Multiple endocrine neoplasia type 1 associated with malignant lymphoma and other complications.

A 49-year-old female with multiple endocrine neoplasia (MEN) type 1 associated with malignant lymphoma, lipoma, functioning adenomatous goiter, non-functioning adrenal tumor, polyneuropathy, postoperative primary hyperparathyroidism, and hepatitis B virus was a human T lymphotropic virus type 1 (HTLV-1) carrier. She underwent parathyroidectomy for primary hyperparathyroidism at age 44. At age 49, examinations of the enlarged para-aortic lymph nodes revealed diffuse small non-cleaved B cell lymphoma in stage II, and other various complications were also found. Multiple tumorigenetic factors were considered to be involved in the present case.

123I-MIBG myocardial scintigraphy in diabetic patients: relationship to autonomic neuropathy.

The aim of this study was to investigate the relationship between autonomic nerve dysfunction and myocardial uptake of 123I-meta-iodobenzyl guanidine (MIBG) in patients with diabetes mellitus. Twenty-two non-insulin-dependent diabetic patients, 9 with autonomic neuropathy [ANP(+)] and 13 without autonomic neuropathy [ANP(-)], and 8 controls were included in the study. Both planar and single photon emission tomographic (SPET) images were obtained 30 min (early) and 3 h (delayed) after the 123I-MIBG injection. The heart-to-mediastinal uptake ratio (H/M) and the washout ratio of 123I-MIBG (%WR) were calculated from planar images. The uptake ratio of the inferior wall to the anterior wall (I/ A) and the %WR of both the inferior and anterior walls were calculated from the SPET images. On the early plantar images, the mean H/M ratio in the ANP(+) group was significantly lower than that of the control group. The mean %WR on the planar images in the ANP(-) group was significantly higher than that of the controls. The SPET images demonstrated a reduction in MIBG uptake and significantly increased clearance in the inferior wall of the ANP(-) patients. These findings extended to other areas of the heart in the ANP(+) patients. In the quantitative analysis of the SPET images, the ANP(+) group had significantly lower I/A values and significantly higher %WR values in the anterior wall. The ANP(+) group showed significantly increased clearance of 123I-MIBG in the inferior wall. We conclude that 123I-MIBG myocardial scintigraphy is a useful diagnostic tool both in the early detection and evaluation of the progression of myocardial sympathetic nerve dysfunction in patients with diabetes mellitus. Both the I/A and %WR calculated from SPET images are useful parameters.

Thyroid anaplastic carcinoma producing granulocyte-colony-stimulating factor and parathyroid hormone-related protein.

A 65-year-old woman noticed a rapidly enlarging neck mass with tenderness and complained of dyspnea. She was diagnosed as having anaplastic thyroid carcinoma. She died of respiratory failure 14 days after admission. Marked leukocytosis and hypercalcemia were observed in the clinical course. Both serum granulocyte-colony-stimulating factor and parathyroid hormone-related protein levels were elevated. The cancerous tissue was also immunohistochemically stained for both peptides. We conclude that the leukocytosis and hypercalcemia of this patient were induced by these two factors produced by the tumor.

[123I-MIBG myocardial scintigraphy in diabetic patients: association with autonomic neuropathy].

