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Biomedical subjects

G O Perez

Publications and source records attributed to G O Perez.

At least 19 recordsLinked to original sources

Interaction of cyclosporine A and nonsteroidal anti-inflammatory drugs on renal function in patients with rheumatoid arthritis.

PURPOSE: To determine the additive renal effects of nonsteroidal anti-inflammatory drugs (NSAIDs) and cyclosporine A (CYA) in patients with rheumatoid arthritis (RA) and to determine the effects of CYA on active RA. PATIENTS AND METHODS: Eleven patients with RA refractory to other agents were treated separately for 2-week periods with an NSAID (sulindac or naproxen), CYA (5 mg/kg/d), and NSAID plus CYA in combination (NSAID/CYA). The NSAID/CYA combination was continued for an additional 20 weeks. Clinical parameters of RA, electrolytes, renal function, and the renin-aldosterone system were evaluated at each interval to determine the potential interaction of these two agents. RESULTS: Combined therapy was effective in suppressing many measures of active RA in 9 of the 11 patients. Adverse drug reactions were common, but withdrawals were limited to hirsutism (one) and peripheral neuropathy (one). In about half of the patients, CYA or NSAID resulted in a decrease in the glomerular filtration rate (GFR) and effective renal plasma flow (ERPF), with a mild reduction in the filtration fraction. With NSAID or CYA, early morning renin-aldosterone system values were mildly suppressed, and their response to ambulation/intravenous (IV) furosemide was not blunted. When combined, NSAID/CYA caused more marked reductions of GFR and ERPF at 2 weeks, and this persisted at 20 weeks. The morning renin-aldosterone system values during administration of NSAID/CYA were suppressed, with an added blunted response to ambulation/IV furosemide. CONCLUSION: As previously suspected, the impairment of renal function when CYA and NSAID are combined is greater than that obtained with either agent alone. This hemodynamic effect was reversible and appeared to be, at least in part, due to renal vasoconstriction.

Adult

Low anion gap resulting from unexplained exposure to bromide in a patient with renal amyloidosis.

A patient with nephrotic syndrome secondary to renal amyloidosis was consistently observed to have serum anion gap levels as low as -1 mEq/L and averaging approximately 2 mEq/L. Neither multiple myeloma nor extreme hypertriglyceridemia was present, and the patient's serum albumin concentrations were not low enough to depress the anion gap to this degree. An increased serum bromide level (below the range expected to produce clinical toxicity) was the apparent cause of the low anion gap. The patient's parents, who live in the same apartment, also manifested low anion gaps and inexplicably elevated serum bromide levels. Despite detailed investigation, no environmental or pharmacologic source of bromide was uncovered. Although the source of the bromide in the present instance remains elusive, this report illustrates the necessity to measure serum bromide when a low anion gap cannot be explained by other factors, even when there is no history to suggest bromide exposure.

Acid-Base Equilibrium

Severe cerebral edema in a patient with anasarca and hypernatremia.

We describe a woman whose fatal post-liver transplantation cerebral edema was unexpected and of unusual pathogenesis. Her severe cerebral edema is of considerable pathophysiologic interest: 1) it developed in the setting of marked anasarca and persistent hypernatremia, and 2) although hepatic function was poor, it was not considered sufficiently deranged to induce cerebral edema. Furthermore, there was no histologic evidence of hepatic rejection or antemortem hepatic necrosis. We postulate that an impairment of the blood brain barrier in association with a degree of hepatic dysfunction insufficient by itself to cause cerebral edema permitted the brain interstitial fluid volume to increase pari passu with ECF expansion. Cytotoxic cerebral edema and vascular engorgement may also have contributed to a life-threatening increase in intracranial pressure.

Adult

Effect of hyperkalemia on insulin secretion.

The effect of hyperkalemia on insulin secretion remains undefined. We evaluated portal and peripheral insulin levels in anesthetized dogs after infusions of KCl. The mean maximal increase in peripheral plasma potassium at infusion rates of 0.2 mEq/kg/h was 0.68 +/- 0.20 mEq/l. There were no significant increases in either portal or peripheral insulin levels. In contrast, in six dogs whose plasma potassium concentration increased in each case by more than 2.0 mEq/l (infusion rate of 0.5 mEq/kg/h), portal insulin levels increased fivefold (p less than 0.05). We concluded that only marked increases in plasma potassium concentration stimulate pancreatic insulin secretion.

Animals

Effect of hypertonic versus isotonic sodium bicarbonate on plasma potassium concentration in patients with end-stage renal disease.

