Measurement of glomerular filtration rate and renal plasma flow in the diabetic rat by the single-injection isotopic technique: effects of altered distribution volumes of 51Cr-EDTA and 125I-hippuran.

Following an intravenous injection of an isotopically-labelled clearance marker, glomerular filtration rate (GFR) or renal plasma flow (RPF) can be measured from the rate of plasma isotope disappearance, without collecting urine. The plasma disappearance curve can be closely approximated from a single, timed plasma measurement, if the volume of distribution (V) of the marker is known. Although V is generally predicted from body weight, effects of disease states on the relationship between V and body weight have not been studied. To apply this method of measuring GFR and RPF in streptozotocin-diabetic rats, we investigated the effects of diabetes and insulin treatment on V of 51Cr-EDTA and 125I-orthoiodohippuran (OIH). In untreated diabetic, insulin-treated diabetic and control rats, highly significant linear relationships were found between body weight and V of either isotope (r = 0.68-0.97). However, the slopes and intercepts of these relationships showed that diabetes and insulin treatment significantly altered V of 51Cr-EDTA and 125I-OIH. The greatest change was observed in untreated diabetic rats, in which V of 125I-OIH was increased approximately 12% compared to V in weight-matched control rats. Insulin treatment partially reversed this effect, but V of 125I-OIH in insulin-treated diabetic rats remained increased compared to controls. Using the relationships we derived for V vs body weight, GFR and RPF were measured in the three groups of rats by the single-injection, single-plasma sample method. Severely hyperglycemic, untreated diabetic rats showed reduced RPF (p less than 0.005) but no significant reduction in GFR, compared to age-matched control rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Schistocytosis, aminotransferase elevation and thrombocytopenia in preeclampsia/eclampsia.

Some preeclamptic patients have schistocytosis, abnormal liver function tests and thrombocytopenia. To determine how strongly these three abnormalities cluster with each other, a sequential series of 49 preeclamptic or eclamptic patients was analyzed for the presence of schistocytosis, serum aminotransferase elevation and thrombocytopenia. These three abnormalities were found less often together (the HELLP syndrome) than singly or in pairs. These data do not clearly separate HELLP patients from other preeclamptic patients.

A modified scleroderma skin scoring method.

The extent of skin thickness in scleroderma has been reported to correlate with the degree of internal organ involvement. An objective method for the clinical evaluation of skin involvement (skin score) in scleroderma is described. In this preliminary study, the method was tested in twenty scleroderma patients. An acceptable degree of inter-observer reproducibility was noted. This method is proposed as a means of monitoring the degree of skin involvement and the overall disease activity.

Evidence of accelerated platelet production and consumption in nonthrombocytopenic preeclampsia.

Platelet size and the distribution of platelet sizes are both increased in preeclamptic patients with normal platelet counts. These changes suggest that accelerated platelet production and consumption are both widespread in preeclampsia.

Predictive value of fibronectin levels in normotensive gravid women destined to become preeclamptic.

The plasma fibronectin concentration was abnormally elevated (greater than 400 micrograms/ml) in 16 of 17 normotensive gravid women who subsequently developed preeclampsia. Of this group, 13 had elevated levels detectable greater than or equal to 4 weeks before the onset of hypertension. Our results indicate that plasma fibronectin levels can be abnormally increased long before the onset of clinical symptoms and that abnormalities of this glycoprotein may be an early indication of this pathologic process.

Oral ciramadol: a new analgesic for postoperative pain.

Ciramadol, a new synthetic narcotic agonist-antagonist analgesic, was compared in 30 and 60 mg doses with pentazocine 50 mg, aspirin 650 mg, and placebo in the treatment of 153 patients with postoperative pain. All drugs were administered between six and 72 hours after surgery. Analgesic efficacy was assessed for six hours after study drug administration using verbal pain intensity, analog pain intensity, and verbal pain relief scales. Significantly (P less than .05) higher analgesic efficacy scores were seen with ciramadol 30 mg than with pentazocine 50 mg and placebo at most of the evaluation points. Doses of ciramadol 30 mg were significantly (P less than .05) more effective than aspirin 650 mg at several time periods, and ciramadol 60 mg was better than pentazocine and placebo at several evaluation times. The 30-mg dose of ciramadol was generally more effective than the 60-mg dose. The mean six-hour cumulative sum of pain intensity difference scores, total pain relief scores, and sum of pain analog intensity difference scores showed that the best analgesic response occurred in the ciramadol 30 mg group, followed by the ciramadol 60 mg, aspirin 650 mg, pentazocine 50 mg, and placebo groups. Side effects were rare and mild. There were no medically important changes in vital signs in any treatment group.

Glomerular anionic site distribution in nonproteinuric rats. A computer-assisted morphometric analysis.

