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Biomedical subjects

M Jonas

Publications and source records attributed to M Jonas.

At least 19 recordsLinked to original sources

[Comparison of different stool tests for the detection of cancer of the colon].

BACKGROUND AND OBJECTIVE: Colonoscopy is the gold standard for the diagnosis of colonic neoplasia. Because of the low compliance, the discomfort of bowel preparation and the procedure itself and the (albeit small) risk of perforation or bleeding alternative procedures such as stool tests are being focused on. PATIENTS AND METHODS: After informed consent stool samples of 116 patients (44 male, 72 female, median age 47 years), scheduled for colonoscopy and 22 patients (17 m, 5 f, 69 y) with known colorectal cancer stool samples were collected. The samples were investigated by three methods: a biochemical (Guajak) test for fecal occult blood, an immunological test for fecal occult blood and a test determining the dimer pyruvat kinase M2 (tumor M2-PK). RESULTS: Sensitivity for detection of colorectal cancer or polyps was 27 % and 10 % for the biochemical test, 91 % and 19 % for the immunological test and 77 % and 48 % for the M2-PK-test, respectively. Specificity was 89 %, 94 % and 72 %, respectively. CONCLUSIONS: Both methods for detection of occult blood had a similar specificity. The sensitivity of the immunological test for the detection of colorectal cancer was significantly higher. The M2-PK-test had a markedly lower specificity in diagnosing cancer. Because of the low sensitivity for polyps the usefulness of stool tests is questionable. Reducing incidence and mortality of colorectal cancer should be achieved by colonoscopy, a recommendation that requires specific communication to the public.

Aged↗

[Mild head injury].

Mild injuries to the head are a common everyday occurrence. Only one out of 30,000 patients suffering mild traumatization of the brain subsequently goes on to develop a complication that requires treatment. Such patients can be identified on the basis of the Glasgow Coma Scale and the determination of risk factors, and these data also serve as an aid for deciding whether surveillance at home or hospitalization is indicated.

Ambulatory Care↗

[On the prognosis of hip fractures. Assessment of mortality after hip fractures by analyzing overlapping segments of longitudinal data].

BACKGROUND: Data on the treatment of hip fractures in acute care settings have been collected in a report card system for quality assurance in Germany since the beginning of the 1990s. However, there are no data on the long-term outcome and long-term quality of care. MATERIAL AND METHOD: In a retrospective study, data on 1393 patients from 1999 were collected from different sources: from the department of quality assurance at the medical association of Westfalia-Lippe, the Statutory Health Insurance Funds (AOK), and the Medical Review Board of the Statutory Health Insurance Funds (Medizinischer Dienst der Krankenkasse, MDK). Statistical analyses were performed by the Center for Clinical Studies of the University of Düsseldorf. RESULTS: Uni- and multivariate analyses reveal the following prognostic parameters for survival after hip fracture: sex, age, nursing care dependency, living in a nursing home, risk stratification according to ASA, and postoperative complications. Timing of the operation had no affect on survival. CONCLUSIONS: Prognostic factors for the outcome after hip fracture can only be obtained by analyzing data from the hospital stay and the post-hospital setting as well. Chances of survival can be significantly improved by rehabilitative care.

Age Distribution↗

Increase in laminin expression in allergic airway remodelling and decrease by dexamethasone.

Lung expression of the extracellular matrix protein, laminin, and its receptor, laminin-1 receptor, were examined in a mouse model of asthma with airway remodelling. Ovalbumin (OVA) was administered to BALB/c mice, intraperitoneally on days 0 and 14, and intranasally periodically between days 14 and 75. The mice developed airway eosinophil and mononuclear inflammatory cell infiltration and fibrosis. On day 76, a marked increase in total laminin was seen in the airways of OVA-treated mice compared to controls by Western blot analysis. The increased laminin expression was detected immunocytochemically in the thickened subepithelial basement membrane and around airways and blood vessels. The OVA-treated mice showed increased expression of the alpha1, beta1, and gamma1 chains of the laminin-1 isoform in monocytes, macrophages and eosinophils infiltrating the airways. Laminin-1 receptor expression was increased in inflammatory and endothelial cells in the lungs of OVA-treated mice compared to controls. Treatment of OVA-sensitised/challenged mice with dexamethasone reduced airway expression of laminin and laminin-1 receptor in OVA-treated mice but not airway hyperresponsiveness to methacholine. Laminin deposition may be an important component of the airway remodelling observed in chronic allergic lung inflammation and is a process modulated by corticosteroids.

