Search PubMed⌕ Search

Biomedical subjects

R Mader

Publications and source records attributed to R Mader.

At least 19 recordsLinked to original sources

Morbidity and mortality of hospitalized patients with diffuse idiopathic skeletal hyperostosis.

Diffuse idiopathic skeletal hyperostosis (DISH) has been associated with various metabolic disorders considered to be cardiovascular risk factors such as obesity, diabetes mellitus, hyperinsulinemia, and hyperlipidemia. To evaluate morbidity and mortality of hospitalized patients with DISH admitted to the department of medicine. One hundred patients from a cohort of 1020 consecutive patients, aged 45 years and more, admitted to the department of medicine were diagnosed as suffering from DISH. Another group of 100 patients, age- and gender matched, admitted without DISH, served as controls. Clinical and demographic characteristics, diagnoses on admission, previous chronic diseases, chronic medical therapy, laboratory tests, and the rates of in-hospital mortality and readmissions within 1 month of discharge were collected from the hospital database, for the two groups. Uncompensated or paroxysmal atrial fibrillation was more often encountered on admission in patients with DISH (p = 0.038). Patients with DISH were more likely to suffer from elevated body mass index, arterial hypertension, diabetes mellitus, and previous cerebral vascular accidents, although the differences did not reach statistical significance. However, significantly more patients had an electrocardiographic evidence of left ventricular hypertrophy (p = 0.03). The mortality rate was similar between the two groups. The lack of significant associations for cardiovascular risk factors such as diabetes mellitus, hypertension, and high BMI should be interpreted cautiously considering the characteristics of the control group. Identification of comorbid conditions and proper therapeutic interventions may prove useful in reducing the morbidity and mortality associated with this disorder.

Aged↗

Subacute necrotizing fasciitis caused by gas-producing Staphylococcus aureus.

Presented here is a case of necrotizing fasciitis that developed bilaterally on the thighs of a 54-year-old diabetic woman following subcutaneous insulin injection. Severe localized pain was the presenting symptom; later, soft-tissue gas appeared. Incisional biopsy, performed on day 10 following admission, confirmed the diagnosis. Staphylococcus aureus was the only pathogen isolated. The disease had a slowly progressive course despite appropriate medical treatment, and recovery of the patient was achieved only after fasciotomy, drainage, and debridement of necrotic tissue was undertaken 4 weeks following admission. Staphylococcus aureus may cause subacute necrotizing fasciitis, and infection with this organism should be considered in cases of soft-tissue infection with gas formation in diabetics. The development of soft-tissue infection at the site of insulin injection should alert physicians to the possibility of infection with Staphylococcus aureus.

Anti-Bacterial Agents↗

Duodenal necrosis as the presenting manifestation of polyarteritis nodosa.

Polyarteritis nodosa involves necrotising vasculitis of small and medium-sized arteries. Multiple organ systems are involved. A non-specific and slow course of disease is common. Gastrointestinal involvement is characterised by abdominal pain, nausea and vomiting. Bowel infarction and perforation, cholecystitis and hepatic infarction are well known complications. However, bowel infarction as the presenting symptom of the disease is rare. The case of a 20-year-old male with necrosis of the duodenum heralding polyarteritis nodosa is reported. The patient made a slow recovery after extensive abdominal surgery and a stormy course. The postoperative management and treatment of polyarteritis nodosa are discussed. A high index of suspicion and prompt multidisciplinary approach are needed in order to improve survival in these rare but potentially fatal conditions.

Adult↗

Antiphospholipid antibodies in a heterogeneous group of patients: experience from a central laboratory.

