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Two low-density lipoprotein (LDL) apheresis methods allowing a specific extracorporeal removal of atherogenic lipoproteins from plasma were compared concerning their efficacy and safety in the long-term therapy of severe familial hypercholesterolemia. Five patients were treated with immunoadsorption (IMA) at weekly intervals over 3 years each, and three patients received weekly therapy with dextran sulfate cellulose adsorption (DSA) for up to 2 years. The mean plasma volume processed per session to decrease total cholesterol to a target level of 100-150 mg/dl at the end of LDL apheresis was significantly lower in DSA than in IMA: 143% vs. 180% of the individual plasma volume. Both LDL apheresis procedures achieved a mean acute reduction of plasma LDL cholesterol by more than 70%. The average interval concentrations of plasma LDL cholesterol obtained without concomitant lipid-lowering medication were 151 +/- 26 mg/dl compared to 351 +/- 65 mg/dl at baseline in the IMA-treated patients and 139 +/- 18 mg/dl compared to 359 +/- 48 mg/dl at baseline in the DSA-treated patients. Two patients from the DSA group died after 2 years of study participation due to a stroke and a sudden cardiac death several days after the last plasma therapy. Treatment-related side effects were infrequent. Long-term therapy with IMA and DSA was associated with symptomatic improvement of coronary artery disease and mobilization of tissue cholesterol deposits. Analysis of coronary angiograms after 3 years of weekly LDL apheresis with IMA revealed in five patients nearly identical atherosclerotic lesions without definite regression or progression.

We present the case of an adrenal incidentaloma of considerable size which turned out to be a stomach-like diverticular mass, probably a malformation arising from the embryonic foregut. We discuss whether results possibly obtained by extensive and costly investigative techniques would have changed the management.

Cardiovascular reflex tests are used extensively to screen diabetic patients for autonomic cardiac neuropathy. Since alcohol abuse must often be considered the cause of nerve damage in internally ill patients, we examined 66 nonalcoholic type 1 (insulin-dependent) diabetics and 63 nondiabetic alcoholics matched for age, weight, and duration of disease to determine whether specific patterns of complaints, symptoms, signs, and results of the cardiovascular reflex tests can differentiate between alcoholic and diabetic nerve damages. In these carefully selected diabetic and alcoholic patients the medical history, clinical neurological assessment, and reflex test results all showed significant differences, resulting in different patterns which allow the correct allocation of nerve damage to either diabetic or alcoholic origin with easily available clinical means.

Although pituitary hormones play only a minor role in acute hormonal counterregulation during insulin-induced hypoglycemia, their concomitant secretion with the profound sympathoadrenal response provides an indicator of hypothalamic-pituitary activation. The release of different amounts of beta-endorphin, growth hormone, and adrenocorticotropin during human (HI) and porcine (PI) insulin-induced hypoglycemia would serve as a pointer to a different insulin species effect on hypothalamic-pituitary response. We performed a controlled, double-blind study with randomization to either HI or PI to compare insulin effects during developing and established hypoglycemia. The glucose clamp technique was used to lower the blood glucose concentration stepwise (3.3, 2.2, 1.7 mmol/l) over similar periods in ten patients with insulin-dependent diabetes mellitus. beta-endorphin, growth hormone, and adrenocorticotropin levels were determined by radioimmunoassay from arterialized blood at the above plateaus. A different action of HI or PI on peripheral glucose metabolism was not found. Pituitary hormones increased significantly during hypoglycemia (analysis of variance for hypoglycemic effects: beta-endorphin, P < 0.02; growth hormone, P < 0.04; adrenocorticotropin, P < 0.05). No insulin species effect was detected. Hypothalamic-pituitary activation during insulin-induced hypoglycemia is independent of the insulin species used, which supports earlier observations of an identical sympathoadrenal response during HI- and PI-induced hypoglycemia.

