Exogenous interleukin-3 enhances IL-4 production by splenic CD4+ cells during the early stages of a Trichinella spiralis infection

We determined serum advanced glycation end-products (AGE) levels in patients with NIDDM and evaluated the relationship between these levels and diabetic complications. The subjects consisted of 125 patients (mean age, 59.2 +/- 11.1 years, duration of diabetes 11.6 +/- 8.9 years, mean HbA1c, 6.8 +/- 1.0%) with stable blood sugar control. Sixty-three healthy volunteers (mean age, 58.3 +/- 12.7 years) served as controls. Serum AGE were measured by a newly developed ELISA method. Serum AGE levels were significantly higher in the diabetic group compared with the normal control group (7.2 +/- 14.6 vs. 3.3 +/- 1.0 mU/ml, P < 0.05). Significant correlations were seen between serum AGE and the degree of diabetic nephropathy. Serum AGE levels of diabetic patients with proliferative retinopathy were significantly higher than those of patients without proliferative retinopathy (5.7 +/- 1.8 vs. 3.1 +/- 1.0 mU/ml, P < 0.025) in the patient groups whose serum creatinine levels were between 2.0 and 3.9 mg/dl, although serum creatinine levels of both groups were not significantly different. Serum AGE levels reflected the severity of diabetic complications, including nephropathy and retinopathy.     

Plasma levels of carbamazepine and carbamazepine-10,11-epoxide during treatment of epilepsy

Carbamazepine and its epoxide in plasma were measured by liquid chromatography in 25 patients treated with a mean dose of carbamazepine of 12.5 +/- 3.3 mg/kg body weight. The mean concentrations of parent drug and metabolite were 5.4 +/- 2.5 mug/ml and 1.10 +/- 0.42 mug/ml, respectively. A singificant correlation was found between the plasma concentrations of the two compounds (r = 0.64; p less than 0.001), but marked interindividual variation existed in the ratio of carbamazepine to carbamazepine to epoxide. Based on simultaneous measurements in plasma and cerebrospinal fluid, the unbound fraction of carbamazepine in plasma was of the order of 20% as compared to 45% for the epoxide. Thirteen ambulant patients suffering from partial epilepsy with complex symptomatology, who were already being treated with phenytoin in optimal doses (plasma level 14-20 mug/ml) were also given carbamazepine. At plasma levels of the latter of about 5 mug/ml there was no further reduction in the frequency of partial or generalized epileptic seizures. In five patients the dose was increased to produce plasma concentrations of 7 - 8 mug/ml. There was still no improvement and side-effects were seen in three patients.     

Prolactin and beta-endorphin responses to hypoglycemia are reduced in well-controlled insulin-dependent diabetes mellitus

