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Biomedical subjects

F Harder

Publications and source records attributed to F Harder.

At least 73 records · Page 4Linked to original sources

Ileocecal interpositional graft as gastric replacement after total gastrectomy and distal esophagectomy.

The ileocecal interpositional graft is an alternative method for replacing the distal esophagus and the stomach. A pedunculated ileocecal interpositional graft rotated 180 degrees clock-wise and placed across the hiatus between the proximal esophagus and the duodenum could act as a reservoir and protect against reflux (ileocecal valve) while preserving the duodenal passage. Two patients underwent this operation (the first patient has been observed for 12 postoperative months). We also used this technique to replace the stomach alone below the diaphragm, a technique that had been abandoned in the surgical literature since 1952, although the concept and initial experiences were already promising at that time. In favor of these attractive features of the ileocecal interpositional graft as gastric replacement, we have begun a controlled examination of this method.

Adenocarcinoma↗

[Incisional hernias].

Incisional hernias are a common complication following abdominal surgery. Surgical treatment as a whole has the disadvantage of having a high recurrence rate. Far better results are obtained by tension-free closure, if necessary backed up by a synthetic prosthesis (PTFE, polypropylene). However, even then, a recurrence rate of about 10% can be expected.

Abdominal Muscles↗

[Agenesis of the gallbladder in adults: a laparoscopic diagnosis].

Failure to find the gallbladder at the usual or most common atypical sites during surgery for cholecystolithiasis is a rare but known problem. Although ultrasonography has 95% sensitivity for the diagnosis of cholelithiasis, occasionally a small contracted gallbladder with stones and chronic cholecystitis will be difficult to visualize and can lead to erroneous interpretation. We report on the case of a patient presenting with abdominal colic and ultrasonographically confirmed cholecystolithiasis. During laparoscopic cholecystectomy, the gallbladder could not be detected. After laparoscopic staging followed by endoscopic retrograde cholangiopancreatography and abdominal computed tomography, agenesis of the gallbladder was confirmed. This method can be considered for diagnosis of gallbladder agenesis without the need for laparotomy and thorough exploration.

Adult↗

Increased surface expression of CD18 and CD11b in leukocytes after tourniquet ischemia during elective hand surgery.

The surface expression of beta2-integrins was investigated in leukocytes from patients undergoing ischemia induced by tourniquet application for elective hand surgery. Blood samples were obtained before initiation, at the end of ischemia, and after 15 minutes of reperfusion from ischemic and contralateral arms of five patients. Comparable expression of CD18, CD11a, CD11b, and CD11c could be detected by immunofluorescence in leukocytes from samples drawn from either arm before tourniquet application. In contrast, a significant increase in the expression of CD18 was detectable in monocytes, granulocytes, and lymphocytes from the ischemic arm compared with that in the nonischemic contralateral control, at the end of the ischemia time (80 +/- 16 minutes). A significantly increased expression of CD11b, but not CD11a or CD11c, determinants was also observed in granulocytes and monocytes. Concomitantly, a significant reduction in the percentages of granulocytes in samples from ischemic areas was detectable. After 15 minutes of reperfusion, differences in the expression of these adhesion molecules were no longer significant. The expression of the genes encoding interleukins IL-1alpha, IL-1beta, and IL-6 and tumor necrosis factor alpha (TNFalpha) proinflammatory cytokines was also studied by reverse polymerase chain reaction (rPCR) in peripheral blood mononuclear cells (PBMCs) obtained from the same samples in three patients. IL-1beta or IL-6 gene expression was never observed. Expression of IL-1alpha and TNFalpha genes, as detected in two patients, was not related with induction of ischemia. However, in these patients expression of one or both these genes was observed in samples derived from the ischemic but not the control arm after 15 minutes of reperfusion. These data document that overexpression of adhesion molecules and sequestration of leukocytes take place following short ischemia times, as routinely applied clinically for minor surgical procedures.

Adult↗

Ileocecal segment transposition does not alter whole gut transit in humans.

