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H Mayan

Publications and source records attributed to H Mayan.

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

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

Fatal liver infarction after transjugular intrahepatic portosystemic shunt procedure.

Hepatic infarction is a rare disease. We describe here a cirrhotic patient with end-stage renal failure and recurrent tense ascites with fatal hepatic infarction after transjugular intrahepatic portosystemic shunt (TIPS) procedure. Abdominal ultrasound, radionuclide liver scan, abdominal computed tomography scan, and finally liver biopsy established the diagnosis. The mechanism causing the infarct is not clear. However, as the infarct appeared after the patient had an episode of shock and disseminated intravascular coagulation, it could well be that the concomitant hepatic arterial insufficiency contributed to the infarct. Physicians should be aware of this possible catastrophic complication.

Aged↗
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

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

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

The pharmacokinetics of morphine and lidocaine in critically ill patients.

OBJECTIVE: To evaluate the pharmacokinetic parameters of morphine and lidocaine after a single intravenous dose in critically ill patients. DESIGN: Prospective, clinical study. SETTING: General intensive care unit (ICU) in a university hospital. PATIENTS: Patients admitted to the ICU with severe systemic inflammatory response syndrome of various etiologies. INTERVENTIONS: A single intravenous dose of morphine (0.025 mg/kg) and lidocaine (1.5 mg/kg) were given separately 12-36 h after admission, and arterial blood samples for serum drug levels were taken. MEASUREMENTS AND RESULTS: Morphine pharmacokinetics were studied in 30 patients. The clearance (Cl) was found to be 5.7+/-2.3 ml/kg per min, volume of distribution of the central compartment (Vc) 0.16+/-0.12 l/kg and volume of distribution at steady state (Vss) 1.08+/-0.69 l/kg. These values are lower then those described previously for healthy volunteers (33.5+/-9 ml/kg per min, 1.01+/-0.31 l/kg, and 5.16+/-1.4 l/kg, respectively), and similar to those described in trauma and burned patients. Lidocaine pharmacokinetics were tested in 24 subjects. The Cl was 6.9+/-3.8 ml/kg per min, Vc 0.25+/-0.1 l/kg and Vss 0.78+/-0.26 l/kg. These values are not different from parameters published previously for healthy volunteers (10 ml/kg per min, 0.53 l/min and 1.32 l/min, respectively). No correlation was found between clinical variables and pharmacokinetic parameters of both drugs (ANOVA). CONCLUSIONS: Both morphine and lidocaine have a reduced volume of distribution in critically ill patients. The normal lidocaine clearance indicates preserved hepatic blood flow and suggests that other mechanisms are involved in the reduced morphine clearance. These findings may have application for the treatment of ICU patients.

Adult↗
PubMed1999

Atropine pharmacokinetics and pharmacodynamics following endotracheal versus endobronchial administration in dogs.

Emergency endotracheal and endobronchial drug administration provide an effective alternative for intravenous drug delivery during cardiopulmonary resuscitation. The purpose of the present study was to determine the immediate pharmacokinetic and pharmacodynamic properties of atropine following administration by either of these routes. Atropine (0.02 mg/kg) was given to seven anaesthetized mongrel dogs. Each dog was studied twice: once when atropine was injected into the endotracheal tube, and on another day when atropine was given via a flexible catheter wedged into a peripheral bronchus. Plasma atropine concentrations and blood gases were measured during 60 min following drug administration. Both routes of atropine administration differed significantly in three measures: the maximal atropine concentration (Cmax) was significantly higher with the endobronchial administration 40.0 +/- 7.8 ng/ml compared to 23.9 +/- 5 ng/ml endotracheally (P = 0.008); atropine's elimination (t1/2beta) half-life was significantly longer with the endobronchial route (39.3 +/- 5.2 min vs. 28.0 +/- 7.9 min; P = 0.05); Endobronchial administration resulted in an increase of 16% in heart rate, beginning immediately after drug delivery and peaking after 5 min. Other pharmacokinetic parameters were not significantly different. We conclude that endobronchial administration of atropine has a clear advantage over the endotracheal route.