Several pituitary hormones, including corticotropin (ACTH), growth hormone (GH), prolactin, and beta-endorphin (but not thyrotropin, follicle-stimulating hormone, or luteinizing hormone), are released in response to hypoglycemia in normal subjects. In patients with insulin-dependent diabetes mellitus (IDDM), the degree of glycemic control is known to alter ACTH and GH responses to hypoglycemia. The current study was performed to examine the effect of glycemic control on prolactin and beta-endorphin responses to hypoglycemia in subjects with IDDM. We performed 3-hour stopped hypoglycemic-hyperinsulinemic clamp studies (12 pmol/kg/min) during which plasma glucose was decreased from 5.0 mmol/L to 2.2 mmol/L in steps of 0.6 mmol/L every 30 minutes in 20 subjects with uncomplicated IDDM (12 males and eight females; age, 26 +/- 2 years; IDDM duration, 10 +/- 1 years; body mass index, 23.6 +/- 0.6 kg/m2) and 10 healthy subjects (five males and five females aged 30 +/- 1 years). The 10 diabetic subjects in good glycemic control (mean hemoglobin A1 [HbA1], 7.5% +/- 0.3%; normal range, 5.4% to 7.4%) were compared with the 10 poorly controlled patients (mean HbA1, 12.6% +/- 0.5%; P < .001 v well-controlled diabetic group). During hypoglycemia, prolactin levels in the well-controlled diabetic group did not change (7 +/- 1 microgram/L at plasma glucose 5.0 mmol/L to 9 +/- 2 micrograms/L at plasma glucose 2.2 mmol/L), whereas prolactin levels increased markedly in the poorly controlled diabetic group (7 +/- 2 micrograms/L to 44 +/- 17 micrograms/L) and healthy volunteers (12 +/- 2 micrograms/L to 60 +/- 19 micrograms/L, P < .05 between IDDM groups). The plasma glucose threshold required for stimulation of prolactin secretion was 2.2 +/- 0.1 mmol/L in well-controlled IDDM, 3.0 +/- 0.4 mmol/L in poorly controlled IDDM, and 2.4 +/- 0.1 mmol/L in healthy subjects (P < .05 between IDDM groups). Responses in males and females were similar. The increase in beta-endorphin levels was also attenuated in well-controlled IDDM patients (4 +/- 1 pmol/L at plasma glucose 5.0 mmol/L to 11 +/- 4 pmol/L at plasma glucose 2.2 mmol/L) versus poorly controlled IDDM patients (5 +/- 1 pmol/L to 26 +/- 7 pmol/L) and healthy subjects (8 +/- 1 pmol/L to 56 +/- 13 pmol/L). The plasma glucose threshold required for stimulation of beta-endorphin release was again lower in well-controlled IDDM versus poorly controlled IDDM patients (2.2 +/- 0.1 v 3.0 +/- 0.3 mmol/L) and healthy subjects (2.5 +/- 0.4 mmol/L, P < .05 between IDDM groups). In conclusion, prolactin and beta-endorphin responses to a standardized hypoglycemic stimulus (plasma glucose, 2.2 mmol/L) are reduced and plasma glucose levels required to stimulate release of prolactin and beta-endorphin are lower in well-controlled IDDM compared with poorly controlled IDDM and healthy subjects. Thus, stress hormones not previously considered to have a primary role in plasma glucose recovery from hypoglycemia are affected by glycemic control, suggesting a more generalized alteration of hypothalamic-pituitary responses to hypoglycemia in IDDM patients with strict glycemic control.     

Prevention of diabetic glomerulopathy in streptozotocin diabetic rats by insulin treatment. Kidney size and glomerular volume

Kidney weight and glomerular volume have been studied in groups of insulin-treated streptozotocin diabetic rats maintained at high, or nearly normal plasma glucose levels. Kidney weight and glomerular volume in these groups were compared to a non-diabetic control group. --Rats with nearly normal plasma glucose levels (95 +/- 35 to 182 +/- 20 mg/100 ml) had the same kidney weight as the non-diabetic controls, 1.04 +/- 0.14 and 1.07 +/- 0.09 g, respectively. In the rats with constant high plasma glucose (338 +/- 71 to 555 +/- 86 mg/100 ml) kidney weight was significantly increased, 1.73 +/- 0.20 g, compared to each of the two other groups. Glomerular volume was 0.559 millimicron3 in the diabetic animals with nearly normal plasma glucose, a value very close to that of the non-diabetic controls, 0.587 milimicron3. In animals with high plasma glucose concentrations glomerular volume was 0.775 millimicron3, 2 p less than 0.03 compared with both other groups. --The study indicates that good diabetic control for 6 months prevents the development of large kidneys and large glomeruli in dibatic rats.     

Cooperative study on the radioimmunological thyrotropin determination (hTSH) in serum (author''s transl)

The increased incidence of drowsiness in hypoalbuminemic patients administered diazepam and more rapid clearance of tolbutamide in cirrhotics may be due to changes in plasma protein binding. The binding of diazepam and tolbutamide was studied by equilibrium dialysis at 37degreesC over a total drug concentration range of 1 to 10 mug/ml and 50 to 300 mug/ml, respectively, in plasma from 21 normal and 14 alcoholic subjects. At 1 mug/ml, diazepam plasma protein binding (+/- S.D.) was 98.5+/-0.4 per cent in normals and 97.8+/-1.2 per cent in alcoholics; at 100 mug/ml, tolbutamide binding was 97.8+/-0.3 per cent in normals and 95.1+/-4.2 per cent in alcoholics. For both agents at all concentrations, the binding to plasma from alcoholics was significantly decreased (P less than 0.01-less than 0.02). The extent of binding of both drugs was dependent on the albumin concentration. These findings suggest that important changes in pharmacologic effect, distribution, and clearance of diazepam and tolbutamide can be anticipated in alcoholics with hypoalbuminemia.     

