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Biomedical subjects

Z Farfel

Publications and source records attributed to Z Farfel.

At least 19 recordsLinked to original sources
PubMed2005

WNK4 regulates airway Na+ transport: study of familial hyperkalaemia and hypertension.

BACKGROUND: WNK [With No K (lysine)] kinases are essential for regulation of blood pressure and potassium homeostasis. WNK4 expression was recently found not only in the distal nephron but also in chloride-transporting epithelia. To establish a physiological role for this distribution we studied patients with familial hyperkalaemia and hypertension (FHH), [pseudohypoaldosteronism type II (PHAII)], which is caused by mutations in WNK4. DESIGN: Measurement of nasal potential difference (NPD) and sweat electrolytes were performed in controls, in six subjects with FHH and ten subjects with cystic fibrosis (CF). RESULTS: Basal NPD was higher in FHH compared with controls (n = 20): 22.8 +/- 5.7 vs. 16.2 +/- 5.3 mV, respectively (P = 0.014). Maximal response to amiloride was also higher in FHH compared with controls: 14.8 +/- 3.5 vs. 10.0 +/- 4.8 mV, respectively (P = 0.03). In CF these values were 42.9 +/- 9.3 and 29.9 +/- 7.4 mV, respectively. The kinetics of the amiloride effect were faster in FHH, and as first reported here also in CF, compared with controls. At 30 s, amiloride-inhibitable residual PD in FHH was 50 +/- 30 vs. 81 +/- 9% in controls (P = 0.0003) and 56 +/- 7% in CF. The response to chloride-free and isoproterenol solutions, which determines chloride transport activity, was similar in FHH compared with controls [16.0 +/- 8.6 vs. 10.4 +/- 5.9 mV (P = 0.08)]. Sweat conductivity in FHH was 49.7 +/- 7.3 vs. 38.2 +/- 8.1 mmol (NaCl eq) L-1 in 16 controls (P = 0.007) and 94.0 +/- 19.3 in CF. CONCLUSIONS: Mutant WNK4 increases Na+ transport in airways, and therefore it is regulated by wild-type WNK4. This may be caused by a regulation of ENaC or a K+ channel.

Cystic Fibrosis↗
PubMed2003

Hepatic infarctions during pregnancy are associated with the antiphospholipid syndrome and in addition with complete or incomplete HELLP syndrome.

Antiphospholipid antibody syndrome (APS) is associated with adverse pregnancy outcomes and maternal complications including thrombotic events and early pre-eclampsia. HELLP syndrome (Hemolysis, Elevated Liver enzymes, Low Platelets) represents a unique form in the spectrum of pre-eclampsia. This report describes four patients with pregnancy-associated hepatic infarctions. All four had APS and HELLP syndrome, which was complete in one patient and incomplete in three patients, with elevated liver enzymes in all, and either thrombocytopenia or hemolysis in two. In the literature, we found descriptions of an additional 24 patients who had 26 pregnancies with concomitant hepatic infarction. Of the total 28 patients, anticardiolipin antibodies (aCL) and/or lupus anticoagulant (LAC) were assessed in 16 patients, out of whom 15 were found to be positive. Hepatic infartction during pregnancy was associated almost always with APS, with HELLP (2/3 complete, 1/3 incomplete), and only in one-third of the pregnancies with pre-eclampsia (PE).

Abortion, Habitual↗
PubMed2002

gammadelta T cell subsets in patients with arthritis and chronic neutropenia.

BACKGROUND: An abnormal distribution of subsets of gammadelta T cells, which are a component of the inflammatory infiltrate in arthritic synovium, has been demonstrated in the peripheral blood (PB) of patients with arthritis and neutropenia. OBJECTIVE: To evaluate whether the clinical manifestations of patients with arthritis and neutropenia are related to the specific gammadelta T cell subset predominant in the PB. METHODS: Flow cytometry of PB lymphocytes in six consecutive patients with chronic neutropenia and arthritis was performed. Variable (V) gamma and delta gene families were analysed by polymerase chain reaction. cDNA was subjected to direct automated sequencing of T cell receptor (TCR) genes. RESULTS: Three patients had non-deforming and non-erosive rheumatoid factor (RF)(+) polyarticular rheumatoid arthritis, RF(+) oligoarticular arthritis, or RF(-) non-deforming oligoarticular psoriatic arthritis with persistent expansions of Vgamma1(+)/Vdelta2(+), Vgamma2(+)/Vdelta2(+), or Vgamma1(+)/Vdelta (undetermined (2- 1-)) T cells, respectively. The other three patients, without persistent expansion of gammadelta T cells, had either non-deforming and non-erosive oligo- or polyarthritis with a balanced distribution of several Vdelta and Vgamma genes, or severe erosive RF(+) arthritis with deficiency of all but Vgamma1(+)/Vdelta1(+) T cells. CONCLUSIONS: gammadelta T cell lymphoproliferations in chronic neutropenia and arthritis use different Vgamma and Vdelta gene families, often forming T cell receptor (TCR) structures that are infrequent in normal adult PB. Arthritis with Vgamma1(+)/Vdelta2(+), Vgamma2(+)/Vdelta2(+), or Vgamma1(+)/Vdelta2(-)/Vdelta1(-) gammadelta T cells in the PB is non-deforming and non-erosive, suggesting a protective effect of these cells, as opposed to a more pathogenic contribution of Vgamma1(+)/Vdelta1(+) cells.

