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Biomedical subjects

F Harder

Publications and source records attributed to F Harder.

At least 127 records · Page 7Linked to original sources

[Risk factors of persistent or recurrent bleeding and mortality in peptic ulcer hemorrhage].

The mortality rate of peptic ulcer haemorrhage has remained unchanged, mainly attributed to rebleeding in an increasingly elderly population with more coexisting systemic diseases. The value of clinical factors and endoscopic findings in predicting in-hospital further haemorrhage and death are analysed. Over a 2-year period, 157 consecutive patients were admitted with bleeding from peptic ulcer, 19 died and 37 had further bleeding. The predictive value of each factor was determined by the chi 2 test with a Yates-correction (significant, p < 0.05). Significant predictive factors of further bleeding were shock, a transfusion requirement > 4 units during the first 48 hours and endoscopic stigmata of recent haemorrhage. The combination of these factors was not of better predictive value than shock alone. The number of coexisting illnesses per patient was strongly related to fatality rate. Other significant factors indicative of an increased mortality included steroid, onset of bleeding during a hospital stay, alcohol, further bleeding, and > 4 units transfused over the first 48 hours. Shock remains the most valuable sign in predicting further bleeding and is superior to endoscopic stigmata. The close relationship between the mortality rate and coexisting illnesses underlines the fact that the majority of deaths result from non peptic ulcer disease.

Aged↗

Operative treatment of distal humeral fractures in the elderly.

We treated 49 patients at an average age of 80 years (75 to 90) with distal mostly intraarticular humeral fractures by open reduction. There were 8 class A, 13 class B and 28 class C fractures on Müller's classification. The patients were reviewed at a postoperative average of 18 months. The patients' assessment of the result was very good in 31%, good in 49%, fair in 15% and poor in 5%. The flexion-extension range was very good in 41%, good in 44% and fair in 15%. The incidence of implant failure, pseudarthrosis of the olecranon osteotomy and ulnar nerve lesion was no higher in these elderly patients than in younger patients. Old age is not a contraindication to open reduction and internal fixation; it is important to restore full function.

Age Factors↗

Complete traumatic transection of the thyroid gland.

A case of traumatic transection of the thyroid gland with secondary substantial hematoma and respiratory distress is presented. Hemorrhage into the altered thyroid gland is well known. However, there are only a few reports of severe hemorrhage associated with trauma. A short review of the literature is given and the mechanism of trauma is discussed.

Aged↗

[Portal venous thrombosis following splenectomy in portal hypertension: risks and management].

Splenectomy intended to treat hypersplenism can, in the presence of portal hypertension (PTH), lead to extrahepatic portal and mesenteric vein thrombosis. The management of possible variceal bleeding in patients with extrahepatic portal vein occlusion following splenectomy in portal hypertension is a problematic and challenging undertaking. We report on the management of variceal bleeding in 2 noncirrhotic patients with PTH who developed portal vein thrombosis following ill-advised splenectomy. It must be stressed again that splenectomy alone intended to control hypersplenism in portal hypertension is to be avoided at all costs. Options for the treatment of portal and mesenteric vein thrombosis and variceal bleeding are proposed.

Adult↗

[Developments in the surgical therapy of colonic diverticulitis].

All patients admitted to our department with diverticulitis of the left sided colon between 1980 and 1990 were retrospectively evaluated. Staging was performed according to the Hinchey classification. Altogether, 263 patients were evaluated; 71% had complicated diverticulitis and 29% simple diverticulitis. Of those patients with complicated diverticulitis, 68% required surgery due to abscess formation and/or perforation, 19% because of obstruction, 10% because of fistula formation, and 3% due to intestinal hemorrhage. While primary resection (primary reanastomosis in 82% or Hartmann procedure in 13%) was carried out in 250 patients (95%), 13 patients (5%) did not obtain this result (colostomy) following the initial operation. None of the patients who presented with simple diverticulitis died in the postoperative period. The total operative mortality and mortality for complicated diverticulitis amounted to 6.5% and 9%, respectively. In comparison to a former analysis from our department, resection of the primary focus during the initial operation led to a significant decrease in morbidity and mortality. In patients with complicated diverticulitis and peritonitis, primary resection and anastomosis also achieved favourable results in 78%.

Abscess↗

Cytokine gene transcription in renal cell carcinoma.