Effect of 1-deamino-5-D-arginine vasopressin (DDAVP) on plasma cortisol (hydrocortisone)

The influence of 1-deamino-8-D-arginine vasopressin (DDAVP), the new antidiutetic polypeptide without any side effects on plasma cortisol, was investigated in 30 healthy persons. A dose of 4 mug DDAVP administered intravenously induced a rise in plasma cortisol (hydrocortisone) levels greater than 3.5 mug/100 ml in 12 out of 20 persons studied. In this group (group I), the average increase at 15 minutes was 6.92+/-1.74 mug/100 ml (P less than 0.005), while in the remaining eight persons (group II) plasma cortisol levels decreased according to the usual normal daily rhythm. DDAVP, 80 mug, administered intranasally had no demonstrable influence on physiologic plasma cortisol regulation. On the basis of the present findings with relatively low doses, pituitary responsiveness (ACTH release) might be expected to occur in a higher percentage of persons after giving high intravenous doses of DDAVP. Further efforts are necessary to develop a safe vasopressin test for clinical examination of adenohypophyseal function.     

Plasma prolactin responses to thyrotropin-releasing hormone in patients with breast cancer

Plasma human prolactin levels were measured by homologous radioimmunoassay in patients with primary breast cancer and in normal women of similar age. In normal controls mean (+/- SEM) basal plasma prolactin levels were 11.9 +/- 1.5 ng/ml and intravenous injection of synthetic thyrotropin-releasing hormone (TRH), 500 mug, caused a significant rise in plasma prolactin in all subjects examined with a maximum response of 52.6 +/- 3.3 ng/ml (mean +/- SEM). Markedly high plasma prolactin levels and exaggerated plasma prolactin responses to TRH were demonstrated in some patients with breast cancer. However, mean basal plasma prolactin levels and mean plasma prolactin increments following TRH in patients with breast cancer did not differ significantly from those in normal subjects. Plasma prolactin responses to TRH were slightly blunted during the administration of androgen in patients with breast cancer. These results suggest that some of the patients with primary breast cancer have abnormal prolactin secretion.     

Growth retardation and zinc nutrition

Based on a previous report of a zinc deficiency syndrome in children characterized by low hair zinc, anorexia, poor growth, and hypogeusia, 12 children attending a pediatric endocrinology clinic for growth retardation and judged as having short stature as a variant of normal (SVN) were evaluated as to their zinc nutriture to learn whether zinc deficiency was a contributory factor. None was found to have the above syndrome, although one child did have a hair zinc concentration below 70 mug/g. The mean hair zinc of the SVN subjects was lower than the hair zinc of 40 apparently normal adolescents, 131+/-37 mug/g vs. 168+/-44 mug/g (P less than 0.02), but there was no difference found in plasma levels of zinc or in taste acuity. In contrast, five patients with total growth arrest secondary to juvenile Crohn's disease (CD) were found to have multiple findings consistent with zinc deficiency including low plasma zinc, low hair zinc, or hypogeusia.     

