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Biomedical subjects

A H Sklar

Publications and source records attributed to A H Sklar.

At least 19 recordsLinked to original sources
PubMed2000

Symptomatic hypercalcemia of immobilization in a patient with end-stage renal disease.

The phenomenon of hypercalcemia in immobilization is well known, but there is limited awareness of the potential for this complication in patients with end-stage renal disease (ESRD) on maintenance hemodialysis with reduced capacity for disposition of calcium. We describe such a patient who showed a calcemic response to just 3 days of immobilization in the setting of an acute illness marked by coma. Despite intensive initial therapy for hypercalcemia, including withdrawal of all calcium products and daily hemodialysis treatments using low calcium baths, her serum calcium rose to 14.0 mg/dL during the hospitalization; this metabolic abnormality appeared to perpetuate her stuporous state. Mobilization as an outpatient was the most effective therapy. Extensive testing was performed to rule out other causes for this patient's hypercalcemia. Greater recognition of acute hypercalcemia in patients with ESRD immobilized by various illnesses would preclude unnecessarily expensive and invasive testing for other causes of hypercalcemia.

Female↗
PubMed1998

Postdialysis fatigue: lack of effect of a biocompatible membrane.

Tumor necrosis factor-alpha (TNF-alpha) has been shown to have somnogenic properties. Plasma levels of this cytokine have been found to increase significantly during dialysis with a bioincompatible (cuprophane) membrane in patients with postdialysis fatigue (PDF). We conducted a crossover study with random assignment to ascertain whether a biocompatible membrane might attenuate the increase of TNF-alpha and severity of PDF. Sixteen patients on maintenance hemodialysis underwent dialysis with either cuprophane (n = 8) or polymethylmethacrylate (PMMA; n = 8) membranes for 1 week and then switched to the opposite membrane during the second week. Predialysis and postdialysis measurements of plasma TNF-alpha levels were performed during the first and last dialysis treatments of each week. A fatigue score was determined from the sum of duration of fatigue and sleep within 6 hours of the completion of dialysis. TNF-alpha levels increased by an average of 18.3% during dialysis with cuprophane membranes but only 2.4% with PMMA membranes (P = 0.04). Despite this, fatigue scores remained unaltered (approximately 4 of 6). Hence, the biocompatible membrane, PMMA, failed to alleviate PDF. This suggests that dialytic stimulation of TNF-alpha plays no substantial role in the pathogenesis of PDF.

Biocompatible Materials↗
PubMed1998

Elevated levels of tumor necrosis factor alpha in postdialysis fatigue.

Postdialysis fatigue (PDF) has been ascribed to excessive ultrafiltration and decline in osmolality during hemodialysis. We evaluated the potential role for the sommogenic cytokines, interleukin-1 beta (IL-1beta) and tumor necrosis factor alpha (TNFalpha), in the genesis of PDF Patients dialyzing with cuprophane membrane were assigned to PDF (N=25) and non-PDF (N=25) groups based on a fatigue index questionnaire. Pre- and postdialysis samples were obtained from 3 consecutive treatments and later assayed for serum levels of IL-1beta and TNFalpha by ELISA. Our results show significant intradialytic elevation of TNFalpha in both non-PDF groups (non-PDF: pre- 3.36+/-0.80 pg/ml to post 3.75+/-0.88 pg/ml, p<0.04; PDF: pre- 5.95+/-0.80 pg/ml to post- 8.66-/+1.35 pg/ml, p<0.02). The degree of intradialytic augmentation was significantly greater for TNFalpha in the PDF group (46+/-18% vs 11+/-5%; p<0.03). There were no significant intradialytic changes in serum levels of IL-1beta in either the PDF or non-PDF groups. There also were no significant differences in dialysis-related body weights, systolic blood pressures, or osmolalities. These findings suggest that TNFalpha may be involved in the pathogenesis of PDF.

Aged↗
PubMed1996

Postdialysis fatigue.

