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Biomedical subjects

M Stein

Publications and source records attributed to M Stein.

At least 163 records · Page 9Linked to original sources

[Autologous keratinocyte culture on hyaluronic acid ester membranes: an alternative in complicated wound management?].

Cultivation and transplantation of autologous keratinocytes has been used in the last 15 years to treat complicated wounds of different origin. In spite of excellent technical advancements and clinical experiences cultured keratinocyte grafting still is associated with practical limitations. Application of hyaluronic acid ester membranes as carrier substrate for the transfer of keratinocytes allows improved graft handling: reduces total time required for tissue cultivation and furthermore enhances vitality of the keratinocytes because of possible grafting at semiconfluence.

Aged↗

Combination therapy with cyclosporine and methotrexate in severe rheumatoid arthritis. The Methotrexate-Cyclosporine Combination Study Group.

BACKGROUND: Patients with severe rheumatoid arthritis who are treated with methotrexate frequently have only partial improvement. METHODS: In a six-month randomized, double-blind trial, we compared combination therapy with cyclosporine (2.5 to 5 mg per kilogram of body weight per day in two divided doses at 12-hour intervals) and methotrexate (at the maximal tolerated dose) with methotrexate and placebo in 148 patients with rheumatoid arthritis who had residual inflammation and disability despite partial but substantial responses to prior methotrexate treatment. The primary outcome measure was the change in the number of tender joints. RESULTS: The mean (+/- SD) dose of cyclosporine at the final treatment was 2.97 +/- 1.02 mg per kilogram per day. As compared with the placebo group, the patients in the treatment group had a net improvement in the tender-joint count of 25 percent, or 4.8 joints (95 percent confidence interval, 0.7 to 8.9; P = 0.02), and in the swollen-joint count of 25 percent, or 3.8 joints (95 percent confidence interval, 1.3 to 6.3; P = 0.005); improvement in overall disease activity as assessed by the physician (19 percent, P < 0.001) and the patient (21 percent, P < 0.001); and improvement in joint pain (23 percent, P = 0.04) and in the degree of disability (26 percent, P < 0.001). The mean erythrocyte sedimentation rate increased by 4.2 mm per hour in the cyclosporine group and decreased by 4.8 mm per hour in the placebo group (P = 0.006). Thirty-six patients (48 percent) in the cyclosporine group and 12 patients (16 percent) in the placebo group (P < 0.001) met the 1993 criteria for improvement of the American College of Rheumatology (more than 20 percent improvement in the numbers of both swollen and tender joints and improvement in three of five other variables). Seventeen patients in the cyclosporine group and 12 patients in the placebo group were withdrawn from the study; 2 patients in the cyclosporine group died, 1 from viral pneumonia and the other in a motor vehicle accident. Serum creatinine concentrations increased by a mean of 0.14 +/- 0.27 mg per deciliter (12 +/- 24 mmol per liter) in the cyclosporine group and by 0.05 +/- 0.19 mg per deciliter (4 +/- 17 mmol per liter) in the placebo group (P = 0.02). CONCLUSIONS: In a six-month study, patients with severe rheumatoid arthritis and only partial responses to methotrexate had clinically important improvement after combination therapy with cyclosporine and methotrexate. Side effects were not substantially increased. Long-term follow-up of patients treated with this combination is needed.

Arthritis, Rheumatoid↗

[Structure and process components of trauma care services in emergency departments].

Increasing attention is being paid by staffs of hospitals and directors of our national health agencies to providing emergency medical services for trauma care. The results of a nationwide survey documenting the structure and process components of trauma care in all 24 acute care hospitals in Israel are presented. Although these hospitals provide 24-hour trauma service, there are no formal guidelines for required resources in emergency departments. The results show extreme interhospital variation in physical structure of trauma services and in manpower, protocols and critical resource. However, it is evident that the main focus for intervention in the quality of initial trauma care in hospitals in Israel, is to establish and implement organizational standards.

Emergency Service, Hospital↗

1H, 13C, 15N-NMR resonance assignments of oxidized thioredoxin h from the eukaryotic green alga Chlamydomonas reinhardtii using new methods based on two-dimensional triple-resonance NMR spectroscopy and computer-assisted backbone assignment.

