[Tetany due to excessive use of alcohol: a possible magnesium deficiency]. / Tetanie bij overmatig alcoholgebruik: mogelijk een magnesiumtekort.

Two alcoholic patients, a woman aged 64 and a man aged 69 years, were admitted with tetany. Both had severe electrolyte disorders, with low plasma levels of calcium, magnesium and potassium. Following mineral supplementation both patients recovered. Hypomagnesaemia plays a central role in the pathophysiology of this syndrome. Chronic alcohol abuse results in hypomagnesaemia in 30% of patients by decreasing renal tubular reabsorption. Hypomagnesaemia leads to suppression of parathyroid-hormone secretion, parathyroid-hormone resistance and vitamin-D suppression, resulting in hypocalcaemia. Hypomagnesaemia also causes kaliuresis leading to hypokalaemia. Supplementation with magnesium is crucial in the treatment of this combined electrolyte disorder.

Gall bladder dysmotility: a risk factor for gall stone formation in hypertriglyceridaemia and reversal on triglyceride lowering therapy by bezafibrate and fish oil.

BACKGROUND AND AIM: The aim of this study was to unravel the mechanisms responsible for the increased risk of gall stone disease in hypertriglyceridaemia (HTG) and to compare the effects of triglyceride lowering therapy by bezafibrate and fish oil on determinants of cholelithiasis (biliary lipid composition and gall bladder motility) in HTG patients. PATIENTS AND METHODS: Gall bladder motility (ultrasonography) was studied postprandially and during infusion of cholecystokinin (CCK). Determinants of cholelithiasis and serum lipids were compared between nine HTG patients and 10 age, sex, and body mass index matched normolipidaemic controls. The effects of bezafibrate and fish oil in HTG patients were studied in a randomised cross over trial. RESULTS: HTG patients showed 14-fold higher serum triglyceride (TG) levels than controls. Biliary lipid composition, fasting gall bladder volumes, and CCK levels did not differ between HTG patients and controls. Gall bladder emptying was reduced in HTG patients compared with controls during CCK infusion (-22%) as well as in response to a meal (-37%; both p<0.001). Postprandial CCK levels were significantly higher in HTG patients. Both bezafibrate and fish oil reduced serum TG levels (-68% and -51% v baseline, respectively; both p<0.01). Fasting CCK levels were not affected whereas CCK induced gall bladder emptying increased during bezafibrate (+29%; p<0.001) and tended to increase on fish oil therapy (+13%; p=0.07). Postprandial gall bladder motility improved on bezafibrate and fish oil (+47 and +25% v baseline, respectively; both p<0.02) at least partly due to increased gall bladder sensitivity to CCK (both p<0.05 v baseline). Bezafibrate but not fish oil increased the molar ratio of cholesterol to bile acids (+40%; p

Strong decrease of high sensitivity C-reactive protein with high-dose atorvastatin in patients with type 2 diabetes mellitus.

OBJECTIVE: Statins are known to reduce CRP concentrations, but whether high doses are more effective is not known. METHODS: In a prospective double-blind multicenter study in 186 DM2 patients without manifest coronary artery disease and with dyslipidemia, the effect of a 30-week treatment with 10 and 80 mg atorvastatin or placebo on the reduction of hs-CRP levels was measured. RESULTS: Median CRP levels increased with 6.6% in the placebo group and were reduced by 15 and 47%, respectively, with atorvastatin 10 and 80 mg (P<0.001; significantly different from 10 mg atorvastatin and from placebo (P<0.001). Variation in IL-6 and plasma lipids associated for 21 and 8%, respectively, with variation in CRP levels (P<0.001 and P=0.01). Of patients with a baseline CRP level above an arbitrary threshold of 3.0 mg/l, 56% in the 80 mg atorvastatin group reached a level of less than 3.0 mg/l, versus 23% randomized to 10 mg atorvastatin (P<0.01) and 17% in the placebo group (P<0.005). CONCLUSIONS: In DM2 patients high dose atorvastatin induced a strong reduction in CRP levels. The decrease in CRP was mainly independent of effects on lipid lowering and changes in IL-6 levels. The pleiotropic effect of high-dose atorvastatin on inflammation could add to its cardioprotective effect in high-risk patients.