Smoking can be detected by the determination of cotinine in urine. We compared the performance of an automated modification of the 'König' reaction adapted to a centrifugal analyzer with an automated commercial fluorescence polarization immunoassay (TDX system). In the latter assay, cotinine, as the primary metabolite of nicotine, can be measured with high specificity. In contrast, the 'König' reaction also detects nicotine metabolites other than cotinine by a group colour reaction. Analysis speed of the 'König' reaction was about 66 samples/h with a detection limit 2 S.D. above the mean value of urine samples of non-smokers. Analysis speed of the TDX system was 41 samples/h. The coefficient of variation (C.V.) of both methods in smokers' urine was 8.6% ('König' reaction) vs. 3.4% (TDX system) in the high range and 16.4% vs. 9.5% in the low range. In a controlled, prospective study recruiting 86 cigarette-smoking volunteers, 83.7% were correctly classified as being smokers by both systems, 13.9% were classified as smokers by the 'König' reaction only and 2.4% were misclassified as non-smokers by both systems. Thus, the sensitivity of the 'König' reaction seems to be higher than in the TDX system (97.6% vs. 83.7%). Of 33 non-smoking individuals, 81.8% were correctly classified as non-smokers by both systems, 18.2 were misclassified as smokers by the 'König' reaction and no person was misclassified by the fluorescence polarization immunoassay. Thus, the specificity of the TDX system seems to be higher than that of the 'König' reaction (100% vs. 81.8%). We conclude that both systems are applicable to detect individuals who smoke regularly by simple urine testing. The higher specificity of the TDX system is outweighed by the higher sensitivity of the 'König' reaction at much lower cost.

A 57-year-old male patient suffering from dramatically deteriorating diffuse and focal central nervous system symptoms was admitted to hospital after a short prodromal period in a somnolent state. He was diagnosed as having systemic vasculitis positive for circulating anti-neutrophil cytoplasmic antibodies, primarily involving the brain, but also most other organ systems. Circulating anti-neutrophil cytoplasmic antibodies are highly specific for Wegener granulomatosis, though they have been detected in rare cases of other vasculitic syndromes. Central nervous system lesions as presenting signs in Wegener granulomatosis have to be regarded as rare. This case nonetheless suggests that Wegener granulomatosis has to be considered in patients with a predominantly cerebral manifestation of a vasculitic syndrome.

Thiols have been shown to be related to insulin secretion and to uptake of glucose into tissues. In the present study the effects of i.v. administration of acetylcysteine (N-acetylcysteine, NAC, CAS 616-91-1) on glucose consumption and plasma free thiols were studied in young healthy volunteers during hyperglycemic clamp. NAC (0.5-2.0 mg/kg) significantly increased glucose consumption. This effect was not obvious at higher doses of NAC. Plasma free NAC depended on the dose of NAC injected. The t1/2 of NAC was 11 min. NAC produced significant increases of plasma cysteine concentrations, and a slight but insignificantly increase of plasma glutathione. These data suggest that a moderate increase in plasma thiols augments glucose consumption during hyperglycemic clamp.

Recently, there have been reports on a diminished awareness of hypoglycaemia after a switch from purified pork insulin (PPI) to human insulin (HI) in insulin-dependent diabetes mellitus (IDDM). To clarify this phenomenon we investigated nine IDDM patients without signs of autonomic neuropathy. After an overnight euglycaemic clamp, blood glucose was lowered to hypoglycaemic levels by means of an artificial pancreas (Biostator) on 2 days. Insulin was used in a double-blind, randomized, cross-over fashion, either PPI or HI. The symptomatology and the hormonal counterregulation of developing hypoglycaemia was recorded. Venous concentrations of free insulin, cortisol, glucagon, growth hormone and the prevailing blood glucose were similar under both insulins. Eight out of nine IDDM patients felt more symptoms and at a higher blood glucose concentration under PPI than under HI. The first symptom of developing hypoglycaemia appeared at a mean blood glucose concentration of 61.1 +/- 5.4 mg.dl-1 under PPI and 44.4 +/- 5.3 mg.dl-1 under HI respectively (P less than 0.05). We conclude that HI may cause symptoms of hypoglycaemia to appear later and with a lesser number in comparison to PPI.

