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Biomedical subjects

D Lev

Publications and source records attributed to D Lev.

52 records · Page 3Linked to original sources
PubMed1999

Skewed X-inactivation in a manifesting carrier of X-linked myotubular myopathy and in her non-manifesting carrier mother.

X-linked recessive myotubular myopathy (XLMTM) is a muscle disorder usually affecting newborn males. In the majority of cases, muscle weakness and hypotonia lead to a rapid demise at neonatal age. The responsible MTM1 gene is located in proximal Xq28. Heterozygous carriers are described as being asymptomatic but, in a few cases, mild facial weakness has been reported. We report a family in which a 39-year old female showed severe progressive muscle weakness. XLMTM was initially diagnosed in the male offspring of one of the patient's sisters. The patient, one of her sisters, and their mother were heterozygous carriers for a common MTM1 gene mutation. We found an extremely skewed X-inactivation pattern in the patient and, in the opposite direction, in her non-manifesting carrier mother, thus explaining her normal phenotype and indicating a possible inheritance of skewed X-inactivation. Linkage analysis excluded a possible involvement of the XIST locus at Xq13.

Adult↗
PubMed1999

Gastrointestinal stromal sarcomas.

BACKGROUND: Gastrointestinal stromal sarcomas are a rare group of malignancies originating in the bowel wall. METHODS: The treatment of 12 patients with gastrointestinal stromal sarcoma who underwent operation between 1994 and 1998 was reviewed. RESULTS: Eight tumours originated in the stomach; others were in the small bowel or rectum. Five of the tumours were of myogenic origin, two were gastrointestinal autonomic nerve tumours, one was a mixed neural-myoid tumour, and four could not be differentiated. Complete resection was possible in ten patients; in two of the ten en bloc resection of adjacent organs was required to ensure adequate margins. The tumours in the remaining two patients were irresectable because of diffuse intra-abdominal metastatic disease. All patients who underwent complete resection were alive after 4-48 (median 14) months. Two of the ten patients developed recurrence, which was reresected completely. The patients with metastatic disease died less than 1 year after operation. CONCLUSION: Aggressive surgical resection, achieving complete resection, can lead to prolongation of life and may be a potential cure for patients with gastrointestinal stromal sarcoma.

Adult↗
PubMed1999

Multiple presentation of mitochondrial disorders.

The aim of this study was to assess the heterogeneous clinical presentations of children with mitochondrial disorders evaluated at a metabolic neurogenetic clinic. The charts of 36 children with highly suspected mitochondrial disorders were reviewed. Thirty one children were diagnosed as having a mitochondrial disorder, based on a suggestive clinical presentation and at least one of the accepted laboratory criteria; however, in five children with no laboratory criteria the diagnosis remained probable. All of the patients had nervous system involvement. Twenty seven patients also had dysfunction of other systems: sensory organs in 15 patients, cardiovascular system in five, gastrointestinal system in 20, urinary system in four, haematopoietic system in four, and endocrine system in nine. The clinical presentation was compatible with an established syndrome in only 15 children. Severe lactic acidosis or ragged red muscle fibres were encountered in very few patients. These results suggest that mitochondrial disorders should be evaluated in children presenting with a complex neurological picture or multisystem involvement.

Adolescent↗
PubMed1999

[Severe heat stroke in an intensive care unit: course of the disease in the intensive care unit, and early and subsequent treatment results].

During the August 1998 heat wave in Tel Aviv we admitted many patients for acute heat-related illness; 6 had severe heat stroke and were admitted in critical condition. We describe their clinical courses during the first 5 days of hospitalization, including response to treatment and implications for future management of this disorder. The mean APACHE II score of the 6 was 30 +/- 3.5 and mean Glasgow Coma Scale rating 3.5 +/- 0.5; they were in hypovolemic shock and respiratory failure, necessitating mechanical ventilation. Despite early effective therapy (core temperature in all was reduced to less than 39 degrees C in less than 1 hour), there was 1 death (mortality 15%) and 4 required further intensive care for life-threatening multiple organ failure. During severe heat waves a significant number of referrals for acute heat-related illness must be anticipated, possibly overwhelming admission capacity of regional intensive-care units. Severe heat stroke complicated by multi-organ failure is not necessarily related to prior physical activity. Although important in determining prognosis, early treatment does not prevent severe complications. Mechanisms regulating body heat may remain disturbed for days following early treatment and apparent stabilization, mandating continued hospitalization.

APACHE↗
PubMed1998

Neurotoxicity of isolated limb perfusion with tumor necrosis factor.