123I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy was performed in 20 diabetic patients (NIDDM) and 8 control subjects to investigate the association between clinical autonomic nerve dysfunction and myocardial accumulation of MIBG. We used coefficient variance of R-R interval (CVR-R) as a index of the autonomic neuropathy and categorized diabetes into two groups (CVR-R > or = 2.0: non-autonomic neuropathy. CVR-R < 2.0: autonomic neuropathy). In planar imaging studies, heart to mediastinum MIBG uptake ratio (H/M) was calculated on both early and delayed images. The washout ratio of 123I-MIBG in the heart (%WR) was also obtained using myocardial tracer activity on the both images. Mean value of these indices in diabetic group did not reveal any significant difference with the value in the control group. On the SPECT images, low uptake was observed in the posterior-inferior wall with normal uptake of 201Tl in diabetic patients with non-autonomic neuropathy. These areas extended in patients with autonomic neuropathy. The mean value of count ratio of posterior-interior to anterior wall (posterior-inferior/anterior ratio: PI/A) in the diabetic autonomic neuropathy group was significantly higher than in the control group on the both early and delayed images. And the mean value of regional %WR in the posterior-inferior wall calculated by the both MIBG SPECT images was significantly higher in the non-autonomic neuropathy group than in the control group. In the diabetic patients, retention mechanism of 123I-MIBG was considered to be involved at an early stage without autonomic nerve dysfunction clinically. As autonomic neuropathy progressed severely, uptake mechanism was also supposed to be involved. Therefore, 123I-MIBG myocardial scintigraphy was useful for early detection of cardiac sympathetic nervous dysfunction in diabetic patients.

Stimulation of cholecystokinin (CCK) release from superfused rat hypothalamo-neurohypophyseal complexes by interleukin-1 (IL-1).

This in vitro study examined the effects of interleukin-1 (IL-1) and interferon-gamma (Ifn-gamma) on the release of cholecysto-kinin (CCK) from superfused hypothalamo-neurohypophyseal complexes (HNC) of rats. An increase of CCK from HNC was elicited in a dose-dependent manner by recombinant human IL-1 alpha and -1 beta in concentrations of 0.1-10 nM. In contrast, the release of CCK from HNC was not affected by recombinant human Ifn-gamma at any dose tested (0.1, 1 and 10 nM). The increased release of CCK elicited by IL-1 was calcium-dependent, as was that induced by potassium (60 mM), but it was biphasic and had a different time course and a lower magnitude than those induced by potassium and veratridine. These results suggest that IL-1 activates pituitary-adrenal axis by stimulating CCK neurons in the hypothalamus and/or neurohypophysis to release CCK, since CCK has been implicated in the regulation of adrenocorticotropin release.

Interleukin-1 (IL-1) stimulates the release of corticotropin-releasing factor (CRF) from superfused rat hypothalamo-neurohypophyseal complexes (HNC) independently of the histaminergic mechanism.

We demonstrated previously that interleukin-1 (IL-1) (recombinant human IL-1 alpha and -1 beta) stimulated the release of corticotropin-releasing factor (CRF) from the superfused rat hypothalamo-neurohypophyseal complex (HNC), independently of the cholinergic system. In the present study we studied the effects of IL-1 on the release of CRF not only from the HNC but also from the isolated hypothalamus of rats in a superfusion system to define the origin of measured CRF and the site of IL-1 action. We also studied the possible involvement of the histaminergic system in the mediation of the stimulation by IL-1. An increase in CRF was elicited from the HNC and the isolated hypothalamus in a dose-dependent manner by human recombinant IL-1 beta in concentrations of 0.1-10 nM with similar time courses. Histamine in concentrations of 1-100 nM also elicited qualitatively similar increases of CRF from these two types of explants. The increases in CRF release from the HNC induced by 10 nM of histamine were completely suppressed in the combined presence of pyrilamine (10 microM) and cimetidine (10 microM), an H1 and an H2 receptor antagonist, respectively. On the other hand, the increase in CRF release induced by 10 nM IL-1 beta was not affected by the combination of these two antagonists. These results indicate that IL-1 stimulates CRF release from the median eminence through an action on the hypothalamus, and that the stimulatory effect of IL-1 is probably independent of the histaminergic system.

Interleukin-1 (IL-1) stimulates arginine vasopressin (AVP) release from superfused rat hypothalamo-neurohypophyseal complexes independently of cholinergic mechanism.