Animals↗
PubMed1999

The pharmacokinetics of morphine and lidocaine in nine severe trauma patients.

STUDY OBJECTIVE: To study the pharmacokinetic parameters of morphine and lidocaine after a single intravenous (i.v.) bolus in severe trauma patients. DESIGN: Clinical case study. SETTING: Department of Anesthesiology and Intensive Care of a university hospital. PATIENTS: Nine patients, ages 24 to 91 years (mean 54.4 yrs), admitted to the hospital with severe trauma (Injury Severity Score > 20) were included in the study. INTERVENTIONS: After initial evaluation and stabilization, a single i.v. dose of morphine 0.025 mg/kg and lidocaine 1.5 mg/kg was given separately, and blood samples were drawn for each drug serum concentration. MEASUREMENTS AND MAIN RESULTS: Morphine pharmacokinetics was studied in eight patients, lidocaine pharmacokinetics in seven patients, and both drugs were studied in six patients. Morphine clearance 2.5 to 10 ml/kg/min (6 +/- 2.6, mean +/- SD) and volume of distribution 0.28 to 3.30 L/kg (1.4 +/- 1.0) were found to be lower than values described previously for healthy volunteers (33.5 +/- 9 ml/kg/min and 5.16 +/- 1.40 L/kg, respectively), and are similar to those described in trauma patients (5 +/- 2.9 ml/kg/min and 0.9 +/- 0.2 L/kg, respectively). In contrast, lidocaine clearance 4.5 to 9.4 ml/kg/min (6.7 +/- 1.7) and volume of distribution 0.39 to 1.20 L/kg (0.72 +/- 0.28) were similar to the value described in healthy volunteers (10 ml/kg/min and 1.32 L/kg, respectively). CONCLUSION: Changes in pharmacokinetics of drugs eliminated by the liver may occur in patients with severe trauma. The preserved lidocaine clearance indicates an almost normal hepatic blood flow and suggests that other mechanisms may be involved in the lower morphine clearance. The findings may have applications for the treatment of severe trauma patients and suggest that drug monitoring might be needed in some instances so as to avoid toxicity.

Adult↗
PubMed1999

Pharmacokinetics of endobronchial tolazoline administration in dogs.

Tolazoline is a potent vasodilator of arteries and veins and has a powerful effect on the pulmonary vasculature, reducing hypoxic pulmonary vasoconstriction and lowering pulmonary artery pressure. Intravenous tolazoline lowers the mean pulmonary arterial pressure and resistance and increases the cardiac index when given to infants with persistent pulmonary hypertension (PPHN). Endotracheally administered tolazoline decreases mean pulmonary arterial pressure and pulmonary vascular resistance, and improves oxygenation without the harmful decline in the systemic arterial pressure. The purpose of our study was to examine the pharmacokinetic and pharmacodynamic characteristics of endobronchial tolazoline to determine the relationship between endobronchial tolazoline administration, plasma concentration, and its effects on the cardiovascular and respiratory systems. Tolazoline was administered endobronchially to seven dogs, and its serum concentration and the hemodynamic parameters were monitored for 270 min postdelivery. It was found that 15 sec after dosing, tolazoline plasma concentrations started to increase significantly above baseline levels, reaching a maximum of 9.3+/-8.0 microg x mL(-1) The volume of distribution was 1657+/-321 mL x kg(-1) after 1 2.4+/-1 6.6 min. The extent of tolazoline absorption was 319+/-38 microg x min(-1) mL(-1). The total body clearance was 10.9 +/-4.8 mL x min(-1) x Kg(-1) and the elimination half-life was 156+/-81 min. Endobronchial tolazoline produced an initial short-lived decrease in the mean blood pressure in all the dogs, but thereafter the blood pressure increased gradually above baseline levels. Immediately following endobronchial tolazoline a significant tachycardia developed, peaking at 90 min. Subsequently, the heart rate gradually decreased and stabilized at values above baseline for 200 min. We conclude that an endobronchial bolus dose of tolazoline is effectively absorbed, produces measurable pharmacological effects, and may be beneficial in the therapy of persistent pulmonary hypertension of the newborn.