Airway Resistance↗

Hospital and 1-year outcome after acute myocardial infarction in patients with diabetes mellitus and hypertension.

Hypertension (HT) and diabetes mellitus (DM) lead to structural and functional cardiac impairment and worsen the prognosis after myocardial infarction (MI). However, the prognosis of male or female patients with the coexistence of HT and DM after MI has not been clearly demonstrated. The study sample comprised 4317 consecutive patients with an acute MI from a prospective nationwide survey conducted in 1992, 1994 and 1996 in all 25 coronary care units operating in Israel. The in-hospital, 30-day and 1-year outcome of diabetic hypertensive patients (n=546) was compared with that of diabetic normotensive patients (n=547) and with that of nondiabetic hypertensive patients (n=1192) and nondiabetic normotensive subjects (n=2032). The crude in-hospital, 30-day and 1-year mortality rates of diabetic hypertensive patients (11.7, 16.5 and 27.6%, respectively) were significantly higher than those of the diabetic normotensive patients (9.5, 15.4 and 22.9%, respectively) and nondiabetic hypertensive patients (7.1, 11.6 and 17.6%, respectively). Kaplan-Meier survival curves showed increased mortality rates during the 1-year follow-up in diabetic hypertensive patients. Adjusted risk for 1-year mortality was increased in diabetic patients. However, the risk was similar in diabetic hypertensive and normotensive patients (hazard ratio (HR) 1.55, 95% confidence interval (CI) 1.25-1.93, and 1.62, 95% CI 1.29-2.04, respectively). Adjusted Kaplan-Meier survival curves of diabetic hypertensive patients converged with those of the diabetic normotensives. The existence of DM increases the 1-year mortality after MI by about 60%. However, controlled hypertension did not worsen the outcome of diabetic male or female patients after MI.

Aged↗

[Treatment of spinal fracture in ankylosing spondylitis].

Clinical guidelines for the treatment of vertebral fractures associated with ankylosing spondylitis are derived from case reports and a review of literature. The coincidence of paravertebral calcifications and fracture formations leads to problems in the establishment of a proper initial diagnosis. Therefore computed tomography and magnetic resonance imaging have to be employed to define the extent of fracture and the presence of spinal lesions. As a rule vertebral fractures based upon spondylitic alterations are extremely unstable and tend to secondary dislocation with a high risk of spinal cord injuries. Operative osteosynthesis is the method of choice in the fracture treatment. A successful stabilization requires an extended spondylodesis comprising at least five vertebral segments by a dorsal or a combined ventral instrumentation.

Adult↗

Topical L-arginine gel lowers resting anal pressure: possible treatment for anal fissure.

PURPOSE: Exogenous nitric oxide donors, such as glyceryl trinitrate, have been used as treatment for anal fissures; however, headaches develop in 60 percent of patients. Nitric oxide produced from the cellular metabolism of L-arginine mediates relaxation of the internal anal sphincter. This study investigated whether topical L-arginine gel reduces maximum anal resting pressure in volunteers. METHOD: In a two-center study, volunteers received a single topical dose of L-arginine or placebo (Aquagel ). Anal manometry was performed for two hours after application of 400 mg of L-arginine gel or placebo gel to the anal verge in 25 volunteers. Side effects were recorded after single application and also after repeated dosing for three days. RESULTS: L-Arginine reduced maximum anal resting pressure by 46 percent from a median of 65 cm of water to a minimal value of 35 cm of water ( P< 0.001, Wilcoxon's signed-rank test). The difference between L-arginine and placebo using repeated-measures testing was significant at P< 0.005. No side effects occurred with either gel; in particular, no episodes of headache were recorded. CONCLUSION: Topical L-arginine gel significantly lowers maximum anal resting pressure; its onset of action is rapid, and duration is at least two hours ( P< 0.01). L-arginine may have therapeutic potential, but further evaluation is needed before it can be used as a possible alternative treatment for chronic anal fissure.

Administration, Topical↗

The role of topical diltiazem in the treatment of chronic anal fissures that have failed glyceryl trinitrate therapy.