For more than 2 years now it has been controversially debated whether awareness of hypoglycemia is reduced when type I diabetic patients are switched from porcine to human insulin. In order to address this question, we studied nine C-peptide negative diabetics (age 27.6 years, Broca index 106%, duration of diabetes 5.7 years, HbA1, 8.8%) in comparison with eight healthy volunteers (age 22.4 years, Broca index 104%). Following euglycemic monitoring overnight, a controlled hypoglycemia was induced by altering the algorithms of the Biostator. This was done in a double-blind, cross-over fashion using porcine or human insulin on 2 nonconsecutive days. There were no differences between the results obtained with respect to the time course of the study, blood glucose, amount of insulin infused, and concentration of venous free insulin achieved. Of the nine diabetics, eight were aware of hypoglycemia at a higher blood glucose level under porcine insulin. The first symptom of hypoglycemia was perceived at a mean blood glucose level of 61.1 +/- 5.4 mg/dl under porcine insulin and of 44.4 +/- 5.3 mg/dl under human insulin (P less than or equal to 0.05). Thirty symptoms were noted under porcine insulin exclusively or preferentially as opposed to only eight which were observed exclusively or preferentially under human insulin. The healthy volunteers evidenced fewer symptoms at lower blood glucose concentrations than the diabetics. The clear difference between human and porcine insulin could not unequivocally be reproduced in this group.(ABSTRACT TRUNCATED AT 250 WORDS)

In order to facilitate the management of sports and work for insulin injecting diabetic patients we analyzed 6 different situations: 1) In the morning before injecting insulin stepwise increasing bicycle ergometry until exhaustion with a duration of less than one half hour may be performed without previous reduction of insulin or additional oral carbohydrates. Maximal work load can thus be determined with ECG monitoring. After insulin injection we advise our patients to estimate their reaction by calculating with exercise units. One exercise unit equals 20 minutes of half maximal exercise or one hour of 30% maximal exercise. 2) Performing one exercise unit the diabetic will have to anticipate a blood glucose reduction of -60 mg/dl. In order to maintain normal blood glucose levels he will have to reduce the regular insulin bolus 3) in the morning by -3,3 IU or 4) by -1.7 IU in the evening or he should 5) take +12 g of oral glucose (quickly absorbable carbohydrates). 6) A reduction of basal rate (CSII) or NPH insulin (ICT) is not advisable for exercise up to 3 hours. On the basis of these mean values every diabetic patient has to monitor blood glucose during exercise and adapt the measures to his individual reactions.

Cardiovascular reflex tests are used to assess cardiac autonomic neuropathy in diabetes mellitus. Cardiovascular diseases (CVD) are known to alter baroreflex mechanisms. Diabetic patients are at a high risk for cardiovascular complications. In order to prove whether cardiovascular diseases reduce the diagnostic value of the cardiovascular reflex tests in diabetic autonomic neuropathy unselected groups of 274 nondiabetic and 103 diabetic patients were studied: E/I, 30/15, and Valsalva ratios, sustained handgrip test and blood pressure response to standing. Both groups were subdivided into young (less than or equal to 45 years) and older (greater than 45 years) patients and into subjects with and without CVD. In young nondiabetic patients with CVD, E/I and Valsalva ratios were significantly lower than in those without CVD. In young diabetic patients with CVD, only E/I ratios were significantly reduced compared to those without CVD. The tests reflecting sympathetic nerve function did not differ between patients with and without CVD, neither in the nondiabetic nor in the diabetic subjects. In the older nondiabetic and diabetic patients, cardiovascular reflexes were generally impaired, but did not show any difference between subjects with and without CVD. In young diabetic patients suffering from CVD, the diagnostic value of cardiovascular reflex tests is reduced as far as cardiac autonomic neuropathy is concerned. In older patients, the tests are not suitable for the diagnosis of diabetic autonomic neuropathy. More specific methods are required.