The cytosolic thioredoxin h (112 amino acids, 11.8 kDa) cDNA from the eukaryotic green alga Chlamydomonas reinhardtii has been over-expressed in Escherichia coli and the protein was uniformly labelled with 13C and 15N. For the backbone resonance assignments (HN, N, C alpha, CO and H alpha) we used a new set of two-dimensional triple-resonance correlation experiments [Simorre, J.-P., Brutscher, B., Caffrey, M. S. & Marion, D. (1994) J. Biomol. NMR 4, 325-333; Brutscher, B., Simorre, J.-P., Caffrey, M. S. & Marion, D. (1994) J. Magn. Reson. B 105, 77-82] and the new computer assignment protocol ALPS (Assignment for Labelled Protein Spectra) developed in our laboratory [Morelle, N., Brutscher, B., Simorre, J.-P. & Marion, D. (1995) J. Biomol. NMR 5, 154-160]. The assignment was extended to the side chains using three-dimensional HC(C)H-TOCSY correlation experiments together with a set of regular two-dimensional proton spectra. The secondary and super-secondary structures were deduced from the C alpha chemical-shift differences to the random-coil values, the measure of the exchange rates of slow-exchanging amide protons using 15N-HSQC spectroscopy, and the assignment of medium and long-range NOEs. The oxidized C. reinhardtii thioredoxin h is based on an open alpha/beta motif consisting of a five-stranded beta-sheet surrounded by four helices in a manner similar to the bacterial E. coli thioredoxin [Katti, S. K., LeMaster, D. M. & Eklund, H. (1990) J. Mol. Biol. 212, 167-184; Jeng, M.-F., Campbell, A. P., Begley, T., Holmgren, A., Case, D. A., Wright, P. E. & Dyson, H. J. (1994) Structure 2, 853-868] and the human thioredoxin [Qin, J., Clore, G. M. & Gronenborn, A. M. (1994) Structure 2, 503-522] for which C. reinhardtii thioredoxin h shares 32 and 44 sequence identities, respectively. From the analysis of the secondary structure characteristics, the C. reinhardtii thioredoxin h is closer to the human thioredoxin structure than to the bacterial thioredoxin structure. Conversely, the latter would share several structural features with the previously reported [Lancelin, J.-M., Stein, M. & Jacquot, J.-P. (1993) J. Biochem. (Tokyo) 114, 421-431] highly thermostable chloroplast C. reinhardtii thioredoxin m that is involved in the thiol-redox enzymic control of photosynthetic intermediate carbon metabolism.

Amides↗

Elevated mast cell tryptase in cerebrospinal fluid of multiple sclerosis patients.

Multiple sclerosis (MS) lesions are associated with infiltration of T lymphocytes and macrophages that appear to mediate myelin destruction and gliosis (scarring). Mast cells are located perivascularly in the brain, are juxtaposed to neurons, and have been shown to secrete vasoactive and inflammatory mediators in response to neuropeptides and direct nerve stimulation. Mast cells have been previously identified in MS lesions, are activated by myelin basic protein, and can participate in the regulation of blood-brain barrier permeability, as well as in myelin destruction. Here, cerebrospinal fluid from MS patients and controls with other neurologic diseases was assayed for histamine, its major metabolite methylhistamine, and the specific mast cell marker tryptase. Histamine and methylhistamine were not elevated in MS. However, the mast cell specific proteolytic enzyme tryptase was significantly elevated in MS, suggesting that mast cell activation may be involved in the pathophysiology of this disease.

Adult↗

Primary Hodgkin's disease of the bone.

A primary extranodal presentation occurs in less than 0.25% of patients with Hodgkin's disease (HD) and we describe the primary clinicopathologic findings in a rare case of a 21-year-old female with primary bony involvement of Hodgkin's disease. The patient presented with microcytic, hypochromic anemia and shoulder pain. The diagnosis of HD (lymphocyte depleted type) was made by biopsy taken from a lytic lesion in the lateral third of the clavicle. Staging work-up revealed an additional lesion in the ilium, but there was no evidence of lymph node involvement. MOPP/ABV (nitrogen mustard, Oncovin, procarbazine, prednisone/adriamycin, bleomycin, and vinblastine) chemotherapy resulted in complete response lasting, to date, 36 months. To the best of our knowledge, this is only the second reported case of disseminated primary Hodgkin's disease of the bone and all have had a favourable response to combination chemotherapy. A review of the literature is also presented.

