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Biomedical subjects

S Adler

Publications and source records attributed to S Adler.

At least 145 records · Page 8Linked to original sources

Brain pH in acute isocapnic metabolic acidosis and hypoxia: a 31P-nuclear magnetic resonance study.

It is well known that brain pH changes rapidly in acute hypercapnia or hypocapnia. The effect of acute isocapnic metabolic acid-base change on brain pH is less certain. To study this problem, acute isocapnic metabolic acidosis was induced by HCl or lactic acid infusions in rats, and recovery from acidosis was accomplished by NaHCO3 infusion. Brain pH was measured by 31P-nuclear magnetic resonance. Despite decreases in blood pH of 0.34 and 0.36 units, respectively, in less than 1 h of acid infusion and rapid recovery during bicarbonate infusion, brain pH was unaffected (ranging between 7.08 and 7.11) and was uncorrelated with blood pH. The blood pH minus brain pH gradient was eliminated by the acidosis. By contrast, hypoxia-induced endogenous lactic acidosis lowered blood and brain pH equivalently, but the fall in brain pH preceded that in blood. During normoxic recovery, brain pH overshot and became alkaline when blood pH was still significantly reduced and blood lactate levels were markedly elevated. Presumably, this is due to stimulated active H+ transport. The results demonstrate that brain pH is affected differently in metabolic, respiratory, and endogenous acid-base disturbances. Thus brain pH cannot be predicted solely from blood pH values.

Acid-Base Imbalance↗

Effect of acid-base changes on urinary hydrolases in Fabry's disease after renal transplantation.

Fabry's disease, which is characterized by alpha-galactosidase A (AG) deficiency, causes early renal failure. Kidney transplants do not reliably supply the deficient enzyme. To assess both urinary excretion of AG by the transplant and the relationship between urine and serum hydrolase activity, acute and chronic acid-base studies were performed in normal control subjects and in the patient with Fabry's disease who had undergone renal transplantation. For the acute studies, alkalosis was induced by intravenous infusion of sodium bicarbonate and acidosis was induced by ingestion of ammonium chloride. The chronic study involved long-term ingestion of NH4Cl by only the patient with Fabry's disease. The results show that AG is secreted by the renal graft. Urinary hydrolase excretion was increased by acute alkalinization and decreased by acute acidification. Acute, but not chronic, acidification increased the patient's serum AG activity, indicating that long-term acidification is not useful for treating Fabry's disease after transplantation. The large changes in hydrolyase excretion induced by acute and chronic acid-base changes show the difficulty of using lysosomal enzymuria as a diagnostic marker for renal disorders without knowledge of acid-base conditions.

Adult↗

Reversal of inhibition of rat glomerular epithelial cell growth by growth factors.

The ability of several growth factors to reverse heparin-induced inhibition of rat glomerular epithelial cell (GEC) growth and the mechanism of growth inhibition were explored in vitro. Insulin-like growth factor-1, rat multiplication-stimulating activity, and platelet-derived growth factor had no effect on proliferation of cultured GEC exposed to heparin (100 micrograms/ml). Epidermal growth factor (EGF) partially reversed heparin-induced growth inhibition in a dose-dependent fashion with a maximum effect seen at 1 ng/ml. No additive effect was seen with combinations of EGF and the other growth factors assayed. A decrease in EGF-stimulated incorporation of 3H-thymidine by GEC was seen with as little as 2 hours of heparin exposure and persisted for up to 48 hours. Heparin consistently increased binding of 125I-EGF to GEC with a significant increase apparent after 2 hours of exposure and a further increase with a 24-hour exposure. Increased EGF binding to heparin-treated cells was due to a significant increase in the association constant of EGF and its receptor with no effect on receptor number. Interactions between GEC and heparinlike glycosaminoglycans in the glomerular basement membrane may play a role in the regulation of GEC proliferation in normal and diseased states.

Animals↗

Design and performance of POSICAM 6.5 BGO positron camera.

A high-resolution, whole-body positron camera, POSICAM 6.5 BGO, has been designed, built, and tested; results from it are presented. The camera utilizes 1,320 BGO crystals and 720 PMTS in a staggered geometry to produce high resolution of 5.8 mm FWHM and 21 image planes simultaneously. The axial resolution of the camera is measured at 11.9 mm at the center. High axial sampling is achieved with 5.125 mm separation of the image planes such that three-dimensional imaging of an object can be carried out in a single scan. Recovery of volumetric distribution of radioactivity and object dimensions in axial and sagittal views is demonstrated by imaging spherical objects 13 mm to 39 mm in diameter.

Equipment Design↗

[The saccharin test in the pediatric broncho-pneumonologic outpatient clinic. A noninvasive screening method for the assessment of ciliary function of the respiratory tract in children].

