Biomedical subjects
J Adler
Publications and source records attributed to J Adler.
Daily low-dose carboplatin as a radiation sensitizer for newly diagnosed malignant glioma.
Surgical resection followed by local field radiotherapy is currently our most effective approach to treatment for most patients with malignant glioma. Carboplatin chemotherapy has direct cytotoxic effects on glioma cells and acts as a radiation sensitizer to enhance cell killing. Its demonstrated efficacy as a sensitizer in other solid tumors led to this clinical trial of carboplatin as a radiation sensitizer in the treatment of newly diagnosed glioblastoma multiforme (GBM) and anaplastic astrocytoma (AA). Fourteen patients (nine GBM and five AA) were treated with daily low-dose carboplatin 25 mg/m2 intravenously within 2 h of their fractionated radiotherapy to a total dose of 600 mg/m2. No significant toxicities attributable to this combined therapy were observed. All patients have progressed, with median time to progression of 16 weeks. Eleven patients have died, with median survival of 38 weeks for the entire cohort. Although this regimen appeared safe, there was no benefit in survival time compared to historical patients treated with radiotherapy. The limitations and future potential for the strategy of radiation sensitization are discussed.
Clinical fluoroscopic fiducial-based registration of the vertebral body in spinal neuronavigation.
We present a system involving a computer-instrumented fluoroscope for the purpose of 3D navigation and guidance using pre-operative diagnostic scans as a reference. The goal of the project is to devise a computer-assisted tool that will improve the accuracy, reduce risk, minimize the invasiveness, and shorten the time it takes to perform a variety of neurosurgical and orthopedic procedures of the spine. For this purpose we propose an apparatus that will track surgical tools and localize them with respect to the patient's 3D anatomy and pre-operative 3D diagnostic scans using intraoperative fluoroscopy for in situ registration and embedded fiducials. Preliminary studies have found a fiducial registration error (FRE) of 1.41 mm and a Target Localization Error (TLE) of 0.48 mm. The resulting system leverages equipment already commonly available in the operating room (OR), providing an important new functionality that is free of many current limitations, while keeping costs contained.
MdfA, an interesting model protein for studying multidrug transport.
The resistance of cells to many drugs simultaneously (multidrug resistance) often involves the expression of membrane transporters (Mdrs); each can recognize and expel a broad spectrum of chemically unrelated drugs from the cell. Despite extensive research for many years, the actual mechanism of multidrug transport is still largely unknown. In addition to general questions dealing with energy coupling, the molecular view of substrate recognition by Mdrs is generally obscure. This mini-review describes structural and functional properties of the Escherichia coli Mdr, MdfA, and discusses the possibility that this transporter may serve as a model for studying the multidrug recognition phenomenon and the mechanism of multidrug transport.
[Recommendations for earthquake preparedness in Israel].
Earthquakes have occurred in the past in our region, along the Afro-Syrian fault line and along the eastern border of Israel. Several earthquakes had a magnitude between 6.25 and 6.5 on the Richter scale and caused severe damage to the populated areas in the Galilee, the Judean Hills and along the coastline. The last major earthquake occurred in 1927 in the Jordan Valley and caused more than 300 fatalities and extensive property damage. If we consider the present densely populated regions in the areas at risk, the occurrence of an earthquake with a magnitude of > 6.25 will constitute a major disaster, causing thousands of casualties and extensive property and economic damage. Israel is presently planning a comprehensive response to mitigate the damages by enforcing existing anti-seismic building codes, retrofitting of public buildings, including hospitals and utilizing all available manpower and material resources in case of such an event. The health sector is a vital part of the overall preparedness and response. Hospitals have to plan alternative sites for continued activity and increase the number of beds. Army medical teams will have to operate in the disaster area in conjunction and coordination with the Home Front Command rescue teams and the EMS. Public and primary health services will have to be reinforced to deal with acute and chronic health problems in the wake of the disaster. The burial of the dead and their identification will become a major logistic and emotional problem and must be planned in advance. Preparedness includes establishing contact with NGOs and agencies in countries, which may render medical assistance in such an event.