Progression of nephropathy in long-term diabetics with proteinuria and effect of initial anti-hypertensive treatment

The rate of progression of nephropathy was studied in 6 young male diabetics with intermittent proteinuria (Albustix) and in 10 young male diabetics with constant proteinuria by measuring glomerular filtration rate (GFR), renal plasma flow (RPF), and urinary albumin excretion by exact techniques. Albumin excretion was elevated in both the recumbent and the erect position in patients with intermittent proteinuria. GFR and RPF were at the same level as in diabetics without proteinuria, and no deterioration in renal function was noted during a mean control period of 32 months. In the patients with constant proteinuria the fall rate during a mean period of 33.6 months for GFR and RPF was 0.91 ml/min/month +/- 0.68 (S.D.) and 4.38 ml/min/month +/- 3.23 (S.D.) respectively. Initial fall rate in GFR correlated well with long-term fall rate, both of which were studied in 7 patients. In the same patients there was a positive correlation between the fall rate in GFR and diastolic blood pressure as well as albumin clearance. In 8 patients with constant proteinuria and mean blood pressure of 159/101 mmHg, antihypertensive treatment was started with propranolol alone or combined with hydralazine and furosemide. During a treatment period of 47 days blood pressure was reduced to 143/93 mmHg, and in the same period urinary albumin excretion was reduced significantly from a mean value of 3547 mug/min to 2414 mug/min (P less than 0.01). Further control studies will clarify whether end-stage of renal insufficiency will be postponed by antihypertensive treatment.     

Estrogen improves endothelial function

PURPOSE: To determine the effect of estrogen on endothelium-dependent relaxation in the cutaneous microcirculation of women. METHODS: Three groups of women participated in the study. Group 1 (n = 20) was premenopausal and had a mean age of 39 years (range 24-50 years). Group 2 (n = 9) was postmenopausal and had a mean age of 58 years (range 53-65 years). Group 3 (n = 11) was postmenopausal and taking estrogen replacement therapy; the mean age was 53 years (range 43-58 years). Eleven women in group 1 underwent testing twice, once during menstruation (mean serum estradiol level 73 +/- 30 pg/ml) and once during midcycle (mean serum estradiol level 268 +/- 193 pg/ml; p = 0.003). Single-point laser Doppler ultrasound and laser Doppler imaging with a scanner were used to measure vasodilatation in the forearm skin in response to iontophoresis of 1% acetylcholine (endothelium dependent) and 1% sodium nitroprusside (endothelium-independent smooth muscle relaxant). RESULTS: All three groups were matched for body mass index and fasting glucose, total, high-density lipoprotein, and low-density lipoprotein cholesterol and triglyceride levels. All women had normal blood pressure, and none smoked. Mean serum estradiol levels were 196 +/- 170 pg/ml (group 1), 35 +/- 12 pg/ml (group 2), and 107 +/- 78 pg/ml (group 3) (p = 0.004). Maximum microvascular vasodilatation (percentage increase over baseline) in response to acetylcholine was reduced in group 2 (93% +/- 43%) compared with group 1 (187% +/- 63%) and group 3 (142% +/- 56%) (p = 0.001). The response to sodium nitroprusside also was diminished in group 2 (73% +/- 27%) compared with group 1 (126% +/- 45%) and group 3 (100% +/- 32%) (p = 0.02). Within group 1 the acetylcholine response was higher during the midcycle phase (186% +/- 31%) compared with the menstrual phase (147% +/- 57%) (p < 0.05). The sodium nitroprusside response also was higher during the midcycle phase (144% +/- 31%) compared with the menstrual phase (94% +/- 41%) (p < 0.05) CONCLUSION: The results indicate that estrogens might enhance endothelium-dependent and endothelium-independent vasodilatation in the microcirculation of women.     

