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Biomedical subjects

J Moreb

Publications and source records attributed to J Moreb.

48 records · Page 3Linked to original sources

Lead poisoning in a West Bank Arab Village.

Eleven patients from the West Bank village of Es-Sawiyeh were admitted with lead poisoning to two Jerusalem hospitals between November 1982 and January 1983. They all belonged to several households of a single large family. Colicky abdominal pains were present in five patients, weakness in four, behavioral changes ranging from irritability to frank psychosis in four, and paralysis in one. Anemia of various degrees was seen in all patients. Basophilic stippling and reticulocytosis were encountered in all patients with moderate to severe anemia. Therapy with edetate disodium calcium and penicillamine resulted in clinical improvement in all patients. A preliminary survey of 270 subjects in the same village disclosed 84 subjects with abnormally elevated blood lead levels, 17 of whom had grade IV lead burden according to the Centers for Disease Control risk classification. Contamination of homemade flour by lead used for stabilizing the metal parts of stone mills was the source of poisoning. As the method of milling in many West Bank villages is similar, these findings may have important implications to the well being of a large section of the rural West Bank population.

Adolescent↗

Iron depletion and blood lead levels in a population with endemic lead poisoning.

The effect of iron depletion on blood lead levels was studied in a group of 558 schoolchildren aged 10 to 18 residing in two West Bank Arab villages with a high prevalence of excessive lead exposure and clinical lead poisoning. Thirty percent of the subjects studied had whole-blood lead levels greater than 30 micrograms/dl, and 45% had whole-blood zinc erythrocyte protoporphyrin greater than 50 micrograms/dl. The percentage of abnormal blood lead values in subjects with normal serum ferritin and transferrin saturation (31%) was similar to that in subjects with one (28%) or two (25%) abnormal iron parameters. Likewise, there was no correlation between serum ferritin and blood lead levels in individual patients (r = 0.059). Normal distribution plots and mean levels of blood lead (27.3 micrograms/dl) were identical in the iron-deficient and iron-replete groups. These findings indicate that iron depletion does not affect blood lead levels and suggest that in man, unlike in experimental animals, iron depletion may not have a significant effect on lead absorption.

Adolescent↗

Angioimmunoblastic lymphadenopathy. A case with an unusual clinical course with marked tumorous infiltration of multiple organs and striking intestinal involvement.

An unusual case of angioimmunoblastic lymphadenopathy (AILD) with a rare clinical course and marked gastrointestinal involvement is reported. Two years after the onset of AILD, there was a dramatic alteration in the clinical picture which appeared to take on a malignant course. Despite the clinical course and the presence of macroscopic tumors in multiple sites at autopsy, there was no transformation to immunoblastic sarcoma. The typical histologic picture of AILD was still evident in all organs examined. The rarity of massive gastrointestinal involvement in AILD is stressed.

Aged↗

Evaluation of iron status in patients on chronic hemodialysis: relative usefulness of bone marrow hemosiderin, serum ferritin, transferrin saturation, mean corpuscular volume and red cell protoporphyrin.

The diagnostic usefulness of bone marrow hemosiderin, serum ferritin, transferrin saturation, mean corpuscular volume (MCV) and red cell protoporphyrin (EPP) in the evaluation of iron status in patients on chronic hemodialysis was studied in 39 subjects. The correlation between serum ferritin and the number of transfusions received per month was slightly higher (r = 0.717; p less than 0.001) than the correlation between bone marrow hemosiderin and transfusions (r = 0.685; p less than 0.01). Serum ferritin was useful in identifying subjects with both increased or reduced iron stores. In contrast, transferrin saturation could only be used for indicating iron overload. MCV for indicating iron deficiency, and EPP was not useful in either case. The abnormal increase of EPP in chronic uremia has not been previously described. It is unrelated to iron deficiency and is most probably explained by the known reduction in red cell ferrochelatase activity associated with chronic uremia. Serum ferritin is clearly the most useful diagnostic aid for assessing iron stores in patients on chronic hemodialysis. Whether ferritin is also the best predictor of response to iron therapy, cannot be determined on the basis of the present data.

Adolescent↗

Transient methimazole-induced bone marrow aplasia: in vitro evidence for a humoral mechanism of bone marrow suppression.

A patient with methimazole-induced aplastic anemia is described. Despite severe pancytopenia and the complete disappearance of hemopoietic elements from the bone marrow, recovery of hemopoiesis has been observed within 14 days of discontinuing methimazole therapy. In vitro studies of CFU-C inhibition of peripheral mononuclear cells harvested in remission, were performed by incubation with autologous sera collected at earlier phases of the disease. These studies provide evidence in favor of a humoral, and most probably autoimmune mechanism as the cause of transient bone marrow aplasia.

Adult↗

Reduced frequency of iron deficiency anaemia in sickle cell trait.

The prevalence and causes of anaemia among the inhabitants of a Southern Lebanese village were studied. Of the 317 patients examined 75, or 24% were found to be heterozygotes for Hb S. There was a reciprocal relation between the presence of sickle cell trait and of iron deficiency anaemia. The prevalence of iron deficiency anaemia defined as the coexistence of Hb below 13 g/dl in adult males and below 12 in adult females and children with two laboratory indicators of iron deficiency, was 10.3% in the normal population as against 1.3% in the sickle cell trait group (P less than 0.008). The reduced frequency of iron deficiency anaemia in sickle cell trait may be explained by increased iron absorption, or alternatively by reduced iron requirements and a lower risk of discrepancy between iron supply and demand. Because of the central role of iron in the function of a great number of enzymes and proteins, it is possible that protection against iron deficiency anaemia by the sickle cell trait may result in improved working capacity and a lower incidence of infections.

