Meconium and amniotic fluid embolism: effects on coagulation in pregnant mini-pigs.

OBJECTIVE: A hallmark of amniotic fluid embolism is the induction of coagulation defects. Little is known about the nature of these defects or the causative agent or agents. The purpose of this study was to assess the effects of meconium containing (native) meconium-amniotic-fluid infusion (MAFI) and meconium-free (centrifuged) amniotic-fluid infusion (AFI) on the coagulation system in the mini-pig model. DESIGN: Laboratory study. SETTING: University institute animal laboratory. SUBJECTS: Near-term pregnant Göttingen bred mini-pigs in three groups (control, MAFI, AFI) of six animals each. INTERVENTIONS: After induction of anesthesia, amniotic fluid was collected by cesarean section in all animals. Depending on the group, animals received either Ringer's solution (control), native amniotic fluid (MAFI), or centrifuged amniotic fluid (AFI) via an ear vein. MEASUREMENTS AND MAIN RESULTS: Blood samples were taken from a central vein before infusion (baseline), immediately after infusion, every 10 mins until 90 mins after infusion, and finally, every 20 mins until 150 mins after infusion. The following parameters were measured: Platelets, partial thromboplastin time, prothrombin time, fibrinogen, factors V, VII, VIII, antithrombin III, and protein C. The values relative to baseline in the MAFI and AFI groups were compared with control by rank order test. A p<.05 was considered statistically significant. Compared with the control group, platelets were lower in the MAFI group (p<.005), PTT was prolonged in both the MAFI and AFI groups (p<.005), fibrinogen was lower in both the MAFI and AFI groups (p<.05), prothrombin index was lower (i.e., prothrombin time was prolonged) in the MAFI group (p<.05), and protein C was lower in the MAFI group (p<.005). CONCLUSIONS: Both MAFI and, to a much lesser extent, AFI cause an activation of coagulation in mini-pigs. The changes induced by meconium-free AFI are probably not sufficient to explain the high mortality of the condition.

Fish oil and glycemic control in diabetes. A meta-analysis.

OBJECTIVE: Hypertriglyceridemia is associated with cardiovascular disease in diabetes. Fibrates effectively lower, but do not always normalize, serum triglyceride levels. Fish oil supplements may then be added to lower serum triglyceride levels. Doubt remains whether the net effect of fish oil intake on glycemic control is beneficial in diabetes. We therefore performed a meta-analysis from published clinical trials. RESEARCH DESIGN AND METHODS: Data sources were Medline (Cologne, Germany), Excerpta Medica, Current Contents, review articles, and published reference lists. Publications of 26 trials were selected, and all trials included more than five diabetes (IDDM and NIDDM) patients and addressed the effects of fish oil (eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) on serum lipids and glucose tolerance. We (C.E.F., M.J.F.M.J.) extracted data independently based on predetermined criteria. Studies were classified according to design. RESULTS: All studies combined showed a decrease in mean triglyceride concentrations in association with fish oil: -0.60 mmol/l (95% CI, -0.84 to -0.33, P < 0.01) and a slight but significant increase in serum LDL cholesterol: 0.18 mmol/l (95% CI, 0.04-0.32, P = 0.01), with both findings most prominent in NIDDM. No significant changes in HbA1c percentages occurred in diabetic subjects treated with fish oil. Fasting blood glucose levels were increased with borderline significance in NIDDM subjects (0.43 mmol/l [95% CI, 0.00-0.87], P = 0.06) and were significantly lower in IDDM subjects (-1.86 mmol/l [95% CI, -3.1 to -0.61], P < 0.05). Significant dose-response effects of EPA (g/day) on HbA1c and triglycerides and of DHA (g/day) on fasting blood glucose levels, HbA1c, and triglycerides were demonstrated only in NIDDM subjects. CONCLUSIONS: The use of fish oil has no adverse affects on HbA1c in diabetic subjects and lowers triglyceride levels effectively by almost 30%. However, this may be accompanied by a slight increase in LDL cholesterol concentration. Fish oil may be useful in treating dyslipidemia in diabetes.

[MRI and oncoscintigraphy with 99m-Tc-MIBI in the follow up of thyroid cancer]. / KST und Onkoszintigraphie mit 99mTc-MIBI in der Nachsorge des Schilddrüsenkarzinoms.

Magnetic resonance imaging (MRI) and 99mTc-MIBI oncoscintigraphy are new procedures for the detection of recurrent differentiated thyroid cancer. We evaluated the utility of both techniques compared to ultrasonography, radioiodine scanning, and measurement of serum thyroglobulin in patients with (n = 21) or without suspicion (n = 34) of tumor relapse. Although MRI was most effective in detecting local recurrencies (sensitivity: 100%), additional diagnostic information was only obtained in patients with mediastinal lesions. On the other hand, oncoscintigraphy was less sensitive (67%) but highly specific in differentiating reactive lymph node enlargement from metastatic disease (specificity: 93.5%). Oncoscintigraphy may be used instead of radioiodine scanning in patients with doubtful lymph node findings and spare them withdrawal of TSH-suppressive hormone medication. Routine estimation of serum thyroglobulin proved to be highly efficient in screening for tumor relapse using a cut-off level of 3 ng/ml (accuracy: 100%).