Role of protein degradation in the growth of livers after a nutritional shift

Four patients with idiopathic pituitary dwarfism were shown to have growth hormone (GH), adrenocorticotropin (ACTH), and luteinizing hormone (LH) deficiencies. Basal levels of thyrotropin (TSH) were within normal range in three patients and slightly elevated in one. Exaggerated and delayed responses were obtained after TSH-releasing hormone (TRH) stimulation. Serum thyroxine (T4) values were low (2.3 +/- 0.4 mug/100 ml), while triiodothyronine (T3) levels were in the normal range (1.22 +/- 0.25 ng/ml), both rising substantially after exogenous TSH and consecutive TRH administration. Their hypothyroid state was, therefore, probably due to TRH deficiency. To examine the dose of L-T4 necessary to produce inhibition of the TSH response to TRH, 50 mug/m2/day of L-T4 was administered to these patients. At the end of 4 weeks of replacement, serum T4 rose to 5.2 +/- 0.5 mug/100 ml, whereas T3 was unchanged from the previous levels, after which TSH responses to TRH were completely suppressed in all patients. As a control group, six patients with primary hypothyroidism received gradually increasing doses of L-T4 for 4-week periods, and TSH response to TRH was tested at the end of each dosage of L-T4, until complete inhibition of TSH release was obtained. The primary hypothyroid patients required approximately 150 mug/m2/day of L-T4 for suppression of TSH response to TRH. At this dosage, serum T4 and T3 levels were 8.5 +/- 0.9 mug/100 ml and 2.34 +/- 0.5 ng/ml respectively, which were significantly higher than those levels in the pituitary dwarfs (P less than 0.001 for T4 and P less than 0.01 for T3). These observations indicate that the set point of TSH release in feedback inhibition by throxine is low in idiopathic hypopituitarism with TRH deficiency, and TRH seems to control the pituitary sensitivity to feedback regulation of thyroid hormones.     

A case of infiltration of scar of sarcoidosis after blepharoplasty

Plasma viscosity is mainly determined by large non-spherical proteins. In Type 1 diabetes mellitus, plasma viscosity increases with deterioration of diabetic control. Since protein glycation and formation of advanced glycosylation end products (AGEs) alter the structural and functional properties of proteins, AGEs might influence the rheological properties of plasma proteins. Therefore, we investigated the influence of plasma-AGEs on plasma viscosity in 34 normoalbuminuric diabetic patients (17 Type 1, 17 Type 2) with normal renal and liver function. In an additional experiment, 6 ml plasma of 9 healthy volunteers were incubated under sterile conditions for 14 days at 37.5 degrees C in the presence of 5.2 and 32.9 mmol l(-1) glucose. In diabetic patients, plasma-AGE levels were not correlated with plasma viscosity. Plasma-AGE levels in healthy controls (246 +/- 37 U ml[-1], mean +/- SD) were raised significantly (p<0.001) after the incubation at 37.5 degrees C (392 +/- 57 U ml[-1] and 552 +/- 58 U ml[-1], respectively). However, no difference was found in plasma viscosity pre- and post-incubation (pre-incubation: 1.25 +/- 0.04 mPas, post-incubation: 1.23 +/- 0.03 and 1.24 +/- 0.03, respectively). We conclude that there is no influence of plasma-AGEs on plasma viscosity.     

Thiamine, riboflavin, folate, and vitamin B12 status of infants with low birth Weights receiving enteral nutrition

The purpose of the present study was to monitor the vitamin status of 14 low-birth-weight (LBW) infants (< 1,750 g birth weight) at 2 weeks and an additional four infants at 3 weeks who were receiving an enteral formula providing 247 micrograms/100 kcal thiamine, 617 micrograms/100 kcal riboflavin, 37 micrograms/100 kcal folate, and 0.55 micrograms/100 kcal vitamin B12. The mean birth weight of the 18 infants was 1,100 +/- 259 g, and mean gestational age was 29 +/- 2 weeks. Weekly blood, 24-h urine collections, and dietary intake data were obtained. For thiamine, red blood cell (RBC) transketolase activity was within the normal range for all infants. For riboflavin, RBC glutathione reductase activity was normal for all infants except one. We calculated from intake and urinary excretion data that these infants require 225 micrograms/100 kcal thiamine and 370 micrograms/100 kcal riboflavin, respectively. Mean plasma folate levels were 21 +/- 11 ng/ml at 2 weeks and 18 +/- 5 ng/ml at 3 weeks. RBC folate levels were 455 +/- 280 ng/ml at 2 weeks and 391 +/- 168 ng/ml at 3 weeks. All folate blood values were normal, except for one subject with an elevated level (59 ng/ml). Vitamin B12 plasma values were 737 +/- 394 pg/ml at 2 weeks and 768 +/- 350 pg/ml at 3 weeks, and all values were normal except for three infants with elevated values. In conclusion, appropriate vitamin status was maintained during this short observational period, during administration of this enteral formula; however, riboflavin concentrations in the enteral feed may be excessive.     