The aim of this study was to evaluate the prevalence and the performance of lupus anticoagulant (LA) tests in a heterogeneous group of patients and to investigate the sociodemographic characteristics, patterns of referral, clinical manifestations and outcomes among these patients. The medical charts of 725 patients referred to a central coagulation laboratory during a 12-month period for LA were reviewed. The data collected included demographic characteristics, the specialty of the referring physicians, the clinical indications for ordering the test, and the influence of the test results on the diagnosis and the treatment approach. Special attention was paid to identifying clinical manifestations known to be associated with antiphospholipid antibodies (APLA). A positive test was defined by abnormal results obtained by at least two techniques from the reagents used and confirmed by a platelet-neutralising procedure. Chi(2) and t-tests were used for independent samples. Fifty-six patients (7.7%) were found to have LA. Rheumatologists and gynaecologists emerged as the major contributors to this group. The presence of LA was significantly associated only with systemic lupus erythematosus and thrombocytopenia. The number of patients treated with antiaggregants or anticoagulants tripled following the test results. A positive dRVVT test strongly correlated with elevated anticardiolipin antibodies. We concluded that LA tests are ordered by a variety of physicians but yield better results when ordered by rheumatologists and gynaecologists. In this heterogeneous cohort, it was most useful in the investigation of thrombocytopenia and suggests a pathogenetic role in this condition. The dRVVT test correlates most closely with elevated anticardiolipin antibodies.

Adult↗

[Craving for alcohol and prevention of relapse].

The long term course of alcohol dependence often includes one or several relapses, which can be divided into low (< 5 standard drinks = lapse, slip) and high intake of alcohol with loss of control (relapse). The biological etiology of relapse is derived from different phenomena such as alcohol craving, psychosocial reasons, development of withdrawal symptoms, different primary psychiatric diseases and "addiction memory". Moreover, the metabolism of alcohol itself substantially contributes to alcohol dependence. For about 100 years different definitions for subgroups of alcohol dependence have been described, of which the Lesch typology is internationally acknowledged, especially for medical treatment. This typology differentiates between four types of alcohol dependent patients in which prevention and treatment of relapse should be specific to the primary psychiatric disease of the patient and to alcohol related disabilities. The aim is a long term improvement of sobriety rates of alcohol dependent patients as well as quality of life and life expectancy.

Adult↗

Tumour promoter mediated altered expression and regulation of ornithine decarboxylase and S-adenosylmethionine decarboxylase in H-ras-transformed fibrosarcoma cell lines.

Alterations in cellular growth are important in the progression of malignant disease. Cell growth regulation by tumour promoters can be complex. The present study demonstrates a novel link between alterations in phorbol ester tumour promoter mediated regulation during malignant conversion and the expression of ornithine decarboxylase and S-adenosylmethionine decarboxylase, key rate-limiting and regulatory activities in the biosynthesis of polyamines. H-ras-transformed mouse 10 T 1/2 cell lines exhibiting increasing malignant potential were investigated for possible phorbol ester tumour promoter mediated changes in ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (SAMDC) gene expression. Selective induction of ODC and SAMDC gene expression was observed, since in contrast to nontransformed parental 10 T1/2 cells, ras-transformed cells capable of benign tumour formation (NR3 cells) and ras-transformed cells capable of metastasis formation (C2 cells) exhibited marked alterations in the levels of ODC and SAMDC gene expression. Increased ODC gene and SAMDC gene expression in response to phorbol-12-myristate-13-acetate (PMA) treatment was found to involve transcriptional events in both NR3 cells and in C2 cells. Post-transcriptional events also played a role in the regulation of ODC gene expression in NR3 cells and in C2 cells, and in the regulation of SAMDC gene expression in C2 cells but not in NR3 cells. In NR3 cells, alterations in ODC and in SAMDC gene expression was an event requiring de novo protein synthesis, whereas in highly malignant C2 cells, protein synthesis inhibition following cycloheximide treatment in cooperation with PMA resulted in an augmentation of both ODC and SAMDC gene expression. Evidence is presented to suggest that the PMA-mediated alterations in ODC and in SAMDC gene expression in NR3 cells and in C2 cells involved protein kinase C - mediated events. The status of the cellular polyamine levels was also an important determinant of the PMA-mediated alterations that occurred in ODC and in SAMDC expression in these H-ras transformed cells. Collectively, these results suggest that PMA can modulate ODC and SAMDC expression in H-ras transformed cells and that the mechanisms involved in the PMA- mediated regulation of ODC and SAMDC gene expression changes as a function of H-ras mediated cellular transformation and malignant progression. This study further suggests a mechanism of PMA stimulation of transformed cells wherein early alterations in the regulatory control of ODC and SAMDC gene expression are important and critical.