To clarify the demographic and clinicolaboratory features of postdialysis fatigue (PDF), we enrolled 85 patients on maintenance hemodialysis in a cross-sectional study using validated questionnaires and chart review. Forty-three patients complained of fatigue after dialysis. On formal testing using the Kidney Disease Questionnaire, the PDF group had statistically greater severity of fatigue and somatic complaints than the group of patients without subjective fatigue (P = 0.03 and 0.04, respectively). On a scale measuring intensity of fatigue (1 = least to 5 = worst), the PDF group average was 3.4 +/- 1.2. PDF subjects reported that 80% +/- 25% of dialysis treatments were followed by fatigue symptoms. In 28 (65%) of patients, the symptoms started with the first dialysis treatment. They reported needing an average of 4.8 hours of rest or sleep to overcome the fatigue symptoms (range, 0 to 24 hours). There were no significant differences between patients with and without PDF in the following parameters: age; sex; type of renal disease; presence of diabetes mellitus, heart disease (congestive, ischemic), or chronic obstructive lung disease; blood pressure response to dialysis; type or adequacy of dialysis regimen; hematocrit; electrolytes; blood urea nitrogen; creatinine; cholesterol; albumin; parathyroid hormone; ejection fraction; and use of antihistamines, benzodiazepines, and narcotics. In the fatigue group, there was significantly greater use of antihypertensive medications known to have fatigue as a side effect (P = 0.007). Depression was more common in the fatigue group by Beck Depression score (11.6 +/- 8.0 v 7.8 +/- 6.3; P = 0.02). We conclude that (1) postdialysis fatigue is a common, often incapacitating symptom in patients on chronic extracorporeal dialysis; (2) no routinely measured parameter of clinical or dialytic function appears to predict postdialysis fatigue; and (3) depression is highly associated with postdialysis fatigue, but the cause-effect relationship is unclear.

Antihypertensive Agents↗
PubMed1996

Prerenal azotemia: differentiation of hyperureagenesis from renal hypoperfusion using urinary urea nitrogen data.

Blood urea nitrogen (BUN) rises disproportionately to serum creatinine in patients with prerenal azotemia whether due to impaired hemodynamics or excessive ureagenesis. To determine whether urinary urea nitrogen excretion rates can distinguish between these caused of hyperuremia we performed a cross-sectional observational study to compare urinary urea nitrogen excretion rates in a highly selected group of patients with prerenal azotemia. Patients who had stable serum creatinine levels, BUN: serum creatinine ratios exceeding 20:1, and progressive azotemia were identified from the hospital laboratory data base. Using conventional clinicolaboratory criteria, 27 patients were diagnosed with either renal hypoperfusion (group I; n = 17) or hyperureagenesis ((group II; n = 10). Random urine sampling for electrolytes, osmolality, creatinine, and urea nitrogen was followed by 24 h collection for creatinine clearance and urinary urea nitrogen. There were no significant differences in age, gender, absolute levels of BUN, or BUN: serum creatinine ratios between the groups. Creatinine clearance (ml/min/1.73 m2) (ml/s/1.73 m2) was lower in group I than in group II (21 +/- 16 vs 36 +/- 13; p < 0.05) (0.35 +/- 0.27 vs 0.60 +/- 0.22; p < 0.05). Twenty-four hour urinary urea nitrogen levels were significantly different (group I, 4.8 +/- 2.9 vs. group II, 13.6 +/- 3.2 gm; p < 0.001) (group I, 171 +/- 300 vs. group II, 486 +/- 114 mmol; p < 0.001). Random urine urea excretion indices were less discriminating but nevertheless still capable of separating the groups. Timed as well as random urine urea nitrogen determinations may assist in differentiating prerenal azotemia due to renal hypoperfusion from hyperureagenesis. Differentiation of these causes of prerenal azotemia might prevent iatrogenic overhydration of patients with azotemia incorrectly attributed to hemodynamic disturbances.

Aged↗
PubMed1992

Correlates of brain edema in uncontrolled IDDM.

