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Biomedical subjects

C B Loadholt

Publications and source records attributed to C B Loadholt.

At least 19 recordsLinked to original sources

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)

Animals

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.

Aspartate Aminotransferases

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.

Adolescent

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.

Blood Pressure

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.

Adolescent

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)

Adenosine Diphosphate

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.

Action Potentials

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.

Aspirin

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.

Animals

Perioperative cephalosporin prophylaxis in cesarean section: effect on endometritis in the high-risk patient.

A total of 120 patients who were to be delivered by cesarean section and who were at high risk of postoperative infection received three doses of either cefamandole, cephalothin or placebo perioperatively. Maternal serum levels for both antibiotics were in the therapeutic range. Although both drugs reduced the incidence of febrile morbidity and endometritis, only cefamandole significantly reduced the fever index. Risk factors for postoperative infections were the presence of ruptured membranes, labor, and internal fetal monitoring. Cefamandole beneficially influenced all risk factors while cephalothin was able to reduce only the risk of ruptured membranes. When a new method for obtaining endometrial tissue was utilized, 50% of cultures were negative. There was no difference in the organisms isolated from patients with and without endometritis.

Adult

Association between immunoglobulin allotypes and immune responses to Haemophilus influenzae and Meningococcus polysaccharides.

Serum samples were collected from 20 healthy White and 33 Black infants before and after immunisation with three doses of diphtheria-pertussis-tetanus vaccine and with one dose of Haemophilus influenzae type b polyribose phosphate vaccine and meningococcal group A and group C polysaccharide vaccines. Antibodies to these immunogens were measured and sera were allotyped for several Gm, A2m, and Km antigens. A highly significant association was found between the Km(1) allotype and the immune responses (difference between post-immunisation and pre-immunisation antibody levels) to H. influenzae and meningococcus C polysaccharides in the White children.

Antibodies, Bacterial

Autoantibodies in healthy subjects of different age groups.

Autoantibody determinations in 1284 healthy Caucasian subjects of various age groups were made by indirect immunofluorescence for anti-nuclear, anti-gastric, and anti-thyroglobulin antibodies. A sex-dependent relationship between age and prevalence of anti-gastric and anti-thyroglobulin antibodies was found. No association was found between age and anti-nuclear antibodies.

Adult

Renin aldosterone system and potassium levels in chronic lead intoxication.

Renin activity and aldosterone were evaluated relative to potassium levels and lead intoxication in 33 patients with a history of "moonshine" ingestion. Patients were divided into three groups: I, lead intoxicated with hyperkalemia; II, lead intoxicated without hyperkalemia; and III, not lead intoxicated without hyperkalemia. Those in group I demonstrated suppressed plasma renin activity, baseline and after furosemide, and blunted aldosterone responsiveness to furosemide. Plasma renin activity was not different in groups II and III, whereas aldosterone responsiveness was less in group II than in III. Group I patients tended to be older, had lower creatinine clearances, and six of nine had mild hyperchloremic acidosis. Diabetes and cortisol insufficiency were not present. Chronic lead intoxication due to illicit alcohol ingestion is associated with hyporeninemic hypoaldosteronism and hyperkalemia which appear to develop as the lead nephropathy progresses with duration and/or aging.

Adult

Evidence for the synthesis and release of strongly immunosuppressive, noncytotoxic substances by Streptococcus intermedius.

Products secreted by Streptococcus intermedius were studied for their effects on the immune response. Three different preparations of crude extracellular products from S. intermedius (CEP-Si) were found to have powerful suppressor activity in vitro as shown by inhibition of human lymphocyte proliferation (uptake of [3H]thymidine) and protein synthesis in response to a wide variety of stimulants, including mitogens and antigens, and suppression of plaque formation by human cells in response to sheep erythrocytes. CEP-Si was noncytotoxic, because cells incubated with high concentrations of CEP-Si and subsequently washed were viable and recovered their ability to respond to mitogens, and because leukocyte migration was not inhibited by CEP-Si, nor was the release of leukocyte migration inhibitory factor from sensitized lymphocytes. The possibility of antigen or mitogen competition was excluded. The effects of CEP-Si in vitro were time dependent and did not require the presence of monocytes. Cells pretreated with CEP-Si and then washed suppressed plaque formation by fresh autologous cells in highly stimulated cultures. CEP-Si injected into C57BL/6 mice also strongly suppressed their immune response to sheep erythrocytes, and the in vivo suppression was correlated with the effects of CEP-Si in vitro.

Animals