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Biomedical subjects

M Kunz

Publications and source records attributed to M Kunz.

At least 55 records · Page 3Linked to original sources

Dual chamber pacing with a single-lead DDD pacing system.

The successful application of single-lead VDD pacing during the last few years has generated the idea of single-lead DDD pacing. Preliminary data from several single-lead VDD studies attempting to pace the atrium by a floating atrial dipole are unsatisfactory, causing an unacceptably high current drain of the device. We studied the feasibility as well as the short- and long-term stability of atrioventricular sequential pacing, using a new single-pass, tined DDD lead. In eight consecutive patients (age 73+/-16 years) with symptomatic higher degree AV block and intact sinus node function, this new single-pass DDD lead was implanted in combination with a DDDR pacemaker. Correct VDD and DDD function was studied at implantation; at discharge; and at 1, 3, and 6 months of follow-up. At implant, the atrial stimulation threshold was 0.6+/-0.1 V/0.5 ms. During follow-up, the atrial pacing thresholds in different every day positions averaged 2.1+/-0.5 V at discharge, 2.9+/-0.5 V at 1 month, 3.8+/-0.4 V at 3 months, and 3.4+/-0.4 V at 6 months (pulse width always 0.5 ms). The measured P wave amplitude at implantation was 4.5+/-2.2 mV; during follow-up the telemetered atrial sensitivity thresholds averaged 2.1+/-0.3 mV. Phrenic nerve stimulation at high output pacing (5.0 V/0.5 ms) was observed in three (38%) patients at discharge and in one (13%) patient during follow-up; an intermittent unmeasurable atrial lead impedance at 3 and 6 months follow-up was documented in one (13%) patient. This study confirms the possibility of short- and long-term DDD pacing using a single-pass DDD lead. Since atrial stimulation thresholds are still relatively high compared to conventional dual-lead DDD pacing, further improvements of the atrial electrodes are desirable, enabling lower pacing thresholds and optimizing energy requirements as well as minimizing the potential disadvantage of phrenic nerve stimulation.

Aged↗

Macrophage marker 27E10 on human keratinocytes helps to differentiate discoid lupus erythematosus and Jessner's lymphocytic infiltration of the skin.

Chronic inflammatory discoid lupus erythematosus (DLE) and Jessner's lymphocytic infiltration of the skin (LIS) are both characterized by dermal infiltrates of activated T lymphocytes. However, an inflammatory involvement of the epidermis is only found in DLE. We therefore compared the phenotypic properties of the keratinocytes using immunohistochemical stainings of biopsies from typical DLE and LIS. Keratinocytes failed to express HLA-DR in LIS and surprisingly also in DLE. The adhesion molecule ICAM-1 was only expressed in DLE, with focal staining of the basal keratinocytes in close association with intraepidermal lymphocytes. The monoclonal antibody 27E10, a distinct marker for macrophage activation and differentiation, revealed a strong band-like labelling of the suprabasal and upper keratinocytes in DLE. In contrast, no epidermal expression of this biologically active heterodimer of the calcium-binding proteins MRP-8 and MRP-14 was found in LIS. The staining patterns provide a new method to differentiate DLE and LIS by immunohistochemistry and suggest a distinct type of keratinocyte activation and differentiation in DLE which would in turn mediate epidermal T cell infiltration.

Antigens, Differentiation↗

[Ultrasensitive TSH screening for detection of thyroid gland dysfunctions in women of a medical ambulatory care patient group].

This aim of the study was to identify the prevalence of unsuspected thyroid dysfunction in a female population attending a medical primary care unit (case-finding study). A TSH assay of the third generation was used as a screening test. The overall prevalence of unsuspected thyroid dysfunction in 1061 female patients was 2.5% (0.5% overt hyperthyroidism, 0.3% overt hypothyroidism, 0.5% subclinical hyperthyroidism, and 1.2% subclinical hypothyroidism). The prevalence of thyroid disease is clearly age dependent with 4.3% over the age of 40 and 5.9% for 50-60 year-olds. The ratio for females below 40 and over 40 was 10.75 (Odds ratio, p < 0.0001). We conclude from our study and from the literature that TSH screening as a case-finding strategy is indicated, and also seems cost-effective, in women over 40 years of age.