Behavior of plasma levels of endothelin 1 and noradrenaline in patients with stable angina during the cold pressor test

The aim of this study was to evaluate the behaviour of plasma endothelin-1 (ET-1) and norepinephrine (NE) levels in patients with stable angina during a sympathetic stimulation test as the cold pressor test. We enrolled in the study 29 subjects: 14 patients with stable angina (all men, mean age 58.3 +/- 7.3 years) and 15 healthy subjects (all men, mean age 54 +/- 5 years). All patients with stable angina had a stenosis of the coronary arteries (at least 70% of the stenosis in one of the coronary arteries) confirmed by angiography. Before (-15 min; 0 min) during (+2 min) and after the cold pressor test (+5 min, +10 min, +20 min, +30 min) were measured the blood pressure and the heart rate. At the same time were collected venous samples for the ET-1 and NE determination. ET-1 levels increased only in the patients with stable angina (ET-1: O' = 9.8 +/- 3.7 pg/ml; +2' = 11.1 +/- 4.5 pg/ml; +10' = 14.8 +/- 7.1 pg/ml; +20' = 11.6 +/- 5.1 pg/ml; p < 0.05 vs 0', +2'; +20'). The NE levels increased in both groups (NE stable angina: 0' = 105 +/- 31 pg/ml; +2' = 206 +/- 127 pg/ml; +5' = 223 +/- 135 pg/ml; p < .05 vs +2', +5'); (NE healthy subjects 0' = 85 +/- 10 pg/ml; +2' 165 +/- 49 pg/ml; p < 0.05 vs + 2'). In conclusion, our study showed that cold pressor test is a stimulus for the sympathetic system in both groups. The increased levels of ET-1 detected only in the patients with stable angina suggest that this peptide can take part to the pathogenesis of the coronary artery disease.     

A simple radioimmunoassay for plasma cortisol: comparison with the fluorimetric method of determination

A quick and simple method for the radioimmunoassay of plasma cortisol is described. The mean morning plasma cortisol concentration in 43 normal subjects was 9.8 +/- 3.1 (S.D.) microgram/100 ml with a range of 5.0-19.5 microgram/100 ml. Mean midnight concentration in 24 normal subjects was 4.3 +/- 2.3 (S.D.) microgram/100 ml with a range of 1.4-9.6 microgram/100 ml. When compared with the fluorimetric method the mean results by radioimmunoassay of 154 routine specimens were 23% lower. In samples from unstimulated patients, regression analysis of results obtained by the two methods gave a correlation coefficient (r) of 0.93, regression line slope of 1.1, and intercept of 1.4 microgram. Mean radioimmunoassay results were 15% lower. When plasma cortisol concentration was above the normal range (greater than 30 microgram/100 ml) the regression line slope was 0.87, the intercept 17.9 microgram, r = 0.87 and mean radio immunoassay results were 37% lower. Plasma cortisol concentration in patients after insulin or Synacthen stimulation exhibited similar responses when measured by either method. Plasma cortisol concentration in normal subjects given metyrapone was lower when measured by radioimmunoassay (mean +/- S.D. = 8.7 +/- 2.7 microgram/100 ml) than when measured by fluorimetry (18.5 +/- 10.8 microgram/100 ml). The diagnostic usefulness of the two methods, ease of assay, and costs are compared.     