Aged↗
PubMed2002

Successful treatment by cyclooxyenase-2 inhibitor of refractory hypokalemia in a patient with Gitelman's syndrome.

Gitelman's syndrome is manifested by hypokalemic alkalosis, hypomagnesemia, hypocalciuria, normotensive hyperreninemia and hyperaldosteronism. Hypokalemia can at times be refractory to treatment. We present a patient refractory to a variety of drugs including indomethacin, the nonspecific COX inhibitor. Rofecoxib, a specific COX 2 inhibitor, promptly elevated serum potassium concentration with normalization of plasma aldosterone and near normalization of renin without a change in serum magnesium. Our patient also had rhabdomyolysis, a rarely reported complication, which was also ameliorated by COX 2 inhibition.

Adult↗
PubMed2001

Human hypertension caused by mutations in WNK kinases.

Hypertension is a major public health problem of largely unknown cause. Here, we identify two genes causing pseudohypoaldosteronism type II, a Mendelian trait featuring hypertension, increased renal salt reabsorption, and impaired K+ and H+ excretion. Both genes encode members of the WNK family of serine-threonine kinases. Disease-causing mutations in WNK1 are large intronic deletions that increase WNK1 expression. The mutations in WNK4 are missense, which cluster in a short, highly conserved segment of the encoded protein. Both proteins localize to the distal nephron, a kidney segment involved in salt, K+, and pH homeostasis. WNK1 is cytoplasmic, whereas WNK4 localizes to tight junctions. The WNK kinases and their associated signaling pathway(s) may offer new targets for the development of antihypertensive drugs.

Amino Acid Sequence↗
PubMed2001

Trans-tubular potassium gradient in patients with drug-induced hyperkalemia.

BACKGROUND: Trans-tubular potassium gradient (TTKG) is considered to reflect mainly aldosterone bioactivity with regard to its kaliuretic response. We determined both TTKG and aldosterone serum concentrations in patients with severe drug-induced hyperkalemia (DIH). METHODS: Ten hyperkalemic patients with serum potassium of more than 5.5 mEq/l, and serum creatinine of less than 2.5 mg/dl (221 micromol/l) were studied prospectively. Two control groups of 10 patients each were used. Control 1 group with normal renal function, and control 2 group with normokalemia and renal failure of the same magnitude as that of the hyperkalemic patients. Serum osmolarity, electrolytes, creatinine, aldosterone and urine electrolytes and osmolarity were measured and TTKG calculated. RESULTS: DIH patients had lower TTKG values than control 1 patients (2.58 +/- 0.36 vs. 6.68 +/- 0.55, p < 0.001), and also lower than that of the control 2 patients (2.58 +/- 0.36 vs. 5.51 +/- 0.87, p < 0.01). Serum aldosterone concentration in the DIH group was higher than that of the control 1 group [24.30 +/- 5.0 vs. 7.4 +/- 2.1 pg/ml (674 +/- 139 vs. 205 +/- 58 pmol/l), p < 0.006] but not different from that of the control 2 group [24.3 +/- 5.0 vs. 15.3 +/- 3.8 pg/ml (674 +/- 139 vs. 424 +/- 106 pmol/l), respectively, p = 0.18]. Although there was some overlap in TTKG between DIH and control groups, 6 of 10 DIH patients had TTKG of less than 2.5, while none of the control patients had such a low value. CONCLUSION: DIH is characterized by lower TTKG values than those observed in patients with normal or mild-to-moderate renal failure. Other factors in addition to aldosterone seem to be involved.

Aged↗
PubMed2001

Lithium intoxication due to carbamazepine-induced renal failure.