The Saccharin test is a non-dangerous, inexpensive, suitable and repeatable method for assessing the mucociliary function of the respiratory epithelium. A small quantity of Saccharin (R) is deposited on the inferior nasal concha; the chemical agent will be transported by the respiratory epithelium (kinocilia) from the nasopharynx to the oropharynx and can be tasted here as "sweet". The time interval between the deposition of Saccharin and the "sweet" taste is the "nasal mucociliary transport time (nmctt)"; data in minutes. In 381 children (age: 3-17 years) we found an average nmctt of 6.6 (+/- 4.8) min (healthy controls) and 8.8 (+/- 5.2) min resp. (CNSRD children). A nmctt longer than 30 min leads one to suspect disturbances of the mucociliary function, the aetiology of which can be analysed by mucosa biopsy and subsequent examination under the electron microscope. We hold the view that Saccharin test is an essential part of the diagnostic program for children suffering from CNSRD; after 3 tests the mucociliary function can be evaluated correctly. The test can be used both for diagnosing the aetiology of respiratory diseases and for the assessment of the efficiency of therapeutic and prophylactic measures.

Adolescent↗

Long-term follow-up of aggressively treated idiopathic rapidly progressive glomerulonephritis.

PURPOSE: We wanted to examine the long-term effects of aggressively treating idiopathic rapidly progressive glomerulonephritis (RPGN), with a particular focus on clinically characterizing the patient population, assessing the short- and long-term effects of therapy on renal function, and determining complications of the therapy. PATIENTS AND METHODS: Twenty-three consecutive patients with RPGN were treated and followed from one to 11 years. On renal biopsy, 13 had immune complexes, eight had no immune complexes, and two had antiglomerular basement membrane deposits. All had greater than 25 percent crescents and 19 of 23 had greater than 50 percent crescents. Every patient responded on a short-term basis to either large-dose pulse methylprednisolone or plasma exchange, with reduction of the mean plasma creatinine level from 6.5 +/- 2.0 mg/dl to 2.9 +/- 1.0 mg/dl (p less than 0.001). Each patient received oral prednisone and all but one received cyclophosphamide. RESULTS: Three died of non-renal causes. Fifty percent of the remaining 20 patients maintained stable renal function for at least two years. Four of nine patients followed-up for longer than two years had a relapse, but all responded again to therapy. No characteristic clinical symptoms predicting relapse were found, although nearly all had hematuria and proteinuria. Complications of therapy were frequent and may have contributed to death in two patients. CONCLUSION: Thus, long remissions are seen in most patients with RPGN treated aggressively.

Adult↗

The role of individual difference in determining the nature of comprehension defects in aphasia.

This study was concerned with the relationship between locus of lesion and subtypes of language comprehension defect in aphasia. Previous studies had indicated that performance in sound recognition identified two subtypes of aural comprehension deficit and that performance in pantomime recognition identified two subtypes of reading comprehension defect. Defects in sound recognition and pantomime recognition were found in association with a variety of lesion loci. However, comprehension defective aphasics with normal sound recognition or pantomime recognition had lesions closely similar in location and size to those of aphasics who performed poorly on these tests. Findings suggest that whether an aphasic with a language comprehension defect is impaired in sound recognition or pantomime recognition depends, at least in part, on individually variable predisposing factors. It would appear possible that this phenomenon reflects a separate dimension of hemispheric cerebral dominance.

Adult↗

Cyclosporin A inhibits prostaglandin E2 formation by rat mesangial cells in culture.

A reversible reduction in glomerular filtration rate (GFR) is a frequent side effect in patients treated with the immunosuppressant cyclosporin A (CsA). The pathophysiology of acute CsA nephrotoxicity, however, is unclear. Since eicosanoids are local mediators of glomerular hemodynamics, they might be involved in CsA induced changes in GFR. We therefore studied the effect of CsA on prostaglandin E2 (PGE2) production by rat mesangial cells in culture. PGE2 production by mesangial cells following stimulation with angiotensin II (AII) (10(-6) M) or the Ca2+-ionophore A23187 (1 microgram/ml) was significantly inhibited when cells were grown for 24 hours in media which contained CsA (800 to 3200 ng/ml). CsA did not affect viability of mesangial cells as determined by 51Cr release or by cell proliferation measured by 3H-thymidine incorporation. CsA (3200 ng/ml) did not inhibit PGE2 formation by rat MC microsomes incubated with arachidonic acid. However, CsA, in a dose dependent manner, inhibited A23187 and angiotensin II induced release of 3H-labelled arachidonic acid from rat mesangial cells. These data demonstrate that CsA reduces PGE2 formation by rat mesangial cells in culture, probably by inhibiting the release of substrate arachidonic acid from cell membranes rather than by inhibition of cyclooxygenase. This effect may contribute to the reduction in GFR which accompanies CsA therapy.

Angiotensin II↗

Effect of acute hyponatremia on rat brain pH and rat brain buffering.