OBJECTIVE: The treatment of anal fissures has evolved over the last 5 years with the development of topical treatments aimed at reducing sphincter hypertonia. This is thought to improve anal mucosal blood flow and promote healing of the fissure. This study reports the use of topical diltiazem in patients with chronic anal fissures that have failed previous treatment with topical 0.2% glyceryl trinitrate (GTN). PATIENTS AND METHODS: Forty-seven patients with chronic anal fissure who had previously failed at least one course of topical GTN were recruited prospectively from a single centre. Patients were instructed to apply 2 cm (approximately 0.7 g) of 2% diltiazem cream to the anal verge twice daily for eight weeks. Symptoms of pain, bleeding and itching were recorded on a linear analogue score prior to starting the cream and then repeated at 2 weekly intervals. Patients were asked to report side-effects throughout the study period. Healing of the fissure was assessed after 8 weeks of treatment. RESULTS: Forty-six patients completed treatment; of these, 22 had healed fissures (48%). Ten of the 24 patients with persistent fissures were symptomatically improved and wished no further treatment. Of the 14 patients who remained symptomatic, one was given a repeat course of 0.2% glyceryl trinitrate with subsequent healing of the fissure, 10 were recruited into an ongoing study involving injections of botulinum toxin into the internal anal sphincter and three were referred for surgery. CONCLUSION: This study shows that topical 2% diltiazem is an effective and safe treatment for chronic anal fissure in patients who have failed topical 0.2% GTN. The need for sphincterotomy can be avoided in up to 70% of cases.

Journal Article↗

Photochemically induced electron transfer (PET) catalyzed radical cyclization: a practical method for inducing structural changes in peptides by formation of cyclic amino acid derivatives.

A new radical cyclization reaction of unsaturated amino acid derivatives is presented. The reaction is induced by photoelectron transfer (PET) catalysis and proceeds, in comparison to commonly applied methods, under mild, nonoxidizing, and nontoxic conditions in neutral medium. This type of radical cyclization reaction can be used in peptide chemistry for inducing structural changes in peptides.

Amino Acids, Cyclic↗

Conformational study and enantioselective, regiospecific syntheses of novel aminoxy trans-proline analogues derived from an acylnitroso Diels-Alder cycloaddition.

The cis/trans isomerization of the proline amide bond has many implications in biological processes. The conformations of representative acylnitroso-derived proline analogues derived from cyclopentadiene were shown to exist exclusively as the E or trans conformation in CD2Cl2. The energetically favored conformations were determined using COSMO self-consistent reaction field calculations at the B3LYP/6-31G level of theory in addition to low temperature 1H NMR studies. The syntheses of the acylnitroso-derived peptides utilized two methods to selectively functionalize either of two chemically similar esters in the acylnitroso-derived amino acids. A novel transpeptidation of the amino acid that controlled the absolute stereochemistry in the acylnitroso Diels-Alder cycloaddition took advantage of an activated aminoxy amide linkage to control regiochemistry. Alternatively, an enantioselective and regiospecific enzymatic resolution of a racemic dimethyl ester provided a novel aminoxy acid.

Amides↗

Selectively increased risk of cancer in men with coronary heart disease.

Cancer incidence was assessed among a cohort of 10,923 male coronary patients in Israel screened for participation in a secondary prevention trial and compared with national cancer incidence rates. Higher total and age-specific incidence rates of cancer were observed among male coronary patients than among the Israeli male population, but this excess was limited to cancers of the lung, bladder, and colon.

Aged↗

Impaired survival of bone marrow hematopoietic progenitor cells in cyclic neutropenia.

Cyclic neutropenia (CN) is a congenital hematopoietic disorder characterized by remarkably regular oscillations of blood neutrophils from near normal to extremely low levels at 21-day intervals. Recurring episodes of severe neutropenia lead to repetitive and sometimes life-threatening infections. To investigate the cellular mechanism of CN, the ultrastructure and the proliferative and survival characteristics of bone marrow-derived CD34(+) early progenitors, CD33(+)/CD34(-) myeloid progenitors, and CD15(+) neutrophil precursors from CN patients and healthy volunteers were studied. The ultrastructural studies showed profound apoptotic features in bone marrow progenitor cells in CN. Colony-forming assays demonstrated a 75% decrease in the number of early myeloid-committed colonies compared with controls. Long-term culture-initiating cell assays demonstrated a 6-fold increase in production of primitive progenitor cells in CN. To determine whether accelerated apoptosis might account for the underproduction of myeloid progenitors, the hematopoietic subpopulations were labeled with fluorescein isothiocyanate-annexin V and analyzed by flow cytometry. Short-term culture of CN cells resulted in apoptosis of approximately 65% of CD34(+) cells, 80% of CD33(+)/CD34(-) cells, and more than 70% of CD15(+) cells, as compared with 20%, 7%, and 15% apoptosis in respective control subpopulations. Evidence of accelerated apoptosis of bone marrow progenitor cells was observed in all 8 patients participating in the study, regardless of the stage in the CN cycle in which bone marrow aspirations were obtained. Granulocyte colony-stimulating factor therapy of CN patients significantly improved survival of bone marrow progenitor cells. These data indicate that ineffective production of neutrophils is due to accelerated apoptosis of bone marrow myeloid progenitor cells in CN.

