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Biomedical subjects

M Mouallem

Publications and source records attributed to M Mouallem.

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↗
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↗
PubMed2001

Olanzapine-induced respiratory failure.

Olanzapine is considered a safe drug. However, somnolence appears in up to 39% of the patients treated with 15 mg./day of this drug. The authors describe an elderly patient with chronic lung disease who developed CO2 narcosis and respiratory failure after treatment with olanzapine. The sedative effect of this drug was probably the cause of this life-threatening complication. The authors suggest that elderly patients with chronic lung disease who are treated with olanzapine should be carefully observed, especially during the first weeks of treatment.

Aged↗
PubMed2000

[Minocycline pneumonitis and eosinophilia].

Pneumonitis with eosinophilia is one of the less common and severe adverse effects of minocycline. The disease evolves in days or weeks from the beginning of treatment, and is usually characterized by dyspnea, fever and bilateral infiltrates in the chest X-ray. With cessation of the antibiotic, and sometimes adding cortico-steroids, clinical and roentgenological resolution follow. We present a case given minocycline for folliculitis and 3 weeks later fever, cough and shortness of breath developed. The clinical and roentgenological course was consistent with minocycline pneumonitis accompanied by eosinophilia.

Adult↗
PubMed2000

[Sclerosing mesenteritis--an unusual cause of abdominal pain].

Sclerosing mesenteritis (SM) is rare and fewer than 300 cases had been reported up to 1997. We describe a 29-year-old woman who had abdominal pain for 1 year and presented with a palpable abdominal mass. The diagnosis of SM was made only after diagnostic laparoscopy and biopsy of the peritoneum.

Abdominal Pain↗
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

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↗
PubMed1999

[Multiple organ damage due to cholesterol embolization].

Cholesterol crystal embolization can affect multiple organ systems and mimic other systemic diseases. We describe a 65-year-old woman who had renal failure, diarrhea, transient ischemic attacks and purple toes due to spontaneous cholesterol crystal embolization.

Acute Kidney Injury↗
PubMed1999

[Polyneuropathy in critical illness].

Critical illness polyneuropathy developed in 8 patients aged 22-84 years in our intensive care units. This acute polyneuropathy, predominantly axonal and motor, develops in the setting of the systemic inflammatory response syndrome and multi-organ failure. It is found in about 50% of patients treated in intensive care units for more than 2 weeks. In those who survive, neurological and functional recovery is the rule.

Adult↗
PubMed1999

Nimesulide-induced hepatitis and acute liver failure.

BACKGROUND: Nimesulide is a relatively new non-steroidal anti-inflammatory drug that is gaining popularity in many countries because it is a selective cyclooxygenase 2 inhibitor. Occasionally, treatment is associated with mild elevation of liver enzymes, which return to normal upon discontinuation of the drug. Several cases of nimesulide-induced symptomatic hepatitis were also recently reported, but these patients all recovered. OBJECTIVES: To report the characteristics of liver injury induced by nimesulide. PATIENTS AND METHODS: We report retrospectively six patients, five of them females with a median age of 59 years, whose aminotransferase levels rose after they took nimesulide for joint pains. In all patients nimesulide was discontinued, laboratory tests for viral and autoimmune causes of hepatitis were performed, and sufficient follow-up was available. RESULTS: One patient remained asymptomatic. Four patients presented with symptoms, including fatigue, nausea and vomiting, which had developed several weeks after they began taking nimesulide (median 10 weeks, range 2-13). Hepatocellular injury was observed with median peak serum alanine aminotransferase 15 times the upper limit of normal (range 4-35), reversing to normal 2-4 months after discontinuation of the drug. The remaining patient developed symptoms, but continued taking the drug for another 2 weeks. She subsequently developed acute hepatic failure with encephalopathy and hepatorenal syndrome and died 6 weeks after hospitalization. In none of the cases did serological tests for hepatitis A, B and C, Epstein-Barr virus and cytomegalovirus, as well as autoimmune hepatitis reveal findings. CONCLUSIONS: Nimesulide may cause liver damage. The clinical presentation may vary from abnormal liver enzyme levels with no symptoms, to fatal hepatic failure. Therefore, monitoring liver enzymes after initiating therapy with nimesulide seems prudent.

Adolescent↗
PubMed1998

Meningeal carcinomatosis and syndrome of inappropriate antidiuretic hormone in a patient with metastatic carcinoma of the stomach.

We describe a patient who had metastatic carcinoma of the stomach and severe headaches, weakness, and diplopia. The patient had meningeal carcinomatosis that was confirmed by examination of the cerebrospinal fluid after computed tomography of the brain was normal. Weakness was explained by the finding of hyponatremia due to the syndrome of inappropriate antidiuretic hormone (SIADH). We believe this is the first reported case of meningeal carcinomatosis in which stomach carcinoma caused SIADH. The differentiation between SIADH and cerebral salt wasting due to malignant tumors is emphasized.

