Use of ciprofloxacin to control a Salmonella outbreak in a long-stay psychiatric hospital.

An outbreak of diarrhoea due to Salmonella virchow phage type 8 occurred in a major block of a large psychiatric hospital. The two other major blocks of the hospital remained unaffected. No source of infection was identified and the epidemiological investigations pointed to cross-infection as the mode of transmission. Infection control measures were implemented at an early stage but a total of 55 patients and four members of staff were affected. The disease was self-limiting and of short duration. During the course of the outbreak, Salmonella typhimurium phage type 66 also emerged as a pathogen and was isolated from the stools of symptomatic cases with diarrhoea. Owing to the size of the hospital, the lack of facilities for infection control, the nature of the patients' illnesses and an increasing number of affected patients, it was decided to treat all symptomatic and asymptomatic patients with oral ciprofloxacin 500 mg twice daily for 7 days. A quantitative stool culture for salmonellae was undertaken on days 3, 7, 10, 30, 60 and 90 from the start of treatment. All patients' and staff's stool cultures became negative on day 7 and remained negative for a period of 6 months during follow-up. We conclude that cross-infection outbreaks due to Salmonella spp. in psychiatric and geriatric hospitals can be controlled by isolation in a designated ward and supportive therapy, together with ciprofloxacin treatment.

Prolactin secretion and biological activity in females with galactorrhoea and normal circulating prolactin concentrations at rest.

Prolactin secretion and biological activity have been investigated in 20 females with persistent idiopathic galactorrhoea who had normal resting serum prolactin levels at presentation. Results were compared with those in 34 normal controls. Hyperprolactinaemia, which was persistent in one and intermittent in the other, developed in two patients over an observation period of 1.5 to 8.5 years. Resting prolactin levels stayed normal in the remaining eighteen who were further investigated. Menstruation was disordered in only six of the 18, while ovulation occurred (serum progesterone greater than 20 nmol/l) in all seven patients who were studied over a 5 week period. Serum prolactin concentrations over 24 h were similar in patients and controls (24 h mean +/- SEM prolactin, 288 +/- 36 mU/l, patients, n = 7; 291 +/- 21 mU/l, controls, n = 9) as were prolactin levels estimated twice weekly for 5 weeks. Prolactin responses to thyrotrophin-releasing hormone, 200 micrograms (at 20 min, 2417 +/- 658 mU/l, patients, n = 7; 2113 +/- 424 mU/l, controls, n = 8), the dopamine antagonist, domperidone, 10 mg (at 30 min, 5949 +/- 536 mU/l, patients, n = 7; 5858 +/- 460 mU/l, controls, n = 8) and insulin-induced hypoglycaemia (at 60 min, 1441 +/- 551 mU/l, patients, n = 7; 1298 +/- 183 mU/l, controls, n = 7) were similar in patients and controls. Two different radioimmunoassays using two different antisera gave similar estimates of serum prolactin levels and prolactin bioactivity in serum was normal in an in-vitro bioassay based on the ability of prolactin to stimulate proliferation of Nb2 node rat lymphoma cells (basal bioassayable prolactin, patients 355 +/- 43 mU/l, n = 10; controls 348 +/- 64 mU/l, n = 7). Metabolic abnormalities similar to those previously noted in hyperprolactinaemia were observed in the patients' 24 h profiles. These included mild hyperglycaemia (24 h mean +/- SEM glucose, 5.47 +/- 0.08 mmol/l, patients; 5.05 +/- 0.14 mmol/l, controls; P less than 0.05) and elevations in circulating lactate, pyruvate and alanine. Blood glycerol was decreased (24 h mean +/- SEM, 0.044 +/- 0.004 versus 0.058 +/- 0.004 mmol/l, P less than 0.05). In the majority of patients with idiopathic galactorrhoea, prolactin concentrations, regulation of secretion and bioactivity in vitro are normal. The galactorrhoea and metabolic abnormalities suggest increased tissue sensitivity to the lactogenic and metabolic actions of prolactin, while ovarian cyclical function is relatively spared.