Blood glucose, plasma sodium, bicarbonate (HCO3-), vasopressin, and hematocrit were monitored before and during treatment in patients with uncontrolled insulin-dependent diabetes mellitus (IDDM). These parameters were correlated with simultaneous serial cranial computed tomography readings of brain edema. Six of seven patients had positive computed tomography readings for brain edema on admission. Initial brain edema correlated directly with blood glucose (r = 0.79, P = 0.033) and inversely with HCO3- (r = -0.76, P = 0.047). At 6 h, brain edema still correlated with acidosis (HCO3-; r = -0.79, P = 0.033) but no longer with blood glucose. At that time, however, brain edema correlated with the rate of change in blood glucose (r = 0.915, P = 0.005). Results of interactive stepwise regression analysis suggest that the change in the calculated effective plasma osmolality plays a predominant role in the progression of brain edema during therapy (r = 0.995, P less than 0.001). Thus, although hyperglycemia and acidosis probably predispose to diabetic brain edema, osmotic factors may be major predictors of its evolution. No relationships were detected between brain edema and initiation of insulin therapy, plasma vasopressin, or changes in hematocrit. The factors responsible for initial brain edema and its progression, statistically identified in this study, require reassessment of common theories that attribute brain edema exclusively to therapy.

Adolescent↗
PubMed1990

Osmoregulation of vasopressin in diabetic ketoacidosis.

Osmoregulation of arginine vasopressin (AVP) is altered in diabetic ketoacidosis (DKA). With hyperglycemia, the AVP-plasma sodium (PNa) curve is displaced to the left, whereas the AVP-osmolality (Posm) curve is displaced to the right. The shift in the Na curve is explained by either resetting of the Na set point or by glucose acting as a nonpermeable solute, substituting for Na. Conversely, putative unmeasured solutes that, like urea, fail to affect AVP have been postulated to account for the right shift in the AVP-Posm curve. Therefore the respective roles of Posm = sigma [Xi] and plasma tonicity (Pton = sigma [sigmaiXi]), i.e., the sum of concentrations of all solutes [Xi] corrected (Pton) or not (Posm) for their relative cell permeability (sigma i), were studied in DKA. Indeed, Posm = sigma [Xi] exceeds Pton = sigma [sigma iXi] in DKA, since sigma i less than 1 for glucose. Potential determinants of AVP release (Posm, Pton, and PNa) were monitored in 7 patients with DKA. Conventional correlation analysis and two-dimensional (2D) graphs reproduced the paradox of an opposite shift in PNa and Posm set points for AVP release. However, by using the concept of tonicity instead of osmolality, 3D plots instead of 2D graphs, and multiple regressions instead of correlations, the AVP-PNa and AVP-Pton curves did not appear displaced. The concept of tonicity resolved the paradox of both osmolality and Na thresholds reset in opposite directions. Indeed, in states where a solute like glucose (with sigma less than 1) contributes substantially to plasma osmolality, Posm measured in vitro by the osmometer greatly exceeds Pton perceived in vivo by the osmoreceptor.

Adolescent↗
PubMed1990

A population study of renal function in sickle cell anemia.

To define normal limits for serum creatinine levels, as well as to explore the relationship between age and the prevalence and severity of renal disease in patients with sickle cell anemia (SCA), we retrospectively analyzed renal function parameters in 368 patients followed in our SCA clinic. Dipstick proteinuria was present in 78 patients (20.6%). Chronic renal insufficiency (CRI) was present in 17 patients (4.6%) and showed a high degree of association with proteinuria and increased age. In patients with CRI, the severity of renal dysfunction was also age-related. In the 284 patients without proteinuria or CRI, mean serum creatinine levels were lower than predicted. We conclude that in patients with SCA, serum creatinine levels at the upper limit of normal should be regarded with suspicion, and that the prevalence and severity of proteinuria and CRI in SCA is high and increases with age.

Adult↗
PubMed1990

Acute renal failure in sickle cell anemia.