A method is described for the quantitative determination of 20-ketosteroids in urine during the application of a 3alpha, 20beta-hydroxysteroid: NAD oxidoreductase. In the presence of NADH H+ the enzyme catalyses in an "equimolar" developing reaction the reduction of 20-keto groups of C-21 steroids giving 20 beta-alcohols. The measurable NADH H+ consumption is a measure for the quantity of those 20-ketosteroids present in the reaction mixture. The 3alpha-hydroxysteroid: NAD oxidoreductase activity of the enzyme does not influence the specificity of the method to determine the 20-ketosteroids because,-under the present extraction and purification conditions-those 3alpha-hydroxy-5alpha-androstan derivatives are not reaching the reaction mixture of determination. The demands towards the criterions of reliability (correctness and exactitude) come to be fulfilled by this method.

It was the aim of the workshop to summarize present knowledge of the variant creatine kinases in human blood. Discussion was centered on the nature, measurement, and clinical significance of these variants. On the basis of the presented results, the different creatine kinase variants can be classified as follows: Normal size variants (80000 Daltons). These originate from postsynthetic modifications of the three dimeric isoenzymes creatine kinase-MM, MB or BB. The M subunit can be transformed by a serum constituent and these modifications result in at least three different creatine kinase-MM and two creatine kinase-MB variants, which still show catalytic activity. The mechanism of the postsynthetic alterations of creatine kinase-BB seems to be more complex: In vitro incubation of this isoenzyme even in a non-serum matrix changes its electrophoretic mobility and decreases activity. In vivo there is evidence that on the one hand intact creatine kinase-BB molecules are directly removed from the circulation. On the other hand, however, inactive creatine kinase-BB-protein is reported to occur in serum. Variants with higher molecular weights (greater than 200000 Daltons). These are termed macro creatine kinases. Macro creatine kinase type 1 comprises the immunoglobulin-bound creatine kinase isoenzymes. Of these immune complexes, IgG-linked creatine kinase-BB is well known and has been described in detail, whereas the occurrence of creatine kinase-MM-containing macro creatine kinases is still questionable. Macro creatine kinase type 1 is found in the blood of about 2% of all hospitalized patients. It occurs mainly in elderly women, but it is not known whether it has any special clinical significance. Macro creatine kinase type 2 is the term for an oligomeric form of mitochondrial creatine kinase released after breakdown of mitochondria in liver, heart and some tumours. After treatment with urea this oligomeric form is converted into a normal sized, dimeric creatine kinase-MiMi. Macro creatine kinase type 2 is found exclusively in seriously ill patients, and may occur in more than 3% of all hospitalized patients. This classification of the creatine kinase variants seems logical, since it takes into account the nature of the creatine kinase variants, and it permits the classification of all atypical creatine kinases described in the literature. As quantification and differentiation now become possible, further experimental and clinical investigations should provide the information necessary for a better understanding of the physiology and pathobiochemistry of these multiple forms of creatine kinase.

The paper presents an analysis of clinical symptoms, signs and laboratory data of 330 diabetic patients who developed lactic acidosis after having been treated with biguanides (phenformin, buformin, metformin). From the review of the literature an attempt is made to find special features that predisposed patients to develop lactic acidosis such as accompanying illnesses and additional medications, to describe the course of illness and also the factors that influenced the prognosis. Of the patients that developed lactic acidosis 50.3% died. These patients were older, they suffered more frequently from cardiovascular shock, their acidosis was more severe, the whole blood lactate concentration was higher, and the degree of renal insufficiency was more advanced. From our observations we conclude the the treatment of diabetes mellitus with biguanides should be reserved for specially selected patients.