Copper, iron, and zinc contents of mature human milk

Daily, weekly, and within-day variations in copper, iron, and zinc contents of human milk were investigated in order to determine whether one sample from an individual is representative of these elements. Total solids, fat, and protein contents were also measured. Fifty women in their 6th to 12th week of lactation each provided seven milk samples consisting of five consecutive daily samples and two additional samples collected either within a single day or at weekly intervals. Fat varied the most of all constituents and total milk solids reflected this variability. Values ranged from 0.2 to 10.4 g/100 ml for fat and from 8.58 to 17.49 g/100 ml for total solids. Protein varied from 0.76 to 2.04 g/100 ml among individuals, with little variation within an individual. Copper content varied considerably among women and within the same woman. With a large proportion of low values, the range was 0.09 to 0.63 mug/ml. Iron content was also found to vary within women as well as among women. Values ranged from less than 0.1 to 1.6 mug/ml with a preponderance of low values. Zinc content was more evenly distributed over the range of 0.14 to 3.95 mug/ml,and within an individual it did not vary widely. A representative estimate of copper and iron contents would therefore require multiple samples, whereas only one sample may provide a representative estimate of zinc content. Comparison of morning, midday, and evening values showed that copper and zinc are higher in the morning and iron is lower at this time. Increased amounts of copper, iron, and zinc were found in multiparous women whether or not they had previously lactated. Milk from older women had lower iron and higher copper and zinc contents than that from younger women. No differences were found in milk of women receiving dietary mineral and vitamin supplements. Calculations indicated that fully breast fed infants under 3 months of age receive approximately 0.35 mg/kg per day of zinc and 0.05 mg/kg per day of both copper and iron.     

Effect of intensive treatment on diabetic nephropathy in patients with type I diabetes

We evaluated the long-term effect of an intensive treatment of diabetic nephropathy (anti-hypertensive drugs, low protein diet, multiple insulin injections to achieve a good metabolic control) on glomerular filtration rate (GFR) and albumin excretion rate (AER). Fourteen type I diabetic patients (mean age 45 +/- 9.5 years, mean duration of diabetes 23.5 +/- 7.3 years, 8 males/6 females) with glomerular filtration rate < 70 ml/min-1/1.73 m2 and albumin excretion rate > 30 micrograms/min were treated intensively for 36 months. This intensive treatment consisted of multiple insulin injections, antihypertensive therapy with ACE inhibitors and a low-protein diet (0.8 g/kg body wt/day.) Renal function was evaluated as GFR and AER. HbA1c mean value decreased significantly from 8.7 +/- 0.8% to 6.5 +/- 0.5% (P < 0.0002). GFR rose from 58 +/- 12 ml/min-1/1.73 m2 to 84 +/- 11 ml/min-1/1.73 m2 (P < 0.0008). AER decreased from 208 micrograms/min (range: 73 to 500) to 63.8 micrograms/min (range 15 to 180; P < 0.05). Systolic and diastolic blood pressure decreased respectively from 144 +/- 26 mm Hg to 120 +/- 15 mm Hg and from 89 +/- 9 mm Hg to 75 +/- 8 mm Hg (P < 0.01). We obtained a rise of GFR and a reduction of proteinuria after three years of this treatment. We suggest that this intensive treatment in all patients with early stage diabetic nephropathy may be effective in slowing the progression to renal failure.     

Capillary transfer constant of Gd-DTPA in the myocardium at rest and during vasodilation assessed by MRI

The purpose of this study was to determine whether the capillary transfer constant (Ki) of gadolinium-DTPA was sensitive to perfusion changes and whether ischemic regions in the myocardium could be identified using the modified Kety formula. Ki was measured at rest and during dipyridamole-induced vasodilation in 10 healthy volunteers and in 10 patients with ischemic heart disease. Ki increased by a factor of 2.5+/-1.2 (mean +/- SD) from 55+/-16 ml 100 g(-1)min(-1) at rest to 136+/-46 ml 100 g(-1)min(-1) (P < 0.01) during vasodilation in the healthy subjects. In the patients, there were no changes in Ki during vasodilation in ischemic regions (50+/-18 versus 49+/-30 ml 100 g(-1)min(-1) (P > 0.4)). Ki increased in nonischemic regions by a factor of 2.0+/-0.8 from 44+/-17 to 81+/-32 ml 100 g(-1)min(-1) during vasodilation (P < 0.02). It is concluded that the capillary transfer constant is sensitive to perfusion changes and that regional ischemia can be detected with MRI. This noninvasive and quantitative method may prove useful in the evaluation of patients with ischemic heart disease.     