Adenosylmethionine Decarboxylase↗

Behçet's disease in Israel: the influence of ethnic origin on disease expression and severity.

OBJECTIVE: To evaluate the relationship between ethnic origin and manifestations of Behçet's disease (BD) in Israel. METHODS: We studied 100 Israeli patients with BD, 66 Jews and 34 Arabs. The 3 largest ethnic groups of Jewish patients originated from Iran/Iraq (n = 21), Turkey (n = 12), and North African countries (n = 21). Patients were evaluated with respect to the entire spectrum of disease manifestations, and a systemic severity score for BD was calculated for each patient. Disease expression was compared between Jewish and Arab patients and among Jewish ethnic groups. RESULTS: There were no statistically significant differences between Jewish and Arab patients with respect to male:female ratio, prevalence of HLA-B5, age of disease onset, or disease duration. Disease expression and severity score were also similar in the 2 groups, but Arab patients had a higher rate of posterior uveitis (20.6 vs 4.6%; p < 0.03). Among the 3 largest Jewish ethnic groups, patients of North African origin had a significantly higher rate of ocular disease (p < 0.01), mainly in the form of anterior uveitis (p < 0.01). These patients also had higher rates of arthritis, overall vascular disease, deep vein thrombosis, and neuro-Behçet without reaching statistical significance. The disease severity score in this group was significantly higher compared to the other Jewish ethnic groups (p < 0.02). CONCLUSION: The expression of BD is similar in Israeli Jewish and Arab patients but the latter have more severe eye disease. The disease in Israeli Jewish patients is most severe in those originating from North African countries.

Adult↗

Tumor antigen pulsed dendritic cells enhance the cytolytic activity of tumor infiltrating lymphocytes in human hepatocellular cancer.

OBJECTIVE: Tumor infiltrating lymphocytes (TILs) stimulated with interleukin-2 (IL-2) ex vivo have been successfully used therapeutically in some cancer patients, but their potency in eliciting an effective anti-tumor response is variable. We have tried to augment killing activity of tumor infiltrating lymphocytes derived from hepato-cellular carcinoma (HCC) using autologous monocytes derived dendritic cells. METHODS: Tumor infiltrating lymphocytes (TILs) from 6 patient with hepatocellular carcinoma were isolated and the phenotype were further characterized. From the same patients, autologous dendritic cells were generated from CD14+ monocytes that were cultured for 6 days in the presence of granulocyte macrophage colony-stimulating factor (GM-CSF) and interleukin 4 (IL-4). Those professional antigen presenting cells were pulsed with whole autologous hepatoma tumor lysates (pDC). TILs were cocultured with pDC or unpulsed DC. To assess the cytotoxic potency of TILs, the ability to lyse the tumor cell targets K652, Daudi and an allogeneic HCC celline was determined in a standard cytotoxic assay. RESULTS: Tumor cells targets in vitro are poorly lysed by tumor infiltrating lymphocytes indicating T-cell hyporesponsiveness. In contrast, the killing activity of HCC derived TILs against Daudi (9.15% +/- 7.5) and allogeneic HCC tumor target (18.2% +/- 9.2) could be significantly augmented when stimulated with pDC (Daudi: 38% +/- 6.8 and allogeneic HCC: 55% +/- 10). The killing activity of TILs against K562 was unaffected by pDC. CONCLUSION: The low cytotoxic activity profile of HCC derived TILs in vitro can be increased by tumor lysate pulsed dendritic cells and may therefore be more effective in vivo when used for adoptive immunotherapy.

Antigens, Neoplasm↗

Rheumatic fever in the Nazareth area during the last decade.