Creatine kinase isoenzymes showed decreasing thermal stability and increasing lability towards pH changes in the order: MM, MB, and BB. The three isoenzymes exhibited their highest stability between pH 6.5 and 7.0. At 37 degrees C and an almost physiological pH of 7.5 the decay constants were 0.025, 0.164 and 0.580 h-1 (MM, MB, and BB isoenzyme), respectively. In contrast to free creatine kinase BB, immunoglobulin-linked creatine kinase BB (macro creatine kinase BB, type 1 macro creatine kinase) showed a markedly higher stability; this accounts for the persistence of creatine kinase BB activity in macro creatine kinasaemia. In addition we identified a second type of macro creatine kinase in patients' sera, which is also thermostable. A simple heat inactivation test (20 minutes, 45 degrees C, immunoinhibition of the M-subunits) differentiates thermostable macro creatine kinases from thermolabile creatine kinases and thus completes isoenzyme diagnosis.

The enzyme 3 alpha, 20 beta-hydroxysteroid:NAD+ oxidoreductase (EC 1.1.1.53) catalyses the stoichiometric reduction of 20-oxo groups of C-21 steroids by NADH, and the non-stoichiometric oxidation of 3 alpha-hydroxy groups of 5 alpha-androstane derivatives by NAD. The activity of the enzyme towards the most important C-18, C-19 and C-21 steroids of human urine was tested in the presence of NAD and NADH. The rate of reduction of 20-oxo steroids is influenced by substituents at various positions of the steroid skeleton. These studies are intended as the basis of an eventual clinical chemical application.

In order to assess hemodynamic changes in early phases of insulin-dependent diabetes mellitus, muscle tissue oxygen tensions were determined in 7 newly diagnosed insulin-dependent diabetic patients and in 6 healthy control subjects matched for sex, age and weight. Muscle tissue oxygen tension was measured by polarrographic needle probes while breathing ambient air and oxygen enriched air with an oxygen concentration of 40 per cent as well. Three times during the experiment, heart rates, blood pressures, blood glucose concentrations, and capillary oxygen tensions were obtained. Heart rate, blood pressure, peripheral and autonomic nerve functions did not differ between the 2 groups studied. While breathing ambient air, muscle tissue oxygen tensions were significantly (p = 0.025) higher in the diabetic patients than in the control subjects. In contrast to the control subjects, diabetic patients did not increase muscle tissue oxygen tensions after inhalation of oxygen enriched air despite of an equal increase in capillary oxygen tensions (2p less than 0.05). Local tissue hypoxia does not seem to be a leading cause of hemodynamic abnormalities in the early phases of diabetes.

In order to define clinically relevant lactic acidosis, 12 biochemical variables, eight clinical symptoms and signs, leading diagnoses, and mortality were evaluated prospectively in approximately 2,000 unselected patients with internal diseases, consecutively admitted to the hospital. Patients with incomplete data sets were not considered. Of those patients who repeatedly were admitted to the hospital during the time of the study, only the first admission was included for statistical analysis. In addition to 11 definitions of lactic acidosis given in the literature, sequential cluster analyses of the biochemical variables were used to estimate the incidence of lactic acidosis in 1,467 patients. Depending upon which definition was used, 0.5-3.8% of all patients were classified as suffering from lactic acidosis, with a mortality rate ranging from 30-88%. From this study it is concluded that a limit of less than or equal to 7.35 for pH and of greater than 5-6 mmol/L for the concentration of lactate in whole blood will minimize false-negative or false-positive classifications.

An enzymatic method is described for the determination of total cholesterol in serum using a single aqueous reagent which can easily be prepared from commercial substrates and enzymes. The determination is carried out manually, the resulting stable chromogen is measured at a wavelength of 500-550 nm. The cholesterol concentration may be calculated either using a primary cholesterol standard or a constant factor for a given wavelength. The reliability of the method is reported: Data for the imprecision are given on the basis of a survey in 3 laboratories, the accuracy is established by comparison with a definitive and a reference method. Analytical and biological interferances are briefly discussed and results with this enzymatic method are reported concerning the reference values for serum cholesterol.