Cytokines are powerful modulators of immune responses, the local production of which could be relevant to the interaction between tumour and immune system. This study investigated the transcription of genes encoding interleukin (IL) 2, IL-4, IL-10 and interferon (IFN) gamma in lymphocyte-infiltrated renal cell carcinoma biopsies from ten patients using the reverse polymerase chain reaction technique. Autologous peripheral blood mononuclear cells and healthy renal parenchyma tissue were tested in parallel. The beta-actin gene, used as a positive control, was transcribed in all samples. In contrast, transcription of cytokine genes was confined to tumour biopsies: IL-2 gene transcripts were detectable in five biopsies and IL-10 transcripts in seven. IL-4 and IFN-gamma gene transcripts were detectable in one biopsy each. In two patients no cytokine gene transcription could be identified. These data underline that heterogeneous patterns of cytokine gene transcription can be observed in renal cell carcinoma biopsies. Although transcription of an immunostimulatory lymphokine such as IL-2 was observed in 50 per cent of biopsies, the most frequently transcribed cytokine gene coded for an inhibitory factor, IL-10.

Aged↗

Exogenous glutamine requirement is confined to late events of T cell activation.

Glutamine is required for the proliferation of lymphocytes, but quantitative effects on discrete steps of activation remain unknown to date. Therefore the influence of glutamine (range: 0 mM-1 mM) on the in vitro response of human peripheral blood mononuclear cells (PBMC) to a mitogenic anti-CD3 monoclonal antibody (mAb) was investigated. Expression of surface activation markers by flow cytometry, presence of mRNA of cytokine genes by polymerase chain reaction, release of cytokines by ELISA, and entering into the cell cycle by flow cytometry were sequentially analyzed. Proliferation was measured by a 3H-thymidine incorporation assay. mRNA coding for IL-2, IL-2 receptor, IL-4, IL-5, GM-CSF, and IFN-gamma was detectable independently from exogenous glutamine provision; expression of the cell surface activation marker CD69 was also glutamine independent. In contrast, later activation events including the expression of the surface activation markers CD25, CD45RO, and CD71 as well as the production of IFN-gamma were found to require exogenous glutamine supply. In contrast, production of TNF-alpha could be observed in the absence of glutamine and was increased to a limited extent by exogenous glutamine. The overall lymphocyte response as reflected by entering into the cell cycle and proliferation was directly correlated with the glutamine concentration of the culture medium. Efficient progression through the cell cycle was found to require at least 0.5 mM glutamine and an increase in glutamine concentration from 0.1 mM to 1 mM enhanced proliferation by 50%. These results were supported by data obtained following anti-CD3 stimulation of a CD4+ T cell clone.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, CD↗

Differential effects of interleukin-2 and CD3 triggering on cytokine gene transcription and secretion in cultured tumor infiltrating lymphocytes.

The therapeutic potential of tumor-infiltrating lymphocytes (TIL) is currently under investigation. TIL have been reported to display characteristic functional defects, including impairments of activation mechanisms. In animal models, therapeutic efficacy of adoptive TIL transfer has been correlated with their capacity to produce cytokines rather than with their in vitro cytotoxic potential. In this work we assayed cytokine gene transcription and protein production in eight cultured TIL populations stimulated with recombinant human IL-2 (rhIL-2), solid-phase-bound anti-CD3 monoclonal antibodies (mAb), or a combination of the two. By using a sensitive reverse polymerase chain reaction technique, we observed that transcription of IL-5, GM-CSF, and TNF-alpha could be detected in unstimulated, IL-2-starved TIL from all cultures, while IL-4 and IFN-gamma genes were found to be transcribed in two cultures out of eight. A 50 U/ml dose of rhIL-2 was sufficient to induce IL-4 and IFN-gamma gene transcription in the remaining six cultures and in four more TIL populations, respectively. In contrast, rhIL-2 could not induce IL-2 gene transcription in five of eight TIL cultures. Furthermore, it could not induce IL-10 gene transcription in any TIL population. Anti-CD3 mAb triggering, however, induced transcription of all these cytokine genes. On the other hand, IL-6, IL-7, or TGF-beta 2 gene transcription could not be induced by any of the stimuli used, including the combination of anti-CD3 and rhIL-2. Despite detection of their gene transcripts, GM-CSF, IFN-gamma, or TNF-alpha was never detectable, at the protein level, in unstimulated TIL. Stimulation by rhIL-2 induced GM-CSF secretion, albeit to different extents, in all TIL populations. In contrast, rhIL-2 induced IFN-gamma and TNF-alpha production in three and one TIL population, respectively. CD3 triggering however, induced cytokine production in all TIL populations. Addition of rhIL-2 significantly increased production of GM-CSF, but not of IFN-gamma and TNF-alpha. These data underline that stimulation with a moderate dose of rhIL-2 reveals considerable heterogeneity of TIL populations regarding cytokine gene transcription and secretion. On the other hand, triggering of the CD3-T-cell receptor complex induces transcription of an extended panel of cytokine genes in all TIL populations and secretion of GM-CSF, IFN-gamma and TNF-alpha in virtually all cultures. Thus, if stimulated by properly presented antigenic peptides, TIL are capable of mounting an efficient response in terms of cytokine gene expression and protein production.