Opiate receptor blockade and diurnal pituitary and adrenal hormone levels.

Peripheral pituitary hormone levels exhibit circadian variations though the mechanism of these changes is unknown. In order to investigate the possible role of endogenous opiates in such changes we have studied the influence of opiate receptor blockade with naloxone (6.8 mg) on pituitary hormones in the morning and again in the evening in six normal male volunteers. Basal ACTH, cortisol, aldosterone and prolactin were higher in the morning than in the evening. Following naloxone at 0700h both ACTH and cortisol rose indicating a tonic inhibition of ACTH by endogenous opiates at that time. At 2230h cortisol rose following naloxone but ACTH did not, suggesting that endogenous opiates do not play an important role in the diurnal rhythm of this hormone and consistent with the suggestion that endogenous opiates can effect cortisol levels independently of their action on ACTH. Neither aldosterone nor prolactin were influenced by naloxone. In contrast TSH was unaffected by naloxone in the morning but fell in the evening (mean + SE decrement over 120 min -0.6 +/- 0.3 mU/l as compared with the control +0.6 +/- 0.4 mU/l; p less than 0.01). Thus, endogenous opiates probably tonically stimulates TSH levels in the evening when TSH may increase and possibly play a role in the circadian rhythm of TSH.

Pituitary function following megavoltage therapy for Cushing's disease: long term follow up.

Eight patients who had received megavoltage therapy for Cushing's disease 5-12 years previously have been reviewed. The long term response to this therapy was assessed with respect to efficacy of treatment in inducing continued remission and disturbance of hypothalamic-pituitary function. One patient showed clear evidence of relapse of Cushing's disease. One patient had unequivocal hypopituitarism. Basal levels of growth hormone (GH), TSH, LH, and FSH were not statistically different from controls, but provocative testing revealed significant abnormalities of response of cortisol/ACTH, GH, prolactin and LH. Six out of eight patients had absent diurnal cortisol variation and five patients had elevated serum prolactin levels. Thus, in this group of patients normal pituitary-adrenal function has not been satisfactorily restored. It is clear that significant disturbances of hypothalamic-pituitary function follow mega-voltage therapy and these may progress to overt hypopituitarism.

The inability of dynamic tests of prolactin and TSH secretion to differentiate between tumorous and non-tumorous hyperprolactinemia.

Certain hyperprolactinemic patients have an obvious pituitary tumor while others with normal pituitary radiology may or may not harbor a pituitary microadenoma. A variety of biochemical tests have been proposed to distinguish between those with and those without pituitary tumors. The aims of this study were: firstly to examine these tests to assess their efficacy in differentiating between patients with radiologically-demonstrated pituitary tumors and normal controls; and secondly to establish if those hyperprolactinemic patients with normal radiology formed two distinct groups biochemically as might be expected if some did and some did not have tumors. The prolactin (PRL) and thyroid stimulating hormone (TSH) response to domperidone and the PRL response to TRH and insulin-induced hypoglycemia have thus been examined in hyperprolactinemic subjects with and without radiological evidence of an adenoma and in normal controls. The basal serum PRL was similar in patients with and without radiological evidence of a pituitary adenoma. The serum PRL response to all stimuli studied, expressed as a percentage of initial values, was blunted in patients with known pituitary tumors with total separation from values in control subjects. Results for patients with normal pituitary radiology were similar to those for patients with tumors with minimal overlap with controls. The peak TSH increment after domperidone was exaggerated in patients with known tumors, but overlap with control values was observed in 25%. In patients with normal radiology the peak TSH increment after domperidone was similarly increased but again overlap with control values occurred in 28%. Cluster analysis showed no evidence of two subgroups of response with in the hyperprolactinemic patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Differential TSH and PRL responses to dopamine receptor blockade in acromegaly.