Acute hyponatremia was induced in rats by subcutaneous pitressin and intraperitoneal injection of 17.5 ml of 2.5% dextrose three times over 2 days. Brain pH was measured by use of 31P-nuclear magnetic resonance (31P-NMR). Two-hour infusion of a 500 meq sodium solution raised plasma sodium concentration (PNa) from 124.6 to 147 meq/l. Brain pH rose 0.1 pH units in the absence of changes in phosphocreatine or ATP. By contrast, increasing PNa in normal rats from 141 to 158 meq/l did not affect brain pH. Brain buffering was examined by 58-min exposure to 20% CO2 followed by a 38-min recovery. Intrinsic brain buffering (Bi) in hyponatremic and normal rats following 15 min of CO2 was similar, 49.1 and 45.5, respectively. After the next 40 min of CO2 exposure Bi was unchanged in hyponatremic rats at 45.8 but increased in controls to 102.5. In recovery Bi was higher initially in controls and rose significantly only in the controls. These results are consistent with the hypothesis that acute hyponatremia impairs the function of the Na+-H+ exchanger in brain.

Animals↗

Endogenous candidal endophthalmitis.

The incidence of systemic mycotic infections, though formerly rare, has increased dramatically over the past two decades. Candida albicans has been recognized as the most common pathogen in endogenous fungal endophthalmitis. Accurate antemortem diagnosis of disseminated candidiasis is made, however, only in a few cases. Ocular findings may often provide the first definitive clue to an underlying mycotic infection. We present four cases of candidal endophthalmitis; in each the ophthalmologist played a major role in the early diagnosis of the underlying systemic infection, allowing specific therapeutic measures to be taken. We also discuss the common predisposing factors, ocular symptoms and findings, clinical course, and response to antifungal therapy.

Aged↗

Steroid receptor-mediated inhibition of rat prolactin gene expression does not require the receptor DNA-binding domain.

Prolactin gene expression is negatively regulated by glucocorticoids, and by estrogens when positive estrogen regulatory elements in the prolactin gene are removed. Mutational analysis of estrogen receptor confirms that inhibition is a function of receptor, and that transcriptional activation and inhibition require distinct, separable structural elements. Inhibition is dependent on a 63 amino acid region (amino acids 251-314) distinct from the DNA-binding and steroid-binding domains. The comparable region of glucocorticoid receptor confers inhibitory actions on a hybrid receptor. Multiple, nonoverlapping sequences in the rat prolactin 5'-flanking genomic region that confer inhibition by both steroid hormones contain related cis-active elements that bind a common, tissue-specific positive transcription factor, called Pit-1. Experimental results indicate that positive and negative transcriptional effects of estrogen receptor are mediated by separate functional domains, and suggest the protein-protein interactions between steroid hormone receptors and other transcription factor(s) mediate inhibition.

Amino Acid Sequence↗

Loss of the somatosensory evoked response as an indicator of reversible cerebral ischemia during hypothermic, low-flow cardiopulmonary bypass.

We assessed somatosensory evoked response (SSER) as a monitor of cerebral protection during nonpulsatile, hypothermic cardiopulmonary bypass (CPB). In 13 dogs under CPB, extracorporeal flow rate (EFR) thresholds for loss of SSER were determined by stepwise reduction of the EFR from 2.0 to 0.25 L/min/m2 at perfusion temperatures of 35 degrees C, 30 degrees C, 25 degrees C, and 20 degrees C. Testing began at 35 degrees C in Group 1 (N = 6) and at 20 degrees C in Group 2 (N = 7). Immediately on loss of SSER (denoted as a decrease of 80% or more in the amplitude of the somatosensory evoked potentials), EFR was restored to 2.0 L/min/m. Thresholds for loss of SSER ranged between 0.75 and 0.25 L/min/m2. SSER was always restored on return of EFR to 2.0 L/min/m2; thus loss of SSER was a reversible ischemic change. Both groups had similar threshold values at 35 degrees C, but at lower temperatures, Group 1 thresholds were significantly higher than those in Group 2. Since 35 degrees C was the first test temperature for Group 1 but the last for Group 2, EFR reduction at 35 degrees C apparently caused neurophysiological changes (depletion of cortical energy reserves), which diminished subsequent tolerance to ischemia, but EFR reduction at 20 degrees C did not. Our findings show that loss of SSER warns of reversible cerebral ischemia, and support SSER monitoring as a useful measure of cerebral function during low-flow, hypothermic CPB.

Animals↗

Rupture of ovarian cyst: massive hemoperitoneum in continuous ambulatory peritoneal dialysis patients: diagnosis and treatment.

Two women on continuous ambulatory peritoneal dialysis (CAPD) developed recurrent episodes of hemoperitoneum while in the reproductive age group. Initially, both were thought to have mechanical problems with the peritoneal catheter system. A laparotomy was performed in the first patient, and a bleeding ovarian cyst was identified. The second patient had ovarian cysts documented by ultrasound. Thus, abdominal pain and bloody dialysate should not just be ascribed to catheter-related problems. The second patient's midcycle bleeding was suppressed with birth control pills.

Adult↗