The purpose of the study was to evaluate the potassium-lowering effect of hypertonic versus isotonic sodium bicarbonate (NaHCO3) in patients with end-stage renal disease (ESRD) receiving chronic maintenance hemodialysis. Immediately prior to dialysis, we infused isotonic (1.4%, 150 mEq/l) NaHCO3 in H2O (1 mEq/kg body weight over 2 h) to 10 patients with ESRD. Blood was drawn in heparinized tubes, without the use of a tourniquet, from the angioaccess for Na, K, pH, PCO2, HCO3, and osmolality at baseline (x 3) and after 10, 20, 40, 60, 90, 120, and 180 min of infusion. All patients were acidotic (HCO3 13-21 mEq/l, pH 7.25-7.38) prior to the study. In these patients, plasma HCO3 increased by an average of 3 mEq/l, and plasma K decreased by 0.35 mEq/l at 180 min. Plasma osmolality did not change. In 8 patients, a bolus of hypertonic (8.4%, 1,000 mEq/l) NaHCO3 (1 mEq/kg body weight over 5 min) tended to cause a transient increase in plasma HCO3, an increase in plasma osmolality, and minor changes in the K levels (an initial small and transient albeit significant decrease, followed by a tendency to increase). Finally, plasma K tended to increase in patients receiving infusions of either isotonic (n = 6) or hypertonic (n = 6) sodium chloride. Our data do not support the efficacy of the common practice of administering NaHCO3 for the emergency treatment of hyperkalemia in patients with ESRD receiving maintenance dialysis.

Bicarbonates

Tetany induced on separate occasions by administration of potassium and magnesium in a patient with hungry-bone syndrome.

The case is described of a 68-year-old man whose therapy induced tetany during each of two consecutive hospital admissions. On each occasion the patient had marked hypocalcemia and hypomagnesemia, presumably as a result of the hungry-bone syndrome associated with diffuse prostatic osteoblastic metastases. During the February 1991 admission, marked hypokalemia was the principal initial concern. It seems likely that the tetany associated with the administration of KCl, without sufficient calcium, resulted from attenuation of the protection against hypocalcemia-enhanced neuromuscular excitability conferred by coexisting hypokalemia. The admission in March 1991 was prompted by the finding (without symptoms) of very low levels of both serum Mg and serum Ca. Tetany occurred during the infusion of MgSO4, without calcium. An acute decrement in plasma ionized Ca resulting from complexing of Ca with sulfate ions together with augmented urinary excretion of Ca were likely pathogenic factors.

Aged

Recurrence and clearance of hepatitis B surface antigenemia in a dialysis patient infected with the human immunodeficiency virus.

Hepatitis B vaccination programs have prevented infection in many dialysis patients, although the antibody response to vaccination is still insufficient in approximately 50%. Reinfection or reactivation of latent hepatitis B infection (HBV) has been reported in certain groups of immunosuppressed patients, including those infected with the human immunodeficiency virus (HIV-1). We report the reactivation or reinfection of HBV with resurgence of hepatitis B surface antigen in a dialysis patient coinfected with HIV-1. Thus, in dialysis patients with latent HBV infection, with undetectable hepatitis B surface antigen (HBsAg) levels, the potential exists to reactivate during immunosuppression associated with HIV-1 infection and/or end-stage renal disease. Reinfection with a different subtype is also possible. The development of hepatitis B surface antigenemia in this patient population creates a potential for transmission in the dialysis setting. This is of special concern since the number of patients infected with HIV-1 and with evidence of prior hepatitis B infection is increasing in urban units.

Acquired Immunodeficiency Syndrome

Hepatitis C infection in two urban hemodialysis units.

We determined the prevalence of antibodies to the hepatitis C virus (anti-HCV) in 90 patients and 37 staff members of two hemodialysis units utilizing a recently developed anti-HCV recombinant based assay. Eleven patients (12%) were anti-HCV(+). Of these, eight (73%) had antibodies to the hepatitis B core antigen (anti-HBc) indicating prior hepatitis B infection; one patient was hepatitis B surface antigen (HBsAg)(+). All staff members were anti-HCV(-), although seven (19%) of them were anti-HBc(+). Alanine aminotransferase elevations were present at the time of the study in four anti-HCV(-) patients and in only one anti-HCV(+) patient. All anti-HCV(+) (mean 59 +/- 74; range 3 to 269 units) and 85% of anti-HCV(-) patients (mean 16 +/- 27; range 0 to 204 units) had received multiple blood transfusions (P = 0.348). Among 50 patients tested for human immunodeficiency virus (HIV), 43% of anti-HCV(+) as compared to only 7% anti-HCV(-) were positive (P = 0.003). There was a history of intravenous drug abuse (IVDA) in eight (72%) of the anti-HCV(+) patients and in only seven (9%) of the anti-HCV(-) group (P = 0.00001). The results of this serologic survey suggests that anti-HCV positivity is prevalent, although much less than anti-HBc, among our dialysis patients, whereas it was not detected among staff members. The prevalence rate of anti-HCV was statistically significantly higher among anti-HIV(+) and IVDA patients but not in multi-transfused patients.

