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Biomedical subjects

S L Atkin

Publications and source records attributed to S L Atkin.

At least 73 records · Page 4Linked to original sources

Multiple cerebral haematomata and peripheral nerve palsies associated with a case of juvenile diabetic ketoacidosis.

A 15-year-old girl presented de novo in diabetic ketoacidosis having been comatose for 24 h (day 1). A CT scan and lumbar puncture performed on admission were normal and her conscious level slowly improved over several days. On day 7 she had central neurological signs of bilateral knee clonus and an extensor plantar response. In addition, she had developed lower motor neurological signs of an ulnar nerve palsy of the left forearm, and ulnar, median, and radial nerve palsies of the right forearm. Magnetic resonance imaging (MRI), performed on day 12, showed multiple small cerebral haematomata with appearances at least several days of age. The scattered lesions were localized particularly to the parieto-occipital region, with sparing of the basal ganglia and without cerebral oedema, a novel feature not previously described in juvenile ketoacidosis. Four months later there was minimal residual disability of her right arm. The clinical findings together with the MRI images suggested that the peripheral nerve and central lesions were temporally related, suggesting a common aetiology. However, it is likely that MRI showed cerebral lesions which may have been missed by the conventional CT scanning performed initially.

Adolescent↗

Effects of basic fibroblastic growth factor on the function and proliferation of human clinically non-functional pituitary adenomas which secreted glycoprotein hormones in vitro.

The effects of human recombinant basic fibroblastic growth factor (bFGF) on the secretion, viability, proliferation, attachment and morphology of ten dispersed human clinically non-functional (NF) adenomas were examined in vitro. Four clinically NF adenomas secreting FSH and/or LH in vitro were unaffected by 10 nM bFGF over a 4-h period. Over 4 days 10 nM bFGF stimulated LH secretion (66% and 72%, P < 0.01) from two out of seven clinically NF adenomas secreting LH, whilst FSH (three tumours) and alpha-subunit secretion (three tumours) were unaffected. One adenoma co-secreting LH and alpha-subunit and one secreting LH alone were studied over 21 days; LH secretion fell progressively, but the decline was significantly less (P < 0.05) with bFGF (10 nM) treatment after 14 and 21 days in both adenomas, whilst the fall in alpha-subunit secretion was unaffected by bFGF treatment. A 24-h GnRH test performed at the start and end of the 21-day period in one of these tumours showed an increase in both basal and stimulated LH secretion in the bFGF-treated group over control (124%, P < 0.001). There was no effect of bFGF (10 nM) on viability, S-phase proliferation, attachment or morphology of adenoma cells over a 4-day period. These results suggest that bFGF has a role in tumorous LH secretion from these adenomas, but is not mitogenic (at least over 4 days) and is without effect on other parameters of in vitro differentiated function.

Adenoma↗

Hyperthyroidism secondary to a pituitary adenoma secreting TSH, FSH, alpha-subunit and GH.

A 51-year-old man had been treated for hyperthyroidism with antithyroid drugs for 8 years. He was then found to have a large pituitary adenoma with biochemical evidence of overproduction of TSH, FSH and alpha-subunit. Subsequent immunocytochemical and tissue culture studies confirmed secretion of these hormones. In addition, the tumour stained for GH and was capable of GH production in vitro. This combination of hormones produced by a pituitary adenoma has not been previously reported.

Adenoma↗

Effects of insulin-like growth factor-I on growth hormone and prolactin secretion and cell proliferation of human somatotrophinomas and prolactinomas in vitro.

OBJECTIVE: IGF-I inhibits GH secretion from normal and some tumorous pituitary tissue, and has been shown to be mitogenic for gonadotrophinoma cells in vitro. It is not known whether IGF-I affects somatotrophinoma cellular proliferation or the secretion of other hormones, such as PRL and alpha-subunit, which are often co-secreted by these tumours. We have therefore examined the effects of IGF-I on proliferation and hormonal secretion of human somatotrophinomas and prolactinomas in vitro. DESIGN: Pituitary adenoma tissue was dispersed to single cells in monolayer culture. The effects of 100 nM IGF-I on GH, PRL and alpha-subunit secretion were determined over 4-hour and over 4-day periods, and a 4-day dose-response study using 1-100 nM IGF-I was performed on two tumours. Adenoma cell S-phase proliferation was determined after bromodeoxyuridine incorporation for 1 hour after 4 days, using a double immunostaining method. RESULTS: Over 4 hours, 100 nM IGF-I had no effect on GH, PRL or alpha-subunit secretion in 7 tumours. Over 4 days, 100 nM IGF-I reduced GH secretion in 5/8 somatotrophinomas (range 17-84%, P < 0.05) compared to controls, with tumours responding to IGF-I having lower basal serum and in-vitro GH levels than tumours unaffected by IGF-I (P < 0.05). There was no effect on alpha-subunit secretion in any of the three tumours studied. PRL cosecretion was increased in 3/5 somatotrophinomas compared to control (20, 30 and 37%, P < 0.05), with tumours responding to IGF-I being associated with lower basal serum and in-vitro PRL levels than those tumours unaffected by IGF-I. IGF-I also increased PRL secretion in 2/2 prolactinomas (27 and 32%, P < 0.05) compared with control. GH was inhibited and PRL secretion was stimulated by 1 and 10 nM IGF-I in the two dose-response studies. The proliferative labelling index did not exceed 1.9% in any tumour and no proliferative effect was found with 100 nM IGF-I in any somatotrophinoma. CONCLUSION: IGF-I inhibited tumorous GH in 62% and stimulated PRL secretion in 71% of tumours over 4 days, without affecting alpha-subunit secretion or being mitogenic for somatotrophinoma cells in vitro. No hormonal effects were observed over short (4-hour) incubations. IGF-I may be a newly recognized factor directly stimulating tumorous PRL secretion.