We performed a case-control study of acute renal failure (ARF) in patients hospitalized with sickle cell anemia (SCA). Twelve of the 116 patients (10.3%) whose records were suitable for analysis were diagnosed as having ARF based on a minimum of doubling of their serum creatinine levels (mean rise was 205 +/- 49%). ARF patients were more likely to have been admitted with infection and had a lower mean hemoglobin level than the control group. Volume depletion was the most common identifiable cause for ARF. Two of 3 patients with severe ARF received dialytic support. Ten of 12 ARF patients survived and subsequently had recovery of renal function.

Acute Kidney Injury↗
PubMed1989

Nocturnal urinary protein excretion rates in patients with sleep apnea.

We observed nocturnal urinary protein excretion to be 16.2 +/- 5.5 micrograms/min (mean +/- SE) in 9 healthy control subjects (group I), 29.3 +/- 9.5 micrograms/min in 12 obese patients suspected to have obstructive sleep apnea syndrome (OSAS) but with negative polysomnographic studies (group II), and 94.0 +/- 31.8 micrograms/min in 14 patients with documented OSAS (group III) (II vs. I, NS; III vs. I, p less than 0.05; III vs. II, p less than 0.05). The frequency of abnormal proteinuria, defined as protein excretion greater than the highest rate observed in group I (46 micrograms/min), was 14% in group II and 64% in group III (p less than 0.05). There were no significant differences in age, body weight, body surface area, blood pressure, or indices of sleep apnea between OSAS patients with and without proteinuria. Although the mechanism is unclear, this study shows that nocturnal protein excretion rates are commonly elevated in patients with OSAS.

Adult↗
PubMed1989

Atrial natriuretic peptide (ANP) is removed by peritoneal dialysis in humans.

Atrial natriuretic peptide (ANP) is a hormone liberated from the heart during atrial stretch (volume overload). In order to determine if ANP levels are altered in patients on continuous ambulatory peritoneal dialysis (CAPD) or affected by the dialysis procedure itself, we measured plasma ANP in patients before and after peritoneal infusion of two liters of 1.5% Dianeal dialysate and in dialysate subsequently drained from these patients. Plasma ANP is elevated in CAPD patients, but is not affected by infusion of dialysate. ANP is cleared from plasma by peritoneal dialysis.

Adult↗
PubMed1988

Severe hyponatremia without severe hypoosmolality following transurethral resection of the prostate (TURP) in end-stage renal disease.

A 55-year-old man on chronic hemodialysis underwent a transurethral resection of the prostate (TURP), during which 3% sorbitol solution was used for urethral irrigation. Following the procedure, he developed symptomatic hyponatremia (serum sodium, 106 mEq/L), but had only mild hypoosmolality (serum osmolality, 269 mosm/kg). The "osmolal gap" was 47 mosm/kg, probably from sorbitol absorbed systemically during the TURP. Hemodialysis raised the serum sodium to 118 mEq/L, and the serum osmolality to 284 mosm/kg, while lowering the osmolal gap to 26 mosm/kg. The presence of severe hyponatremia with only modest hypoosmolality may occur in patients with renal failure following the systemic absorption of hypotonic fluids containing solutes such as sorbitol and mannitol. Hemodialysis offers the advantages of correcting the hyponatremia while removing the unmeasured solute, thus preventing rapid increases in the serum osmolality.

Humans↗
PubMed1988

Sleep apnea, proteinuria, and nephrotic syndrome.

Renal abnormalities in patients with obstructive sleep apnea syndrome (OSAS) have not been previously described. Medical records of patients who had been evaluated for possible sleep apnea syndrome and had had complete polysomnograms and urinalyses were reviewed to determine the frequency of proteinuria. High-grade proteinuria (greater than or equal to 3+ on urinalysis) was found in 6 of the 34 patients with obstructive sleep apnea, but in none of 34 patients in a control group matched for sex, age, and weight. In three patients, proteinuria was in the nephrotic range (3.5 g/24 h). The weight (mean +/- SD) of the patients with obstructive sleep apnea (112.7 +/- 35.3 kg) was not significantly different from the control group (109.2 +/- 30.3 kg). Microscopic examination of renal tissue in one patient with OSAS showed minimal changes. In four patients who were followed for 3 years, proteinuria improved after therapy for sleep apnea syndrome. We suggest that proteinuria may not be uncommon in patients with severe obstructive sleep apnea syndrome and may be reversible with correction of the sleep apnea syndrome.

