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Biomedical subjects

M Dan

Publications and source records attributed to M Dan.

At least 73 records · Page 4Linked to original sources

Malaria Imported by Travelers: The Israeli Experience.

Indigenous malaria has been successfully eradicated in North America, Europe, and a few other previously endemic locations. Extensive antimalarial programs, improvement of health care services, and advances in socioeconomic development have all contributed to one of the most significant achievements in public health of the 20th century.1 Nevertheless, a new malaria transmission pattern is increasingly seen in these areas nowadays. The constantly mounting movement of travelers from developed countries to the tropics and the affluent immigration to the industrialized world from countries where malaria has remained endemic are responsible for the emergence of imported malaria.2 Most physicians who studied medicine in developed countries, although familiar with the classic presentation of the disease, have rarely seen a single case of malaria during training and believe that it is an exotic illness existing elsewhere. It is important therefore to characterize the demographic and clinical features of imported malaria, which is practically the only malaria now seen in the industrialized world, and to make it more familiar to health care providers. This need is further emphasized by the emerging problem of drug-resistant malaria, which may be atypical in patients who had received inappropriate prophylaxis. In Israel malaria is almost exclusively an imported disease. It occurs in Israelis who visit or work in endemic areas and in immigrants, invariably from Ethiopia. The majority of Ethiopian immigrants arrived in two waves in 1985 and 1991 and do not represent an ongoing malaria problem.3 The features of the disease in this population were extensively reported elsewhere.3,4 In the present report we examine the characteristics of malaria imported to Israel by travelers.

Journal Article↗

Schistosomiasis Acquired in Lake Malawi.

Background: Schistosomiasis is second only to Malaria in its prevalence in the tropics. The mode of transmission of this disease is unknown to many travelers, whereas other travelers consciously choose to ignore recommendations offered by travel clinics. Methods: We present a descriptive analysis of 22 patients who presented with S. haematobium (SH) infection to two travel clinics in Israel during 1993 and 1994. Results: All 22 patients (mean age 24.2 yrs) apparently acquired SH in lake Malawi. The group contained seven couples, which indicates a very high attack rate. Three of the cases were asymptomatic, thereby causing a diagnostic delay of up to 52 weeks. Diagnosis was established in 18 cases by finding eggs in the urine, and in eight cases, by serology. Conclusion: All cases of SH diagnosed at two medical centers in Israel in 1993 and 1994 were acquired in Lake Malawi. A few of the cases were totally asymptomatic, which raises the question of routine screening. Travel clinics should warn travelers to the Lake Malawi region of this specific hazard.

Journal Article↗

Penetration of cefetamet pivoxil and cefuroxime axetil into the maxillary sinus mucosa at steady state.

The penetration of cefetamet and cefuroxime into the maxillary sinus mucosa after the administration of cefetamet pivoxil and cefuroxime axetil was investigated in patients undergoing elective surgery of the maxillary sinus. A total of 27 patients, 13 for cefetamet pivoxil and 14 for cefuroxime axetil, ranging from 15 to 70 years of age participated in this study. Each patient received three oral doses of either one tablet of cefetamet pivoxil (500 mg of GLOBOCEF) or two film tablets of cefuroxime axetil (125 and 250 mg of ZINAT) every 12 h. Sinus mucosa tissue samples were removed during surgery at times ranging from 2 to 4.5 h after the last oral administration. Blood samples were collected before drug administration, 2 h after the first and third doses, and concomitantly with tissue sample collection during surgery. All samples were analyzed by high-performance liquid chromatography. The concentrations of cefetamet and cefuroxime in plasma samples measured concomitantly with those in tissue samples ranged between 0.83 and 4.5 micrograms/ml for cefetamet and 0.59 and 3 micrograms/ml for cefuroxime. The mean tissue-to-plasma ratios calculated with reference to total (bound plus unbound) plasma drug concentrations were 0.60 (range, 0.52 to 0.77) for cefetamet (n = 4) and 0.38 (range, 0.28 to 0.44) for cefuroxime (n = 6). Both drugs seem to penetrate freely and easily into the sinus mucosa. The antibacterial activities of cefetamet pivoxil and cefuroxime axetil in cases of sinusitis therefore depend mainly on their achieved active plasma drug concentrations and their intrinsic activities in inhibiting the causative organism(s).

Adolescent↗

Penetration and bactericidal activity of cefixime in synovial fluid.