Adolescent↗

[Annular erythema in childhood--a new eosinophilic dermatosis].

Annular erythema of infancy is a rare and little-known entity. Since its initial description by Peterson and Jarratt in 1981 only 4 further cases have been reported. We present the first case in the German literature. A 4-year-old boy developed non-itching erythematous papules on the trunk which evolved into annular and gyrate erythemas within weeks. The condition showed a relapsing course with disease-free intervals of several months duration. There were no general complaints. Laboratory investigations including detailed serological tests for infectious diseases were normal. Histopathology showed a striking eosinophilic inflammatory infiltrate predominantly in perivascular areas, without peripheral blood eosinophilia. The clinical differential diagnosis of annular erythema of infancy includes erythema annulare centrifugum, while microscopically one must exclude eosinophilic cellulitis (Wells' syndrome). The etiology is unknown and there is no effective therapy. In our case, as well as in all previously published cases, the disease resolved spontaneously. Therefore, it may be considered benign and self-limited.

Biopsy↗

Minimally invasive coronary artery bypass techniques as adjunct to extracardiac procedures.

BACKGROUND: Surgical management of coronary artery disease has improved dramatically over the last decades in terms of short- and long-term results. Nevertheless, elderly patients (more than 75 years); patients with reduced ejection fraction (less than 0.25), heavily calcified aorta, or coexisting noncardiac diseases; and patients requiring cardiac reoperation have an increased perioperative risk when operated on with cardiopulmonary bypass. Successful minimally invasive coronary artery bypass grafting without cardiopulmonary bypass has been reported in selected cases. METHODS: In 8 of 40 high-risk patients undergoing operation on a beating heart, minimally invasive coronary bypass grafting was combined with vascular (carotid endarterectomy, n = 3; aortic replacement, n = 2) and abdominal procedures (a second look after combined pancreas and kidney transplantation) or defibrillator implantations (n = 2). RESULTS: Postoperatively, there was no mortality, no morbidity, and no blood transfusion. Patients are free of symptoms at an average follow-up time of 5.5 +/- 5 months. CONCLUSIONS: Our results indicate that minimally invasive coronary artery bypass grafting technique can be particularly useful if noncardiac procedures have to be performed in high-risk patients with significant coronary artery disease.

Abdomen↗

Interleukin-13 selectively induces monocyte chemoattractant protein-1 synthesis and secretion by human endothelial cells. Involvement of IL-4R alpha and Stat6 phosphorylation.

Chemokines secreted by endothelium have been demonstrated to promote leucocyte recruitment to sites of inflammation. In the present study we investigated the effect of the T lymphocyte-secreted cytokine interleukin (IL)-13 on endothelial expression of chemokines. Employing in situ hybridization and enzyme-linked immunosorbent assay (ELISA) techniques we demonstrate that IL-13, which shares many of its activities with IL-4, selectively induces expression of the C-C chemokine monocyte chemoattractant protein (MCP)-1 in human umbilical vein endothelial cells (HUVEC). However, it fails to up-regulate other C-C and C-X-C chemokines potentially inducible in endothelium such as RANTES (regulated on activation, normal T expressed and secreted), gro-alpha, or IL-8. IL-13 dose-dependently induces monocyte chemotactic activity by HUVEC which can be efficiently blocked by neutralizing antisera against MCP-1. In contrast to the synergistic effect of IL-13 and tumour necrosis factor-alpha (TNF-alpha) on endothelial vascular cell adhesion molecule-1 (VCAM-1) surface expression, TNF-alpha-induced secretion of MCP-1 is not augmented by IL-13. Studying the signalling pathway activated by IL-13 it is demonstrated that a neutralizing monoclonal antibody (mAb) to the 140,000 MW component of the IL-4 receptor (IL-4R alpha) inhibits the effect of IL-13. Immunoprecipitation studies reveal that endothelial IL-4R alpha is rapidly tyrosine phosphorylated upon treatment with IL-13 and IL-4. We furthermore show that both cytokines activate the signal transducer and activator of transcription (Stat) protein-6 in endothelial cells. Our data suggest that IL-13 partly utilizes components of the IL-4 receptor signalling pathway for induction of endothelial MCP-1 expression to facilitate recruitment of blood leucocytes.