Medical relief operation in rural northern Ethiopia: addressing an ongoing disaster.
BACKGROUND: Following the recent drought in Ethiopia, the Jewish Agency, aided by the Israel Ministry of Foreign Affairs, launched a medical relief mission to a rural district in Ethiopia in May-August 2000. OBJECTIVES: To present the current medical needs and deficiencies in this representative region of Central Africa, to describe the mission's mode of operation, and to propose alternative operative modes. METHODS: We critically evaluate the current local needs and existing medical system, retrospectively analyze the mission's work and the patients' characteristics, and summarize a panel discussion of all participants and organizers regarding potential alternative operative modes. RESULTS: An ongoing medical disaster exists in Ethiopia, resulting from the burden of morbidity, an inadequate health budget, and insufficient medical personnel, facilities and supplies. The mission operated a mobile outreach clinic for 3 months, providing primary care to 2,500 patients at an estimated cost of $48 per patient. Frequent clinical diagnoses included gastrointestinal and respiratory tract infections, skin and ocular diseases (particularly trachoma), sexually transmitted diseases, AIDS, tuberculosis, intestinal parasitosis, malnutrition and malaria. CONCLUSIONS: This type of operation is feasible but its overall impact is marginal and temporary. Potential alternative models of providing medical support under such circumstances are outlined.
[Arthroscopic treatment of the unstable knee joint by ligament reconstruction using allografts].
PURPOSE OF THE STUDY: Recurring and multidirectional instability of the knee joint is a therapeutic problem mainly due to a limited possibility of harvesting grafts for its treatment. The authors present the methodology of the solution of recurring and multidirectional instabilities of the knee joint by means of allografts. They inform about the technique of harvesting and preservation of grafts and include the necessary examinations and early results. MATERIAL: Due to the above mentioned reasons the authors concentrated on the possibility of harvesting grafts for ligamentoplasty from donors. They developed the technique of harvesting, examination and preservation of allografts and their application by arthroscopy both in recurring and multidirectional instability. They used grafts from lig. patellae and m. quadriceps femoris. In the group of 21 patients operated on they used allograft for ligamentoplasty of 15 anterior cruciate ligaments (ACL) and 9 posterior cruciate ligaments (PCL), (4 times multidirectional instability of ACL + PCL, 14 times patellar tendon and 10 times tendon of m. quadriceps femoris). METHODS: Harvesting of grafts for ligamentoplasty from donors, examination according to EATB rules, preservation at the temperature of -80 degrees C. Prior to the application an antibiotic bath for 10 minutes. Application of grafts by arthroscopy, for ACL the grafts were used from patellar tendon and m. quadriceps femoris, for PCL the grafts from m. quadriceps femoris anchored in two channels. Operation in multidirectional instabilities in one step procedure--ACL, PCL and posterolateral capsular complex. Fixation by orthesis for 6-8 weeks according to the type of operation, early physiotherapy starting from 2nd day after operation. RESULTS: No differences were found in the postoperative course (immune or any other reaction) in comparison with autografts (duration of hospitalization, postoperative regime, pain), physiotherapy in the replacement of one ligament is faster in comparison with autografts. Ingrowth of allografts according to radiographs is without any special reaction. Results were evaluated according to Lysholm score and they show a significant improvement as compared to the condition prior to operation. No peroperative and postoperative complications were found. There was no immune reaction after the operation, in all patients there occurred a significant improvement of the stability of the knee joint. The results according to Lysholm score prior to the operation and after the ligamentoplasty show both a subjective and objective improvement after the operation. DISCUSSION: Application of allografts for the reconstruction of recurring and multidirectional instability of the knee joint is a method offering new possibilities. Its advantages include reduction of the duration of surgery, significantly reduced morbidity of the joint operated on, the possibility of adjustment of the graft, if need be. Disadvantages are the following: the possibility of a transfer of a virus disease which can be eliminated by a careful examination of donors; a longer period of graft remodelling, which can be compensated by a correct physiotherapy and postoperative regime. CONCLUSION: Application of allografts in the surgical treatment of instability of the knee joint is suitable in the current period of well developed examinations and surgical techniques. Early results are optimistic. Observation of all rules for the application of allografts will allow to extend in the correct indications the range of the possibilities of surgical treatment of recurring and multidirectional instabilities of the knee joint.