[Addisonian crisis provoked by levothyroxine substitution therapy]. / Addison-crisis uitgelokt door substitutietherapie met levothyroxine.

A women aged 36 with a positive family anamnesis for autoimmune endocrine diseases and a history of thyroid diseases, developed major complaints of general malaise, orthostatic hypotension and loss of appetite after the start of a treatment with levothyroxin because of (sub)clinical hypothyroidism. She was found to suffer from primary adrenocortical insufficiency masked by excessive use of liquorice and a lowered metabolism, but which via the suppletion with thyroid hormone had led to an addisonian crisis.

No effect of consumption of green and black tea on plasma lipid and antioxidant levels and on LDL oxidation in smokers.

Intake of flavonoids is associated with a reduced cardiovascular risk. Oxidation of LDL is a major step in atherogenesis, and antioxidants may protect LDL from oxidation. Because tea is an important source of flavonoids, which are strong antioxidants, we have assessed in a randomized, placebo-controlled study the effect of consumption of black and green tea and of intake of isolated green tea polyphenols on LDL oxidation ex vivo and on plasma levels of antioxidants and lipids. Healthy male and female smokers (aged 34+/-12 years, 13 to 16 per group) consumed during a 4-week period 6 cups (900 mL) of black or green tea or water per day, or they received as a supplement 3.6 grams of green tea polyphenols per day (equivalent to the consumption of 18 cups of green tea per day). Consumption of black or green tea had no effect on plasma cholesterol and triglycerides, HDL and LDL cholesterol, plasma vitamins C and E, beta-carotene, and uric acid. No differences were found in parameters of LDL oxidation. Intake of green tea polyphenols decreased plasma vitamin E significantly in that group compared with the control group (-11% P=.016) but had no effect on LDL oxidation ex vivo. We conclude that consumption of black or green tea (6 cups per day) has no effect on plasma lipids and no sparing effect on plasma antioxidant vitamins and that intake of a high dose of isolated green tea polyphenols decreases plasma vitamin E. Although tea polyphenols had a potent antioxidant activity on LDL oxidation in vitro, no effect was found on LDL oxidation ex vivo after consumption of green or black tea or intake of a green tea polyphenol isolate.

[Hypertension caused by licorice consumption]. / Hypertensie door dropgebruik.

In a 38-year-old woman who was hospitalized because of hypertension and hypokalaemic alkalosis, the intake of liquorice (200 g per day) was proven to be the cause. A liquorice provocation test produced all the expected clinical and biochemical abnormalities. Some kinds of liquorice contain glycyrrhetic acid which inhibits the enzyme 11-beta-hydroxysteroid dehydrogenase (e.g. in the kidney) leading to decreased transformation of cortisol into cortisone. The mineralocorticoid action of cortisol causes a drop in serum potassium and an increase in serum sodium concentration, together with a metabolic alkalosis, which in the patient described led to retention of water resulting in weight increase and hypertension.

Effects of hypoxia and atrial natriuretic peptide on aldosterone secretion in healthy subjects.

To evaluate the inhibitory effect of hypoxia and atrial natriuretic peptide (ANP) on aldosterone secretion, 11 healthy male subjects were infused with 5 ng.kg-1 x min-1 ANP or placebo. The subjects were exposed in a stepwise fashion to incremental hypobaric hypoxia, which decreased arterial oxygen saturation to 79 +/- 2% in the placebo and 84 +/- 2% in the ANP condition (P < 0.05). In the placebo condition, the plasma ANP concentration increased from 13.8 +/- 1.0 to 19.6 +/- 2.3 pmol/l (P < 0.01) at the lowest barometric pressure. Plasma renin activity did not change, whereas the plasma aldosterone levels increased consequent to the increase of plasma adrenocorticotropic hormone (ACTH). Continuous infusion of ANP increased the plasma levels twofold (P < 0.001) and the level of guanosine 3',5'-cyclic monophosphate threefold (P < 0.001). However, the plasma aldosterone concentrations were not different in the two experimental conditions. Administration of supplementary oxygen significantly decreased ACTH to baseline values (P < 0.01) together with a decrease in aldosterone. Free water clearance (P = 0.05) but not sodium excretion (P = NS) increased during continuous ANP infusion. The data indicate that the aldosterone secretion in hypoxia is not inhibited by (patho)physiological plasma ANP levels. The inhibition of aldosterone secretion may well be explained by a direct effect of hypoxia on the adrenal cells. ACTH is a major stimulus of aldosterone secretion in hypoxia, which overrides the natriuretic effect of ANP.