Antigens, CD↗

Community violence and inpatient assaults: neurobiological deficits.

The goals of this study were to examine the relationship between community violence and inpatient assaults and to identify neurological and neuropsychological deficits underlying violent behavior. Thirty-three inpatients with a history of community violence were compared with 69 patients who did not have such a history. Inpatient assaults were recorded for 4 weeks; a neurological/neuropsychological battery was then administered. Patients without community violence were more likely to show transient or no violence while in the hospital. Patients with community violence performed more poorly on the Wisconsin Card Sorting Test and on psychomotor tasks, impairments that are consistent with frontal lobe dysfunction. Inpatient assaults were not associated with these neuropsychological impairments. They were related, however, to impairment on frontal motor programming tasks and a history of community violence.

Adolescent↗

Importance of simultaneous active cytomegalovirus and Epstein-Barr virus infection in renal transplantation.

BACKGROUND: Although being the most common infective complication after transplantation, cytomegalovirus (CMV) infection does not always produce disease symptoms in immunosuppressed patients. Development of CMV disease may depend on different factors such as virulence of particular CMV strains and impairment of CMV-specific immune reactions. OBJECTIVE: Demonstration of the importance of simultaneous Epstein-Barr virus (EBV) activation for development of symptomatic CMV infections. STUDY DESIGN: 208 renal transplantation patients were monitored for 3 years with respect to (i) CMV and EBV replications, and (ii) clinical symptoms associated with combined and single infections, respectively. RESULTS: CMV and EBV replications were observed in 22% and 19% of the patients, respectively. Many of these active virus infections were found to overlap in time (59% and 74% of all active CMV and EBV infections, respectively). The increased detection of combined CMV and EBV infections probably does not result from higher initial immunosuppression in these patients, since the percentage of patients receiving OKT3 or ATG was almost identical in the groups of single and combined infections. In 18 cases of combined infections, CMV replication preceeded EBV replication, while EBV replication prior to CMV replication was observed in one case only, indicating that activation of latent EBV infection may be induced during active CMV infection. CONCLUSIONS: Simultaneous replication of both viruses seems to be clinically important, since severe clinical symptoms were observed only in the group of combined CMV and EBV infections. Symptoms were similar to the clinical pictures of CMV disease. Thus, simultaneous EBV replication may be an important co-factor for the development of CMV disease, possibly by further decreasing the number of functional CD4 T cells or enhancing the CD8-positive cytolytic/suppressor T-cell subset as reflected by the comparatively stronger decrease of CD4/CD8 ratio during simultaneous CMV and EBV replication, particularly in the case of symptomatic infections.

Journal Article↗

Serotonin in violent patients with schizophrenia.

CSF levels of 5-hydroxyindolacetic acid (5-HIAA), the serotonin metabolite, were assayed in 10 violent and 10 matched nonviolent patients with schizophrenia. Mean group levels of 5-HIAA in cerebrospinal fluid were found to be nearly identical. Possible explanations, including effects of medications, are discussed.

Adult↗

Sclerosis of the skin in the GEMSS syndrome. An overproduction of normal collagen.

BACKGROUND: We describe a recently observed set of autosomal dominant GEMSS (glaucoma, lens ectopia, microspherophakia, stiffness of the joints, and shortness) syndrome in a 47-year-old woman and her 23-year-old son. In addition, sclerosis of the skin, from which both patients suffered, is investigated in detail. OBSERVATIONS: The histologic examination of skin biopsy specimens obtained from the upper aspects of the backs of both patients revealed a markedly thickened dermis. Immunohistochemical examination of the dermal collagen bundles showed a collagen pattern similar to systemic sclerosis and normal control skin. In situ hybridization showed a markedly enhanced gene expression of transforming growth factor beta 1. CONCLUSION: The sclerotic skin changes in GEMSS syndrome are the result of an abnormally increased production of normal collagen that might be attributable to the enhanced in situ production of transforming growth factor beta 1.

Abnormalities, Multiple↗

Open-label trial of venlafaxine in adults with attention deficit disorder.