Annexin A5↗

Topical 0.2 percent glyceryl trinitrate ointment has a short-lived effect on resting anal pressure.

PURPOSE: Glyceryl trinitrate ointment applied to the anal verge lowers anal resting pressure, but its duration of action is uncertain. This study investigated the effect and duration of action of 0.2 percent glyceryl trinitrate on anal resting pressure and hemodynamic parameters. METHODS: A total of 15 volunteers, 9 male, with a median age of 30 (range, 20-71) years, underwent continuous static anal manometry using a solid state catheter for ten minutes before and two hours after applying 0.2 percent glyceryl trinitrate ointment to the anoderm with a gloved finger. Pulse and blood pressure were recorded every 15 minutes. RESULTS: A significant reduction in maximal anal resting pressure compared with preglyceryl trinitrate values was observed at 15, 30, 45, 60, and 90 minutes after application, but no significant difference thereafter. There was no significant change in pulse during the study. Systolic and diastolic blood pressures dropped significantly after application of glyceryl trinitrate, but had recovered and were not significantly different from original values after 90 minutes. A significant fall in blood pressure did not correlate with the onset or duration of side effects. CONCLUSIONS: Continuous static manometry (as opposed to interval measurements reported in previous studies) demonstrates that 0.2 percent glyceryl trinitrate ointment significantly lowers anal resting pressure, but only for 90 minutes. Twice daily application of topical 0.2 percent glyceryl trinitrate heals two-thirds of fissures after eight weeks, but its apparently short duration of action may indicate that more frequent application might heal more fissures, more rapidly.

Administration, Topical↗

A randomized trial of oral vs. topical diltiazem for chronic anal fissures.

INTRODUCTION: Chemical sphincterotomy has proved effective in treating chronic anal fissure. Glyceryl trinitrate is the most widely used agent, and topical 0.2 percent glyceryl trinitrate ointment heals up to two thirds of chronic anal fissures. Unfortunately, however, many patients experience troublesome headaches as a side effect of this treatment. This study assessed the effectiveness of oral and topical diltiazem in healing chronic fissures. METHODS: Fifty consecutive patients with chronic anal fissures were randomly assigned to receive oral (60 mg) or topical (2 percent gel) diltiazem twice daily for up to eight weeks. Anal manometry was performed before and after the first dose, and blood pressure was recorded at 15-minute intervals. Patients were reviewed fortnightly, pain was expressed with a visual linear analog scale, blood pressure was recorded, fissure healing was assessed, and side effects were noted. RESULTS: Twenty-four patients received oral diltiazem, and 26 received topical diltiazem. Mean (+/- standard error of the mean) maximum resting anal pressures fell by 15 and 23 percent from 95 +/- 4 to 81 +/- 4 and from 102 +/- 5 to 79 +/- 5 cm H2O in the two groups, respectively. There was no significant reduction in blood pressure during the study or at follow-up in either group. Fissure healing was complete in 9 patients (38 percent) receiving oral diltiazem and 15 (65 percent) on topical treatment by eight weeks. Oral diltiazem caused side effects in eight patients (rash, two; headaches, two; nausea or vomiting, three; reduced smell and taste, one), whereas no side effects were seen in those receiving topical therapy (P = 0.001). CONCLUSION: Oral and topical diltiazem heal chronic anal fissures. Topical diltiazem is more effective, achieving healing rates comparable to those reported with topical nitrates, with significantly fewer side effects.

Administration, Oral↗

[Morbidity and mortality in para-articular femoral fractures in advanced age. Results of a prospective study].