BACKGROUND: Acute rheumatic fever is considered a relatively uncommon disease in developed countries. Although cases are encountered in the Nazareth area in Israel, no systematic study of this disease has been done in the last 20 years. OBJECTIVE: To study the incidence and characteristics of acute rheumatic fever cases in the Nazareth area during the last decade. METHODS: Cases of acute rheumatic fever diagnosed according to the modified Jones criteria were identified in two hospitals in the Nazareth area during the 10 years. These two hospitals receive about 75% of non-obstetric referrals to the emergency room. Clinical, laboratory and treatment data of these patients were documented and the incidence of disease calculated. The population census in the Nazareth area was obtained from the Central Bureau of Statistics. RESULTS: Forty-four patients, with a mean age of 18 years, were identified. The mean annual incidence was 5 cases/100,000 population. Arthritis was found in 98% of the patients (migratory in 52%) and carditis in 34%, but only one patient had a subcutaneous nodule, and none had either erythema marginatum or chorea. Only one patient with carditis developed heart failure a few months later due to severe mitral stenosis. CONCLUSION: Rheumatic fever in the Nazareth area is still manifest. The mean age of the patients was higher than found previously. In only half of the patients was the arthritis migratory, with other major manifestations of rheumatic fever found only rarely.

Acute Disease↗

Relation of pro- and anti-inflammatory cytokines and the production of nitric oxide in patients receiving high-dose immunotherapy with interleukin-2.

Immunotherapy with intravenous recombinant human interleukin-2 (rh IL-2) may be accompanied by hypotension and the emergence of capillary leak syndrome. Nitric oxide (NO) is supposed to be responsible for both side effects. The aim of the current investigation was to elucidate the relationship between pro- and anti-inflammatory cytokines and the production of NO in eight tumor patients receiving intravenous rh IL-2 continuously over a time period of 120 hours. Markers of systemic inflammation, as well as nitrate plasma levels, were consecutively determined. Significant changes in the levels of pro-inflammatory cytokines IL-6 and IL-8 were observed (p < 0.05). In contrast to the anti-inflammatory cytokine IL-10, which did not increase significantly, the serum concentrations of the soluble tumor necrosis factor receptors (sTNFr) I and II rose continuously and significantly during the observation period (p < 0.05). In parallel, a significant rise in nitrate plasma levels was observed (p < 0.05). Moreover, there were highly significant correlations between nitrate and IL-6 serum levels (p < 0.05), nitrate and sTNFr-I (p < 0.05), nitrate and sTNFr-II (p < 0.05), and between IL-6 and IL-10 (p < 0.05), respectively. We conclude that immunotherapy with IL-2 promotes a pro-inflammatory state, parallelled by an increased production of nitric oxide. Although anti-inflammatory responses accompany this process, they are not able to diminish the production of nitric oxide.

Adult↗

Pseudomonas osteomyelitis of the symphysis pubis after inguinal hernia repair.

Osteitis pubis (OP) is a term used to describe an entity characterised by severe pelvic pain, a wide-based gait and bony destruction of the margins of the pubic symphysis. It is usually assumed that OP is a non-infectious, self-limiting, relatively benign condition. Infectious osteomyelitis of the symphysis pubis (IOSP) is very unusual and the clinical presentation can resemble OP. IOSP following inguinal hernia repair is extremely rare. A case of IOSP caused by Pseudomonas aeruginosa is described. We reiterate the assumption that IOSP can be misdiagnosed as OP.

Adult↗

Atypical clinical presentation of ankylosing spondylitis.

OBJECTIVES: To describe a subgroup of patients with ankylosing spondylitis (AS), whose disease evolved without the characteristic inflammatory back pain or significant disability. METHODS: Three patients who were diagnosed in their late 5th decade of life as having AS are described. Information about asymptomatic cases of AS or patients who were unaware of their disease was gathered from case reports and from studies involving HLA-B27-positive individuals. Another source of information derived from studies that investigated conditions known to be a complication of AS, such as heart block or aortic regurgitation. RESULTS: The data collected from the literature suggest that 1.5% to 10% of the patients with AS are asymptomatic or have very mild disease. These patients are diagnosed late in the course of the disease. CONCLUSIONS: Because of the mild nature of the symptoms, the real prevalence of atypical AS is unknown. The information gathered from the literature allows to delineate 4 subgroups of patients with AS: (1) Classic AS with characteristic clinical and radiographic manifestations; (2) Asymptomatic AS with characteristic radiographic findings; (3) Asymptomatic AS with extra-articular features as the presenting manifestations; (4) Symptomatic AS without radiographic supporting evidence. Patients with asymptomatic or mild symptoms deserve more attention, because a better understanding of the factors that affect the expression of pain in different individuals may generate better pain control therapies.