Determinants of insulin sensitivity and consequences for lipoproteins and blood pressure in subjects with non-insulin-dependent diabetes mellitus.

The aim of the present study was to investigate the possible determinants of insulin sensitivity and the relationships of these determinants and insulin sensitivity to lipoprotein levels and blood pressure in patients with non-insulin-dependent diabetes mellitus (NIDDM). We studied 46 patients with NIDDM (26 women, 20 men) treated either with diet alone or in combination with sulfonylureas. Insulin sensitivity was assessed as the insulin-mediated glucose uptake rate (M value) with the hyperinsulinemic euglycemic clamp technique. In a multiple regression model, only percent body fat, waist to hip ratio (WHR), and resting energy expenditure (REE) emerged as significant independent determinants of the M value, with a multiple R2 for the model of 44%, whereas age, hemoglobin A1c (HbA1c) level, thyroid function, fitness level, smoking status, alcohol consumption, and dietary habits did not contribute significantly. The M value was independently and negatively associated with the concentrations of triglyceride (TG) and very-low-density lipoprotein (VLDL) cholesterol and positively associated with high-density lipoprotein (HDL) cholesterol subfractions and apolipoprotein A1. In our predominantly normotensive subjects, we found no association between the M value and blood pressure. Moreover, fasting insulin contributed directly, ie, independent of the M value, to the variation of TG, but not to the other lipoproteins and not to blood pressure. The results suggest that in NIDDM (1) insulin sensitivity is determined mainly by percentage body fat and REE, (2) the insulin level determines the TG level directly, whereas the lipoproteins are influenced indirectly as a reflection of the degree of insulin resistance, and (3) insulin sensitivity is not related to blood pressure in a normotensive population.

Insulin increases sodium reabsorption in diluting segment in humans: evidence for indirect mediation through hypokalemia.

To examine the mechanism of renal sodium (Na) and potassium (K) retention during insulin infusion, seven healthy volunteers underwent clearance studies without (time control) and with insulin infusion (40 mU bolus, followed by 1 mU/kg/min for 150 min). Maximal free water clearance and fractional lithium clearance (FELi) were used to analyze renal sodium handling. Insulin decreased Na excretion (from 189 +/- 25 to 121 +/- 19 mumol/min, P less than 0.01) and K excretion (from 64 +/- 8 to 19 +/- 1 mumol/min, P less than 0.01), but did not change in glomerular filtration rate. FELi increased from 29.8 +/- 1.9 to 32.3 +/- 1.9% (P less than 0.05), minimal urine osmolality decreased from 59 +/- 3 to 46 +/- 3 mOsm/kg (P less than 0.01), and the diluting segment reabsorption index increased from 88.0 +/- 0.9 to 93.7 +/- 0.9%, P less than 0.01). Insulin also decreased plasma K, from 3.91 +/- 0.08 to 3.28 +/- 0.08 mmol/liter, P less than 0.01. In a third clearance study KCl was infused simultaneously (3.75 mumol/kg/min) to prevent this fall in plasma K. In this study insulin had no effect on Na and K excretion and diluting segment reabsorption, but the rise in FELi remained. In a fourth clearance study NaCl (3.75 mumol/kg/min) instead of KCl was infused together with insulin. This maneuver did not prevent the Na and K retaining effect of insulin, nor any of its effects on renal sodium handling parameters. These data suggest that Na and K retention during insulin infusion are largely secondary to hypokalemia, which causes increased reabsorption in the diluting segment.

Sodium retention by insulin may depend on decreased plasma potassium.

Evidence is accumulating that insulin is a hypertensive factor in humans. The involved mechanism may be its sodium-retaining effect. We examined whether insulin causes sodium retention through a direct action on the kidney, as is generally assumed, or indirectly through hypokalemia. Insulin was infused (euglycemic clamp technique) with and without potassium infusion to prevent hypokalemia in six healthy subjects. Without potassium infusion, insulin caused a marked decrease in plasma potassium (-0.75 mmol/L), and decreased urinary sodium and potassium excretions by, approximately 38% and 65%, respectively. Simultaneous potassium infusion largely prevented the decrease in plasma potassium, as well as the decrease in urinary sodium and potassium excretions. These data suggest that the acute antinatriuretic effect of insulin may be largely mediated in an indirect way, ie, through hypokalemia.

Clinical experience with proton beam radiation therapy.

Our experience with modulated energy proton beams in the definitive treatment of cancer patients indicates that, for the patients accepted, treatment volumes have been smaller and total doses higher than would have obtained for photon techniques alone used in our institution. The reactions of normal tissue have, with very few exceptions, been readily acceptable. The higher radiation doses employed should yield higher tumor control frequencies. Clearly, we cannot assess the efficacy of this modality because of the small number of patients followed for short periods. However, the results are judged by use to warrant intensive evaluation of this modality.