Adult↗
PubMed1988

Four-hour atrial natriuretic peptide infusion in conscious rats: effects on urinary volume, sodium, and cyclic GMP.

Atrial natriuretic peptide (ANP) is released from the cardiac atria in response to acute volume loads; when infused acutely ANP causes diuresis and natriuresis. Cyclic GMP (cGMP) appears to be the second messenger for ANP in the kidney. The role that ANP plays in the long-term regulation of salt and water balance is unclear, however, since resistance to ANP's natriuretic and diuretic activity develops during prolonged administration. The purpose of the present study is to examine the relationship between the rate of cGMP excretion in response to ANP and the development of resistance to ANP's diuretic and natriuretic activity. Following a 30-min baseline period of infusion of Ringer's solution conscious rats received ANP at 15 micrograms/kg/hr (n = 6) or Ringer's alone (n = 5) for 240 min. ANP-infused rats had a significant diuresis and natriuresis during the first hour of infusion; urinary cGMP excretion also increased compared to baseline. By 120 min after initiating the infusion in ANP-rats urinary volume and sodium excretion had declined to values not significantly different from those of baseline or control. In contrast, urinary cGMP excretion remained elevated for the duration of the ANP infusion, whether compared to baseline values or the control group. Resistance to the diuretic and natriuretic activity of ANP is not a result of mechanisms that involve cGMP generation.

Animals↗
PubMed1988

Reversible proteinuria in obstructive sleep apnea syndrome.

Two patients with severe obstructive sleep apnea syndrome and high-grade proteinuria (greater than 1 g/d [1000 mg/d]) were studied. Three remissions in proteinuria coincided with correction of obstructive sleep apnea syndrome and improvement of blood oxygen levels. These remissions could be dissociated from reductions both in dry body weight and in hematocrit levels. We propose that sleep apnea may cause a functional and reversible type of proteinuria.

Adult↗
PubMed1988

Effect of arteriovenous shunting on plasma vasopressin levels in the anesthetized dog.

Studies were performed in dogs anesthetized with chloralose to establish the plasma arginine vasopressin (AVP) response to 30-minute periods of femoral arteriovenous (AV) shunting at levels of either 10%, 30%, or 50% of control cardiac output. Significant increases in cardiac output, heart rate, and total body peripheral resistance (shunt resistance excluded), suggesting decreased sinoaortic baroreceptor activity, occurred at shunt fractions greater than 10%. There were no significant changes in plasma concentrations of AVP at any level of AV shunting. In separate studies, significant elevations in plasma AVP levels were observed in vagotomized dogs during AV shunting of 50% of control cardiac output. These results indicate that AV shunting less than or equal to 50% of cardiac output does not acutely alter plasma AVP levels in the intact dog and that cardiopulmonary receptors with vagal afferents suppress AVP release that might otherwise occur in this canine model of AV shunting.

Anesthesia↗
PubMed1987

Renal infections in autosomal dominant polycystic kidney disease.

Renal infection is a common occurrence in autosomal dominant polycystic kidney disease (ADPKD) and often leads to serious complications, including perinephric abscess, septicemia, and death. Important predisposing factors include age, female sex, and recent instrumentation of the urinary tract. Renal infections in ADPKD are most commonly caused by gram-negative enteric organisms. Diagnosis of these infections may be difficult since some patients do not have bacteriuria. Eradication of cyst infections with conventional antibiotic therapy can be difficult despite in vitro sensitivity of responsible organisms to the agents administered. We review recent studies of the anatomic and functional characteristics of renal cysts and discuss their possible relevance to the treatment of renal cyst infections. Finally, we set forth guidelines for the use of diagnostic studies, antimicrobial therapy, and surgical intervention for polycystic kidney infections.

Abscess↗