Adenoma↗

Pituitary apoplexy and sudden blindness following the administration of gonadotrophin releasing hormone.

Pituitary apoplexy has been reported as a rare complication of combined tests and of TRH administration in prolactinomas. A 54-year-old man with a pituitary macroadenoma had a single injection of 100 micrograms GnRH. Twenty minutes later he complained of increasing headache and vomited. These symptoms settled spontaneously and were attributed to the pharmacological effects of GnRH. Five hours later he was found to be blind and disorientated without spontaneous complaint. Emergency CT showed a large adenoma with central necrosis, consistent with pituitary apoplexy. An urgent surgical decompression was carried out and necrotic haemorrhagic debris removed. Baseline bloods revealed non-pulsatile FSH of 40 U/l with LH 0.3 U/l with no hormonal response to GnRH administration, but the sequence of events strongly suggests a causal relationship between this and pituitary apoplexy. To our knowledge this is the first time that GnRH administration has been associated with pituitary apoplexy of a glycoprotein secreting pituitary adenoma.

Adenoma↗

Basic fibroblastic growth factor stimulates prolactin secretion from human anterior pituitary adenomas without affecting adenoma cell proliferation.

The effects of human recombinant basic fibroblastic growth factor (bFGF) on the secretion and/or proliferation of 26 human anterior pituitary adenomas secreting PRL alone (6 tumors), PRL and GH (18 tumors), or GH alone (2 tumors) were examined. Secretory studies were performed over 4 h, 4 days, and 21 days, and proliferation studies over 4 days. The acute effect of bFGF on secretion over 4 h was examined in 10 tumors. bFGF (10 nmol/L) increased PRL compared to that in controls (100%) in 2 tumors (126% and 290%; P < 0.05) and PRL and GH in a third tumor (183% and 133%, respectively; P < 0.05), whereas 7 tumors remained unaffected. Fourteen tumors were studied over 4 days. bFGF (10 nmol/L) increased PRL secretion in 9 of 11 tumors (117-525%; P < 0.05) cosecreting PRL and GH and in all 3 tumors secreting PRL alone (156%, 183%, and 691%; P < 0.01). Dose-response curves with 0.1, 1, and 10 nmol/L bFGF in 2 of these tumors cosecreting GH and PRL showed that stimulation was achieved with all 3 concentrations. bFGF (10 nmol/L) stimulated GH secretion in 2 of 11 mixed tumors (159% and 196%, respectively; P < 0.05). In 2 tumors studied over 3 weeks, 5 nmol/L bFGF stimulated PRL secretion progressively without affecting GH secretion (106% and 207%; P < 0.05). Tissue proliferation was determined by double immunostaining after bromodeoxyuridine incorporation for 1 h in 7 tumors after 4 days. The labeling index did not exceed 1.2% in any tumor, and there was no effect of 10 nmol/L bFGF on the proliferation of adenoma cells. These results suggest that bFGF may have a paracrine role in the stimulatory regulation of PRL secretion in human pituitary adenomas, and these effects are most likely due to increased hormonal synthesis. An in vitro cell culture system can be used to study proliferative potential. However, bFGF is not mitogenic for human anterior pituitary adenomas secreting PRL and PRL plus GH in vitro.

Adenoma↗

Differential effects of insulin-like growth factor 1 on the hormonal product and proliferation of glycoprotein-secreting human pituitary adenomas.