A fully enzymatic triglyceride determination utilizing enzymatic hydrolysis with a lipase-esterase mixture and subsequent enzymatic glycerol determination, has been adapted for use in a continuous flow 12-channel-analyzer. The method is linear up to 7.9 mmol/l (700 mg/100 ml). The analytical precision in the concentration range of 1.5 to 5.4 mmol/l (133 to 478 mg/100 ml) is characterized by relative standard deviations of 0.8 to 4.8%. In the lower measuring range at concentrations around 0.7 mmol/l (62 mg/100 ml) a mean relative standard deviation of 7.2% is found for 1140 measurements under routine conditions. For triglyceride concentrations of 0.9 to 7.7 mmol/80 to 680 mg/100 ml) a mean relative coefficient of verspill Q = 2.0 is determined. Bilirubin caused no observable interference in the determination. In comparison with the manual method by Eggstein & Kreutz (1966) Klin. Wochenschr. 44, 262-267) the results from the fully enzymatic method on the 12-channel-analyzer were lower by approximately 16%, corrected by an additive factor of 0.029 mmol/l (2.59 mg/100 ml). The accuracy controls with controls sera showed a difference of 10%.

Exhaustive graded exercise leads to changes of hormones, carbohydrate, and lipid metabolism in normal controls and obese patients after prolonged starvation. Concomitant with a large increase of plasma catecholamines, insulin concentration is reduced and blood glucose levels slowly increase. More glucose is made available by glycogenolysis and gluconeogenesis than can be oxidized in the mitochondria. Lactate associated metabolic acidosis appears. Starving obese patients in the basal state have reduced blood glucose concentrations, but their initial values for free glycerol, free fatty acids, and ketone bodies are much higher than in normal controls. This is caused by the starvation induced lipolysis. With exhaustive exercise adrenaline, noradrenaline, and free glycerol increase. In contrast, free fatty acids and ketone bodies decrease, because they are consumed as fuel. Prolonged starvation changes basal values of hormones and metabolites, but it does not change the quality of exercise-induced shifts in these values when compared with those of the normal controls.

One year after total duodenopancreatectomy a clinical and laboratory evaluation including exhaustive bicycle ergometry was performed in 6 male patients. The insufficiency of the exocrine pancreas can be compensated by at least 10 g pankreatin per day. During physical exercise patients had higher arterial values of lactate and free glycerol after duodenopancreatectomy than 7 healthy individuals and 6 diabetic patients type I. This metabolic overreaction was due to a deficiency of pancreatic glucagon and resulted in an impaired hepatic gluconeogenesis. There was no detectable increase in growth hormones and only a small one in catecholamines. The physical condition of patients after duodenopancreatectomy was clearly worse.

Typical signs of so-called hyperthyroiditis are hyperthyroidism, low iodine uptake by the thyroid, absence of local, general or humoral signs of inflammation, and absence of significant antibody titres against thyroid tissue. These features are illustrated by the case report of a 51-year-old man. Since the course of hyperthyroidism is short and has a good prognosis, the importance of the diagnosis lies in avoiding unnecessary therapeutic measures. This cause of hyperthyroidism can be recognized only by including tests of intrathyroid iodine metabolism among diagnostic procedures.