The serum TSH and prolactin responses to dopamine receptor blockade (domperidone 10 mg i.v.) were measured in eight acromegalic subjects and seven normal controls. The serum TSH response was exaggerated in acromegalics when compared to controls (sum of the increments 12.2 +/- 2.8 mU/l and 4.0 +/- 1.2 mU/l respectively P less than 0.05), whereas the serum prolactin response was blunted (sum of the increments 5029 +/- 1377 mU/l and 14 673 +/- 2889 mU/l respectively P less than 0.01). Dopamine receptor blockade did not significantly alter basal growth hormone levels in either group. To ascertain whether this response was merely a reflection of high circulating growth hormone levels six normal controls were pretreated for 24 h with either intramuscular growth hormone (three injections of 4 IU) or an equivalent volume of saline before the administration of domperidone (10 mg i.v.). The serum TSH and prolactin responses were not affected by prior growth hormone treatment. The opposite TSH and prolactin responses to dopamine blockade do not allow any firm conclusions to be made about the level of hypothalamic dopamine activity in acromegaly.

Effect of an oral serotonin antagonist, ketanserin, on plasma ACTH concentrations in Nelson's syndrome.

A study was performed to see whether ketanserin, a serotonin antagonist, would reduce the raised concentrations of adrenocorticotrophic hormone (ACTH) in patients with Nelson's syndrome. Six patients who had undergone bilateral adrenalectomy for Cushing's disease and who had Nelson's syndrome were given ketanserin 40 mg twice daily and placebo, for at least two months each, in a double blind crossover study. Ketanserin had no effect on ACTH concentrations. In healthy people serotonin seems to have a stimulatory role in the regulation of ACTH secretion, and the effect of ketanserin in reducing the ACTH response to hypoglycaemia suggested that it might prove useful in Nelson's syndrome. These results show that it is not indicated in these patients.

The effect of ketanserin, a specific serotonin antagonist on the PRL, GH, ACTH and cortisol responses to hypoglycaemia in normal subjects.

The role of serotonin in the prolactin, growth hormone, ACTH and cortisol responses to hypoglycaemia has been investigated in normal subjects using a selective serotonin (5HT2) receptor antagonist, ketanserin. Circulating concentrations of these hormones were measured after administration of insulin (0.1 units/kg body weight iv) to eight normal male subjects with and without simultaneous iv ketanserin (10 mg). Plasma glucose fell to less than 2.0 mmol/1 in all subjects and was unaffected by ketanserin. Ketanserin induced a 50% decrease in the serum prolactin response to hypoglycaemia, 45 and 60 min after administration of insulin (increase in serum prolactin at 60 min: 1145 +/- 295 mU/l without ketanserin; 558 +/- 176 mU/l with ketanserin, P less than 0.05). The peak ACTH response was reduced by 30% (95.3 +/- 33.6 ng/l without ketanserin; 60.0 +/- 22.9 ng/l with ketanserin, P less than 0.05) but the plasma cortisol response was not significantly altered. The serum growth hormone response was unaffected by serotonin blockade. These findings suggest that serotonin, probably acting through 5HT2 receptors, is involved in the stimulation of prolactin and ACTH release but not in the release of growth hormone, during insulin induced hypoglycaemia.

Hyperprolactinemia. Long-term effects of bromocriptine.