Aged↗

Extraperitoneal manifestation of perforated diverticulitis.

We observed five cases of unusual extraperitoneal presentation of diverticulitis during an 11 year period. During that time, a total of 263 patients were operated for diverticulitis. Patients 1-4 presented with an inflammatory spread of diverticulitis through the abdominal wall; in patient 5 multiple abscesses were present in the left thigh. Inadequate resection and previous radiotherapy in patient 4 might have contributed to the complicated course. In patient 5, poor condition initially allowed only local drainage of the thigh abscesses. Despite laparotomy and sigmoid resection a few days after drainage, the fatal outcome could not be prevented. A more extensive resection and a protecting colostomy might have prevented the fistulous complication in patient 4. A primary resection and abscess drainage might have averted the fatal outcome in patient 5.

Abdominal Muscles↗

Effects of different culture protocols on the expression of discrete T-cell receptor variable regions in human tumour infiltrating lymphocytes.

Therapeutic effects of tumour infiltrating lymphocytes (TIL) rely on T-cell receptor (TCR) engagement. In this work, the expression of five TCR alpha/beta variable (V) domains was quantitatively analysed by means of a panel of monoclonal antibodies (Mab) recognising gene products from TCR V alpha 2, V beta 5, V beta 6, V beta 8 and V beta 12 families in freshly isolated TIL and in autologous peripheral blood mononuclear cells (PBMC) from patients with neoplasms. In 3 out of 6 cases, differences in the expression of V beta 5, V beta 6, V beta 8 or V beta 12 could be detected. TIL populations were expanded by using recombinant human interleukin-2 (rhIL-2) alone or in addition to solid phase bound anti-CD3 Mab. Cultured TIL showed similar CD4/CD8 ratios and cytotoxic activity against autologous neoplastic target cells, regardless of the activation protocol. In 4 patients, the expression of TCR alpha/beta V gene products, as compared with TIL from freshly excised tumours, was found to be modified in cultured TIL, especially in cell populations activated with rhIL-2 only. These results indicate that TCR V gene usage in TIL may quantitatively differ from that in PBMC. TIL culture protocols using rhIL-2 alone or in combination with solid phase bound anti-CD3 may result in differential expression of discrete TCR V families.

Aged↗

Marginal tissue response adjacent to Astra Dental Implants supporting overdentures in the mandible.

The aim of this study was to evaluate the marginal tissue response adjacent to implant supported overdentures. Twenty edentulous patients had 2 Astra Dental Implants placed in the canine region of the lower jaw. New overdentures were retained by individual ball attachments in 11 patients and by a bar attachment in 9 patients. Periodontal registrations were recorded 0 months, 6 months, 12 months and 24 months after the overdentures were inserted. One of the 40 fixtures was lost at the stage of abutment connection. No fixtures were lost during the 2- to 4-year observation period and no fixtures showed any periodontal signs of failure. At the 2-year examination, no pocket depths adjacent to the implants exceeded 4 mm and no bone loss exceeded 3 mm. The mean annual bone loss was less than 0.2 mm during the first 2 years. The preliminary results from this limited study were promising and showed that two osseointegrated Astra Dental Implants could successfully retain an overdenture in the lower jaw. However, long-term observation is needed for a definitive evaluation of this treatment concept.

Aged↗

Antibiotic prophylaxis with two doses of cephalosporin in patients managed with internal fixation for a fracture of the hip.

A prospective, randomized, double-blind study was performed to evaluate the effects of antibiotic prophylaxis on the development of a wound infection in 239 patients who had immediate stabilization of a fracture of the proximal part of the femur with a dynamic hip screw. The effects of two perioperative doses of cefotiam, given twelve hours apart, were compared with those of two doses of a placebo. Sixteen perioperative risk factors were evaluated to determine whether it was possible to identify patients who were at risk for a wound infection. All patients were followed for a minimum of six weeks. Antibiotic prophylaxis significantly reduced the prevalence of wound infection (p < 0.05): the rate of major wound infection decreased from 5 to 1 per cent and the rate of minor wound infection, from 11 to 4 per cent. The most powerful predictors of major wound infection were the duration of the operation, the interval between the accident and admission to the hospital, and the duration of postoperative urinary catheterization. The preoperative level of serum albumin and the absolute lymphocyte count were significant predictors (p < 0.05) of minor wound infection and systemic infection, respectively.