The cationic ultrastructural tracer polyethyleneimine (PEI: pI approximately equal to 11.0), binds electrophysically to uniformly spaced discrete electron-dense anionic sites present in the laminae rarae of the rat glomerular basement membrane (GBM), mesangial reflections of the GBM, Bowman's capsule, and tubular basement membranes when administered intravenously. Computer-assisted morphometric analysis of glomerular anionic sites reveals that the maximum concentration of stainable lamina rara externa (lre) sites (21/10,000 A GBM) occurs 60 minutes after PEI injection with a site-site interspacing of 460 A. Lamina rara interna (lri) sites similarly demonstrate a maximum concentration (20/10,000 A GBM) at 60 minutes with a periodicity of 497 A. The concentration and distribution of anionic sites within the lri was irregular in pattern and markedly decreased in number, while the lre possesses an electrical field that is highly regular at all time intervals analyzed (15, 30, 60, 120, 180, 240, and 300 minutes). Immersion and perfusion of renal tissue with PEI reveals additional heavy staining of the epithelial and endothelial cell sialoprotein coatings. PEI appears to bind to glomerular anionic sites reversibly: ie, between 60 and 180 minutes the concentration of stained sites decreases. At 300 minutes, the interspacing once again approaches the 60-minute concentration. This suggests a dynamic turnover or dissociation followed by a reassociation of glomerular negatively charged PEI binding sites. In contrast, morphometric analysis of anionic sites stained with lysozyme and protamine sulfate reveals interspacings of 642 A and 585 A, respectively; in addition, these tracers produce major glomerular ultrastructural alterations and induce transient proteinuria. PEI does not induce proteinuria in rats, nor does it produce glomerular morphologic alterations when ten times the tracer dosage is administered intravenously. These findings indicate that the choice of ultrastructural charge tracer, the method of administering the tracer, and the time selected for analysis of tissue after administration of tracer significantly influences results. Morphometric analysis of the distribution of glomerular anionic sites in nonproteinuric rats provides a method of evaluating quantitative alterations of the glomerular charge barrier in renal disease models.

Platelet function during continuous insulin infusion treatment in insulin-dependent diabetic patients.

Patients with diabetes mellitus manifest increased in vitro platelet aggregation and increased synthesis of the proaggregant and vasoconstrictor, thromboxane A2 (TXA2). We studied the effects of continuous insulin infusion treatment on platelet aggregation and arachidonic acid (AA)-stimulated platelet TXA2 synthesis (15 and 30 s post-AA, 1 mM) in 16 type I diabetic patients. Strict glycemic control was induced with the Biostator for 2 days and maintained for 12-14 days with continuous subcutaneous insulin infusion (CSII). The average premeal plasma glucose level (4/day) fell from 184 +/- 15, before treatment, to 107 +/- 6 mg/dl on the final day (P less than 0.001). After control, platelet synthesis of TXA2, measured by radioimmunoassay of its stable metabolite, immunoreactive TXB2 (iTXB2), decreased in all patients (30 s: 276 +/- 31 versus 199 +/- 28 ng iTXB2/ml/5 X 10(5) platelets; P less than 0.05). The reduction in platelet iTXB2 synthesis (15 and 30 s) was greater in poorly controlled patients (HbA1c greater than 12%; N = 8), and for all patients the decrease in iTXB2 (15 and 30 s) was correlated with the prestudy HbA1c level (15 s: r = 0.6; P less than 0.01). In contrast, platelet aggregation responses did not improve during intensive insulin treatment. The ED50 for AA (dose producing 50% maximum aggregation at 1 min) was unchanged after 2 wk of treatment and the ED50 for aggregation induced by ADP fell significantly in patients with HbA1c greater than 12% (2.8 +/- 1.3 versus 1.2 +/- 0.6 microM; P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of estrogen therapy on vaginal physiology during menopause.

Vaginal physiology was evaluated in 23 postmenopausal women before estrogen replacement therapy and at 1, 3, 6, 12, 18, and 24 months while receiving conjugated equine estrogens (Premarin). Reversal of hormonal levels (17 beta-estradiol, gonadotropins) and vaginal cytology occurred within one month. Vaginal pH levels significantly decreased from a baseline mean of 5.2 to a level of 4.2 at 24 months (P less than .05). Women who were sexually active showed a greater decline in pH levels than did women who were sexually inactive. Maximum increases in amount of vaginal fluid and potassium levels were observed after three months of therapy. Vaginal blood flow and vaginal electropotential difference were significantly increased over baseline values at one month and again at 12 months (P less than .05) with a slow progressive improvement continuing throughout 24 months of estrogen replacement therapy. This study provides documented laboratory evidence to suggest that restoration of vaginal tissue function requires 18 to 24 months and explains why dyspareunia may persist in the early months of replacement therapy despite hormonal and cytologic return to premenopausal values.

Lack of effect of glucocorticoids upon plasma thromboxane in patients in a state of shock.

Twenty-five patients with sepsis were studied retrospectively to examine the effects of methylprednisolone on plasma thromboxane B2 levels. Although the plasma iTxB2 level was elevated in patients dying from sepsis, the use of glucocorticoids did not reduce plasma iTxB2. Aspirin, a cyclo-oxygenase inhibitor, did reduce the plasma iTxB2 value in four patients. It does not appear that glucocorticosteroids significantly affect the conversion of arachidonic acid to thromboxane in septic patients.