Patients with hyperprolactinemia may be managed by pituitary surgery or irradiation, bromocriptine treatment, or a combination of these methods, and some patients remain untreated. Little is known of the long-term consequences of some of these therapeutic regimens. Forty-six hyperprolactinemic patients (40 female and six male) managed solely with bromocriptine or no treatment over a period of 12 months to six years were therefore evaluated in this study. Nine patients with radiologically normal pituitary fossae were untreated and 10 received bromocriptine, 7.5 to 10 mg daily, while 20 patients with radiologic evidence of a pituitary tumor were treated with bromocriptine, generally 10 to 20 mg daily. Patients were assessed clinically, biochemically, and radiologically before treatment and at least six weeks after discontinuation of therapy. A further seven patients were similarly assessed before and after eight bromocriptine-induced pregnancies. Symptoms persisted in the untreated group of nine patients, although menstruation returned in four of the females with previous amenorrhea; serum prolactin levels remained elevated, other pituitary function did not change, and pituitary fossae remained normal radiologically. In all patients treated with bromocriptine, symptoms improved irrespective of radiologic findings on the pituitary, and were abolished in 67 percent during treatment associated with a decrease in serum prolactin levels in all, and a return of levels to within normal limits in 80 percent of patients. Persistent side effects were usually dose-related, but remained troublesome in 13 percent. Bromocriptine-induced tumor regression was evident radiologically in all patients with suprasellar tumor tissue and in some with purely intrasellar adenomas. This effect occurred rapidly and persisted or increased throughout follow-up. On discontinuation of treatment, prolactin levels remained significantly lower than before therapy (mean 2,934 versus 5,052 mU/liter, p less than 0.05) but were within the normal range in only two patients. Other pituitary function was unaltered, or improved in some patients with definite tumors. Bromocriptine-induced pregnancy produced no permanent change in clinical, biochemical, or radiologic status. Long-term bromocriptine treatment for hyperprolactinemia is thus highly effective in alleviating symptoms and suppressing prolactin secretion, and induces persistent tumor regression on treatment without deterioration of other pituitary function in patients with macroadenomas. On discontinuation of therapy, however, hyperprolactinemia usually recurs, and treatment may therefore need to be continued for years.

Reduction in size of prolactin-secreting tumours in men treated with pergolide.

The effect of pergolide mesylate was studied in two previously untreated men with large prolactinomas and exceptionally high prolactin concentrations. The study was designed to determine whether pergolide would be effective in alleviating symptoms, correcting hormonal abnormalities and shrinking the tumour. Starting with 50 micrograms daily the dose of pergolide was slowly increased over 10 weeks to 1 mg once daily, when repeat assessment was performed. Both patients reported complete relief of symptoms, with no side effects. Serum prolactin concentration was suppressed to normal in both subjects, and evidence to suggest tumour shrinkage was observed. Pergolide appears to be effective treatment for men with large prolactinomas.

Hyperprolactinaemia in men-response to bromocriptine therapy.

Men with hyperprolactinaemia present with large tumours. Conventional therapy with surgery and/or irradiation is unsatisfactory, with up to 100% of patients remaining hyperprolactinaemic (or subsequently developing pituitary insufficiency). In view of reports of bromocriptine-induced regression of prolactinomas, eight consecutive male hyperprolactinaemic patients with impotence and/or symptoms related to local tumour effects were treated with bromocriptine 20 mg daily as sole therapy for 3-11 months. Symptoms were relieved partly or completely in seven patients and serum prolactin was restored to normal or near normal in all men. Serum thyroxine and plasma cortisol response to hypoglycaemia became normal in two men who had subnormal values before therapy. Mean serum growth hormone response to hypoglycaemia rose significantly as did plasma testosterone concentrations. Evidence of tumour regression, sometimes massive, was seen in the six patients who underwent repeat radiology. The symptomatic relief and biochemical and radiological improvement in these patients indicate that bromocriptine therapy may now be the treatment of choice for hyperprolactinaemic men with large tumours.

Total and free thyroid hormone concentrations after elective surgery.

Changes in thyroid hormone concentration and distribution and plasma cortisol levels have been followed in 11 patients undergoing elective cholocystectomy. A significant rise in total and free thyroxine (T4) and fall in total and free triiodothyronine (T3) were noted after surgery. Reverse T3 concentrations rose substantially, suggesting that peripheral conversion of T4 to T3 is diminished and that there is preferential formation of reverse T3. Serum thyroid stimulating hormone concentrations did not change. There was no direct correlation between the change in cortisol and the change in thyroid hormone or reverse T3 concentrations.