Hillel J. Gitelman

Gitelman's variant of Bartter's syndrome, inherited hypokalaemic alkalosis, is caused by mutations in the thiazide-sensitive Na-Cl cotransporter.

Maintenance of fluid and electrolyte homeostasis is critical for normal neuromuscular function. Bartters syndrome is an autosomal recessive disease characterized by diverse abnormalities in electrolyte homeostasis including hypokalaemic metabolic alkalosis; Gitelmans syndrome represents the predominant subset of Bartters patients having hypomagnesemia and hypocalciuria. We now demonstrate complete linkage of Gitelmans syndrome to the locus encoding the renal thiazide-sensitive Na–Cl cotransporter, and identify a wide variety of non-conservative mutations, consistent with loss of function alleles, in affected subjects. These findings demonstrate the molecular basis of Gitelmans syndrome. We speculate that these mutant alleles lead to reduced sodium chloride reabsorption in the more common heterozygotes, potentially protecting against development of hypertension.

An improved automated procedure for the determination of calcium in biological specimens

Abstract An improved automated spectrophotometric method for calcium has been described which is directly applicable to serum, plasma, urine, and tissue ash samples. Calcium is determined colorimetrically with CPC in the presence of 8-hydroxyquinoline, which eliminates significant magnesium error. Iron interference, which may be encountered in the analysis of specimens prepared from ashed tissue, has been eliminated by the precipitation of iron with cupferron prior to dialysis. Reproducibility studies, recovery data, and comparisons between other manual and automated calcium techniques are presented.

Serum and urinary aluminium levels of workers in the aluminium industry

We have measured serum aluminium and urinary aluminium/creatinine ratios in 235 aluminium workers and 44 controls to examine the association between occupational exposure to airborne aluminium and aluminium absorption. Serum and urine samples were taken before and after a 3- to 5-day work shift. Occupational exposure was estimated from aluminium measurements of respirable and total particulates in air. Median exposure values were 25 and 100 micrograms m-3, respectively. Serum aluminium and urinary aluminium/creatinine ratios did not change significantly during the shift; however, both pre-shift and post-shift serum aluminium and urinary aluminium/creatinine ratios were increased in the exposed group. Occupational exposure was associated with serum aluminium increments of 1.32 micrograms l.-1 (P = 0.01) pre-shift, and 0.96 micrograms l.-1) (P = 0.08) post-shift. Greater and more significant differences were seen between exposed and controls for the urinary aluminium/creatinine ratios [5.67 micrograms g-1 (P < 0.01) pre-shift; 8.01 micrograms g-1 (P < 0.01) post-shift]. Urinary aluminium/creatinine ratios were greater in plants with higher aluminium exposures. These results are consistent with the systemic absorption of aluminium from occupational exposure and suggest the presence of a sensitive uptake process for airway aluminium.

An automated spectrophotometric method for magnesium analysis

Abstract An automated spectrophotometric method for magnesium has been devised which is directly applicable to serum, plasma, urine, and tissue ash samples. Magnesium is determined colorimetrically with EBT in the presence of strontium EGTA, which eliminates significant calcium error and the necessity for separation of calcium from magnesium prior to analysis. Reproducibility studies, recovery data, and comparisons with a manual flame photometric method are presented.

Silicon Accumulation in Dialysis Patients

Plasma silicon measurements have been obtained in patients with end-stage renal disease on chronic dialysis therapy. The mean +/- SE values for normal plasma silicon concentrations are .15 +/- .02 mg/L. All dialysis groups showed marked elevations in their plasma silicon that correlated with the silicon content of their respective dialysis fluids. The values of two different hemodialysis groups and a peritoneal dialysis group were 4.6 +/- .4, 2.5 +/- .2, and 1.9 +/- 1.2 mg/L, respectively. The silicon content of their respective dialysis fluids were 4.0 +/- .7, 0.5 +/- .4, and 0 +/- .1 mg/L. The ultrafiltrability of plasma silicon through Cuprophane membranes was 79 +/- 2%. Hemodialysis patients drinking high-silicon well water showed significantly higher plasma silicon levels than patients drinking lower silicon municipal water. It is concluded that use of dialysis fluid with elevated silicon levels and the consumption of water containing high concentrations of silicon are two important determinants of silicon levels in a dialysis population. We observed no overt effects of silicon accumulation on the health status of our dialysis patients.