Hyperthermic isolated limb perfusion (HILP) with tumor necrosis factor alpha (TNFalpha) is effective for advanced melanoma and sarcoma of the limbs. Ten patients undergoing HILP with TNFalpha were evaluated by neurological examinations, nerve conduction studies (NCS), sympathetic skin responses (SSR) and conventional and quantitative electromyography (EMG), performed before, 7 days and 6 weeks following HILP. Seven patients showed minimal clinical signs of peripheral nerve damage following HILP; in two the injury was evident electrophysiologically: 7 days following HILP five patients had paresthesias and/or hypoesthesia, one had a mild foot drop and one had autonomic disturbances in the affected limb. SSR was low in two patients in the affected limb, sensory nerve action potentials were not elicited in one, with normal motor NCS and EMG. At 6 weeks, four patients continued to have mild paresthesias and one had dysautonomia of the perfused limb. Sensory responses and SSR did not change, motor abnormalities were not found. These findings show that HILP with TNFalpha induces a mild, mainly sensory neuropathy in perfused limbs, not disturbing functionality and improving over time.

Adult↗
PubMed1998

Shedding kinetics of soluble tumor necrosis factor (TNF) receptors after systemic TNF leaking during isolated limb perfusion. Relevance to the pathophysiology of septic shock.

We examined the kinetics of shedding of the soluble TNF receptors (TNF-Rs) in response to TNF leakage during isolated limb perfusion procedures and correlated them to the resulting hemodynamic effects. Shedding of the TNF-Rs started 7 min after TNF leakage into the systemic circulation. Three waves of shedding were observed peaking at 1, 8-12, and 48-72 h both in vivo and in cell cultures. The soluble receptors prolonged the half-life of TNF in the systemic circulation to 2.5-6 h. Excess shedding of the p75 compared with p55 TNF-Rs was noted during the first wave. The amount and speed of shedding of the p75 TNF-Rs were proportional to the serum TNF levels (P < 0.001). A maximal shedding capacity was attained only during the first wave of shedding, at TNF concentrations of approximately 1.5 ng/ml. Above this level, the linearity between TNF and its soluble receptors was lost. TNF-induced hypotension coincided with the initial imbalance between the concentrations of TNF and its soluble receptors. Despite the spontaneous correction of this imbalance at 8-12 h, the hemodynamic and biochemical alterations persisted and were further aggravated at 18 h, suggesting that other factors induced earlier by TNF are responsible for the perpetuation of the hemodynamic instability. This study may provide the basis for a more physiological therapeutic approach to TNF neutralization in septic shock patients.

Adult↗
PubMed1998

Translocation (1;20)(q32;q13.3) in myelofibrosis following polycythemia vera.

We report a novel chromosomal translocation (1;20)(q32;q13.3) in a patient with myelofibrosis following polycythemia vera. This 73-year-old woman developed myelofibrosis 6 years after the initial diagnosis of polycythemia vera (PV). The course of PV was uneventful. Subsequent to the diagnosis, the patient was treated with phlebotomy and low doses of hydroxyurea for 4 years. No therapy was delivered during the remaining 2 years. A bone-marrow biopsy and a karyotype analysis performed because of evolving anemia demonstrated myelofibrosis and a chromosomal aberration-t(1;20)(q32;q13.3). Aberrations in chromosomes 1 and 20 have been reported in myeloproliferative disorders, but a t(1;20) translocation has not been reported. Because a karyotype analysis was not performed at the time PV was diagnosed, whether this translocation is linked to the primary disease (PV) or to the transition to myelofibrosis is not known.

Aged↗
PubMed1998

Distribution of indicator bacteria and bacteriophages in shellfish and shellfish-growing waters.

Shellfish (mussels and clams) and shellfish-growing waters were examined for indicator bacteria according to the EC regulations, Salmonella spp., coliphages and anti-Salmonella phages. Samples were collected both from natural-growing areas along the coast and from authorized shellfish-harvesting beds. The coastal area was affected by organic pollution and extensive faecal contamination and, according to the legal requirements, was unsuitable for shellfish farming. The shellfish collected along the coast also showed faecal contamination at levels which did not conform to legal standards. No significant differences were observed between the frequency of isolation of somatic coliphages and indicator bacteria from sea water. In contrast, both the authorized and wild coastal shellfish were contaminated by coliphages at a significantly higher level than the corresponding bacterial indicators for faecal contamination (chi 2 test, P < 0.01). Coliphage concentrations were significantly correlated with faecal indicators in marine waters (P < 0.001) and sediments (P < 0.05), but no correlation was found in shellfish, thus showing their low specificity as indicators of faecal pollution of human origin in shellfish of economic importance.

Analysis of Variance↗
PubMed1997

A missense mutation in ColA1 in Jewish Israeli patient with mild osteogenesis imperfecta, detected by DGGE.