The effects of human recombinant insulin-like growth factor 1 (IGF-1) on the secretion, viability, and proliferation of dispersed human anterior pituitary adenomas secreting FSH, LH, and alpha-subunit (alpha-su) were examined in vitro over 4 h and 4 days. The acute effect of IGF-1 on secretion over 4 h was examined in four tumors secreting FSH, LH, and alpha-su. IGF-1 (100 nmol/L) reduced LH compared to control (100%) in one tumor (61%, P < 0.01), and three tumors remained unaffected. FSH and alpha-su secretion were insufficient to measure over 4 h. Nine tumors were studied over 4 days; relative to control, IGF-1 (100 nmol/L) increased FSH secretion in all seven tumors secreting FSH (28-266%, P < 0.05) and increased alpha-su secretion in all four tumors studied (36%, 63%, 91%, and 121%, P < 0.05). IGF-1 reduced LH secretion in four/nine tumors (13%, 23%, 32%, and 50%, P < 0.05). Dose response curves (1-100 nmol/L IGF-1) were performed on three tumors cosecreting FSH and LH. Stimulation of FSH was achieved with either 1 or 10 nmol/L IGF-1, a single tumor in which alpha-su was measured showed maximal stimulation at 10 nmol/L IGF-1, and one of three tumors showed LH inhibition with 100 nmol/L IGF-1. In situ viability of attached cells was assessed with fluorescein and propidium iodide in seven tumors. After 4 days' exposure to 100 nmol/L IGF-1, in situ viability was increased in five tumors (range 12-19%, 15 +/- 1.3% SEM, P < 0.05). The effects of IGF-1 on the adenoma cell proliferative S-phase fraction was determined in six tumors after 4 days of treatment using double immunostaining with bromodeoxyuridine incorporation for 1 h. In four/six adenomas that stained positive for bromodeoxyuridine in the controls (1-5.6%), the S-phase fraction was increased by 100 nmol/L IGF-1 [(range 2.1-10.6%, increase 90-220%) (P < 0.05)]. These results show that IGF-1 has differential effects on gonadotropins from human pituitary adenomas, stimulating intact FSH and alpha-su, inhibiting or being without effect on intact LH in vitro, and increasing both viability and number of tumorous glycoprotein-secreting cells entering into the S-phase of proliferation.

Adenoma↗

Carbamazepine-induced lichenoid eruption.

Carbamazepine-induced skin eruptions are common but lichenoid skin rashes associated with this drug are not well documented. We report here a patient with a lichenoid drug eruption secondary to carbamazepine.

Carbamazepine↗

Clinical and laboratory studies in patients with leprosy and enthesitis.

In a combined clinical, radiological, and laboratory study of 77 patients throughout the leprosy spectrum, 10 patients had an enthesitis which has not been described previously as far as is known and which was not associated with the characteristics of erythema nodosum leprosum reactions. C reactive protein and alpha 1 acid glycoprotein values were significantly lowered only in those patients with leprosy and enthesitis. No radiological abnormalities were found.

Adult↗

Clinical and laboratory studies of arthritis in leprosy.

Arthritis associated with leprosy is underreported. In Egypt 66 patients from a leprosy colony were studied, 20 of whom had arthropathy. This was characterised by an inflammatory symmetrical peripheral polyarthritis. The wrist, metacarpal and proximal interphalangeal joints of the hands, the knees, and the metatarsophalangeal joints of the feet were affected with associated morning stiffness. The arthritis was erosive in 11 out of 20 patients, had no features of the arthritis associated with erythema nodosum leprosum reactions, but symptomatically responded to antileprosy treatment. This arthritis would seem to be a previously unrecognised feature of leprosy.

Acute-Phase Proteins↗

Clinical and laboratory studies of inflammatory polyarthritis in patients with leprosy in Papua New Guinea.

The results of a combined clinical and laboratory study in 55 patients throughout the leprosy spectrum are reported. Thirty one of these patients suffered from an inflammatory peripheral polyarthritis which has not been previously described and which was unassociated with the characteristics of erythema nodosum leprosum reactions or with Charcot's joints. alpha 2 Macroglobulin was raised significantly only in those patients with leprosy and arthritis.

Adult↗

Schistosomiasis and inflammatory polyarthritis: a clinical, radiological and laboratory study of 96 patients infected by S. mansoni with particular reference to the diarthrodial joint.

Patients with active Schistosoma mansoni infection attending a medical clinic in an endemic area, 100 miles from Cairo, were asked to participate in this study. Ninety-six patients are reported, 72 of whom presented with musculoskeletal complaints. Nine of these presented with an enthesitis alone; 16 had an inflammatory peripheral polyarthritis alone; the remaining 47 were suffering from the combination of both an arthritis and an enthesitis. Alpha-1-acid glycoprotein was significantly lowered in those patients with musculoskeletal manifestations.

Adult↗