Antidepressants or stimulants are commonly used to treat attention deficit disorder (ADD). We report the results of an open-label trial of the recently marketed antidepressant venlafaxine in 16 adult patients with ADD. Patients were treated with venlafaxine (25 to 225 mg/day) for 8 weeks. Four patients discontinued treatment within the first week because of sedation, agitation, or nausea. In the remaining 12 patients, venlafaxine treatment decreased ADD ratings by almost half.

Adult↗

Electron paramagnetic resonance studies of the methylmalonyl-CoA mutase reaction. Evidence for radical intermediates using natural and artificial substrates as well as the competitive inhibitor 3-carboxypropyl-CoA.

The substrate-dependent homolysis of the cobalt-carbon bond and generation of organic radicals in the coenzyme-B12-methylmalonyl-CoA-mutase complex have been demonstrated by EPR measurements. Both the natural substrate methylmalonyl-CoA, its 13C-substituted analogue and the non-hydrolysable synthetic substrates succinyl-dethia(carba)-CoA, succinyl-dethia(dicarba)-CoA and 4-carboxy-2-oxo-butyl-CoA induced similar but not identical EPR signals. 3-Carboxypropyl-CoA, a novel competitive inhibitor, has been synthesised. Its Ki value of 89 +/- 6 microM was in the same range as the Km of succinyl-CoA. Using [5'-3H]adenosylcobalamin, an enzyme-dependent tritium transfer to the inhibitor has been shown. The enzyme-coenzyme-inhibitor complex also exhibited EPR signals that were less structured and less intensive than the corresponding signals with active substrates. These results prove that the inhibitor also induces cobalt-carbon bond homolysis and undergoes reversible hydrogen transfer but not rearrangement.

Binding, Competitive↗

[Blunt and penetrating diaphragmatic injuries].

Between 1987 and 1992, 17 patients sustaining injury of the diaphragm were treated at our institution. All patients had associated injuries. Blunt diaphragmatic rupture (n = 13) was mostly diagnosed by chest X-ray, additional diagnostic procedures (contrast radiography, sonography) confirmed a suspected diaphragmatic rupture. In all 4 cases with penetrating injury the diagnosis was found by explorative laparotomy. In 2 patients sustaining blunt diaphragm rupture the diagnosis was delayed by 2 and 6 days. 3 patients (all sustaining blunt diaphragm rupture) died related to their associated injuries. All patients sustaining blunt or penetrating thoracoabdominal trauma, specially in high-velocity road accidents and injuries by shots or knives, are suspicious for diaphragmatic injury.

Diagnosis, Differential↗

Resistance of mice to experimental leishmaniasis is associated with more rapid appearance of mature macrophages in vitro and in vivo.

Resistance to murine leishmaniasis has been related to the propagation of specific Th cell subsets (Th1 and Th2). This study shows that there are differences between resistant and susceptible mice in the initial myelomonocytic infiltrate, which precede the specific T cell response. After subcutaneous injection of 2 x 10(7) Leishmania major into footpads of resistant C57Bl/6 and susceptible BALB/c mice we performed immunohistochemical studies on the infiltrate. Two days after infection the percentage of more mature, F4/80-positive macrophages in the lesion increased faster in C57Bl/6 mice (63%) than in BALB/c mice (29%). The same strain-specific differences were observed after infection of corresponding strains of athymic mice (57.2% in C57Bl/6 nu/nu; 33.6% in BALB/c nu/nu), thus excluding a T cell-controlled phenomenon. After 1 wk the infiltrate in susceptible mice began to reveal significantly more cells containing MRP14, which is expressed by granulocytes and less mature monocytes but not by mature macrophages. No corresponding differences were found between athymic strains, suggesting that at this point organization of the infiltrate falls under control of protective T cells. In bone marrow cultures of BALB/c and C57Bl/6 mice, the percentage of F4/80-positive macrophages was also increasing faster in C57Bl/6 mice than in BALB/c mice. Increased expression of the F4/80 Ag was associated with higher leishmanicidal activity of C57Bl/6 macrophages. MRP14-positive bone marrow cells on the other hand were rarely infected by parasites. We suggest 1) that the earlier appearance of leishmanicidal macrophages in lesions of C57Bl/6 mice could influence propagation of either Th1 or Th2 cells by reduction of parasite load or by differential secretion of decisive cytokines and 2) that the diffuse accumulation of granulocytes and inflammatory monocytes in susceptible mice facilitates spread of disease.

