Renal calcium handling in cystic fibrosis: lack of evidence for a primary renal defect.

Because cystic fibrosis (CF) epithelia have ion transport abnormalities that may in part be regulated by intracellular calcium metabolism, and the kidney is actively involved in both ion transport and calcium homeostasis, we have investigated renal calcium handling in CF. Twenty-four-hour urine collections were analyzed in 34 CF patients (age 5 to 35 years) and kidney ultrasound studies were performed in 17 CF patients (age 6 months to 23 years). Renal histologic findings at postmortem examination of 14 CF patients (age 4 months to 23 years) were compared with those of 12 patients (age 11 months to 17 years) with other chronic illnesses (6 congenital heart disease, 6 malignancy). In 30 of the 34 CF patients urinary calcium excretion was normal (less than 4 mg (0.1 mmol)/kg/24 hr). Four CF patients had hypercalciuria (calcium excretion 4.4 to 8.8 mg (0.11 to 0.22 mmol)/kg/24 hr). However, these patients had other possible explanations for hypercalciuria, such as immobilization (n = 2), increased dietary sodium load (n = 1), and glucocorticoid therapy (n = 1). None of the 17 patients examined by renal ultrasonography had nephrocalcinosis. Five CF patients had histologic evidence of sparse nephrocalcinosis at autopsy. However, 6 of 12 autopsy kidney specimens from patients with other chronic illnesses and similar preterminal events also showed nephrocalcinosis. The hypercalciuria and nephrocalcinosis in CF and other chronic debilitating diseases may be explained by factors known to affect calcium handling. Our evidence does not support a primary renal defect as the basis of hypercalciuria and nephrocalcinosis in CF.     

Controlled trial of nebulized albuterol in children younger than 2 years of age with acute asthma.

To determine the response to nebulized beta 2 agonist, 28 children younger than 2 years of age who visited the emergency department during an episode of acute asthma were studied. Each subject had a previous history of recurrent wheezing episodes. They were randomly assigned to receive two administrations of either nebulized albuterol (0.15 mg/kg per dose) or placebo (normal saline) with oxygen, 1 hour apart. After two nebulizations, the albuterol-treated patients had a greater improvement in clinical status (respiratory rate, degree of wheezing and accessory muscle use, total clinical score, and arterial oxygen saturation) than the placebo group. None of the patients in the albuterol group experienced a decrease of arterial oxygen saturation of greater than or equal to 2%. It is concluded that a trial of nebulized beta 2 agonists is warranted in the treatment of acute asthma in infants and young children.     

Lithium regulates protein tyrosine phosphatase activity in vitro and in vivo

RATIONALE: Lithium has been shown to regulate multiple intracellular signaling pathways by affecting various protein kinases. However, the counterpart of protein kinases, i.e., protein phosphatases may play an important role in lithium-regulated cellular signaling and functions. OBJECTIVES: The present work was designed to test the effect of lithium on protein phosphatases in vitro and in vivo. METHODS: PC12 cells were used as an in vitro model to characterize the effect of lithium on protein phosphatase activity. Rats treated with a lithium-containing diet were used to examine the in vivo effect of the drug on brain protein phosphatase activity.RESULTS. Lithium stimulated protein tyrosine phosphatase (PTPase) activity in a dose- and time-dependent manner in PC12 cells. A maximal stimulation of 87% was observed after 6 h of incubation with 3 mM LiCl. In contrast, protein serine phosphatase (PSPase) activity was not changed by lithium. The stimulatory effect on PTPase was not due to a direct action of the ion on the enzymes, but its selectivity was noted since treatment of cells with other monovalent cations exhibited no effect on PTPase activity. Lithium appeared to target specific PTPase(s) as it stimulated membrane-associated PTPase activity without affecting cytosolic or nuclear enzymatic activities. Moreover, the stimulation of PTPase activity in PC12 cells by lithium is independent of de novo protein synthesis. In the rat, 3 weeks of lithium treatment significantly elevated PTPase activity in hippocampus, striatum and cortex. CONCLUSION: The present findings provide the first evidence that lithium treatment selectively increases membrane-associated PTPase activity and suggest that this action may contribute to the pharmacotherapeutic actions of lithium.     

High-level expression of receptor tyrosine kinase Ret and responsiveness to Ret-activating ligands in pheochromocytoma cell lines from neurofibromatosis knockout mice

Pheochromocytoma cell lines derived from neurofibromatosis knockout mice express high levels of the receptor tyrosine kinase Ret, which is involved in the pathogenesis of human pheochromocytomas in hereditary multiple endocrine neoplasia syndrome type 2 (MEN2). Mouse pheochromocytoma (MPC) cells respond to the Ret-activating ligand GDNF by exhibiting Ret phosphorylation, neurite outgrowth, decreased proliferation, and altered expression of catecholamine biosynthetic enzymes. GDNF exerts similar effects on human pheochromocytoma cells in primary cultures. Ret is minimally expressed by normal mouse chromaffin cells, from which pheochromocytomas are derived. Its expression at high levels by MPC cells suggests possible relationships between two previously unrelated tumor syndromes, neurofibromatosis, and MEN2. The responsiveness of these cells to GDNF suggests that they may be a valuable new model for neurobiology.     