[Good results of 100% oxygen treatment for acute carbon monoxide poisoning; temporarily no indication for hyperbaric oxygenation]. / Goede resultaten van behandeling met 100% zuurstof wegens acute koolmonoxide-intoxicatie; voorlopig geen indicatie voor hyperbare zuurstoftoediening.

OBJECTIVE: To describe the complications in patients with acute carbon monoxide intoxication, if treated with 100% instead of hyperbaric oxygen. DESIGN: Retrospective chart review. PATIENTS: Thirty-three patients with acute-carbon monoxide intoxication admitted to the medical Intensive Care Unit of Leiden University Hospital. RESULTS: The mean carbon monoxide level of all patients was 29.4%. Ten patients had a carbon monoxide level above 40%. Seven patients (21%) were in coma on admission. Most complications occurred in the latter group. All patients were treated with normobaric 100% oxygen. Recovery was usually rapid. No patient showed neurological deficits at discharge. CONCLUSION: The short-term prognosis of patients with acute carbon monoxide intoxication is good, even if they are not treated with hyperbaric oxygen. There is still inconclusive evidence from the literature that hyperbaric oxygen improves the prognosis in these patients.

The influence of serotonergic neurotransmission on pituitary hormone release in obese and non-obese females.

It has been suggested that a defect in hypothalamic serotonergic neurotransmission may be partly responsible for the impaired pituitary hormone release in obese subjects. In this study we investigated basal serum pituitary hormone concentrations and pituitary hormone release in response to the sequential injection of four hypothalamic releasing hormones before and after a seven-day course of fluoxetine, which inhibits serotonin re-uptake by presynaptic neurons and acts specifically in the brain. Ten obese women (body mass index (BMI) 35.6 +/- 1.0 kg/m2) and nine women of normal weight (BMI 22.9 +/- 0.9 kg/m2) were studied in the early and mid-follicular phases of the menstrual cycle. Basal concentrations of pituitary hormones were measured at 09.00. Subsequently 200 micrograms of TRH and 100 micrograms of CRH, GnRH and GHRH were injected intravenously. The pituitary hormone response was measured at regular intervals until 180 min after the four injections. The experiment was repeated after a seven-day course of 60 mg fluoxetine orally. We found the basal concentrations of prolactin (PRL) and growth hormone to be significantly lower in obese subjects than in the normal controls. Basal concentrations of ACTH, beta-endorphin, TSH, LH and FSH in the two groups were comparable. Releasing hormone-induced responses in the two groups were not significantly different. Administration of fluoxetine "restored" the basal PRL concentrations in obese subjects. It did not affect the other basal hormone concentrations. Furthermore, fluoxetine treatment reduced TRH-induced TSH release in both normal and obese subjects. It did not influence the other releasing hormone-induced responses.(ABSTRACT TRUNCATED AT 250 WORDS)

Severe hypophosphatemia in a patient with anorexia nervosa during oral feeding.

We report a case of refeeding-associated hypophosphatemia in a 24-year-old malnourished male patient with anorexia nervosa but no history of alcoholism. He was given tube feeding with a low-calory preparation supplemented with phosphate. During refeeding, a severe hypophosphatemia developed after 5 days, i.e., serum phosphate 0.00-0.01 mmol/l for 2 days, accompanied by a reduction in red-cell ATP and 2,3-diphosphoglycerate, mild hemolytic anemia and transient changes in cardiac repolarization; there was, however, a striking lack of clinical symptomatology. Parenteral replacement with phosphate initially was complicated by an unexpected high urinary phosphate excretion due to an extremely low TmP/GFR (0.02 mmol/l) for over 2 days. Only after an increase of the TmP/GFR to supranormal values, i.e. up to 2.5 mmol/l, unrelated to changes in serum PTH or vitamin D3, the serum phosphate concentration became normal. The case report shows that severe hypophosphatemia can occur in nonalcoholic patients after oral feeding, and may induce reversible changes in renal phosphate handling that complicate replacement therapy.

