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Biomedical subjects

H A Bruining

Publications and source records attributed to H A Bruining.

At least 163 records · Page 9Linked to original sources

Ten-year follow-up study of islet-cell antibodies and childhood diabetes mellitus.

To find out whether subclinical autoimmunity precedes onset of nonfamilial insulin-dependent diabetes mellitus (IDDM), 4806 schoolchildren aged 5-19 years from a township in Holland were followed-up for at least ten years after blood was sampled for measurement of islet-cell antibodies (ICA). ICA positivity conferred a relative risk of IDDM of 533 (95% CI 145-1955). In the 10 years of follow-up 4 of the 8 ICA-positive subjects became insulin dependent, whereas the probability of being free of IDDM was 99.9% for those who were ICA-negative at the start of the study. The findings suggest that, although chronic autoimmunity involving the pancreatic beta-cells may precede non-familial IDDM by many years, a positive ICA test on a single occasion predicts the development of IDDM in only 4 out of 8 subjects over a period of 10 years.

Adolescent↗

Day-to-day variability of energy expenditure in critically ill surgical patients.

To determine whether the total energy expenditure (TEE) determined on a single day reliably estimates TEE on subsequent days of a patient's ICU stay, day-to-day variability of TEE and its relation to clinical condition were assessed. TEE was measured by indirect calorimetry in 60 mechanically ventilated critically ill surgical patients during a 2 to 7-day period. Clinical condition was scored by daily determination of the simplified acute physiology score (SAPS). Day-to-day variation of TEE was significantly (p less than .0001) influenced by body temperature, but not by SAPS or day of measurement. In the individual patient, day-to-day variability of TEE may be large. When TEE on day 1 is used to estimate TEE on subsequent days, errors of up to 31% of actual TEE occurred. Addition of a temperature correction reduced the maximum error to 25%. If a balance between caloric supply and demand is intended, it is advised to adapt the caloric supply to the result of daily TEE measurement by indirect calorimetry.

Adolescent↗

The new aromatase inhibitor CGS-16949A suppresses aldosterone and cortisol production by human adrenal cells in vitro.

CGS-16949A is a new orally active nonsteroidal aromatase inhibitor which is more than 100-fold more potent than aminoglutethimide. This compound is an imidazole derivative, and therefore, its possible effect on cytochrome P-450-dependent enzyme activities in the adrenal gland was evaluated. In vitro investigations with dispersed normal and hyperplastic human adrenocortical cells showed that CGS-16949A at 10(-7)-10(-6) M is a potent 11 beta-hydroxylase inhibitor, which inhibits ACTH-stimulated cortisol release to a similar extent as an equimolar concentration of metyrapone (IC50 for both compounds, 10(-7)-5 X 10(-7) M). Etomidate was a more potent 11 beta-hydroxylase inhibitor (IC50, approximately 10(-8) M), while 10(-7)-10(-6) M ketoconazole caused (via 17 alpha-hydroxylase inhibition) a similar inhibition of cortisol release as 10(-7) M CGS-16949A (IC50, 10(-7)-5 X 10(-7) M). The 11 beta-hydroxylase inhibition by CGS-16949A was accompanied by a dose-dependent increase in the release of precursor steroids by the adrenocortical cells in vitro, including deoxycortisol, 17-hydroxyprogesterone, and androstenedione. Aldosterone release was suppressed 50% by 10(-9) M CGS-16949A, while the IC50 for cortisol in the same cells was 10(-7) M. Aldosterone release by the dispersed adenoma cells obtained from a patient with primary aldosteronism was also significantly suppressed by CGS-16949A. We concluded that 1) the new nonsteroidal aromatase inhibitor CGS 16949A is an inhibitor of 11 beta-hydroxylase which is equipotent to metyrapone. At present it is unclear whether the compound at the dose that causes complete aromatase inhibition in vivo also affects stress-induced cortisol release in man. 2) CGS-16949A exerts a very potent inhibitory effect on normal aldosterone release (IC50, 10(-9) M) and on tumorous aldosterone secretion. CGS-16949A might, therefore, be a drug that can be used in the treatment of primary hyperaldosteronism.