Perthes-like changes in geleophysic dysplasia

Geleophysic dysplasia is a rare skeletal dysplasia characterised by 'happy natured' facies, short stature with short limbs, brachydactyly, and joint contractures. This report describes a case of a patient with unilateral Legg-Calvé-Perthes-like changes associated with dysplastic proximal capital femoral epiphysis, typical to geleophysic dysplasia.     

Pain relief in major trauma patients: an Israeli perspective

BACKGROUND: The pain of major trauma patients remains often unrelieved while in the emergency department. Our objective was to examine pain management in several trauma units, and to evaluate the impact of implementation of a trauma pain management protocol. METHODS: Current status was evaluated from questionnaires filled by trauma unit personnel of nine medical centers. In one, a pain management protocol was introduced. Staff and patients evaluated pain management before and after the protocol was instituted. RESULTS: About 80% of staff respondents from various centers were not aware of guidelines for pain management in trauma. The belief that pain assists diagnosis was the main reason (78.6%) for withholding analgesia. Large variability existed on what contraindicates analgesia, with the majority withholding analgesia in abdominal and multiple injuries. When administered, analgesia was delayed, and most commonly intramuscular meperidine was given. After the protocol's implementation, the personnel's awareness of analgesia increased, and consequently it was administered earlier and to more patients, mostly as intravenous morphine. Patients appreciated the timely analgesia (38% after vs. 14% before, p = 0.01), with fewer receiving none. Analgesia was considered beneficial by more patients (70% after vs. 23% before, p < 0.001), and enhanced cooperativity with personnel (p < 0.001). This was reflected in increased overall satisfaction with pain relief during the entire hospitalization. CONCLUSION: The importance of pain management protocols in major trauma was demonstrated by the response of personnel and patients.     

Large bowel obstruction: an unusual presentation of salmonella enterocolitis in infancy

An infant with a large-bowel obstruction due to Salmonella B enterocolitis is presented. The clinical and radiologic findings were suggestive of Hirschsprung's disease with total colonic aganglionosis. Due to further deterioration, an ileostomy was performed. Pathologic examination disclosed ganglia in the colon. At laparatomy, 1 month later the colon, which was almost completely obliterated, was resected and an ileorectal anastomosis carried out. The patient remained a carrier of a multiple antibiotic-resistant group B Salmonella strain, and 2 months later died as a result of severe gastroenteritis. Accepted: 19 July 1999     

Differentiation of human myeloid leukemic cells by phorbol esters: Correlation with tumor promotion

The effect of the plant diterpenes, phorbol derivatives and mezerein, on differentiation of various human myeloid leukemic cells to macrophages was determined. The results indicate that, within the group of phorbol esters tested, a correlation exists between the potency of the compounds as inducers of differentiation and their reported potency as tumor promoters. However, mezerein and 12-O-retinoylphorbol 13-acetate, which promote tumors only weakly or not at all, were found to be efficient inducers. The efficiency of all the active phorbol derivatives, including the weak inducers, also known to be weak promoters, could be potentiated by pretreatment of the cells with retinoids, compounds which have been reported to inhibit tumor promotion. Similar results were obtained in 3 different established cell lines, as well as in short-term cultures of cells obtained from patients with acute myeloid leukemia. The results suggest that the activities of the diterpenes as tumor promoters and inducers of differentiation are not necessarily linked. Moreover, certain conditions which are unfavorable for tumor promotion may not affect or even potentiate induction of differentiation.     

Monoamine oxidase activity and enzyme kinetics in three subpopulations of density-fractionated platelets in chronic paranoid schizophrenics

Platelet monoamine oxidase (MAO) activity was studied in three subpopulations of density-fractionated platelets in 15 unmedicated chronic paranoid schizophrenic patients and contrasted with normal controls. No significant difference in MAO activity was found in any of the three platelet fractions in schizophrenics compared to controls. Enzyme kinetic studies performed on the intermediate-density platelet fraction demonstrated no significant differences in V _max or Michaelis' constant (K _m) between schizophrenics and controls, but showed that the higher platelet MAO activity reported in females compared to male is due to a significantly greater V _max rather than altered K _m. It is suggested that conflicting results reported in the literature regarding platelet MAO in schizophrenia are not related to the platelet subpopulations studied but are largely due to the selected patient population.