Aged↗

T-cell receptor V-gene usage in neoplasms of the central nervous system. A comparative analysis in cultured tumor infiltrating and peripheral blood T cells.

The use of tumor-infiltrating lymphocytes in the treatment of central nervous system (CNS) neoplasms has met with serious obstacles due to difficulty of culture and poor characterization. Since in other tumors the therapeutic effects of tumor-infiltrating lymphocytes have been shown to rely on T-cell receptor engagement, the authors addressed the question as to whether expression of T-cell receptor variable (V) domains in cultured tumor-infiltrating lymphocytes from CNS is different from that of autologous cultured peripheral blood mononuclear cells. Infiltrating lymphocytes from CNS neoplasms, including primary malignancies, metastatic cancers, and meningiomas, were cultured in the presence of interleukin-2 and anti-CD3 monoclonal antibodies (MoAb's) in order to obtain optimum growth of T cells. Autologous peripheral blood mononuclear cells from the same patients were similarly cultured. After 4 to 5 weeks of culture, 97.3% +/- 2.6% (mean +/- standard deviation) of the resulting cell populations were CD3-positive lymphocytes. The expression of T-cell receptor V domains was then studied by using a panel of 12 MoAb recognizing gene products from T-cell receptor V-alpha 2, V-beta 5, 6, 8, and 12, V-gamma 4 and 9 families, and from two subfamilies of V-delta 2. Remarkably, in over 70% of all paired measurements, percentages of T cells expressing discrete T-cell receptor V-gene products were found to be virtually identical in tumor- and peripheral blood-derived cultured cell populations, with differences never exceeding 1%. In contrast, a different expression of individual V-gene products, concerning both alpha/beta and gamma/delta T-cell receptors, could be detected between cultured tumor-infiltrating lymphocytes and autologous peripheral blood-derived T lymphocytes in seven of 12 patients. In two cases, significant differences between the two populations were also observed in the proliferative responses obtained upon stimulation with staphylococcal enterotoxins that trigger defined V-beta T-cell receptors. Altogether, these data suggest that the T-cell receptor repertoire of cultured tumor-infiltrating lymphocytes from CNS tumors, suitable for use in adoptive immunotherapies, differs from that of autologous cultured peripheral blood mononuclear cells.

Adult↗

[Distal humerus fractures in patients over 75 years of age. Long-term results of osteosynthesis].

The aim of this retrospective analysis was to evaluate the adequacy of internal fixation of distal humerus fractures in patients over 75 years of age. 49 patients were evaluated. The mean age was 80 (75-93) years. The fractures were classified as 28 C-, 13 B- and 8 A-types according to the AO-system. Primary stable fixation was followed by early assisted mobilisation. The mean average follow-up time was 18 months. Excellent and good functional results were observed in 85%. 66% of all patients have no pain. There were 6 sensible ulnar nerve lesions, one deep wound infection, one pseudarthrosis of the distal humerus and one non union of the olecranon osteotomy. We conclude from our results that open reduction and internal fixation is indicated also for patients over 75 years with distal intraarticular humeral fractures.

Aged↗

[Polytrauma: comparison of the hospital course after air- (with emergency physician) versus ground transport (without emergency physician)].

We analyzed the influence of initial intensive care at the accident site performed by an emergency physician and followed by helicopter transport on the course during hospital stay in patients with multiple trauma. We therefore compared the dates of 107 patients transported by the swiss air rescue (REGA) and an emergency physician with 131 patients transported by an ambulance and paramedic staff. By similar case material the REGA-patients showed a higher injury severity grade. Mortality of the REGA-patients was significantly higher (21%) than of the ambulance-patients (10%), but length of stay was significantly shorter and morbidity identical. We suspect, that the higher mortality of the REGA-patients is explained by the large number of surgically nontreatable severe traumas. None of the REGA-patients arrived at hospital with circulatory insufficiency whereas 4 of the ambulance-patients were in state of shock. We assume that first of all primary treatment of the scene of injury by an emergency physician and eventually also transport by helicopter have a positive effect on the course of patients with multiple trauma during hospital stay.

Adult↗