Adrenal Cortex↗

Outcome prediction in critically ill patients by means of oxygen consumption index and simplified acute physiology score.

Both oxygen consumption index (VO2-index) and simplified acute physiology score (SAPS) are reported to be reliable predictors of the ultimate outcome in critically ill patients. The purpose of this study was to verify whether survivors and nonsurvivors have different VO2-indices and whether the prognostic potency of SAPS can be improved by addition of VO2-index as a supplemental physiological variable. In 50 mechanically ventilated surgical ICU patients with heterogeneous underlying diseases, SAPS was calculated and VO2-index was determined by continuous 24-h measurement of oxygen consumption. The VO2-indices of survivors and nonsurvivors were not significantly different (p greater than 0.05), which is in contrast to the results of earlier studies. This contrast may be explained by a difference both in methods of VO2-measurement and in study populations. SAPS was significantly lower in survivors than in nonsurvivors (p less than 0.005) and was able to classify the patients correctly into groups of increasing probability of death. However, SAPS failed to be a helpful prognosticator in the individual patient. The addition of VO2-index to SAPS as a supplemental physiological variable did not substantially improve the prognostic potency. Because a higher VO2-index did not necessarily indicate a better survival chance, there is no argument for therapeutic interventions aimed exclusively at increasing VO2-index, as suggested previously.

Adolescent↗

Accuracy of intermittent metabolic gas exchange recordings extrapolated for diurnal variation.

In the treatment of critically ill patients, it may be important to know the values of total diurnal O2 consumption and CO2 production. Often, diurnal values are obtained by extrapolation from the easily obtained short interval values. However, both stochastic and systematic errors can be introduced. This study analyzes the systematic influence of a possible diurnal variation of gas exchange and quantifies the extrapolation accuracy of 16 commonly used recording protocols (one to four times a day for 5, 15, 30, and 60 min). Continuous gas exchange measurements were performed for 24 h in 50 ventilated patients and compared to extrapolated results. Only a small diurnal variation was found, and extrapolation accuracy depended on the duration and, especially, the number of recording periods. In clinical practice, 24-h values can be estimated with sufficient accuracy by extrapolation from two 15-min measurements per day.

Adolescent↗

Successful treatment with SMS 201-995 of Cushing's syndrome caused by ectopic adrenocorticotropin secretion from a metastatic gastrin-secreting pancreatic islet cell carcinoma.

Signs and symptoms of Cushing's syndrome developed rapidly after total gastrectomy in a 37-yr-old man with a metastatic gastrin-secreting islet cell carcinoma. Argyrophilic tumor cells in a lymph node removed during operation immunostained for gastrin and ACTH. Treatment for more than 6 months with the somatostatin analog SMS 201-995 (300 micrograms/day) greatly reduced serum gastrin levels and normalized plasma ACTH and cortisol levels and urinary cortisol excretion, and the signs and symptoms of Cushing's syndrome disappeared. The size of the primary tumor in the head of the pancreas, which had grown rapidly before SMS 201-995 therapy, stabilized after 6 months of treatment with the analog. We conclude that SMS 201-995 can reduce ACTH as well as gastrin secretion from islet cell carcinomas as well as control tumor growth.

Adenoma, Islet Cell↗

Ultrasound-guided percutaneous drainage of intra-abdominal abscesses.

