Modulation by 1,25-dihydroxycholecalciferol of the acute change in cytosolic free calcium induced by thyrotropin-releasing hormone in GH4C1 pituitary cells.

Receptor-mediated regulation of prolactin synthesis by 1,25-dihydroxycholecalciferol (1,25(OH)2D3) in the pituitary cell strain GH4C1 is dependent on the concentration of extracellular calcium. We have now investigated the actions of 1,25(OH)2D3 on cytosolic free calcium concentrations [( Ca2+]i) in these cells using the fluorescent indicator quin2. Basal resting [Ca2+]i was unchanged in cells treated with 1 nM 1,25(OH)2D3 either acutely (from 0 to 15 min) or for periods of up to 48 h. However, the initial peak of the biphasic change in [Ca2+]i induced by thyrotropin-releasing hormone (TRH) was enhanced more than twofold in cells pretreated for 24 or 48 h with 1,25(OH)2D3. This 1,25(OH)2D3-enhanced calcium response was restricted to the initial phase of TRH action; the secondary plateau phase was unaffected. Neither the affinity nor number of TRH receptors nor the early time course of [3H]MeTRH binding to GH4C1 cells were affected by pretreatment with 1,25(OH)2D3. Because TRH binding was not altered, four sites along the intracellular signal transduction pathway of TRH action were examined. Neither protein kinase C activation nor inositol polyphosphate accumulation were enhanced in response to TRH, in 1,25(OH)2D3 pretreated cells, indicating that phosphatidylinositol hydrolysis was unchanged by pretreatment. A low concentration of ionomycin was used to probe the size of the nonmitochondrial intracellular calcium pool that is sensitive to TRH. Ionomycin was not able to mobilize more calcium from 1,25(OH)2D3 pretreated cells, indicating that TRH-responsive intracellular calcium stores were probably not enhanced by pretreatment. Chelation of extracellular calcium, however, did eliminate enhancement of the TRH response in 1,25(OH)2D3-pretreated cells. We conclude that 1,25(OH)2D3 modulates acute dynamic changes in [Ca2+]i induced by TRH without affecting basal [Ca2+]i. The mechanism of the enhanced response of 1,25(OH)2D3-pretreated cells to TRH appears to depend upon a postreceptor event independent of phosphatidylinositol hydrolysis that involves increased calcium conductance at the level of the plasma membrane. A less likely explanation involves enhancement of intracellular calcium stores in an ionomycin-resistant, EGTA-sensitive, TRH-mobilizable reservoir.

Efficacy of carboplatin given in a phase II window study to children and adolescents with newly diagnosed metastatic soft tissue sarcoma.

AIM: The activity of carboplatin was evaluated in a phase II window study in previously untreated children with metastatic soft tissue sarcoma. METHODS: Children with poor-risk metastatic disease (over 10 years and/or with bone/bone marrow involvement) treated in the SIOP MMT 98 study were scheduled to receive two courses of intravenous carboplatin (area under curve [AUC] of 10), 21 days apart. RESULTS: Sixteen eligible patients were entered into the rhabdomyosarcoma (RMS) group. Response (complete remission or partial remission) was seen in five children (31%, 95% confidence interval (CI) 14-56%). Ten eligible patients with other soft tissue sarcomas were recruited into the non-RMS group. Two responses (20%, 95% CI 6-51%) were seen. Toxicity in both groups was predictable nausea, vomiting and marrow suppression and there were no toxic deaths. CONCLUSION: Single-agent carboplatin at AUC of 10 has an acceptable toxicity profile but only moderate efficacy in poor-risk metastatic soft tissue sarcoma.

Endocrine disorders among long-term survivors of childhood head and neck rhabdomyosarcoma.

PURPOSE: Head and neck rhabdomyosarcoma (HNRMS) survivors are at increased risk of developing pituitary dysfunction as an adverse event of radiotherapy. Our aim was to investigate the frequency and risk factors for pituitary dysfunction in these survivors. Secondly, we aimed to compare the prevalence of pituitary dysfunction between survivors treated with external beam radiation therapy (EBRT) and survivors treated with the ablative surgery, moulage technique after loading brachytherapy, and surgical reconstruction (AMORE) procedure. METHODS: Eighty HNRMS survivors treated in London (EBRT based) and Amsterdam (AMORE based: AMORE if feasible, otherwise EBRT) in the period 1990-2010 and alive ≥ 2 years post-treatment were evaluated. Survivors were evaluated in multidisciplinary late-effects clinics, with measurement of linear growth, determination of thyroid function, and growth hormone parameters. Additional data, such as baseline characteristics, anthropometrics, pubertal stage, and the results of additional laboratory investigations, were retrieved from patient charts. RESULTS: Pituitary dysfunction was diagnosed in 24 in 80 (30%) survivors, after a median follow-up time of 11 years. Median time to develop pituitary dysfunction after HNRMS diagnosis was 3.0 years. Risk factors were EBRT-based therapy (odds ratio [OR] 2.06; 95% confidence interval [CI] 1.79-2.46), parameningeal tumour site (OR 1.83; 95% CI 1.60-2.17) and embryonal RMS histology (OR 1.49; 95% CI 1.19-1.90). CONCLUSIONS: Radiotherapy used for the treatment of HNRMS confers a significant risk of the development of pituitary dysfunction. AMORE-based treatment in children with HNRMS resulted in less pituitary dysfunction than treatment with conventional EBRT. Our findings underscore the importance of routine early endocrine follow-up in this specific population.