The penetration of oral cefixime into the synovial fluids of 16 patients (mean age, 50.6 years) who underwent joint taps for rheumatic noninfectious disorders was examined. The patients were each given a single dose (400 mg) 2 to 24 h prior to the tap. Cefixime concentrations in serum and joint fluid samples were measured by high-performance liquid chromatography, and the bactericidal activities of these fluids against three isolates each of Haemophilus influenzae and Escherichia coli were examined. The highest concentrations in serum and synovial fluid were achieved 4 h following drug intake, the mean values being 2.8 and 2.03 micrograms/ml, respectively. Effective bactericidal activities (bactericidal titer, > 1:2) against E. coli and H. influenzae were demonstrated in serum and joint fluid up to 10 h following oral intake of cefixime. These results suggest that cefixime penetrates well into joint fluid, achieving levels above the MIC for E. coli lasting as long as 10 h and levels above the MIC for H. influenzae lasting up to 24 h after administration. Good bactericidal activity against susceptible bacterial isolates was observed for at least 10 h after dosing.

Adult↗

Modified thioglycolate medium: a simple and reliable means for detection of Trichomonas vaginalis.

Despite the declining rate of sexually transmitted diseases in developed countries, trichomoniasis is still one of the most common venereal infections. While diagnosis of this condition is commonly based on the microscopic wet-mount method, culture remains the most accurate single procedure for detecting the presence of Trichomonas vaginalis in clinical samples. In the present study, the efficacy of a modified formula of the commonly available thioglycolate medium was compared with that of the standard Diamond's medium for detection of T. vaginalis in samples from 176 women with vaginal symptoms. Thioglycolate medium supplemented with yeast extract, horse serum, and antimicrobial agents was as reliable as Diamond's medium for detection of T. vaginalis in vaginal fluid samples. Modified thioglycolate medium may be used as a readily available, low-cost substitute for the standard medium for culturing T. vaginalis.

Animals↗

Comparative efficacy of DMP 840 against mouse and human solid tumor models.

BACKGROUND: DMP 840 is a compound from a class of bis-naphthalimide antitumor agents that recently completed Phase I clinical trials at three North American centers and is currently undergoing Phase II testing. Preclinically, it was shown to have curative activity against a variety of human tumor xenograft models. PURPOSE: To test DMP 840 both in vitro and in vivo for antiproliferative activity against predominantly mouse tumor models. METHODS: A disk diffusion soft agar colony formation assay was used to determine the in vitro growth inhibitory activity against a selection of mouse and human tumor cell lines, and the comparable selective mouse solid tumors were used for in vivo testing. RESULT: In vitro DMP 840 exhibited equal cytotoxicity for human tumors (including MX-1 directly cultured from nude mice), mouse tumors and normal cells. In vivo DMP 840 was only modestly active or inactive against the following mouse tumors: Mam 16/C, T/C = 30% (T/C = Percent Tumor Growth Inhibition); Mam 16/C/ADR, T/C = 33%; Colon 38, T/C = 9%; Panc 03, T/C = 53%; Colon 51/A, T/C = 28%; Panc 02, T/C = 52%; P388/0, 36% ILS (Percent Increased Life Span) and P388/ADR, 14% ILS. Furthermore, the antitumor activity was only observed at the highest non-toxic dose and was associated with a large body weight loss. In contrast, the agent was highly active against the human breast tumor MX-1 implanted subcutaneously in either athymic nude or SCID mice (Nudes: T/C = 0%; 1/5 cures; SCIDS: T/C = 0%; 5/5 cures). CONCLUSIONS: Although there was no selective cytotoxicity in our clonogenic assay for human versus mouse tumor cell lines, selective activity in vivo for human xenograft tumors was noted. Overall, this compound is rather unique in its differential degree of in vivo activity for human versus mouse tumors. IMPLICATIONS: Phase II trials, which are ongoing, will help determine if the preclinical in vivo selective activity of DMP 840 translates to clinical activity in man.

Adenocarcinoma↗

Preliminary experience with pulmonary autografts.