Absorption↗
PubMed1999

Endotracheal tolazoline: pharmacokinetics and pharmacodynamics in dogs.

Tolazoline is a potent vasodilator of both arteries and veins and has a powerful effect on the pulmonary vasculature, reducing hypoxic pulmonary vasoconstriction and lowering pulmonary artery pressure. Intravenous tolazoline lowers the mean pulmonary arterial pressure and resistance and increases the cardiac index when given to infants with persistent pulmonary hypertension of the newborn (PPHN). Endotracheally administered tolazoline decreases mean pulmonary arterial pressure and pulmonary vascular resistance, and improves oxygenation without the harmful decline in systemic arterial pressure. The purpose of our study was to examine the pharmacokinetic and pharmacodynamic characteristics of endotracheal tolazoline in order to determine the relationship between endotracheal tolazoline administration, plasma concentration and its effects on the cardiovascular and respiratory systems. Tolazoline was administered endotracheally to 7 newborn dogs, and its serum concentration and the haemodynamic parameters were monitored for 270 min post-delivery. Results are expressed as median and quartiles. It was found that 15 s after dosing, tolazoline plasma concentrations started to increase significantly above baseline levels, reaching a maximum of 2.64 (1.36; 13.16) microg/ml. The extent of tolazoline absorption was 305 (148;453) microg/ min/ml. The volume of distribution was 3.4 (1.6;7.4) 1/kg. The total body clearance was 12.1 (10.9;23.9) ml/min/kg and the elimination half-life was 225 (171;303) min. Endotracheal tolazoline produced an initial short-lived decrease in mean blood pressure in all the dogs, but thereafter the blood pressure increased gradually above baseline levels. Immediately following endotracheal tolazoline significant tachycardia developed, peaking at 90 min. Subsequently, the heart rate gradually decreased and stabilized at values above baseline for 200 min. A single endotracheal dose of tolazoline is effectively absorbed and produces measurable pharmacological effects. Determining the optimal endotracheal dose of tolazoline in the clinical setting requires additional evaluation.

Animals↗
PubMed1997

Epinephrine pharmacokinetics and pharmacodynamics following endotracheal administration in dogs: the role of volume of diluent.

OBJECTIVE: to define the optimal volume of dilution for endotracheal(ET) administration of epinephrine (EPI). DESIGN: prospective, randomized, laboratory comparison of four different volumes of dilution of endotracheal epinephrine (1, 2, 5, and 10 ml of normal saline). SETTING: large animal research facility of a university medical center. SUBJECTS AND INTERVENTIONS: epinephrine (0.02 mg/kg) diluted with four different volumes (1, 2, 5, and 10 ml) of normal saline was injected into the ET tube of five anesthetized dogs. Each dog served as its own control and received all four volumes in different sequences at least 1 week apart. Arterial blood samples for plasma epinephrine concentration and blood gases were collected before and 0.25, 0.5, 0.75, 1, 2, 3, 4, 5, 10, 15, 20, 25, 30 and 60 min after drug administration. Heart rate and arterial blood pressure were continuously monitored with a polygraph recorder. MEASUREMENTS AND MAIN RESULTS: higher volumes of diluent (5 and 10 ml) caused a significant decrease of PaO2, from 147 +/- 8 to 106 +/- 10 torr, compared with the lower volumes of diluent (1 and 2 ml), from 136 +/- 10 to 135 +/- 7 torr (P < 0.05). These effects persisted for over 30 min. Mean plasma epinephrine concentrations significantly increased within 15 s following administration for all the volumes of diluent. Mean plasma epinephrine concentrations, maximal epinephrine concentration (Cmax) and the coefficient of absorption (Ka) were higher in the 5 and 10 ml groups. The time interval to reach maximal concentration (Tmax) was shorter in the 5 and 10 ml groups. Yet these results were not significantly different. Heart rate, systolic and diastolic blood pressures did not differ significantly between the groups throughout the study. CONCLUSIONS: Dilution of endotracheal epinephrine into a 5 ml volume with saline optimizes drug uptake and delivery without adversely affecting oxygenation and ventilation.

Animals↗