We studied whether interleukin-1 (IL-1) affects the release of arginine vasopressin (AVP) from the superfused hypothalamo-neurohypophyseal complex (HNC) of rats. Involvement of the cholinergic system in the mediation of IL-1 on AVP release from HNC was also examined. Both human recombinant IL-1 alpha and -1 beta elicited a rapid increase of AVP from HNC in a dose-dependent manner at concentrations ranging from 0.1 to 10 nM. However, neither IL-1 alpha nor -1 beta at concentrations of 100 nM increased AVP, and even suppressed the stimulatory effect of 10 nM IL-1 alpha and -1 beta added later. Acetylcholine at concentrations of 1 to 100 nM caused a dose-dependent, rapid increase in AVP, whereas AVP release induced by 10 nM acetylcholine was completely suppressed by the combined presence of 10 microM hexamethonium, a nicotinic receptor antagonist, and 50 microM atropine, a muscarinic receptor antagonist. On the other hand, AVP release induced by 10 nM IL-1 alpha and -1 beta was not affected by the combination of the two antagonists. These results suggest that both IL-1 alpha and -1 beta may stimulate AVP release by acting directly on the hypothalamo-neurohypophyseal system, and that the stimulatory effect of IL-1 on AVP release may be independent of the cholinergic system.

Stimulation by interleukin-1 (IL-1) of the release of rat corticotropin-releasing factor (CRF), which is independent of the cholinergic mechanism, from superfused rat hypothalamo-neurohypophysial complexes.

The effects of interleukin-1 (IL-1) and interferon-gamma (Ifn-gamma) on the release of corticotropin-releasing factor (CRF) from superfused hypothalamo-neurohypophysial complexes (HNC) of rats were examined in the present study. In this in vitro system, the release of CRF from HNC was not affected by any dose of human recombinant Ifn-gamma tested (0.1, 1 and 10 nM). In contrast, a rapid increase of CRF from HNC was elicited in a dose-dependent manner by human recombinant IL-1 alpha and -1 beta in concentrations of 0.1-10 nM. The involvement of the cholinergic system in the mediation of the stimulatory effect of IL-1 on CRF release was evaluated. Acetylcholine in concentrations of 1-100 nM also elicited a rapid increase of CRF. The increase in CRF release induced by 10 nM of acetylcholine was completely suppressed in the presence of both hexamethonium (10 microM) and atropine (50 microM), a nicotinic and a muscarinic receptor antagonist, respectively. On the other hand, the increase in CRF release induced by 10 nM IL-1 alpha or -1 beta was not affected by these two antagonists. These results indicate that IL-1 stimulates CRF release through an action on the hypothalamo-neurohypophysial system, most likely on the hypothalamus, and that the stimulatory effect of IL-1 is probably independent of the cholinergic system.

Effects of atropine, proglumide, and somatostatin analogue (SMS 201-995) on bombesin-induced gallbladder contraction and CCK secretion in humans.

The effects of atropine, proglumide, and somatostatin analogue (SMS 201-995) on bombesin-induced gallbladder contraction and plasma cholecystokinin (CCK) secretion were investigated in healthy volunteers. The gallbladder size was measured by real-time ultrasonography and the plasma CCK levels by radioimmunoassay. Bombesin (5 micrograms/30 min infusion) induced gallbladder contractions that reduced the gallbladder area to 36.6 +/- 2.1% of the original area 45 min after bombesin infusion, and caused a significant increase of plasma CCK from a basal level of 10.3 +/- 1.8 pg/ml to a peak level of 42.9 +/- 8.9 pg/ml (p less than 0.01) at 20 min. Atropine (500 micrograms, im) inhibited significantly (p less than 0.01) the gallbladder contraction (maximum contractile rate, 78.7 +/- 6.4%) in response to bombesin without any change of plasma CCK secretion, whereas proglumide (800 mg/day for 3 days, per os) decreased slightly but not significantly the gallbladder contraction, and had no effect on plasma CCK secretion. On the other hand, SMS 201-995 (50 micrograms, sc) almost completely inhibited both bombesin-induced CCK secretion and gallbladder contraction (maximum contractile rate, 93.6 +/- 6.2%). These findings suggest that atropine inhibits bombesin-induced gallbladder contraction, not via suppression of CCK release, but probably by inhibiting cholinergic mechanisms, whereas somatostatin inhibits gallbladder contraction, at least in part, by the suppression of bombesin-stimulated CCK secretion.