Between July 1994 and March 1995, seven patients (six male) with a mean age of 27 years (range 18 to 34 years) were selected for aortic valve replacement with a pulmonary autograft (Ross operation). The aortic valve disease was isolated insufficiency in four cases, stenosis in one and mixed lesion in two. Three patients had a bicuspid aortic valve. Previous cardiac surgical procedures had been performed in two cases (coarctation repair and valvuloplasty in one; isolated aortic valvuloplasty in one). Two patients were in NYHA class II and five in class III. In two cases the autograft was inserted as a scalloped subcoronary implant. Four patients had total aortic root replacement with re-implantation of the coronary ostia. The RVOT was reconstructed with a cryopreserved homograft (five pulmonary two aortic). The aortic cross-clamp time was 150 +/- 10 minutes with a total bypass time of 212 +/- 14 minutes. There was neither operative nor late mortality. Postoperative echocardiography revealed trivial autograft insufficiency in one case with a mean transvalvular gradient of 15.8 mmHg. All patients improved symptomatically (100% in NYHA class I). Freedom from reoperation, valve related complications and endocarditis is 100% at a mean follow up of 5.6 months (range 1-9 months). This preliminary experience supports the concept of pulmonary autograft implantation in selected patients.

Adolescent↗

Phase I trial of sequential cyclophosphamide, cyclosporin A, and interferon-alpha in patients with cancer: attempt to induce autologous graft-versus-host reaction to elicit an antitumor response.

Previous reports of autologous bone marrow transplant (auto-BMT) have demonstrated that myeloablative therapy followed by cyclosporin A (CsA), with and without interferon (IFN), can generate autoreactive cytotoxic T lymphocytes (auto-CTL) with potential therapeutic benefit. This is the first report of an attempt to generate auto-CTL using CsA and IFN after a non-myeloablative regimen. Cyclophosphamide (CTX) 1,200 mg/m2 i.v. day 1 was followed by CsA and IFN-alpha days 2-28, administered in a sequential three-step Phase I dose-escalation scheme. Patients were evaluated twice weekly for clinical evidence of graft-versus-host (GVH) reaction. Peripheral blood mononuclear cells (PBMCs) were obtained before treatment, at time of clinical GVH reaction, and days 21 and 28, and analyzed for auto-CTL, natural killer (NK) cell, and lymphokine-activated killer (LAK) cell activity. Patients also underwent punch skin biopsy at the time of clinical GVH reaction or day 21 to identify histologic evidence of GVH. Fourteen patients completed therapy and were evaluable for immunologic studies and anti-tumor response. No increase in auto-CTL, NK cell, or LAK cell activity was seen. Clinical or histologic evidence of GVH reaction did not occur. We conclude that this myelosuppressive dose of CTX combined with CsA and IFN is unable to generate clinical or immunologic evidence of an auto-GVH reaction. Further efforts are warranted to evaluate other therapeutic attempts to generate auto-CTL with anti-tumor activity based on preliminary results of clinical benefit in auto-BMT.

Adult↗

Evaluation of a portable prototype to analyze heart rate variability.

Power spectrum analysis of heart rate fluctuations provide a quantitative noninvasive means of assessing the functioning of the cardiovascular control system. Until now the equipment used to study heart rate variability (HRV) have been complicated systems utilized mostly in research centers. Simpler systems are needed for routine clinical application. We have evaluated, through clinical practice, the usefulness of prototype equipment which allows acquisition and analysis of ECG signals by a portable electrocardiograph and a personal computer in which sophisticated software is installed. We performed one hundred forty-five recordings in twenty-two patients admitted to ICU. With this technique two different predictive patterns were detected: one concerning survivors, the other concerning nonsurvivors. Reliability, portability, simplicity and quality results are the main advantages of the system. The disadvantage is that it is difficult to perform HRV analysis in patients with ECG arrhythmia. This is because the program does not allow the choice of an arrhythmia-free section of the tachogram to analyze.

Adolescent↗

Comparative serum bactericidal activities of three doses of ciprofloxacin administered intravenously.

The pharmacokinetics and serum bactericidal activities of three intravenous doses of ciprofloxacin were studied comparatively in 30 patients. Single 200-, 300-, and 400-mg intravenous doses of ciprofloxacin were given over 30 min to 10 patients each, and serum samples were obtained at 0.5, 1, 2, 3, 4, 8, and 12 h after the start of the infusion. Serum drug concentrations were determined by high-pressure liquid chromatography. Pharmacokinetic parameters were estimated by using noncompartmental analysis methods. Serum bactericidal activity against clinical isolates of Escherichia coli, Enterobacter cloacae, Pseudomonas aeruginosa, Acinetobacter calcoaceticus, and Staphylococcus aureus was determined for samples obtained at 0.5, 4, 8, and 12 h. Excellent activity was demonstrated up to 12 h by all doses against E. coli and E. cloacae. Much poorer titers were observed for the remaining organisms, although the 400-mg dose prompted improved results against P. aeruginosa with a mean bactericidal titer of 1:2.9 at 8 h. In conclusion, while the 200-mg dose appears to be largely adequate for infections caused by members of the family Enterobacteriaceae, it seems that when P. aeruginosa is involved, 400 mg twice a day or even three times a day is more appropriate. Intravenous ciprofloxacin performs poorly against A. calcoaceticus and S. aureus, even at a higher dose.