Effect of neonatal cerebrospinal fluid on monocyte chemotaxis.

We have reported in our previous study that macrophages constitute 58% of the total number of white cells in noninfected neonatal cerebrospinal fluid (CSF). CSF macrophages are probably derived from blood monocytes. To explain their predominance, we compared the chemotactic response of monocytes from cord and adult blood to neonatal (NCSF) and non-neonatal spinal fluids (NNCSF). Zymosan-activated serum (ZAS) was used as a positive control. Significance was accepted as p less than or equal to 0.05. We observed that both random migratory (RM) activity and chemotactic responses (CM) of cord monocytes to neonatal CSF and ZAS were greater than those of monocytes obtained from adult blood, resulting in a significant increase in the chemotactic differential (CD). Chemotactic responses of neonatal monocytes were significantly greater in the presence of neonatal CSF as compared to CSF from older children as indicated by CD. The CD of neonatal monocytes to neonatal CSF was greater than that of neonatal neutrophils. These findings are consistent with the presence of specific monocyte chemotaxins in noninfected neonatal CSF.

Incidence of coronary heart disease in blacks in Charleston, South Carolina.

We studied a cohort of 2275 blacks and whites of both sexes in Charleston County, South Carolina, during the period of 1960-1961 to 1974-1975. There were 93 prevalent cases of coronary heart disease (CHD) at intake, and 317 new cases occurred by 1975 in persons originally free of CHD. White males had the highest incidence rates for all types of CHD and acute myocardial infarction (AMI). Black males and black females had the next highest rates. The incidence of angina pectoris in black females was double the rate in white females and five times the rate in white males. The rate of sudden death in black males was two and one-half times the rate in black females, three times the rate in white males, and four times the rate in white females. One hundred and one black males who had been selected on the basis of high socioeconomic status (SES) had AMI and CHD rates half that of other black males. None of the high SES black males experienced angina pectoris, AMI death, or sudden death during the observation period.

Urinary kallikrein excretion in insulin-dependent diabetes mellitus and its relationship to glycemic control.

The renal kallikrein-kinin system is thought to be involved in vasoregulatory and epithelial ion-transporting processes. Renal kallikrein has not been studied in patients with diabetes mellitus, a disease in which abnormalities of renal hemodynamics and electrolyte handling occur. The urinary excretion of this kallikrein was measured in 20 type I diabetic patients and 10 normal subjects. On a 120-meq Na diet, daily kallikrein excretion, determined by both esterase activity and direct RIA, in 12 poorly controlled diabetic patients [hemoglobin A1c (HbA1c) = 14.2 +/- 0.5% (mean +/- SEM)] was significantly greater (P less than 0.05) than excretion in 8 diabetic patients in good to moderately good control (HbA1c = 9.4 +/- 0.5%) or in 10 normal subjects. In these groups, urinary esterase activities were 9.4 +/- 1.0, 6.1 +/- 1.4, and 6.7 +/- 0.5 esterase units/24 h, respectively. Corresponding excretion values of immunoreactive kallikrein were 171 +/- 14, 118 +/- 26, and 123 +/- 11 micrograms/24 h. Creatinine clearances were similar in the three groups. Urinary kallikrein was also measured in 8 diabetic and 8 normal subjects during 7 subsequent days of 10 meq Na intake. It increased less in diabetic patients than in normal subjects during Na depletion (P less than 0.02). The increase in urinary kallikrein in the diabetic patients was inversely related to their HbA1c levels (r = 0.88; P less than 0.01). The effect of glycemic control on urinary kallikrein excretion was determined in nine diabetic patients. Initial glycemic control was achieved using an artificial endocrine pancreas (Biostator) and was maintained by continuous sc insulin infusion with a portable pump. Before glycemic control, urinary kallikrein was 190 +/- 30 micrograms/24 h (by RIA). After 8-12 days of glycemic control, excretion fell to 144 +/- 23 micrograms/24 h (P less than 0.02). The abnormalities in kallikrein excretion in diabetic patients were not correlated with differences in water, electrolyte, protein, glucose, or aldosterone excretion in any of the studies. These results show that kallikrein excretion was increased in patients with poorly controlled insulin-dependent diabetes, and excretion rose less in diabetic subjects with low Na intake than in normal subjects. Strict glycemic control decreased urinary kallikrein excretion. These findings suggest that the renal kallikrein-kinin system is functioning abnormally in diabetes mellitus.

Immunoglobulin allotypes and immune response to meningococcal group B polysaccharide.

Serum samples were collected from 120 healthy adult volunteers (105 Caucasians and 15 Negros) before and after immunization with meningococcal polysaccharide (MPS) group B vaccine. Antibodies to MPS group B were measured and sera were typed for several Gm and Km(1) allotypes. A significant association was found between the Km(1) allotype and immune response to MPS group B in Caucasians.