Adult↗

Cardiac tamponade as the initial manifestation of primary pericardial mesothelioma.

Although cardiac tamponade is a known complication of malignancy, it is rarely the initial manifestation. We report a 46-year-old male who presented with malignant cardiac tamponade 6 months prior to the definitive diagnosis of primary pericardial mesothelioma. A thorough literature search has not revealed a similar care.

Cardiac Tamponade↗

Chlamydomonas reinhardtii thioredoxins: structure of the genes coding for the chloroplastic m and cytosolic h isoforms; expression in Escherichia coli of the recombinant proteins, purification and biochemical properties.

Based on known amino acid sequences, probes have been generated by PCR and used for the subsequent isolation of cDNAs and genes coding for two thioredoxins (m and h) of Chlamydomonas reinhardtii. Thioredoxin m, a chloroplastic protein, is encoded as a preprotein of 140 amino acids (15,101 Da) containing a transit peptide of 34 amino acids with a very high content of Ala and Arg residues. The sequence for thioredoxin h codes for a 113 amino acid protein with a molecular mass of 11,817 Da and no signal sequence. The thioredoxin m gene contains a single intron and seems to be more archaic in structure than the thioredoxin h gene, which is split into 4 exons. The cDNA sequences encoding C. reinhardtii thioredoxins m and h have been integrated into the pET-3d expression vector, which permits efficient production of proteins in Escherichia coli cells. A high expression level of recombinant thioredoxins was obtained (up to 50 mg/l culture). This has allowed us to study the biochemical/biophysical properties of the two recombinant proteins. Interestingly, while the m-type thioredoxin was found to have characteristics very close to the ones of prokaryotic thioredoxins, the h-type thioredoxin was quite different with respect to its kinetic behaviour and, most strikingly, its heat denaturation properties.

Amino Acid Sequence↗

Mast cells in colorectal neoplasias and premalignant disorders.

PURPOSE: Mast cells have recently been found to be well correlated with the prognosis of patients with rectal cancer. This work aimed to characterize the role of mast cells in colonic premalignant conditions. METHODS: Mast cells were quantified in various colonic disorders, particularly those with premalignant potential. Possible avenues of mast cell action were investigated using these tissue samples, by measuring basement membrane and collagen layer thickening. RESULTS: The mean number of mast cells in carcinoma sections was 0.967/0.9 mm2, in various colorectal neoplasias and related conditions it ranged from 1.36-3/0.9 mm2, and in normal histologic specimens it was 11.90/0.9 mm2. These data established statistically significant differences in mast cell numbers in the colonic disorders studied. The number of mast cells is greatest in the lamina propria level of the colon, a site often not examined because of the limited depth of samples obtained from endoscopic biopsies. CONCLUSIONS: Mast cell numbers were found to be correlated to the development from premalignancy to colonic malignancy. Mast cells may be useful as markers of colorectal neoplasia.

Basement Membrane↗

5-Fluorouracil and low-dose leucovorin in metastatic colorectal cancer: a pilot study.

A total of 56 consecutive patients with metastatic colorectal cancer received treatment with 5-fluorouracil (5-FU) given at 425 mg/m2 by rapid intravenous infusion, immediately preceded by leucovorin (LV) given at 20 mg/m2, with cycles being repeated every 4 weeks. Of 48 evaluable patients undergoing this treatment, a tumor response was observed in 16 (33%); a complete response, in 2 (4%); and a partial response, in 14 (29%). The median survival was 8.5 months for all patients and 16.5 months for responders. An improvement in symptoms was seen in 9 (26%) of 34 symptomatic patients. In all 15 (27%) of 44 evaluable patients showed an improvement in performance status. The most significant toxicity attributable to the treatment was mucositis of grade 3 or 4, seen in 27% of the patients. Altogether, 2 patients (3.5%) were hospitalized for treatment-related toxicity. We conclude that the combination of 5-FU and low-dose LV is active in advanced colorectal cancer and is associated with acceptable toxicity.

Adenocarcinoma↗

Corpus cavernosum as an emergency vascular access in dogs.

