may provide useful palliation for those who relapse when treatment is discontinued.
The localisation of the gene for Hunter syndrome (MPS II) has been studied in 11 families using 12 polymorphic DNA markers, one on the short arm and the remaining 11 located at various points on the long arm of the X chromosome. Lod scores for seven probes were uniformly negative for all values of theta; positive scores at values of theta = 0.10 or more were obtained for the five probes located most distally on the long arm (52A, F9C, DX13, St14-1, F8C). Current data suggest the most likely order of the loci to be: 52A, F9C, Hunter, DX13, St14-1, F8C-qter; the Hunter locus may thus be close to that for the fragile site at Xq27.