The activity of dipeptidyl aminopeptidase IV was studied in the sera of 378 hospitalized patients. The mean activity of dipeptidyl aminopeptidase IV was elevated significantly in patients with neoplasmata and hepatitis, but not in patients with liver cirrhosis. Significant correlations (p less than 0.001) existed with gamma-glutamyl transferase, glutamate dehydrogenase, alkaline phosphatase and leucine aminopeptidase. A significant correlation with lactate dehydrogenase existed only in patients with neoplasmata. Principal component analysis, performed with aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, leucine aminopeptidase, lactate dehydrogenase and dipeptidyl aminopeptidase IV, revealed correlations between the activities of aspartate aminotransferase and alanine aminotransferase, and between alkaline phosphatase and leucine aminopeptidase, but neither dipeptidyl aminopeptidase IV nor lactate dehydrogenase showed any correlation with either of these two groups. In lectin affinity chromatography with concanavalin A and wheat germ lectin sepharose, serum dipeptidyl aminopeptidase IV from liver cirrhosis patients showed the same binding pattern as that from healthy subjects. The activity and glycosylation of dipeptidyl aminopeptidase IV in serum and hepatic plasma membranes was investigated in rats, following the induction of hepatitis with galactosamine. In the serum, dipeptidyl aminopeptidase IV activity was elevated as early as 6 h after galactosamine injection, and the elevated activity persisted until the 7th day. At the same time dipeptidyl aminopeptidase IV activity was also elevated in the hepatic plasma membrane. Ninety eight percent of hepatic dipeptidyl aminopeptidase IV bound to concanavalin A as well as to wheat germ lectin and this value was unchanged during hepatitis. In the serum of control rats, 90% of dipeptidyl aminopeptidase IV bound to concanavalin A but only 39% to wheat germ lectin.(ABSTRACT TRUNCATED AT 250 WORDS)

In 6 male patients, who had duodenopancreatectomy, oral fat respectively carbohydrate tolerance tests were performed. Intake of at least 10 g pancreatine did reduce the ensuing steatorrhea. Increased oral intake of carbohydrates led to increased levels of glucose in blood and urine. In addition, the patients were subjected to excessive exercise tests; in the course of these tests hormones, substrates and metabolites of fat and carbohydrate metabolism were measured. The values were compared to corresponding values from 6 type I diabetes patients and 7 normal persons. In the operated group lactate and free glycerol increased because of reduced hepatic glucose neogenesis, catecholamines increased little, and HGH not at all. Capacity for work was reduced in the operated group. Malassimilation and diabetes may be compensated for by drug therapy after duodenopancreatectomy. However, endocrine as well as metabolic derangements do follow duodenopancreatectomy, and ought to be taken into account preoperatively, since they may reduce the benefit of surgery in patients with chronic pancreatitis.

The circadian variations of serum intact parathyrin, C-terminal parathyrin (65-84), mid-region parathyrin (44-68) fragments, calcitonin, total calcium, ionized calcium, albumin and phosphate were measured in five healthy subjects. Intact parathyrin, parathyrin (44-68) and calcitonin show a synchronous diurnal fluctuation with a nocturnal increase to a maximum between 24.00 and 2.00 hours. Whereas phosphate has a marked circadian rhythmicity with a zenith between 1.00 and 8.00 hours, total calcium and albumin show a tendency to decrease between 20.00 and 6.00 hours. Ionized calcium concentration remains constant over the whole day.

A micromethod is described for the determination of glucose in 20 microliter of skin-puncture blood for the DuPont aca. For the determination of glucose we prefer whole blood which is deproteinised with uranyl acetate. Some modification of test conditions are programmed into the computer II. The emergency analysis of supernatant on the aca then gives the same values as the Technicon Autoanalyzer II, using glucose dehydrogenase for routine analyses. The aca readout is linearly related to glucose concentrations up to 60 mmol/l.

In the sera of four female patients with proven IgG-linked creatine kinase BB (macro creatine kinase BB) we studied the nature of the binding between creatine kinase isoenzymes and immunoglobulin G. The specificity towards the isoenzyme bound, the recombination of the complex after treatment with acid buffer, the site of the binding between both partners and an apparently monoclonal nature of the immunoglobulin G involved in the complex indicate that a specific antigen-antibody reaction is responsible for the existence of macro creatine kinase BB in the sera investigated.