RATIONALE AND OBJECTIVES: We investigated the feasibility of using the corpus cavernosum as an emergency vascular access in dogs with severe hypovolemia. METHODS: Five male mongrel dogs were brought to hypovolemic shock by withdrawal of blood through an internal jugular venous line. Using the corpus cavernosum as a venous access, normal saline was injected through a 23-gauge needle at the highest possible rate. Cavernosography was performed under fluoroscopy to verify the accurate position of the needle tip. Blood volumes were measured using 125I-labeled human serum albumin. RESULTS: Before the dogs were bled, their mean systolic blood pressure was 121.4 (mean) +/- 5.2 (standard error) mm Hg and their mean blood volume was 1,835.2 +/- 139.7 ml. The mean volume of blood removed from the dogs was 710.0 +/- 67.8 ml. The mean systolic pressure during shock was 40.8 +/- 2.2 mm Hg. After fluid resuscitation, the mean systolic pressure recovered to 114.6 +/- 4.6 mm Hg and their mean blood volume increased to 1,763.2 +/- 112.7 ml. The mean rate of saline infusion into the corpus cavernosum was 50.2 +/- 0.7 ml/min. CONCLUSION: The results of this study demonstrate the feasibility of using the corpus cavernosum as an alternative route for fluid resuscitation in severely hypovolemic dogs.

Animals↗

Delayed embolization of a shotgun pellet from the chest to the middle cerebral artery.

Embolization of metallic missiles into the cerebral circulation is a rare occurrence. Most of the cases reported were due to gunshot wounds and shotgun wounds to the neck and face. Embolization from injuries sustained to the chest are extremely rare. We report a case of delayed pellet embolization to the middle cerebral artery resulting from a shotgun injury to the left chest.

Adult↗

Biofeedback for the treatment of stress and urge incontinence.

Biofeedback and pelvic floor electrical stimulation are new modalities that have been advocated for the treatment of urinary incontinence. To evaluate the long-term effectiveness of biofeedback and identify factors predictive of a positive outcome, we prospectively studied 28 patients with stress and urge incontinence. All patients were evaluated with a complete history, physical examination, urinalysis and culture. Of 28 patients 21 were also studied with video urodynamics. Biofeedback was performed with the InCare PRS 8900* machine with each patient undergoing at least 6 office sessions. Quantifiable symptoms, such as frequency, nocturia and urgency, were evaluated before and periodically after treatment. Patients also graded the overall treatment response on a scale of 0 to 3. Biofeedback successfully treated 5 of 14 patients (36%) with stress incontinence and 9 of 21 (43%) with urgency incontinence. Treatment response was durable throughout followup in all responding patients. Additionally, there was a statistically significant decrease in daytime frequency and nocturia following biofeedback (p = 0.038 and p = 0.044, respectively). No pretreatment factors predictive of a positive outcome could be identified. Improvement in perineal muscle tone with time approached statistical significance. We conclude that biofeedback is a moderately effective treatment for stress and urge incontinence, and should be offered to patients as a treatment option. Few patients, however, choose biofeedback as a primary mode of therapy and, due to the availability of other highly successful treatments for stress urinary incontinence, it is unlikely to become a popular treatment option.

Adult↗

Analysis of proteins that interact with the IL-2 regulatory region in patients with rheumatic diseases.

In order to investigate transcriptional regulation of lymphokine genes in rheumatic diseases, peripheral blood mononuclear cells from patients with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and systemic sclerosis (SSc) were analysed for expression of DNA-binding proteins. Nuclear extracts prepared from unstimulated and mitogen-activated cells were studied for their ability to bind to 32P-labelled oligonucleotides containing the AP-1, NF-AT, NF-B and CD28RC sites of the IL-2 promoter. Using gel mobility-shift assay, detection of protein binding to the AP-1 site was reduced in SLE compared with controls. NF-AT binding activity was enhanced in all groups of patients, and was associated with measures of disease activity in RA. In addition, SSc patients showed increased NF-kappa B binding activity. Altered patterns of DNA-binding proteins suggest disturbed intracellular signalling which may contribute to abnormal lymphokine production in rheumatic diseases.

Adult↗

Immunization with anti-neutrophil cytoplasmic antibody (ANCA) induces the production of mouse ANCA and perivascular lymphocyte infiltration.