The encouraging results of percutaneous abscess drainage (PAD) in simple intra-abdominal abscesses have led us to employ this method in patients with more complex abdominal inflammatory disease, such as those with multiple enteric communicating or multilocular abscesses and patients in whom the percutaneous approach requires puncture routes traversing uninvolved organs. Cure was achieved in 74 per cent of all patients (83 of 112 patients) who underwent PAD, but in only 50 per cent of patients with multiple intra-abdominal abscesses (n = 16), 50 per cent of patients with complex pancreatic inflammatory disease (n = 8) and 57 per cent of patients with complex intraparenchymal abscesses (n = 7). PAD contributed to cure in eight of nine patients with enteric communicating abscesses. The transhepatic route to perihepatic abscesses proved to be safe. Complications occurred in nine patients (8 per cent). No relationship was noted between the severity or number of complications and the indication for PAD. Of the 29 failures of PAD, 17 patients were cured by either surgical intervention (14 patients) or a second PAD (1 patient) or a combination of the two methods (2 patients). Twelve patients (11 per cent) died, eight from sepsis due to inadequate drainage. Frequent reassessment by ultrasonography and computerized tomography (CT) in patients with prolonged sepsis after PAD is mandatory. These results justify a place for PAD in the management of the often critically ill patient with complex abdominal inflammatory disease.

Abdomen↗

Late results of mesocaval interposition shunting for bleeding oesophageal varices.

Survival, encephalopathy and shunt patency were studied in 64 consecutive patients who underwent mesocaval shunting with a wide-calibre Dacron prosthesis. Half of the patients were operated as emergency cases. Operative blood loss in patients who had emergency procedures was significantly higher than during elective operations. Overall, 30-day mortality was 27 per cent. Survival was 61 per cent after 1 year and 39 per cent after 5 years. Serious encephalopathy requiring hospital admission occurred in 5 patients (11 per cent of patients surviving more than 1 month). Shunt patency was assessed by scintisplenoportography and ultrasonography. Cumulative shunt occlusion rate was 16 per cent after 1 year, 33 per cent after 5 years and 52 per cent after 8 years of follow-up. Out of 17 patients with an occluded shunt, 9 had persistent or recurrent bleeding, while 3 patients had recurrent bleeding despite a patent shunt. We conclude that the mesocaval Dacron interposition shunt should not be recommended as the procedure of first choice for portosystemic shunting.

Adult↗

Total parenteral nutrition in critically ill surgical patients: fixed vs tailored caloric replacement.

In critically ill patients accurate measurement of total energy expenditure (TEE) is possible by means of continuous indirect calorimetry. Since in many ICUs the necessary equipment is not available, the Harris-Benedict formula (HB) is frequently used to calculate TEE. Supplemental application of a clinical correction factor (HBc) has been advised. In this study we assessed the reliability of both methods of calculation and of a standard nutritional regimen, all three compared to the calorimetrically measured TEE (gold standard). Although the basic HB-formula did not perform better than the standard regimen, significantly better results were obtained by supplemental application of the clinical correction factor (HBc). It is left undecided, whether or not indirect calorimetry is actually to be preferred in daily clinical practice.

Adolescent↗

Studies on insulin secretion by monolayer cultures of normal and tumorous human pancreatic cells. Effects of glucose, somatostatin and SMS 201-995.

Recently, somatostatin analogs have been introduced which can be used clinically in the treatment of tumorous or functional hypoglycemia. In the present study we investigated in vitro the regulation, the degree of autonomy and the sensitivity to natural somatostatin and its analog SMS 201-995 of insulin secretion by monolayer cultures of human pancreatic cells obtained from patients with insulinomas and from a newborn with nesidioblastosis. All cultures released insulin upon the addition of dibutyryl-cAMP and calcium, demonstrating their intact viability. Insulin secretion from nontumorous pancreatic cells surrounding an insulinoma was dose-dependently stimulated by glucose. In contrast, insulin release by B cells from a patient with nesidioblastosis and from 2 insulinomas was not stimulated by the addition of glucose. Native somatostatin (SRIF) and the synthetic analog SMS 201-995 inhibited insulin secretion from all cultures. The inhibitory effects of SRIF and SMS in the culture from the nesidioblastosis tissue, could be reversed by the addition of 11.2 mmol glucose/l, but not in one of the insulinoma cultures. This demonstrates that some sensitivity to glucose is present in B cells from the nesidioblastosis tissue, despite the unresponsiveness to glucose alone. Insulin release by insulinoma cells was blocked by somatostatin, while it was inhibited to some extent only in the cultures of nontumor B cells and of cells from the nesidioblastosis tissue. In conclusion, it was shown that insulin release by the cultured B cells obtained from several pathological conditions differed with regard to the autonomy of hormone release (glucose sensitivity) and the sensitivity to somatostatin and its analog.