Osteogenesis imperfecta (OI) underlies germline mutations in either Col1A1 or Col1A2. Here we describe, for the first time, the use of the denaturing gradient gel electrophoresis (DGGE) technique for mutation analysis of the Col1A1 gene. By employing this technique, we identified a point mutation in a young Jewish Israeli patient with mild OI. The missense mutation, a G to A alteration at position 888, result in a Gly to Arg substitution at codon 79. Furthermore, the patient's mother, who was clinically labeled as OI based solely on the fact that she has blue sclera, was found not to carry this mutation in two different tissues. We suggest that blue sclera alone should not be used as a parameter for the diagnosis of OI, and that DGGE can be effectively used for mutation analysis of the Col1A1 gene.

Adult↗
PubMed1996

Regional perfusion with hemofiltration (chemofiltration) for the treatment of patients with regionally advanced cancer.

BACKGROUND: Regionally advanced cancer is a common, often unresolved problem. Effective local control with chemotherapy is limited by the toxicity following systemic administration. Chemofiltration (CF) is a form of regional perfusion that enables the administration of cytotoxic drugs into one body area while limiting systemic toxicity. The drug is infused into the artery supplying the involved area. The venous effluent of the same organ is pumped out into a hemofiltration unit at a high flow rate. The drug is then filtered away and the blood returned to systemic circulation. METHODS: Forty-one patients underwent 45 CF. Twenty-four patients had CF of the pelvis for advanced rectal carcinoma (10), malignant melanoma (6), and cancers of the uterine cervix (3), ovary (2), vulva (1), endometrium (1), and anus (1). Seventeen patients underwent CF of the liver for metastatic colon (10), breast (4), pancreas (1), ovary (1), and unknown primary (1) cancer. 5-fluorouracil (1 g/m2) and mitomycin-C (30 mg/m2); cisplatinum (200 mg/m2) alone or combined with bleomycin (50 mg/m2) and mitomycin-C (20 mg/m2); or melphalan (1 mg/kg) were the combinations used. RESULTS: Generally the procedure was well tolerated. Complications included transient leukopenia (18), paralytic ileus (2), hair loss (2), renal failure (1). Two patients died within 40 days following CF. Of 36 evaluable patients, 16 (44%) had partial response, 14 (38%) had stable disease, and 6 (18%) had disease progression. A decrease of at least 30% in carcinoembryonic antigen levels occurred in 12 of 24 patients (50%). Median time to progression was 7 months. Ten of 13 patients (77%) achieved good symptomatic palliation. CONCLUSIONS: The results of CF in our study are not superior to alternative methods of drug delivery to the liver and pelvis. However, considering that previous systemic chemotherapy had failed two-thirds of the patients, some benefit may be attributed to this regional delivery modality. Furthermore, pelvic CF afforded very significant symptomatic relief which was definitely superior to other methods.

Adult↗
PubMed1996

Intra-arterial chemotherapy with concomitant hemofiltration (chemofiltration) for treatment of loco-regional or pelvic metastases from malignant melanoma.

Loco-regional or pelvic metastases from malignant melanoma (MM) of the lower limbs or pelvis are usually refractory to systemic chemotherapy, the limiting factor being systemic toxicity. An attempt to improve this low response rate using a novel loco-regional approach involving intra-arterial high dose chemotherapy with concomitant hemofiltration of the venous effluent of the pelvis, hence chemofiltration, was studied. Chemofiltration was performed in seven MM patients. The arterial catheter and the venous cannula were placed in the aorta and the inferior vena cava just distal to the renal vessels. High-dose melphalan (1 mg/kg) or cis-platinum (200 mg/m2) was injected into the arterial catheter. Blood was pumped out into the hemofiltration unit at a rate of 500-700 ml/min. The filtered blood was returned via a catheter placed in the superior vena cava. Despite the extensive fluid exchange (9,700-15,000 ml), the procedure was well tolerated. Out of six patients who remained with measurable disease, three had a partial response lasting 5-12 months, two had stabilization of their disease for 3 months, and one developed a rapid progression. Chemofiltration is feasible in MM patients and is a viable option in locally advanced or metastatic malignant melanoma confined to the limb or pelvis.

Aged↗
PubMed1996

[Isolated limb perfusion with tumor necrosis factor for malignancies of the limbs].