Wegener's granulomatosis (WG) is a granulomatous necrotizing vasculitis associated with the presence of ANCA, predominantly directed against proteinase 3 (PR3). The titres of ANCA correlate with disease activity and titre increases may precede disease exacerbations. Previously, we have shown that it is possible to induce autoimmune disease (systemic lupus erythematosus (SLE) and anti-phospholipid syndrome) in naive mice following active immunization with human autoantibodies, namely anti-DNA and anti-cardiolipin, respectively. The mice developed first anti-autoantibodies and, after about 4 months anti-anti-autoantibodies (Ab3), simulating auto-antibodies (Ab1) in their binding activities, and their presence was associated with the development of disease manifestations, characteristic of the human disease. So far, there is no good animal model for WG. In the current study we have immunized mice with human ANCA with the aim of inducing experimental WG. In two separate studies 30 mice were immunized in their footpads with autoantigen-purified IgG fraction (ANCA) from the sera of two patients with untreated WG, emulsified in Freund's complete adjuvant, followed 3 weeks later by ANCA injection in PBS. In the first experiment mice immunized with ANCA developed sterile microabscesses in the lungs after 8 months, and died after 8-15 months. In the second experiment, mice immunized with ANCA developed after 4 months mouse ANCA, with specificity both to PR3 and to myeloperoxidase, as well as anti-endothelial autoantibodies (AECA), as shown by radioimmunoprecipitation. Pathologically, the immunized mice developed proteinuria but not haematuria, and histological sections of the lungs demonstrated mononuclear perivascular infiltration, while diffuse granular deposition of immunoglobulins was noted in the kidneys. Our results point to a pathogenic role of ANCA in WG, and confirm the importance of the idiotypic network in the etiopathogenesis of autoimmune conditions.

Animals↗

Complications of laparoscopic cholecystectomy: imaging and intervention.

Cholecystectomy is the most common abdominal operation done in the United States, with more than half a million cholecystectomies performed annually. Recently, there has been a trend to perform laparoscopic, rather than open, cholecystectomy. The introduction of any new technique involves a learning curve for surgeons, and several complications may occur with this procedure. Radiologists may be called on to help diagnose and manage injuries occurring after laparoscopic cholecystectomy. This article will review the complications of laparoscopic cholecystectomy, emphasizing the role of imaging in both diagnosis and nonsurgical management of these injuries.

Biliary Tract↗

Laparoscopy and thoracoscopy in evaluation of abdominal trauma.

The role of laparoscopy and thoracoscopy as diagnostic modalities in blunt and penetrating abdominal trauma was studied in 35 hemodynamically stable patients who otherwise would have undergone exploratory laparotomy because of equivocal diagnostic findings. Minimally invasive laparoscopic techniques (single 5 millimeter port) and minimal abdominal insufflation (8-10 millimeters mercury) were used with general anesthesia. Both laparoscopy and thoracoscopy appear to be safe (no complications), highly sensitive (100%), specific (88%), and accurate (91%) tools for determining the presence of surgically significant abdominal pathology and the need for therapeutic laparotomy. The appropriate application of these techniques, possibly under local anesthesia, offers potential cost savings.

Abdominal Injuries↗

Radiation therapy in epidemic, AIDS-related Kaposi's sarcoma in southern Africa.

AIMS AND BACKGROUND: Acquired Immunodeficiency Syndrome (AIDS) associated Kaposi's Sarcoma (EKS) is widely spread in the Southern African Region. No large studies concerning the role of radiation therapy in the Southern African variant of EKS have been reported to date. METHODS: Over a 10 year period (1982-1992) 25 patients with EKS (disseminated skin involvement) were treated primarily with radiation therapy at the Johannesburg General Hospital. Radiation fields were individually tailored to the extent of the disease. Total administered doses ranged between 8-12 Gy (single fraction) to 24-30 Gy fractionated over 2-3 weeks. RESULTS: Overall response and symptomatic relief rates were 72% and 80%, respectively. Toxicity was mild and manageable. CONCLUSIONS: Our retrospective analysis supports the use of radiation therapy for the Southern African type of EKS.

Acquired Immunodeficiency Syndrome↗