An American epidemic--diabetes.
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[Medical support during the Sinai War of Attrition (1968-1970) from a 30-year perspective].
The War of Attrition between Israel and Egypt along the Suez Canal line lasted 23 months (9/1968-8/1970), during which the Israel Defense Forces (IDF) were mostly in fixed fortifications. A few of the important principles of field medical support, which became cornerstones of IDF procedure, were established during that war. These included use of armored vehicles for evacuation under artillery fire, as well as emergency treatment, physiological stabilization, and maintenance of the wounded until evacuation. The latter objectives were achieved by stationing medical officers and paramedics within the fortifications, where they remained with the troops. A field surgical hospital was established in Refidim which had a trained surgical staff and a well-equipped emergency department. It included an operating theater and post-op recovery facilities for proper surgical care until evacuation to hospitals in the rear. Tables showing the number of casualties throughout 1 year of the War of Attrition are presented. Better personal shielding by helmets and body shields decreased the number and severity of head and thoraco-abdominal injuries. The relative large number of those who died-of-wounds was due to the proximity of medical facilities, so that treatment could be administered within the fortifications. Otherwise, many more would have been included among the killed-in-action.
Norepinephrine and N(G)-monomethyl-L-arginine in hyperdynamic septic shock in pigs: effects on intestinal oxygen exchange and energy balance.
OBJECTIVES: To compare the effects of norepinephrine (NOR) and the nonselective nitric oxide synthase inhibitor, N(G)-monomethyl-L-arginine (L-NMMA), on intestinal blood flow, oxygen exchange, and energy metabolism over 24 hrs of hyperdynamic, normotensive porcine endotoxic shock. DESIGN: Prospective, randomized, experimental study with repeated measures. SETTING: Investigational animal laboratory. SUBJECTS: Twenty-seven pigs were divided into three groups: seven animals received no vasopressor therapy (ETX) during endotoxic shock; ten animals were treated with NOR; and ten animals were treated with L-NMMA. INTERVENTIONS: Pigs were anesthetized, mechanically ventilated, and instrumented. Eight hours later, endotoxic shock was initiated by an infusion of Escherichia coli lipopolysaccharide. Animals were resuscitated by hetastarch directed to maintain the intrathoracic blood volume and a mean arterial pressure (MAP) of >60 mm Hg. Twelve hours after the start of the endotoxin infusion, NOR or L-NMMA was administered for 12 hrs in the treatment groups to maintain a MAP at preshock levels. MEASUREMENTS AND MAIN RESULTS: ETX caused a continuous fall in MAP, despite a sustained increase in the cardiac output achieved by fluid resuscitation. NOR maintained MAP at preshock levels because of a further rise in cardiac output, whereas hemodynamic stabilization during L-NMMA resulted from systemic vasoconstriction. NOR increased portal venous blood flow concomitant with decreased intestinal oxygen extraction, whereas L-NMMA influenced neither portal venous blood flow nor intestinal oxygen extraction. Mean capillary hemoglobin oxygen saturation of the ileal mucosa as well as the frequency distributions reflecting microcirculatory oxygen availability remained unchanged as well. Nevertheless, portal venous pH similarly decreased and portal venous lactate/pyruvate ratios increased in all three groups. The arterial-ileal mucosal PCO2 gap progressively increased in the ETX and L-NMMA groups, whereas NOR blunted this response. CONCLUSIONS: Neither treatment could reverse the ETX-induced derangements of cellular energy metabolism as reflected by the increased portal venous lactate/pyruvate ratios. The NOR-induced attenuation of ileal mucosal acidosis was possibly caused by a different pattern of blood flow redistribution compared with L-NMMA.