OBJECTIVE: To report the case of a patient with manic-depressive disorder who developed lithium intoxcation following carbamazepine-induced acute renal failure. CASE SUMMARY: A 33-year-old white man with bipolar manic-depressive disorder was treated with lithium for the last 18 months. Three weeks prior to admission, carbamazepine 600 mg was added to the drug regimen due to a recurrence of the psychiatric disorder. He was admitted wh signs of lithium intoxication. Acute renal failure due to carbamazepine-induced interstitial nephritis was diagnosed. DISCUSSION: The combination of carbamazepine and lithium is known to cause neurotoxicity. We describe a different interaction in which the toxic lithium concentrations were the result of carbamazepine-induced acute renal failure. CONCLUSIONS: When considering adding carbamazepine to lithium, careful follow-up of the patients is warranted to prevent this indirect drug in interaction.

Acute Kidney Injury↗
PubMed2000

Prolonged oral morphine therapy for severe angina pectoris.

Patients with intractable angina pectoris despite optimal drug therapy, who are not candidates for revascularization procedures, pose a very difficult problem. We evaluated the role of chronic opioid therapy in four such patients. The patients (mean age 79.5 years) were treated by low doses (mean 40 mg/day) of controlled-release oral morphine (CRM) for 1 to 5 years. The treatment was followed by a marked decline in the rate of admissions and hospitalization periods. The number of admissions decreased from a mean of 6 during the year prior to CRM therapy to 1.5 the following year. The duration of hospitalization for angina pectoris during these periods decreased from a mean of 42 +/- 35 days to 6 +/- 10 days (p < 0.05). Side effects were negligible and consisted mainly of lactulose-responsive constipation. We suggest that prolonged oral morphine therapy may be administered with good efficacy and no significant side effects in selected patients with intractable angina pectoris.

Administration, Oral↗
PubMed2000

Acquired hemophilia masked by warfarin therapy.

People without hemophilia but with autoantibodies specifically directed against the procoagulant activity of factor VIII are known to have acquired hemophilia. The bleeding diathesis in these patients is often severe and life-threatening. The definite laboratory diagnosis of this disorder includes demonstration of low factor VIII levels in plasma with a high titer of factor VIII inhibitors, but the initial suspicion for its presence should rise in view of a prolonged partial thromboblastin time (PTT) and a normal prothrombin time associated with an acquired bleeding disorder. Oral anticoagulant treatment is known to prolong PTT as well, and the merger of these 2 situations may cause delayed diagnosis of acquired hemophilia with devastating consequences. We describe here the first reported case of acquired hemophilia diagnosed in a patient treated with warfarin. In such patients prolonged PTT may be ascribed to warfarin therapy rather than to acquired hemophilia, thus causing a dangerous delay in diagnosis.

Aged↗
PubMed2000

Adult celiac disease presented with celiac crisis: severe diarrhea, hypokalemia, and acidosis.

An acute severe onset of celiac disease is very uncommon in adults. We describe a patient with adult celiac disease who presented with acute diarrhea that lead rapidly to a life threatening hypokalemia and acidosis, the so-called celiac crisis. Celiac crisis, described mainly in children younger than two years of age, has become very rare due to earlier diagnosis and effective therapy of the disease. The case described is an example of the heterogeneous clinical course of celiac disease and emphasizes the need to consider it in the differential diagnosis, even in adults suffering from acute diarrhea and acidosis.

Acidosis↗
PubMed2000

Kaposi's sarcoma after lung transplantation in a Sephardic Jewish woman.

One of the four types of Kaposi's sarcoma (KS), KS after organ transplantation under immunosuppression, is a well-known entity and has been abundantly described in renal, heart and liver recipients. We report the second case of cutaneous KS after lung transplantation, under regular immunosuppression, in a Sephardic Jewish woman. This case, when added to the other 10 cases of posttransplantation KS reported from Israel, all being Sephardic Jews, indicates that in Israel, Sephardic Jews are at higher risk than Ashkenazi Jews to develop posttransplantation KS. This observation should be added to the well-known increased risk of Ashkenazi Jews to develop classic KS. Moreover, in Israel Ashkenazi Jews develop classic KS at higher rates than Sephardic Jews. This apparent discrepancy in the ethnic distribution between Sephardic and Ashkenazi Jews in classic versus posttransplantation KS may shed light on the pathogenesis of KS in general.

Female↗
PubMed1999

[High alkaline phosphatase in subacute thyroiditis].

Subacute thyroiditis may be hard to diagnose, therefore patients are sometimes misdiagnosed and subjected to unnecessary work-up. We report a 37-year-old man with subacute thyroiditis and a high concentration of serum alkaline phosphatase. After aspirin treatment there was clinical improvement and decrease in rapid ESR, and in high serum thyroxin and alkaline phosphatase. The increased alkaline phosphatase, seen in as many as 50% of patients, is of hepatic origin, and is not caused by high serum thyroxin. Awareness of this relationship may help in diagnosis and may prevent unnecessary diagnostic procedures, which may be invasive.

Adult↗