Adult↗

Propagation of Waldenström's macroglobulinemia cells in vitro and in severe combined immune deficient mice: utility as a preclinical drug screening model.

Waldenström's macroglobulinemia (WM) represents an indolent incurable human B-cell tumor. We have successfully established a permanent cell line, WSU-WM, without growth factors or viral transformation, from the pleural effusion of a 60-year-old man with IgM kappa WM. Phenotypic characterization of WSU-WM shows IgM lambda and expression of other B-cell markers. Karyotypic analysis shows a male chromosome complement with several clonal aberrations, including t(8;14)(q24;q32). Molecular characterization shows deletion of kappa and rearrangement of lambda light chain genes indicating a class switching. Both the secretory (s mu) and membrane (m mu) components of IgM are expressed. In addition, the breakpoint on 8q24 is downstream of exon 3 of the c-myc oncogene. WSU-WM grows in liquid culture and soft agar. When cells were injected subcutaneously in immune deficient mice, six of seven SCID mice developed subcutaneous tumors as opposed to three of seven in the athymic nude mice. When a WSU-WM SCID tumor was passaged in vivo in the SCID mice, the take rate was 100%. This xenograft model and a soft agar disk-diffusion assay were used to test the efficacy of standard chemotherapy agents against this tumor in vivo and in vitro, respectively. The cell line and the assays described herein can be used as a model to facilitate the discovery of new therapeutic agents or modalities for this disease.

Animals↗

The penetration of ciprofloxacin into bronchial mucosa, lung parenchyma, and pleural tissue after intravenous administration.

We have studied the concentrations of ciprofloxacin in serum, bronchial mucosa, lung parenchyma, and pleural tissue after a single intravenous dose of 200 mg in 20 patients subjected to lung surgery. The concentrations of ciprofloxacin in the tissues exceeded that in the serum by 3-fold to 7-fold: serum 0.6 micrograms.ml-1, bronchial mucosa 1.9 micrograms.g-1, lung parenchyma 3.4 micrograms.g-, and pleural tissue 1.7 micrograms.g-1. The achievable concentrations of ciprofloxacin in the tissues of the lower respiratory tract are above the MICs for most lung pathogens.

Adult↗

Heart rate variability and severe brain damage: preliminary data.

Severe brain damage may cause alterations of cardiovascular function: heart rate, particularly, require the integrity of the vagal, sympathetic and central nervous systems. We studied brain-heart functional relation and neurovegetative modulation by spectral analysis of heart rate variability (HRV). This technique allows separate evaluation of the sympathetic and vagal components of heart rate modulation. In order to correlate changes in HRV with brain damage, we performed 45 recordings in 6 patients (5/1 M/F) by means of autoregressive analysis (AAR). All patients were admitted to the ICU for severe brain damage (anoxic, traumatic or vascular). In 4 patients clinical outcome was brain death, in 2 permanent vegetative status. Two different patterns were found: one in patients with brain death, the other in patients with vegetative status. The small number of patients does not allow definitive conclusions from collected data, but that application of spectral analysis of HRV seems to be a useful monitoring of brain damage subjects.

Adolescent↗

Seroepidemiology of hepatitis B and D virus infection among intravenous drug addicts in Israel.

To evaluate the prevalence of hepatitis B virus (HBV) and hepatitis D virus (HDV) infection among intravenous drug addicts (IVDA) in Israel, serum samples were collected from 400 asymptomatic individuals attending a methadone clinic in Tel Aviv. Overall 5.5% were HBsAg positive, 2.4% HBeAg positive, 52% anti-HBc positive and 6.6% were positive for anti-HD. Anti-HD was identified in 18% of addicts who were HBsAg positive and in 3% who were HBsAg negative and anti-HBc positive. Strong correlation was found between positivity to HBV antibodies and age and duration of drug use. History of jaundice correlated more strongly with anti-HD positivity than with presence of antibodies to HBV. We conclude that Israeli IVDA are less exposed to HBV and HDV infection than their North American and European counterparts.

Adult↗