Adult

Correlates of atherosclerosis in coronary arteries of patients undergoing angiographic evaluation.

The correlations between lipid and lipoprotein measurements and other risk factors of coronary artery disease were evaluated in 101 men undergoing coronary angiography. Clinically significant disease was present in 75 patients, whereas 24 had no observable lesions and 2 had minimal lesions. Comparisons of individual lipid and lipoprotein levels were nearly all significantly different between patients with and patients without clinically significant disease; however, no single variable could predict the presence of disease among patients. Logistic regression analysis identified five factors: apolipoprotein A-I, apolipoprotein B, diabetes, age, and family history of heart disease, which account for most of the differences between the two patient groups. These results could have important implications for the evaluation and management of patients suspected of having coronary atherosclerosis.

Age Factors

The effects of administration of lithium salts and magnesium sulfate on the serum anion gap.

Whether or not an increased serum level of an unmeasured cation will reduce the anion gap (AG) depends on concomitant changes (or lack thereof) in serum unmeasured anions. In the present retrospective study, we sought to determine the effect of lithium carbonate or citrate and magnesium sulfate on the AG. Two groups of psychiatric patients whose average serum lithium levels were 0.6 and 1.0 mEq/L were studied. The AG in each group (10.2 +/- 0.3 [SE] and 9.0 +/- 0.4 mEq/L, respectively) was significantly (P less than 0.05) lower than that of a control group (11.1 +/- 0.3 mEq/L). Separately, we collected 87 pairs of AG and serum magnesium data of patients with toxemia of pregnancy. These included those of 15 patients evaluated both before and during magnesium sulfate infusion. Despite an average serum magnesium level of 4.1 +/- 0.2 mEq/L, the AG of the latter subjects tended to increase slightly from 10.8 +/- 0.5 to 11.7 +/- 0.7 mEq/L during magnesium infusion, instead of decreasing. The other data (72 determinations in the 55 patients without preinfusion values) revealed a mean AG of 11.0 +/- 0.3 mEq/L, coexisting with an elevated serum magnesium of 4.1 +/- 0.1 mEq/L. None of the above-mentioned three mean AG values differed significantly from that of the control group. We conclude that hypermagnesemia resulting from the administration of magnesium sulfate does not reduce the AG, probably because of a concomitant and proportional increase in serum sulfate. The present data reemphasize the need to assess the anion gap as the result of concomitant changes in both unmeasured anions and cations.

Acid-Base Equilibrium

Blunted kaliuresis after an acute oral potassium load in diabetes mellitus.

It is unknown whether diabetic patients without renal failure or aldosterone deficiency respond normally to potassium administration. Acute oral potassium-loading was carried out in eight diabetic patients with modestly reduced creatinine clearance (Ccr) and in 11 diabetic patients and 13 controls with normal clearances. Only one diabetic patient manifested an inappropriately low upright plasma aldosterone level (6 ng/dL). The percentage of potassium excreted in 4 hour by both groups of diabetic patients was significantly less than that of the controls (decreased Ccr:21% +/- 6%, normal Ccr:36% +/- 5%, controls:54% +/- 5%; p less than 0.01 and 0.05 respectively). On the other hand, the estimated amount of potassium translocated intracellularly tended to be greater in the diabetic patients (18 +/- 3 mmol; 11 +/- 3 mmol) than controls(7 +/- 2 mmol; p less than 0.005 and 0.1 respectively), and the ratio of the increase in plasma (K) to the amount of potassium retained, was lower in diabetic patients, probably indicating enhanced intracellular potassium translocation. The authors conclude that diabetic patients with normal or only slightly reduced renal function (and no aldosterone deficiency) may have a reduced capacity to excrete an acute potassium load but an enhanced capacity to transfer potassium intracellularly.

Adult

Use of the anion gap in clinical medicine.

The anion gap (AG) in the serum equals the concentrations of Na-(Cl + HCO3). It is becoming increasingly useful in the interpretation of acid-base disorders and in the diagnosis of other conditions. In an acidemic patient, an elevated AG usually indicates the presence of an organic acidosis, rhabdomyolysis, nonketotic hyperglycemic coma, uremia, or certain intoxications. An increased AG with alkalemia suggests severe alkalosis with hemoconcentration or use of anionic antibiotics (eg, carbenicillin) or salts of organic acids (eg, citrate). An elevated AG with a normal serum pH could be an artifact caused by prolonged exposure of the serum sample to air before processing. A decreased AG with a normal serum pH may indicate hypoalbuminemia, cationic paraproteinemia, halide poisoning, or lithium intoxication. The delta AG/delta HCO3 ratio and the urinary AG may also be quite useful in analyzing complex acid-base disorders.