Adenoma, Islet Cell↗

Human medullary thyroid carcinoma in tissue culture; secretion of calcitonin and carcinoembryonic antigen.

Monolayer cultures of medullary thyroid carcinoma (MTC) cells were prepared from 5 patients with familial and 4 with sporadic MTC. Basal calcitonin (CT) release decreased rapidly during 17 days in culture. Addition of extra calcium (2 mmol/l) or dibutyryl cyclic AMP (dBcAMP, 3 mmol/l) increased CT release in all investigated cultures (p less than 0.01). No significant differences were observed between cell suspensions prepared from familial and those from sporadic MTC. Carcinoembryonic antigen (CEA) was found in 3 out of 5 MTC cell suspensions from patients with familial tumors and in 2 out of 2 sporadic tumors. Only two cultures secreted measurable amounts of CEA, which decreased with culture time but at a much slower rate than that of CT release. CEA release was not affected by the addition of calcium and dBcAMP. This study shows an absent relation between basal and stimulated CT and CEA release by cultured MTC cells.

Bucladesine↗

Correlations of serum potassium fluctuations with body temperature after major surgery.

We have observed an association between hypothermia and hypokalemia in a number of postoperative patients. In order to analyze the incidence and consequences of this correlation, 108 patients undergoing major operations were prospectively studied. Rectal temperature, serum and urinary potassium, arterial blood gases, blood glucose, and routine monitoring were analyzed. Hypothermia occurred in 35 (32%) patients, of whom 20 (57%) suffered from hypokalemia. Hypothermia was accompanied by an undercompensated metabolic acidosis in 15 (75%) and hyperglycemia in 18 (89%), while nine (45%) patients had cardiac dysrhythmias. Urinary potassium excretion was lower in hypothermic patients and therefore cannot explain the finding of hypokalemia. Administration of NaHCO3, insulin, digitalis, and calcium in patients suffering from hypothermia must be done with caution because hypokalemia may coexist with low body temperature and predispose the patients to lethal dysrhythmias.

Acidosis↗

Differential effects of the imidazole derivatives etomidate, ketoconazole and miconazole and of metyrapone on the secretion of cortisol and its precursors by human adrenocortical cells.

The direct effects of etomidate, ketoconazole, miconazole and metyrapone were investigated on the secretion of cortisol and its precursors by dispersed cells from the adrenal cortex of a normal individual and four patients with Cushing's syndrome. The drugs interfered with adrenocorticotropic hormone-stimulated cortisol secretion in a dose-dependent way. Desoxycortisol concentrations in the medium were increased after the addition of metyrapone and low doses of etomidate but were suppressed with higher doses of etomidate. The production of 17-hydroxy-progesterone was stimulated by miconazole and metyrapone but was strongly suppressed by the high doses of etomidate. Ketoconazole caused a stimulation of progesterone release, whereas the release of 17-hydroxyprogesterone was suppressed. Finally, the concentration of progesterone was strongly enhanced with high doses of miconazole, whereas etomidate suppressed progesterone production. It is concluded that etomidate at a low concentration (IC50, 10(-8) M) inhibits 11 beta-hydroxylase, whereas, at higher concentrations (10(-7)-10(-6) M), the side-chain cleavage enzyme system is also inhibited; metyrapone is a weaker (IC50, 10(-7) M) but pure 11 beta-hydroxylase inhibitor; miconazole inhibits adrenal 21-hydroxylase at 10(-6) M; and ketoconazole inhibits 17-hydroxylase. Etomidate, ketoconazole, miconazole and metyrapone inhibit cortisol biosynthesis in the human adrenal gland in different manners, which appear to involve the four cytochrome P-450-dependent monooxygenase reactions. Interestingly, these drugs affect corticosteroidogenesis by normal, hyperplastic and adenomatous adrenal cells in a similar manner.

17-alpha-Hydroxyprogesterone↗