A new glibenclamide-insensitive neuroselective hyperpolarizing agent.

We describe a novel compound, (-)-N-(2-ethoxyphenyl)-N'-(1,2,3-trimethylpropyl)-2-nitroethene-1, 1-diamine), Bay x9227, that demonstrates dose-dependent hyperpolarizing activity of remarkable potency (EC50 3 picomolar) and selectivity for CNS neurons and clonal neurotypic cells compared to smooth muscle cells. Single cell membrane potential measurements were obtained in physiologic buffer using the fluorescent probe, bisoxonol. Unlike K+ATP-channel activators including its (+)-enantiomer (Hoffman et al., 1993, Biochem. Biophys. Res. Commun. 190(2), 551), this activity was insensitive to glibenclamide antagonism. These data suggest a novel pharmacologic site for effecting neuroselective hyperpolarization.

Vestibular dysfunction presenting as syncope.

A case of chronic vestibulitis presented as episodes of recurrent drop attacks that had been interpreted as recurrent syncopal episodes. The importance of distinguishing between syncope and drop attacks-a difficult task-is emphasized. This case stresses the need to include benign vestibulitis in the differential diagnosis of syncope and drop attacks.

Ranitidine hydrochloride-induced hypergastrinemia.

Ranitidine hydrochloride (Zantac) is a recently released H(2)-receptor antagonist that is stated not to cause significant increases in serum gastrin. The case described herein demonstrates that this is not always true. Zantac produced significant acute hypergastrinemia, which was sustained for several days after the discontinuation of the drug.

Zollinger-Ellison syndrome: intermittent diarrhea, relentless hypokalemia, and hypergastrinemia.

A case of hypergastrinemia, diarrhea, and relentless hypokalemia occurring in a middleaged, mildly hypertensive female is described. The presence of a gastrinoma was suggested by the additional findings of an inordinate degree of hypokalemia for the amount of thiazide used for the treatment of her hypertension; failure of her hypokalemia to correct itself with adequate doses of oral potassium that had previously corrected this problem; and amelioration of her symptoms and hypokalemia when she was treated with short-term oral potassium chloride and longterm cimetidine.

Mitral valve prolapse syndrome associated with congenital bicuspid aortic valve.

Mitral valve prolapse (MVP) associated with congenital bicuspid aortic valve (CBAV) is an uncommon finding. In a study of 257 black patients with MVP, the author identified eight patients with associated CBAV. This paper discusses the association of the two lesions in relation to etiologic and surgical implications.

The pill and the thoracic outlet and bilateral carpal tunnel syndromes.

PIP: A case report is reviewed of a 22-year-old woman who presented on July 22, 1980 with a 1-week history of bilaterally recurring complaints of hand paresthesias radiating up both arms followed by coldness, aching, and imperceptible and uncontrollable tremors of her hands. The woman's symptoms usually began within minutes after she began typing, and slowly abated within 10-15 minutes after she was forced by discomfort to discontinue typing and hold her arms at her sides. The woman also described, unilaterally, the same symptoms over the same period of time on awakening each morning. She had previously enjoyed excellent health, had been taking oral contraceptives (OCs)--norgestrol and ethynyl estradiol--during the preceding 4 years without problems, and had gained 12 pounds during the preceding 6 months. Symptoms began exactly 7 days prior to the onset of her menses. Raynaud's phenomena were denied. X-rays of the cervical spine were normal, and specifically revealed no signs of cervical ribs or large lower cervical transverse processes. The patient was given a single oral 80 mg dose of furosemide, and thereafter hydrochlorothiazide 50 mg, orally twice daily for 1 week. Symptoms were dramatically improved within 24 hours. When evaluated again on July 30, 1980, she was asymptomatic except for minimal complaints and physical findings of the carpal tunnel syndrome on the right. There were no complaints referrable to the thoracic outlet syndrome, but physical examination again documented findings of partial thoracic outlet vascular obstruction. Within 2 weeks the patient was asymptomatic. When interviewed on August 29, 1980, the patient was asymptomatic but gave the identical history of onset and recurrence of all her symptoms, to a lesser extent, exactly 1 week prior to the onset of her August menses. The patient's symptoms totally disappeared by the 3rd day of her menses. In sum, both the carpal tunnel syndrome and the thoracic outlet syndrome quickly resolved when treatment with diuretics was extended the patient for a short period of time premenstrually.^ieng