Anti-Inflammatory Agents, Non-Steroidal↗

Thrombophilic factors and their relation to thromboembolic and other clinical manifestations in Behçet's disease.

OBJECTIVE: To evaluate the prevalence of thrombophilic factors known to induce intravascular clotting and to assess their relationship with thromboembolic complications and the other clinical manifestations in Behçet's disease (BD). METHODS: Twenty-five patients with established BD were studied. Twenty patients with rheumatic conditions not known to be associated with venous or arterial thromboembolic phenomena served as controls. Eight of the patients with BD (32%) had either deep vein thrombosis (6 patients), arterial thromboembolic phenomena (2), or both (2). All participants were tested for IgG and IgM anticardiolipin antibody (aCL) levels, the presence of circulating lupus anticoagulant (LAC), protein C, protein S, and antithrombin III activity, activated protein C resistance, and where appropriate factor V Leiden mutation. RESULTS: Elevated levels of IgG aCL were detected in 10 (40%) patients with BD compared to one (5%) in the control group (p = 0.012). No significant differences were noted in the other variables studied between the 2 groups. No statistically significant correlation was found between any variable and the clinical manifestations. CONCLUSION: Patients with BD do not have decreased protein C, protein S, or antithrombin III activity, activated protein C resistance, circulating LAC, or elevated levels of IgM aCL. A significant number of patients have elevated levels of IgG aCL but they are not associated with venous or arterial thrombosis. No correlation was found between any variable and other clinical manifestations of the disease.

Adult↗

Quality of life in systemic lupus erythematosus: a controlled study.

OBJECTIVE: To assess the quality of life (QOL) of patients with systemic lupus erythematosus (SLE) and to compare it with that of healthy women and patients with primary fibromyalgia (FM). METHODS: QOL was evaluated using the QOL scale, which includes 16 items, each scored on a 7 point scale. Healthy controls were chosen from hospital personnel. RESULTS: The study population comprised 75 female patients with SLE, 50 healthy women, and 30 women with primary FM. Compared to controls, patients with SLE had significantly lower scores for the health, work, active recreation, and independence items. The QOL scores were not associated with disease activity. Patients with SLE and FM had significantly lower scores for the health related items compared with patients with SLE without FM. CONCLUSION: The QOL of patients with SLE was found to be impaired compared with controls. FM adversely affects the QOL of patients with SLE.

Adult↗

[Purpura--an unusual presentation of Takayasu arteritis].

Takayasu arteritis is an uncommon vasculitis, often referred to as aortic arch syndrome. It is most prevalent in young women. Physical findings such as the combination of pulseless arms and carotid bruits suggest the diagnosis. Associated skin manifestations such as pyoderma gangrenosum and erythema nodosum have been described. We present a 27-year-old woman with diffuse purpuric eruption and Takayasu arteritis. This appears to be the first description of such an association.

Adult↗

[Bromocriptine for refractory rheumatoid arthritis].

In recent years prolactin (PRL) has emerged as an important immunomodulator in various autoimmune disorders. Bromocriptine (BRC) is a dopamine agonist that suppresses secretion of PRL. Good clinical response to BRC has been reported in patients with psoriatic arthritis, Reiter's syndrome, and systemic lupus erythematosus. 5 mg of BRC at bedtime were given to 5 patients (aged 35-50) with refractory rheumatic arthritis (RA) who had failed to respond to previous treatment with at least 2 disease-modifying antirheumatic drugs. Patients were assessed at 4-6 week intervals for 6 months, 3 showed more than 25% improvement in the number of tender and swollen joints at 12 weeks of treatment. However, in only 2 of them was improvement maintained till the end of the 6 months. There were no changes in other measures of disease activity, 1 patient dropped out of the study due to acute exacerbation of her disease 4 weeks after initiation of BRC and required intra-articular injections of corticosteroid. The remaining patient did not show any significant clinical changes. No correlation was found between serum PRL levels and disease activity over time. It is suggested that some patients with refractory RA might improve with BRC. Its use in larger doses in larger groups of patients may help elucidate its role in the treatment of RA.

Adult↗