Changes in plasma erythropoietin and interleukin-6 concentrations in patients with septic shock after hemoperfusion with polymyxin B-immobilized fiber

OBJECTIVE: To find out whether polymyxin B-immobilized fiber (PMX-F) treatment affects the clinical parameters and plasma concentrations of erythropoietin (EPO) and interleukin (IL)-6. DESIGN: A prospective case series study. SETTING: Intensive care unit of the Department of Internal Medicine, Misato Junshin Hospital, Saitama, and Koto Hospital, Tokyo, Japan. PATIENTS: 17 consecutive patients (10 men, 7 women; mean age 54.6 years) with clinically defined septic shock and 20 healthy volunteers (12 men, 8 women; mean age 52.2 years). MAIN RESULTS: Of the 17 patients with septic shock, 9 (53 %) survived. The systolic blood pressure increased significantly from 78+/-6 to 106+/-8 mm Hg 2 h after PMX-F treatment in patients with septic shock. Plasma endotoxin levels decreased significantly after treatment, from 40+/-6 to 12+/-4 pg/ml. The pretreatment plasma concentrations of EPO and IL-6 were significantly higher in the 8 nonsurviving patients with septic shock (EPO: 400+/-36 mlU/ml; IL-6: 6260+/-1180 pg/ml) than in the 9 surviving patients (EPO: 120+/-22 mlU/ml; IL-6: 680+/-138 pg/ml) and the 20 control subjects (EPO, 12+/-6 mlU/ml; IL-6, 8+/-2 pg/ml). Plasma concentrations of EPO and IL-6 in patients with septic shock decreased significantly after PMX-F treatment (EPO, nonsurviving: 320+/-28 mlU/ml, p < 0.05; survivors: 26+/-8 mlU/ ml, p < 0.001; IL-6, nonsurviving: 3860+/-840 pg/ml, p < 0.01; survivors: 84+/-20 pg/ml, p < 0.001). CONCLUSIONS: Plasma concentrations of EPO and IL-6 may be prognostic indicators in patients with septic shock: PMX-F treatment may be effective in reducing the plasma concentrations of EPO and IL-6 in patients with septic shock.     

Immunohistochemical characterization of the differentiation state of basal cell carcinomas with special interest for infiltrating relapsing tumors

Persistence of nocturia after prostatic resection in healthy patients without symptoms referred to residual bladder instability and to pathological polyuria seems to be caused by an increased urine production at night. The more accreditate mechanism involved is the relevant decreased ADH secretion pattern which occurs at night. In our study, patients with nocturnal poliuria showed significantly low plasmatic vasopressin levels compared with a control group. The aim of this study was to evaluate whether the persistence of nocturia after prostatic resection in healthy patients, without symptoms referred due to residual bladder instability and important polyuria, could be due to a decrease or a lack of increase in antidiuretic hormone (ADH) nocturnal levels following increased urine production at night. Serum ADH, atrial natriuretic peptide (ANP) and osmolality were assessed at 4-h intervals in 12 patients complaining of residual nocturia (group A) and in a control group of 13 patients who had undergone a complete resolution of nocturia after prostate ablation (group B). In the 25 patients involved in the study (mean age 65.8 years), no significant differences were observed in the two groups concerning mean age (67.5 years for group A, 64 years for group B). Mean nocturnal urine volume (1080 +/- 490 ml) in group A patients was significantly higher than in group B (500 +/- 100 ml) (p < 0.001), while no significant differences were found in diurnal diuresis. Mean plasma vasopressin levels of the 12 patients showing an increased nocturnal micturition were found to be significantly lower at all 4-h intervals when compared with the control group (p < 0.05). Individual fluctuations in serum osmolality were slight and insignificant within the normal range in all patients. The diurnal variation of plasma atrial natriuretic peptide was within the reference limits for all subjects during the 24-h period. Our results lead us to believe that residual nocturia after prostatic resection seems to be caused by an increased urine production at night due to a decreased ADH secretion pattern.