A semiautomated procedure for determination of adenosine triphosphate

Abstract We have presented a rapid, accurate, and convenient semiautomated procedure to measure ATP in erythrocytes. The technique employs conventional autoanalyzer equipment in conjunction with a liquid scintillation spectrometer to detect ATP by firefly luminescence. The sensitivity of the detecting system has permitted potential interferences from inorganic ions to be eliminated by dilution. Additionally, a simplified manual technique for the preparation of erythrocyte samples for ATP assay has been devised.

High fluoride exposure in hemodialysis patients.

The observation of higher plasma flouride levels in our hemodialysis (HD) patients than our continuous ambulatory peritoneal dialysis (CAPD) patients (4.0 +/- 0.5 mumol/L [n = 17] v 2.5 +/- 0.3 mumol/L [n = 17], P less than 0.005) prompted an evaluation of fluoride metabolism during HD. We found that serum fluoride was completely ultrafiltrable across cuprophane membranes (99% +/- 4%) and that HD produced acute changes in plasma fluoride levels that correlated well with the fluoride gradient between plasma and dialysis fluid at the start of dialysis. Our HD fluids contained significantly higher fluoride concentrations than were present in commercially prepared peritoneal dialysis fluid. Our fluids are prepared from fluoridated tap water that is purified by reverse osmosis (RO). We conclude that the different concentrations of fluoride in our dialysis fluids account for the differences in the plasma flouride concentrations between our dialysis groups. Since many HD units rely on RO systems to purify fluoridated tap water, it is likely that many HD patients are being exposed inadvertently to increased concentrations of fluoride.

Hemolytic uremic syndrome following cisplatin, bleomycin, and vincristine chemotherapy: a report of a case and a review of the literature

This report describes a patient who developed the hemolytic uremic syndrome while undergoing chemotherapy with cisplatin, bleomycin, and vincristine, for metastatic squamous cell cancer of the floor of the mouth. In spite of dialysis and plasmapheresis, the patient died. This complication has rarely been reported in association with cisplatin, bleomycin, or vincristine therapy. The etiology of this syndrome is uncertain but may be related to scleroderma-like endothelial injury and vasospasm caused by bleomycin combination chemotherapy. It is notable that the development of the hemolytic uremic syndrome in conjunction with this combination of agents has been fatal in all patients over the age of 50 with squamous cell cancers.

Further Evidence for a Humoral Natriuretic Factor

Experiments were performed in dogs, utilizing cross-circulation techniques, to examine the role of humoral factors in the production of the diminished net renal tubular reabsorption of sodium that is provoked by the expansion of the extracellular fluid volume. When the extracellular fluid volume of one of a pair of dogs (donor) was expanded by the intravenous infusion of isotonic saline, the rate of sodium excretion (UNaV) increased in the nonexpanded animal (recipient) as well as in the donor. Although the increase in UNaV of the recipients was statistically significant, its magnitude was approximately one-fifth of that of the donors. Modified cross-circulation experiments were designed in order to increase the blood flow from the donor dog to the kidneys of the recipient and from the recipient dog to the kidneys of the donor. This modification resulted in a greater increase in UNaV in the recipient and a lesser increase in UNaV in the donor when the donor was infused intravenously with isotonic saline so that the magnitudes of increase in UNaV in donor and recipient were not statistically significantly different. Neither dilution per se of the extracellular fluid of the donor nor passage of time resulted in an increased UNaV in donors and recipients. Expansion of the blood volume of the donors by the infusion of whole blood resulted in an increased UNaV in the donors but not in the recipients. It is concluded that a humoral factor is responsible, at least in part, for the natriuresis that accompanies the intravenous infusion of isotonic saline and that elaboration of the factor is not a consequence solely of either simple dilution of the extracellular fluid or expansion of the blood volume.

Calcium dependent ATP losses in intact red blood cells without cellular accumulations of calcium.

SummaryIntact human red blood cells incubated with ionophore A23187 and calcium develop a depletion of ATP that is dependent upon the concentrations of both A23187 and Ca. Incubations of fresh cells with 0.5 μm A23187 and concentrations of Ca at or below 70 μm produce a depletion of ATP without a net cellular uptake of Ca. In contrast, ATP-depleted cells display an ionophore-dependent cellular uptake of Ca, under identical conditions. A hypothesis is proposed that relates these ionophore-produced ATP depletions to active Ca extrusion by the Ca ATPase.