Renal concentrating ability in obesity. Effect of modified fasting and the supplementation of T3, sodium chloride and carbohydrate.

The renal concentrating ability (RCA) was studied in 30 obese subjects before and after modified fasting (MF) and T3 supplementation, and during hypocaloric-carbohydrate refeeding. We also studied the effect of sodium supplementation on the RCA during MF. Modified fasting induced a low T3-high rT3 state ("sick euthyroid"). During T3-supplementation plasma T3 levels increased but were in the normal range for normal weight controls. Plasma sodium, potassium, and calcium remained within the normal range during all study periods. After MF (14 days) the mean maximal urinary osmolality was significantly lower compared to prefast values both after dehydration alone (706 +/- 12 mosm/kg H2O v 975 +/- 14, P less than 0.001) and after dehydration plus sc vasopressin administration (676 +/- 19 v 899 +/- 17, P less than 0.001). After 14 days MF followed by 14 days MF + T3-supplementation plasma urea, urinary urea excretion, and the creatinine clearance were significantly greater than after MF alone as was the RCA (764 +/- 15 v 652 +/- 25, P less than 0.002). Sodium chloride supplementation increased RCA (P less than 0.02) but no additive effect of T3 and sodium chloride supplementation was observed. Severe dietary salt restriction induced a significant decline in RCA (P less than 0.005). Refeeding with carbohydrate increased plasma T3 from 79.9 +/- 7.7 to 97 +/- 7.5 ng/100 mL (NS) and decreased plasma rT3 from 0.33 +/- 0.02 to 0.27 +/- 0.02 ng/mL, (P less than 0.02); no significant change in RCA was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Metabolic responses in grossly obese subjects treated with a very-low-calorie diet with and without triiodothyronine treatment.

Metabolic responses during a very-low-calorie diet, composed of 50 per cent glucose and 50 per cent protein, were studied in 18 grossly obese subjects (relative weights 131-205 per cent) for 28 d. During the last 14 d (period 2) eight subjects (Gp B) served as controls, while the other ten subjects (Gp A) in the low T3 state were treated with triiodothyronine supplementation (50 micrograms, 3 times daily). During the first 14 d (period 1) a low T3-high rT3 state developed; there was an inverse relationship between the absolute fall of the plasma T3 concentrations and the cumulative negative nitrogen balance as well as the beta-hydroxybutyrate (BOHB) acid concentrations during the semi-starvation period, pointing to a protein and fuel sparing effect of the low T3 state. Weight loss in the semi-starvation period was equal in both groups; during T3 treatment the rate of weight loss was statistically significant (Gp A 6.1 +/- 0.3 kg vs Gp B 4.2 +/- 0.2 kg, P less than 0.001). In the control group there was a sustained nitrogen balance after three weeks; in Gp A the nitrogen losses increased markedly during T3 treatment. Compared to the control group, on average a further 45.4 g extra nitrogen were lost, equivalent to 1.4 kg fat free tissue. Thus, 74 per cent of the extra weight loss in the T3 treated group could be accounted for by loss of fat free tissue. During the T3 treatment period no detectable changes occurred regarding plasma triglycerides and plasma free fatty acids (FFA) concentrations; the plasma BOHB acid concentrations decreased significantly as compared to the control group. Plasma glucose concentrations and the immunoreactive insulin (IRI)/glucose ratio increased in Gp A in the T3 treatment period, reflecting a state of insulin resistance with regard to glucose utilization. Our results warrant the conclusion that there appears to be no place for T3 as an adjunct to dieting, as it enhances mostly body protein loss and only to a small extent loss of body fat.