Tumor necrosis factor (TNF) induces rapid necrosis in a variety of experimental neoplasms. However, its clinical application is limited by life-threatening systemic toxicity. Isolated limb perfusion (ILP) enables administration of large doses of TNF and cytotoxic drugs directly to the affected limb, avoiding systemic toxicity. We describe our experience in 20 consecutive patients (10 with melanoma and 10 with soft tissue sarcoma) treated with high-dose TNF and melphalan via ILP. ILP was performed via the external iliac (10 cases), femoral (2), popliteal (5) or brachial (3) vessels. Patients received 3-4 mg TNF to an upper, and 1-1.5 mg/kg to a lower extremity. Isolation efficiency was determined by injection of radiolabelled albumin. The procedure was successful in all 20 patients. Local complications included wound infection in 6 cases and hematoma in 2. 1 patient developed sepsis secondary to extensive necrosis of a large, secondarily infected tumor. The first 6 patients who underwent high-flow perfusion experienced systemic side-effects, mainly hypotension. These side-effects were eliminated when low-flow perfusion was introduced. The response rate was 100%. In the sarcoma group, 5/10 had complete response, and 5 partial response. Amputation or mutilating surgery was avoided in 9/10. Of the 10 with melanoma, 7 had complete, and 3 partial response. We conclude that administration of TNF via ILP is a safe and effective modality for treating advanced neoplasms of the limbs.

Adolescent↗
PubMed1995

Systemic leakage and side effects of tumor necrosis factor alpha administered via isolated limb perfusion can be manipulated by flow rate adjustment.

BACKGROUND: The tolerated systemic dose of recombinant tumor necrosis factor alpha (rTNF-alpha) is very limited, since its administration leads to a severe septic shock-like condition. Its implementation in isolated limb perfusion (ILP) for metastatic melanoma or advanced soft-tissue sarcoma confined to the limb facilitates doses of rTNF-alpha 10 times higher than the systemic tolerated dose. However, with the traditional high flow rate used in ILP, systemic leakage and side effects are not eliminated. OBJECTIVE: To determine if a lower perfusion flow rate would reduce leakage and consequently toxic effects. METHODS: Isolated limb perfusion was performed for melanoma and soft-tissue sarcoma confined to the limb using a flow rate of 869 +/- 122 mL/min in nine patients (group 1) and a lower rate of 286 +/- 62 mL/min in six patients (group 2). RESULTS: The systemic leakage rate was 12.5% +/- 2.9% in group 1, compared with 2.3% +/- 1.0% in group 2 (P = .003). Peak TNF-alpha levels were 29,000 +/- 2700 pg/mL in group 1, higher than 1580 +/- 1355 pg/mL in group 2 (P = .02). The tachycardia, hypotension, increased cardiac output, decreased systemic vascular resistance, bilirubinemia, elevation of liver enzyme levels, hypocholestrolemia, thrombocytopenia, and prolongation of prothrombin and partial thromboplastin times all observed in group 1 were significantly attenuated or eliminated in group 2. The limb PO2, PCO2, pH, and viability remained similar in both groups. Also, the tumor response rate remained high and was unaffected by the decrease in flow rate. CONCLUSIONS: Decreasing perfusion flow rate during ILP results in diminished leakage of TNF-alpha. Consequently, the systemic hemodynamic, metabolic, and hematologic toxic effects are virtually abolished.

Adolescent↗
PubMed1995

Increase in leukocyte adhesiveness and aggregation with stress: a model of human congestive heart failure.

Stress has a significant influence on the function of the human organism. A simple, rapid, inexpensive, and reliable marker for stress would therefore be of great value. We have recently noted that stress increases the state of leukocyte adhesiveness and aggregation in the peripheral blood. We evaluated 64 patients who had various degrees of congestive heart failure, a condition known to induce a state of physiologic stress, to verify whether a relation exists between the intensity of the stress response and the magnitude of leukocyte adhesiveness. Included in the 64 were 53 patients without congestive heart failure, 23 with compensated failure, 22 with significant congestive heart failure, and 19 with florid pulmonary edema. The percentage of aggregated leukocytes in these four group was 6% +/- 4%, 6% +/- 4%, 10.5% +/- 5%, and 15% +/- 14%. Values for the third and fourth group differed in a statistically significant way. Thus, with further investigation into additional stress-inducing conditions, the state of leukocyte adhesion and aggregation may prove to be a reliable marker for the detection of stress and an inexpensive tool for quantifying its severity.

Adhesiveness↗
PubMedDate not supplied

Study of DDT blood level in a group of workers exposed to pesticides.

Blood levels of DDT, DDE, and other DDT metabolites were determined in a group of workers with previous occupational exposure to DDT as spraymen. The larger part of total DDT was in the form of metabolite DDE, which is thought to be introduced into the human body primarily from external sources. Total DDT blood level was correlated positively with both age and occupational exposure (R = 0.58 and 0.52, respectively), and linear regressions between storage and these variables were demonstrated. Although the storage of these compounds in body fat was not studied, the analysis of covariance showed a significant increase of DDT blood level in the group of workers with longer occupational exposure, which was not dependent on age.

Adult↗