UNLABELLED: This study was designed to determine risk factors and individual dispositions associated with morbidity and mortality in the operative treatment of hip fractures in elderly patients. PATIENTS AND METHODS: In a prospective clinical trial, a consecutive series of 278 patients (mean age: 78.7 +/- 6.2 years) with a hip fracture treated by internal fixation or arthroalloplasty was recorded prospectively concerning preexistent diseases and risk factors. Based upon a multivariate analysis the data were related to perioperative complications and mortality. A follow-up during the first postoperative year was performed to determine mortality rate and causes of deaths. Polymorbidity within the meaning of 3 preexistent diseases was present in 117 cases; a solitary disease was found in 25 patients. Only 19 patients were without significant risks representing a comorbidity of 93.2%. In 64.4% diseases of the cardiovascular system were detected followed by diabetes mellitus (21.9%) and diseases of the respiratory tract (20.1%). RESULTS: In the postoperative course systemic complications were observed in 118 patients indicating a general morbidity of 42.4%. According to the preexistent diseases recorded, cardiovascular complications (25.5%), obstructive ventilatory diseases (10.1%) and pneumonias (12.2%) were the most common complications. During hospital stay 21 patients died (mortality: 7.6%). A total of 76 patients died during the first postoperative year corresponding to a mortality rate of 27.3%. Postoperative complications were observed in patients with polymorbidity at 68.4% which differs significantly with the morbidity of low-risk patients at 23.6% (p < 0.001). Multivariate analysis revealed a combination of polymorbidity and age beyond 78 years as significant risk factors towards morbidity and mortality. In detail, a prevalence of cardiovascular insufficiency, pulmonary disease and disturbance of renal function was found to be a significant disposition. CONCLUSIONS: During the preoperative course high risk patients should be identified according to the data presented above in order to take all measures necessary in critical care during the perioperative period. Furthermore, the results underline the importance of an early operative treatment within a posttraumatic period of 12-24 hours. Concerning the method of fracture stabilization procedures allowing a primary full loading should be favoured with regard to early rehabilitation.

Aged↗

Fas (CD95) induces alveolar epithelial cell apoptosis in vivo: implications for acute pulmonary inflammation.

Activation of the Fas/FasL system induces apoptosis of susceptible cells, but may also lead to nuclear factor kappaB activation. Our goal was to determine whether local Fas activation produces acute lung injury by inducing alveolar epithelial cell apoptosis and by generating local inflammatory responses. Normal mice (C57BL/6) and mice deficient in Fas (lpr) were treated by intranasal instillation of the Fas-activating monoclonal antibody (mAb) Jo2 or an irrelevant control mAb, and studied 6 or 24 hours later using bronchoalveolar lavage (BAL), histopathology, DNA nick-end-labeling assays, and electron microscopy. Normal mice treated with mAb Jo2 had significant increases in BAL protein at 6 hours, and BAL neutrophils at 24 hours, as compared to lpr mice and to mice treated with the irrelevant mAb. Neutrophil recruitment was preceded by increased mRNA expression for tumor necrosis factor-alpha, macrophage inflammatory protein-1alpha, macrophage inflammatory protein-2, macrophage chemotactic protein-1, and interleukin-6, but not interferon-gamma, transforming growth factor-ss, RANTES, eotaxin, or IP-10. Lung sections from Jo2-treated normal mice showed neutrophilic infiltrates, alveolar septal thickening, hemorrhage, and terminal dUTP nick-end-labeling-positive cells in the alveolar septae and airspaces. Type II pneumocyte apoptosis was confirmed by electron microscopy. Fas activation in vivo results in acute alveolar epithelial injury and lung inflammation, and may be important in the pathogenesis of acute lung injury.

Acute Disease↗

Anal Fissure.

Anal fissure is a common condition, and although most are short-lived and heal spontaneously, those that persist and require intervention cause considerable morbidity in an otherwise healthy young population. Traditionally, lateral internal sphincterotomy was the gold standard treatment for chronic fissures, but this procedure is associated with a risk of incontinence to some degree in 30% of patients. The discovery of pharmacologic agents that effectively cause a chemical sphincterotomy and heal most fissures has led to approximately two thirds of patients avoiding surgery. Topical 0.2% GTN ointment probably is the most widely used first-line treatment. Other drugs currently under investigation may offer effective treatment with fewer side effects. Another advantage of these novel treatments is that by acting through different pathways, they may be effective in the 30% of cases in which GTN fails, the risks associated with surgery may be avoided. Studies of botulinum toxin injection into the anal sphincter have reported excellent healing rates, although the procedure is more invasive, and patients may find it uncomfortable and less tolerable. Chemical sphincterotomy is particularly suitable in patients with associated inflammatory bowel disease, in whom sphincterotomy for anal fissure generally is contraindicated. When pharmacologic therapy fails or fissures recur frequently and patients have raised resting anal pressure, lateral internal sphincterotomy is the surgical treatment of choice. The results are satisfactory when patients are selected carefully and the incision is limited to the length of the fissure. When chemical sphincterotomy fails and resting anal pressures are not elevated, as is commonly the case with patients developing fissures postpartum, an advancement flap should be considered.

Anal Canal↗