Comparative in vivo and in vitro studies on abnormal GH secretion in patients with acromegaly.

Eight patients with active acromegaly due to GH-producing pituitary adenoma were studied. GH secretory dynamics in vitro was evaluated by adding GRF, CRF, or a somatostatin analog, SMS 201-995 to the perifusate of dispersed cells from tumors. A comparison was made between the data obtained in preoperative tests for GH secretion and those obtained in experiments in vitro. Before operation, the GRF test (100 micrograms, iv) resulted in no GH response in three of six patients examined. The CRF test (100 micrograms, iv) resulted in a paradoxical GH increase in two of the same six patients. In vitro studies performed on adenoma cells revealed that exposure to GRF (100 ng/ml) elicited an increase in GH in seven of eight patients examined. Exposure to CRF (100 ng/ml) caused an enhanced GH secretion in four of the same eight patients. There were cases in which GH response to these hypothalamic hormones was observed in vitro but not in vivo, whereas there was only one case in which CRF caused an increase in GH in vivo but not in vitro. Thus, GH secretory dynamics was not always the same in vivo and in vitro. The discrepancy could be ascribed to the different secretory status of hypothalamic hormone (e.g., GRF or somatostatin) in vivo in each acromegalic patient.

Syndrome of inappropriate secretion of antidiuretic hormone (SIADH) in a patient with multiple sclerosis.

Association of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) with multiple sclerosis (MG) is very rare, although many other disorder of the nervous system have been reported to be associated with this syndrome; there is only one case report in the literature. We describe here a patient with the syndrome associated with MS. A 62-year-old women had a variety of neurologic symptoms, where clinical course was typical of MS. Transient episodes of hyponatremia and disturbance of consciousness occurred repeatedly with deterioration of MS. The concentration of antidiuretic hormone (ADH) was high whereas the plasma osmolality was low in the presence of concentrated urine, during the episodes of hyponatremia. Urinary Na excretions exceeded 20 mEq/day. Computed tomography and magnetic resonance imaging revealed lesions in the brain, especially in the periventricular region. The hypothalamus and pituitary appeared normal by these imaging methods. Since the periventricular region surrounds and may be functionally connected to the hypothalamus which plays the central role in the regulation of ADH secretion, it was concluded that association of SIADH and MS in this patient was not coincidental, and that demyelinating processes in the periventricular region exerted an abnormal influence on ADH secretion resulting in SIADH. Contribution of other mechanisms as increased intrathoracic pressure, however, could not be excluded completely.

[Almost complete disappearance of metastatic pulmonary tumor and reduction of the main hepatic mass in a case of hepatocellular carcinoma treated with UFT].

A 61-year-old female patient with a low density area indicated by abdominal CT was admitted to hospital. Several circular shadows 5-20-mm in diameter were visible on the chest photos. Primary hepatocellular carcinoma complicated by compensatory cirrhosis accompanying pulmonary metastasis was diagnosed from blood biochemistry tests, a high AFP value (390,000 ng/ml) and angiogram findings. After two months of daily administration of 400 mg of UFT as ftorafur, both reduced AFP (46,000 ng/ml) and a reduction of the primary nidus were observed; after four months, the circular shadows were almost completely eliminated on chest photos. Although UFT administration was discontinued (total FT dose 33.6g) due to jaundice, in the eight months after discontinuation no enlargement of the primary nidus, recurrent shadows on chest photos, or recurrent rise of AFP were observed. This case is considered to suggest the effectiveness of UFT against primary hepatocellular carcinoma with accompanying pulmonary metastasis.

Is sperm cheap? Limited male fertility and female choice in the lemon tetra (pisces, characidae).

In the laboratory, fertilization rates achieved by male lemon tetras decline with spawning frequency. Even when the number of females is not limited, males can produce only four times as many offspring as females. Females show a preference for males that have not recently spawned as opposed to those that have. The cost of producing sufficient sperm to maximize fertilization rates may therefore reduce the intensity of sexual selection in this polygamous fish species.