Animals↗

Expression of intercellular adhesion molecule-1 by murine macrophages is up-regulated during differentiation and inflammatory activation.

Intercellular adhesion molecule-1 (ICAM-1, CD54) is a cell-surface glycoprotein which has been shown to play an important role for cell/cell interaction. Little is known about its occurrence in the murine monocyte/macrophage (M phi) lineage; hence, we analyzed ICAM-1 expression in cells and cell lines representing different stages of M phi maturation and studied its regulation during inflammatory activation. Flow cytometric analysis of bone marrow-derived M phi cultured in the presence of M-CSF, of thioglycollate-elicited peritoneal M phi and of M1 myeloblasts differentiated by lipopolysaccharide (LPS) treatment revealed that ICAM-1 is increasingly expressed during monocytic maturation. Accordingly, the myelomonocytic cell lines RMB.TG, WEHI.TG, J774A and P388D, which can be ordered in a linear differentiation sequence, showed increasing levels of ICAM-1 expression. Furthermore, ICAM-1 expression by bone marrow-derived M phi could be up-regulated by tumor necrosis factor-alpha, interferon-gamma and LPS. In two models of murine experimental inflammation, i.e. induction phase of contact hypersensitivity and cutaneous leishmaniasis, which are both dependent on M phi/T cell interaction, M phi expressing ICAM-1 were found to be highly abundant. In addition, it was demonstrated that co-culture of Leishmania maior parasites with bone marrow M phi led to up-regulation of ICAM-1 on these cells. In conclusion, our data clearly demonstrate that ICAM-1 is increasingly being expressed during maturation of murine M phi. Cytokines and inflammatory stimuli modulate M phi ICAM-1 expression as well thus referring to its considerable role during inflammation, e.g. providing accessory or costimulatory signals for T cell activation.

Animals↗

Long-term high-dose neuroleptic treatment: who gets it and why?

OBJECTIVE: High doses of neuroleptic medication are still administered to many patients, although many studies have shown the effectiveness of low-dose strategies. The purposes of the study were to determine whether and in what ways high-dose patients differed from patients on regular dosages and whether the higher dosages were more effective. METHODS: In a case-control study at two large state hospitals, 38 high-dose patients were compared with 29 regular-dose patients. RESULTS: The high-dose patients had a persistent course of illness, with severe chronic symptoms resulting in hospitalizations of much longer duration than those of the regular-dose patients. The high-dose patients evidenced more regressed functioning and were more violent. To control these behaviors, clinicians increased neuroleptic dosages. CONCLUSIONS: The high-dose patients represented a subgroup of chronic regressed and violent patients. Clinicians prescribed high dosages and continued to use them despite a lack of clear evidence that such treatment is effective.

Affective Disorders, Psychotic↗

Technique of laparoscopic cholecystojejunostomy with a Roux-en-Y loop.

In order to avoid laparotomy in patients with biliary obstruction due to inoperable carcinoma of the pancreatic head, we evaluated the feasibility of a bypass operation using minimal invasive measures. A technique of laparoscopic cholecystojejunostomy was tested in adult pigs who had undergone clip occlusion of the distal common bile duct to imitate choledochal obstruction. Complete biliary bypass was restored with a cholecystojejunostomy via a Roux-en-Y loop using two circular staplers (21, 25, or 29 mm diameter), introduced through a prototype 33-mm-diameter trocar, used to effect the proximal and distal anastomoses. Seven pigs operated on in this way recovered easily, with normal weight gain and without technical complications. Contrast radiography of the biliary bypass at autopsy on day 28 confirmed patent and leak-free anastomoses and functional bypass. We conclude that laparoscopic cholecystojejunostomy with a Roux-en-Y loop is a feasible technique and results in an uncomplicated postoperative course and a biliary bypass with optimal function. Endoscopic application of circular staplers for laparoscopic enterobiliary and enteroenteral anastomosis is practical and safe.

Abdomen↗