Acid-Base Equilibrium

Lack of transmission of human immunodeficiency virus in chronic hemodialysis patients.

We carried out a prospective 2-year study on the transmission of human immunodeficiency virus (HIV) infection in a chronic dialysis unit with a high prevalence (11%) of the infection. Only 1 of 45 HIV-negative patients seroconverted, and this was related to the administration of contaminated blood. We conclude that current Centers for Disease Control criteria are sufficient to prevent transmission of HIV infection in dialysis units.

Acquired Immunodeficiency Syndrome

The stability of pH, PCO2, and calculated [HCO3] of urine samples collected under oil.

In order to determine the stability of directly measured pH and PCO2, and calculated [HCO3] in stored urine, 11 alkali-loaded normal subjects provided 33 spot and sixteen 24-hour mineral oil-covered, thymol-preserved, refrigerated urine samples. For the spot samples, pH and PCO2 were measured immediately and again at 4 and 24 h. In addition, immediately after voiding, 24 of the spot samples were split into oil-covered and no-oil moieties and analyzed immediately and again at 4 and 24 h. pH and PCO2 measurements of the 24-hour collections were carried out immediately after completion and again 24 h later. The results demonstrated the importance of using oil to limit the escape of CO2 from stored urine. Thus, after 24 h the oil-uncovered subgroup of 24 spot urine samples sustained a 82% decline in PCO2 and 20% fall in [HCO3]. In contrast, the corresponding percentage decrements in the oil-covered samples were 16 and 1%, respectively. The results also indicated that even with oil there is loss of CO2, which increases with time and which shows a statistically significant direct correlation with the baseline level of PCO2. Nevertheless, modest loss of CO2 usually produces only slight decrements in [HCO3] because of the countervailing influence of the resultant increase in pH. We conclude that the use of mineral oil is necessary in order to obtain adequate stability of PCO2, pH and [HCO3] in refrigerated urine requiring several hours or more of storage.

Bicarbonates

Comparison of the effects of sodium bicarbonate versus sodium citrate on renal acid excretion.

Citrate is used commonly as an alkalinizing agent and in the management of nephrolithiasis, but its quantitative effect on acid-base homeostasis, as judged by changes in renal net acid excretion, has not been delineated. We therefore administered 61 mEq of sodium citrate/day for 4 days to 10 normal volunteers and compared the results to those obtained in 10 normal subjects (4 of whom also participated in the citrate protocol) given 60 mEq/day for 4 days of sodium bicarbonate, the prototypical alkalinizing agent. We found that the sodium citrate group experienced an average reduction in net acid excretion (45.5 +/- 7.2 mEq/day) that was very similar to that (42.0 +/- 7.2 mEq/day) induced by the same amount of sodium bicarbonate. In both groups, the reduction in net acid excretion was equivalent to approximately 70% of the alkali administered. The latter appeared to relate to an average negative hydrogen ion balance of approximately 15 mEq/day, since there was an increase in blood [HCO3] in each group of about 2.5 mEq/l. We conclude that the findings demonstrate that the short-term effects of sodium citrate on acid-base homeostasis in normal subjects are indistinguishable from those of sodium bicarbonate.

Acids

Defect in cholesteryl ester transport in serum of patients with uremia receiving maintenance hemodialysis: increased inhibitor activity for cholesteryl ester transfer.

The rate of cholesterol transfer (RCT) from high-density lipoproteins (HDLs) to very low-density lipoproteins (VLDLs) and low-density lipoproteins (LDLs) was previously found to be lower in the serum of patients with uremia receiving maintenance hemodialysis than in the serum of control subjects, and the defect was associated with the serum density greater than 1.063 gm/ml fraction (Hsia et al. J LAB CLIN MED 1985;106:53). The present study shows that cholesterol transfer from HDLs to VLDLs and LDLs could be increased when the lipoprotein-deficient fraction of control serum was substituted for the patients' fraction. Cholesteryl ester transfer protein (CETP) activity in patient serum was assayed and found to be below that in the serum of control subjects. CETP and CETP inhibitor activities in patient and control sera were separated by hydrophobic chromatography on phenyl-Sepharose. Recovery of CETP activity from patient samples was 214% +/- 62%, and that from controls was 112% +/- 15%. The data indicate that the low RCT of patients was caused by increased levels of an inhibitor to CETP activity in their serum.

Adult