Mitral valve prolapse and lentiginosis profusa.

This report describes the first case of mitral valve prolapse associated with lentiginosis profusa.

Hypothyroidism: a rare cause of the bilateral carpal tunnel syndrome--a case report and a review of the literature.

Reported herein is a patient who developed symptoms of bilateral carpal tunnel syndrome following radioactive iodine induced hypothyroidism. A review of the literature is presented.

Acute low-dose hydralazine induced lupus syndrome (HILS).

A case of acute hydralazine induced lupus syndrome is described. No case has previously been described in which a small daily dose and a small accumulation dose have evoked this syndrome in such a short period of time. A pertinent and selective review of this syndrome is presented. The need for awareness of this syndrome manifesting in a patient exposed to small doses of hydralazine for short periods of time is emphasized.

Transient, benign, serum alkaline hyperphosphatasemia in an adult.

A rare occurrence of transient, benign, serum alkaline hyperphosphatasemia (TBSAH) in an adult is described. This patient's serum alkaline phosphatase rose transiently and asymptomatically to 29 times the upper limit of normal. Although TBSAH has been described in the pediatric literature, no cases of this entity have been reported in adults. Awareness of TBSAH occurring in adults is equally important to physicians who care for adult patients.

Selective malabsorption of vitamin B12 and vitamin B12-intrinsic factor with megaloblastic anemia in an adult.

The first case of megaloblastic anemia due to selective malabsorption of vitamin B(12) and vitamin B(12)-intrinsic factor is described in an otherwise normal female adult, in whom pernicious anemia had previously been diagnosed.

Quinidine-induced nephrotic syndrome.

A case of nephrotic syndrome occurring in an elderly woman who was being treated with quinidine is described. The nephrotic syndrome resolved completely after discontinuation of quinidine treatment. It is felt that the use of quinidine was causally related to the development of nephrotic syndrome in this patient. As far as could be determined, no such case has been described previously in the medical literature in English.

Rare cardiopulmonary complications of chronically decompensated myasthenia gravis.

Although myasthenia gravis (MG) is frequently mentioned in standard textbooks and journal articles as a rare cause for pulmonary hypertension and right heart failure, no case can actually be found in the literature. The case described in this report is the first documented case of chronically decompensated MG manifesting itself as pulmonary hypertension, severe right heart failure, and functional prolapse of both the mitral and tricuspid valves. Interestingly, no hepatic biochemical abnormalities were present in spite of significant congestive hepatomegaly.

Nitrofurantoin induced erythema nodosum.

The present case report clearly establishes nitrofurantoin as a cause for erythema nodosum (EN), presenting with serum sickness-like symptoms, typical and atypical EN skin lesions, and pseudo-splinter hemorrhages in a patient with documented mitral valve prolapse.

Eosinophilic gastroenteritis with rectal involvement: case report and a review of literature.

An unusual case of eosinophilic gastroenteritis (EGE) is reported. Fewer than 150 cases of EGE have been reported in the world literature to date. This is the first case of this disease reported to have rectal involvement, and only the second case in which colonic involvement has been histologically documented. The addition of this case to those previously reported in the literature would suggest that EGE may involve any segment of the gastrointestinal tract.

Hypozincemia, ageusia, dysosmia, and toilet tissue pica.

A 37-year-old female presented with complaints of ageusia, dysosmia, fatigue, and toilet tissue pica. She was found to have hypozincemia and iron deficiency anemia. Her complaints quickly abated when treated with oral zinc and iron.

Bronchogenic carcinoma, leukemoid reaction, marantic endocarditis, and consumptive thrombocytopathy.

This paper details the simultaneous occurrence of a severe leukemoid reaction, non-bacterial thrombotic endocarditis (NBTE) (marantic endocarditis), and a consumptive thrombocytopathy without signs of micro-angiopathic hemolysis on peripheral blood smear in a patient with terminal metastatic, undifferentiated, large cell bronchogenic carcinoma. The case is presented and the condition is discussed in detail.