Aged↗
PubMed1996

Pseudohypoparathyroidism, a novel mutation in the betagamma-contact region of Gsalpha impairs receptor stimulation.

Pseudohypoparathyroidism, type Ia (PHP-Ia), is a dominantly inherited endocrine disorder characterized by resistance to hormones that act by stimulating adenylyl cyclase. It is caused by inheritance of an autosomal mutation that inactivates the alpha subunit (alphas) of Gs, the stimulatory regulator of adenylyl cyclase. In three members of a family, the PHP-Ia phenotype is associated with a mutation (R231H) that substitutes histidine for an arginine at position 231 in alphas. We assessed signaling function of alphas-WT versus alphas-R231H transiently transfected in HEK293 cells. Hormone receptor-dependent stimulation of cAMP accumulation in cells expressing alphas-R231H is reduced by approximately 75% in comparison to cAMP accumulation in cells expressing alphas-WT. A second mutation, alphas-R201C, inhibits the GTPase turnoff reaction of alphas, thus producing receptor-independent stimulation of cAMP accumulation. The double mutant, alphas-R231H/R201C, stimulates cAMP accumulation almost as well (approximately 80%) as does alphas-R201C itself, indicating that the R231H mutation selectively impairs receptor-dependent signaling. In three-dimensional structures of G protein heterotrimers, Arg-231 is located in a region, switch 2, that is thought to interact with the betagamma subunit rather than with the hormone receptor. Thus, the R231H phenotype suggests that switch 2 (perhaps in concert with betagamma) mediates G protein activation by receptors at a site distant from the receptor-G protein contact surface.

Adenylyl Cyclases↗
PubMed1996

Pseudohypoparathyroidism type Ia: two new heterozygous frameshift mutations in exons 5 and 10 of the Gs alpha gene.

Pseudohypoparathyroidism type Ia (PHP-Ia) is a hereditary disease characterized by resistance to PTH and other hormones that act via cAMP. Patients have deficient activity of Gs alpha, the alpha subunit of the G protein, which couples hormone receptors to stimulation of adenylate cyclase. We describe two new mutations discovered in two sporadic patients with PHP-Ia. Using genomic DNA, we have amplified exons 2-13 of the Gs alpha gene (GNAS1) by PCR, and sequenced the resulting products. Both patients had Albright's hereditary osteodystrophy, resistance to multiple hormones, and deficient Gs alpha activity. In the first patient, a deletion of a C in exon 5 at codon 115 was found. In the second patient, an insertion of a C in exon 10 at codon 267 was detected. Both these heterozygous mutations cause frameshift, and predict decreased production of Gs alpha. This report adds two new Gs alpha mutations to the known ten mutations recently described.

Adolescent↗
PubMed1996

Familial Albright's hereditary osteodystrophy with hypoparathyroidism: normal structural Gs alpha gene.

Albright's hereditary osteodystrophy (AHO) is a characteristic skeletal phenotype, including short stature, obesity, round face, and brachydactyly. AHO appears in patients with pseudohypoparathyroidism (PHP) who have resistance to PTH and in their eumetabolic family members who have pseudopseudohypoparathyroidism (PPHP). The differential diagnosis of AHO in families without PHP includes brachydactyly E, whose existence as a distinct entity has been questioned. We studied a patient with familial AHO who presented with hypocalcemia. To our surprise, PTH levels were low, and the response to PTH administration was normal. This is the first case of familial AHO with hypoparathyroidism. The proband's family included 22 affected subjects spanning 3 generations, who had variable degrees of AHO manifestations, with an autosomal dominant inheritance trait. The metacarpophalangeal pattern profile was typical of that of PHP-PPHP. As deficient activity and inactivating mutations of Gs alpha were described in PHP as well as in PPHP, we measured the biological activity of Gs in family members, which was normal. To exclude subtle abnormalities in the Gs alpha gene, we sequenced the entire coding region of Gs alpha in the propositus, which was normal. We conclude that hypocalcemia should be adequately evaluated even in the presence of familial AHO, and that familial AHO can occur with a normal coding structural Gs alpha gene. Identification of the molecular defect in familial AHO without PHP will shed light on the pathogenesis of AHO in general.

Adult↗
PubMed1996

Multiple spurious laboratory results in a patient with hyperlipemic pancreatitis treated by plasmapheresis.

Hyperlipidemia is a known cause for acute pancreatitis. Hyperlipidemia may also produce multiple spurious laboratory results that may complicate the diagnosis and management of pancreatitis. We encountered such a patient who had the following spurious laboratory results: normal serum amylase activity, hyponatremia, and high hemoglobin levels. These laboratory artifacts were previously described, mostly separately. In addition, our patient had artifactual thrombocytopenia. The patient improved dramatically following plasmapheresis, which enhanced reduction of serum lipids.

Acute Disease↗