Evaluating the role of magnetic resonance imaging scans in the surgical management of acoustic neuromas.
OBJECTIVE: To assess the reliability of magnetic resonance imaging (MRI) in predicting the size and position of an acoustic neuroma, with particular reference to the intracanalicular portion. STUDY DESIGN: Prospective study comparing the position of the tumor in the internal auditory canal on fast spin-echo MRI with the actual position measured intraoperatively. METHODS: The study was performed in a tertiary referral neurotology center, encompassing both the public and private health care systems. Fifteen consecutive patients admitted for acoustic neuroma removal via the translabyrinthine approach were studied. The main outcome measure was tumor position in the internal auditory canal expressed in millimeters, accurate to the nearest 0.5 mm. RESULTS: The fast spin-echo MRI was accurate within an error of 1 mm in predicting the lateral extent of the tumor in the internal auditory canal. CONCLUSION: Fast spin-echo MRI can accurately predict the lateral extent of an acoustic neuroma and allow accurate planning of the surgical approach.
Motility and chemotaxis of filamentous cells of Escherichia coli.
Filamentous cells of Escherichia coli can be produced by treatment with the antibiotic cephalexin, which blocks cell division but allows cell growth. To explore the effect of cell size on chemotactic activity, we studied the motility and chemotaxis of filamentous cells. The filaments, up to 50 times the length of normal E. coli organisms, were motile and had flagella along their entire lengths. Despite their increased size, the motility and chemotaxis of filaments were very similar to those properties of normal-sized cells. Unstimulated filaments of chemotactically normal bacteria ran and stopped repeatedly (while normal-sized bacteria run and tumble repeatedly). Filaments responded to attractants by prolonged running (like normal-sized bacteria) and to repellents by prolonged stopping (unlike normal-sized bacteria, which tumble), until adaptation restored unstimulated behavior (as occurs with normal-sized cells). Chemotaxis mutants that always ran when they were normal sized always ran when they were filament sized, and those mutants that always tumbled when they were normal sized always stopped when they were filament sized. Chemoreceptors in filaments were localized to regions both at the poles and at intervals along the filament. We suggest that the location of the chemoreceptors enables the chemotactic responses observed in filaments. The implications of this work with regard to the cytoplasmic diffusion of chemotaxis components in normal-sized and filamentous E. coli are discussed.
Effects of organic antagonists of Ca(2+), Na(+), and K(+) on chemotaxis and motility of escherichia coli.
Various Ca(2+) antagonists used in animal research, many of them known to be Ca(2+) channel blockers, inhibited Escherichia coli chemotaxis (measured as entry of cells into a capillary containing attractant). The most effective of these, acting in the nanomolar range, was omega-conotoxin GVIA. The next most effective were gallopamil and verapamil. At concentrations around 100-fold higher than that needed for inhibition of chemotaxis, each of these antagonists inhibited motility (measured as entry of cells into a capillary lacking attractant). Various other Ca(2+) antagonists were less effective, though chemotaxis was almost always more sensitive to inhibition than was motility. Cells treated with each of these Ca(2+) antagonists swam with a running bias, i.e., tumbling was inhibited. Similarly, some Na(+) antagonists used in animal research inhibited bacterial chemotaxis. E. coli chemotaxis was inhibited by saxitoxin at concentrations above 10(-7) M, while more than 10(-4) M was needed to inhibit motility. Cells treated with saxitoxin swam with a tumbling bias. In the case of other Na(+) antagonists in animals, aconitine inhibited bacterial chemotaxis 10 times more effectively than it inhibited motility, and two others inhibited chemotaxis and motility at about the same concentration. In the case of K(+) antagonists used in animal research, 4-aminopyridine blocked E. coli chemotaxis between 10(-3) M and, totally, 10(-2) M, while motility was not affected at 10(-2) M; on the other hand, tetraethylammonium chloride failed to inhibit either chemotaxis or motility at 10(-2) M.