Adult↗

Metabolic and ultrastructural aspects of the in vitro lysis of chronic lymphocytic leukemia cells by glucocorticoids.

Human chronic lymphocytic leukemia (CLL) cells like prothymocytes and immunoactivated T-lymphocytes are readily lysed in vitro by pharmacological concentrations of glucocorticoids such as cortisol, whereas peripheral blood lymphocytes and thymocytes are unaffected by the hormone. In this study, metabolic and ultrastructural aspects of the cortisol-induced killing process of CLL cells are recorded. In vitro lysis was found to be temperature dependent and was detected only after 6 to 8 hr incubation with cortisol by means of the trypan blue exclusion test. However, 30 min of incubation with cortisol at either 37 degrees or 4 degrees followed by the removal of the hormone was still sufficient to induce the lytic process. Ultrastructural studies demonstrated sequential changes in the cytoplasm, including swelling of mitochondria and cytoplasmic decompartmentalization, followed by loss of surface microvilli with the appearance of "holes" in the cell membrane, and subsequent condensation of nuclear chromatin. The large holes in the membrane appearing after 6 hr of incubation with the hormone may be the cause for the penetration of the viable stain into the dead cells, as seen by light microscopy. Addition of metabolic inhibitors including actinomycin D, puromycin, and cycloheximide following administration of cortisol resulted in inhibition of the cell lysis. An excess of an antagonist such as cortexolone was found to inhibit the cortisol-induced cytolysis of the CLL cells. It is suggested that the glucocorticoid-induced lysis of human CLL cells is similar to the phenomenon observed in rat or murine lymphocytes and is mediated by interaction of the steroid molecule with the cytoplasmic receptor. The resulting complex appears to activate specific gene(s) the products of which eventually cause cytolysis.

Dactinomycin↗

Effects of acute iron loading on contractility and spontaneous beating rate of cultured rat myocardial cells.

Cardiac dysfunction is a well known but poorly understood complication of iron overload. We have previously shown that cultured myocardial cells are able to assimilate large amounts of iron. In the present study, the effect of iron on the rate and amplitude of beating in monolayer cultures of rat ventricular myocytes was studied. Iron had negative chronotropic and inotropic effects, both reversible upon washout. The negative chronotropic effect developed earlier and could be reversed by adrenaline. The negative inotropic effect took longer to develop and was completely reversed by caffeine. Elevated [Ca++] also partially restored impaired contractility, while adrenaline or ouabain did not show any significant effect. These results indicate that iron toxicity in cultured heart cells impairs cellular function at both sarcolemmal and intracellular sites.

Animals↗

Lead poisoning by contaminated flour.

Between October 1982 and June 1983, 43 patients were identified with symptomatic lead poisoning in three Arab villages of the Nablus district. Because of the clustering of clinical poisoning by household units, investigation was focussed on potential sources common to all members of the households. After excluding water, olive oil and a variety of foodstuff, lead in high concentrations was discovered in locally ground flour in all affected households. The source of poisoning was lead poured into the fissures between the metal housing and the driveshaft of the millstone. Significant lead contamination of freshly ground flour was demonstrated in 23% of the 146 community flour mills operating in West Bank villages. Since the completion of these studies, similar outbreaks of lead poisoning caused by contaminated flourmills have been identified in the Upper Galilee and in Spain. As the methods of milling in the Mediterranean area are similar, a coordinated international effort is needed in order to eliminate this health hazard from countries where similar community stone mills are still in use.

Adult↗

Overexpression of the human aldehyde dehydrogenase class I results in increased resistance to 4-hydroperoxycyclophosphamide.

A correlation between overexpression of aldehyde dehydrogenase and resistance to oxazaphosphorines, widely used anticancer agents, has been shown. To investigate the direct role of the human aldehyde dehydrogenase class 1 (ALDH-1) in the resistance to one of these agents, 4-hydroperoxycyclophosphamide (4-HC), an active metabolite of cyclophosphamide, neomycin-selectable plasmid or retroviral constructs harboring the wild-type ALDH-1 complementary DNA in the sense orientation were transfected into K562 leukemic cell lines. Polymerase chain reaction (PCR) analysis confirmed the presence of vector DNA in the stably transfected K562 cells. Reverse transcriptase PCR and Northern and Western blot analysis showed expression of ALDH-1 mRNA and protein in the cells transfected with ALDH-1 in the sense orientation but not in cells transfected with vector alone. The activity of the expressed ALDH-1 was demonstrated using spectrophotometric assay. Stably transfected K562 cells were subjected to various doses of 4-HC, and cell viability was assayed using clonogenic cell culture in semisolid medium. Results demonstrate that K562 cells transfected with ALDH-1 in the sense orientation display increased resistance to 4-HC compared with wild-type or vector-transfected K562 cells. Furthermore, the addition of diethylaminobenzaldehyde, a specific inhibitor for ALDH-1, restored the sensitivity of the ALDH-1-expressing K562 cells to 4-HC. Thus, the data pinpoint the direct role of ALDH-1 in the protection against 4-HC cytotoxicity.

Aldehyde Dehydrogenase↗