The particular questions asked in our study were: 1. does the individual reproducibility of the cardiovascular reflex tests differ between healthy controls and patients suffering from type I diabetes mellitus and 2. if there is a difference, do the different cardiovascular reflexes vary in this regard? Nine healthy controls (4 women, 5 men, age 31 +/- 2.1 years) and 11 type I diabetics (4 women, 7 men, age 30.9 +/- 5.6 years, duration of diabetes 3.23 years) underwent the following tests 6 times in a 12-h period (07:00 to 19:00): variation of heart rate during deep breathing (E/I ratio), variation of heart rate during lying and standing (tachycardia/bradycardia or 30/15 ratio), Valsalva maneuver (Valsalva ratio), response of diastolic blood pressure to sustained hand grip, and response of systolic blood pressure to posture. The test results did not indicate a diurnal fluctuation nor were they systematically influenced by antecedent insulin injections or meals, either in diabetic patients or in healthy controls. The 11 diabetics had significantly lower intraindividual variations of E/I and Valsalva ratios than the controls (p less than 0.05, p less than 0.001, respectively). In the diabetics with parasympathetic failure the intraindividual variabilities of all cardiovascular reflex responses were lower than those of the patients with an intact autonomic nervous system as well as those of the control subjects. On the contrary, in the diabetic patients without autonomic neuropathy, only the intraindividual variability of the Valsalva maneuver was significantly attenuated (p less than 0.025), compared with the healthy volunteers. To conclude, the more pathological the single test result, the greater is its reproducibility and its clinical significance.

A 48-year-old woman with diabetes mellitus (type IIb) had to be treated with insulin because of poor blood-sugar control. Infiltrates at the sight of injection occurred with two different porcine insulin preparations, necessitating a switch to human insulin. After the third injection of the latter an anaphylactic reaction developed within minutes. During a pregnancy in 1968 the patient had briefly received bovine insulin. Tests now revealed an immediate-type allergy against all three available species insulins, which was successfully treated by hyposensitisation.

For evaluation of 2 simple methods gastric emptying was studied simultaneously by ultrasound and scintigraphy. In 12 patients (25-76 years-old) gastric emptying was quantified by scintigraphy after ingestion of 300 ml Tc-99m-labelled orange juice; simultaneously, the region of the gastric antrum was measured in 5-minute intervals in the aortic longitudinal section. In the following day gastric emptying was studied after ingestion of the identical volume of orange juice by planimetry of the maximal gastric area in an anatomical long-axis section in dextro-decline position. By linear regression analysis a significant correlation coefficient (r = 0.83, p less than 0.001) was obtained between the results of the sonographic antrum method and scintigraphy and between scintigraphy and the sonographic dextro-decline method (r = 0.83, p less than 0.001). These results imply that gastric emptying of fluids can be quantified by both simple sonographic methods. The sonographic dextro-decline method is less influenced by air and hence easier to perform.

An ultrasound investigation was undertaken of the neck region of 42 patients with normal neck anatomy in order to determine whether the results of ultrasound-gained topographical data provided pointers to the choice of entry site to the internal jugular vein (IJV). In addition, the IJV was punctured under ultrasound control in 23 patients in an intensive care unit in whom there was a problem of increased bleeding tendency, anatomical difficulty or previously failed "blind" puncture. In all of them a central venous catheter was placed without complication by the Seldinger technique via the primary chosen point for puncture. An approach through the sternocleidomastoid muscle, between the cricoid level and the "central" place of puncture between the two bellies of the sternocleidomastoid muscle proved to be the most satisfactory compromise between easy application of the ultrasound head, large vein diameter and reduction of any risk of mistakenly puncturing artery or pleura. This approach has to be varied according to the ultrasound findings. It is concluded from this experience that ultrasound is suitable for the placement of central venous catheters. But since the equipment is bulky it cannot be used in an emergency.