Evolutionary conservation of methyl-accepting chemotaxis protein location in Bacteria and Archaea.
The methyl-accepting chemotaxis proteins (MCPs) are concentrated at the cell poles in an evolutionarily diverse panel of bacteria and an archeon. In elongated cells, the MCPs are located both at the poles and at regions along the length of the cells. Together, these results suggest that MCP location is evolutionarily conserved.
[Use of skin substitutes in treatment of large hypertrophic scars due to burn injury].
The study concerns a clinical experiment in two patients with a dermal substitute based on atelocollagen and hyaluronic acid, and allogeneic acellular dermis. In both cases two-step grafting was performed. At the first step the dermal substitute was implanted into the wound and it was grafted at the second step with thin dermoepidermal autograft. Large hypertrophic scars after burn injury were treated. In both patients the quality of skin cover was significantly improved.
[The human hepatocyte. II. Cryopreservation].
Human hepatocytes (HH) are an optimal in vitro model for the study of xenobiotics metabolism and toxicity. However, there is still a problem of HH availability. A promising possibility for the storage of HH for later utilization is cryopreservation. Procedures and conditions used for cryopreservation of human hepatocytes and hepatocytes of other species are presented in the present paper. Compared are some biochemical parameters characterizing viability and functionality of fresh and thawed HH.
[Effect of high-dose chemotherapy in patients with relapsing or resistant Hodgkin's disease].
The authors evaluated a group of 48 patients with relapsing or resistant Hodgkin's disease. The patients were treated by life-saving chemotherapy followed by large doses of chemotherapy and autologous transplantation of haematopoietic cells. For life-saving chemotherapy they used most frequently a combination of VIM in 40 patients and combinations of DHAP, MINE, MiniDexaBEAM. In 11 patients they changed the regime of life-saving chemotherapy because of a poor response. After completed life-saving chemotherapy 18 (37.5%) patients were in CR, 27 (56.2%) in PR and in 3 (6.3%) the disease progressed. For large dose chemotherapy the authors used BEAM in 32 patients, CBV in 2, Busulfan with Cyclophosphamide in 13 patients and Busulfan with Melfalan in one patient. After completion of large dose chemotherapy and subsequent autologous transplantation of bone marrow 31 (64.6%) patients were in CR, 8 (16.7%) in PR and the disease progressed in 9 (18.7%). In August 1999 a total of 44.9% patients in CR survive, the median period of follow up after autologous transplantation was 23 months. Life-saving chemotherapy with subsequent large dose chemotherapy led in the investigated group to induction of CR in 64.6% patients which is the basic prerequisite of long-term survival.
[Diagnosis of cytomegalovirus infection with the polymerase chain reaction and antigenemia in patients after allogenic peripheral stem cell transplantation--comparison of 318 paired samples].
BACKGROUND: Cytomegalovirus (CMV) represents a serious infectious complication in patients after allogenic haematopoietic stem cell transplantation. Timely initiation of the therapy at the time of incipient active CMV infection (preemptive therapy) is an important prevention of CMV disease. It is not clear, what is the best indicator of this incipient CMV infection. METHODS AND RESULTS: The significance of the detection of incipient CMV infection by CMV-antigenaemia and DNA-viraemia was compared in this study. DNA-viraemia was detected by the non-nested polymerase chain reaction (PCR). The sensitivity of nested and non-nested PCR was also compared experimentally. We tested 318 blood samples for antigenaemia and DNA-viraemia. Six samples were significantly positive for PCR, no sample was significantly positive for antigenaemia. Timely initiation of therapy resulted in the rapid eradication of the incipient active CMV infection and clearance of DNA-viraemia. CONCLUSIONS: Non-nested PCR is a suitable and more reliable method for the monitoring of incipient active CMV infection and it is a good method for timely initiation of preemptive antiviral therapy.