OBJECTIVES: We have recently described a reservoir for rectal replacement after total mesorectal excision for rectal carcinoma. The ileocecal segment with its intact extrinsic nerve and blood supply is placed between the ascending colon and the anal canal. This reconstruction has been shown to provide good defecation quality and anorectal function. Whether gastric emptying and small as well as large bowel transit are affected by this transposition remains unclear. Our aim was to quantify whole gut transit in such patients and compare it with that of a matched group of controls. METHODS: Gastric emptying rates and small intestinal and colonic transit times were assessed scintigraphically in 12 patients aged 46 to 87 years with ileocecal reservoir reconstruction after total mesorectal excision and compared to a sex-matched group of asymptomatic healthy volunteers of similar age. Gastric emptying rates and small intestinal and colonic transit times were calculated as described previously. Data were compared using Wilcoxon's signed rank test for gastric emptying rates and small bowel transit or by analysis of variance for colonic transit; p < 0.05 was considered significant. RESULTS: Gastric time for half of the meal (T50) was 161 +/- 16 minutes for patients and 201 +/- 22 for the controls. Small bowel transit time was 150 +/- 15 minutes for patients and 177 +/- 22 for the controls. Geometric center at 6 hours was 1.53 +/- 0.13 for patients and 1.27 +/- 0.16 for the controls. Geometric center at 24 hours was 2.96 +/- 0.23 for patients and 2.57 +/- 0.25 for the controls. Data are mean +/- SEM. SUMMARY: Gastric emptying rates and small bowel transit and colonic transit times (expressed as geometric center at 6 and 24 hours) were similar in patients with ileocecal reservoir reconstruction and in a sex- and age-matched group of healthy controls. We conclude that the transposition of an ileocecal segment with intact extrinsic neurovascular supply between the sigmoid colon and the anal canal does not alter whole gut transit, not even in any of the presumably key regions.

Age Factors↗

Kinetics of high-energy phosphates in allopurinol-pretreated ischaemic and post-ischaemic skeletal muscle: an in vivo magnetic resonance spectroscopy study.

Allopurinol (AP) protects skeletal muscle function against ischaemia-induced injury, but the mechanism is not yet clear. As AP acts as a competitive xanthine oxidase inhibitor, both a reduction of oxygen-derived free radicals and an enhancement of purine resynthesis (salvage pathway) might be involved. We investigated the in vivo kinetics of high-energy phosphates in skeletal muscle after AP pretreatment using 31P-magnetic resonance spectroscopy during 2 h of ischaemia and 3 h of reperfusion in rat hindlimbs. Three animals (group A) were pretreated with a total of 160 mg/kg AP i.p., 3 control animals (group B) received the same amount of 0.9% saline solution. ATP decreased to 18.6 +/- 1.3% of the pre-ischaemic value in group A and to 17.3 +/- 2.8% in group B after 2 h of ischaemia, and rose to only 47.7 +/- 1.5 and 50.5 +/- 1.8%, respectively, after 3 h of reperfusion. Phosphocreatine fell to 7.2 +/- 2.9 and 7.6 +/- 2.2% of pre-ischaemic values after 2 h of ischaemia and rose again to 36.5 +/- 12.9 and 45.4 +/- 20.4% after 3 h of reperfusion. Inorganic phosphate (Pi) increased 5-fold after 2 h of ischaemia, irrespective of the treatment. After 3 h of reperfusion, Pi was still 4 times the pre-ischaemic value. The kinetics of ATP, PCr, and Pi levels were not statistically different between the two groups. These results indicate that the ATP salvage pathway does not play an important role in AP-induced attenuation of ischaemia/reperfusion-induced muscle damage.

Adenosine Triphosphate↗

Heterogeneity of melanoma antigen-1 (MAGE-1) gene and protein expression in malignant melanoma.

OBJECTIVE: The authors' objective is to identify MAGE-1 tumor antigen in clinical melanoma specimens and to verify the extent of its expression in tumors where evidence of specific gene transcripts can be obtained. BACKGROUND DATA: The MAGE-1 gene encodes a tumor-associated antigen that can be recognized by specific cytotoxic T lymphocytes. Transcription of the MAGE-1 gene has previously been demonstrated in various malignancies, but the production of the specific gene product and its distribution in neoplastic tissues have not yet been addressed. METHODS: Total cellular mRNA was extracted from six melanoma biopsies, reverse-transcribed and tested in 25-45 cycles of reverse polymerase chain reaction (rtPCR) in the presence of primers' pairs specific for the beta-actin-positive control gene and for the MAGE-1-encoding gene. Concurrently, portions of these specimens were lysed and probed for MAGE-1 protein by immunoblotting. Additional material from the same biopsies was analyzed following immunohistological staining with MAGE-1-specific monoclonal antibodies. RESULTS: MAGE-1 gene transcription could be demonstrated following 25 cycles of rtPCR in one out of six biopsies and in three more following 35 cycles of rtPCR. 2/6 samples were negative even after 45 cycles of rtPCR. MAGE-1 protein production could be detected by immunoblotting in the lysates from biopsies showing evidence of specific gene transcription. Cells positive for MAGE-1 protein expression could be identified by immunohistochemistry on snap-frozen sections in three of the four tumors displaying specific transcripts. Distribution of positivity ranged between focal cellular areas and single positive cells in the different tumors. CONCLUSIONS: The MAGE-1 tumor antigen can be detected by specific monoclonal antibodies in clinical tumor specimens. The pattern of positivity observed in samples showing evidence of MAGE-1 gene expression suggests a relevant heterogeneity regarding MAGE-1 antigen production within individual tumor specimens.

Antibodies, Monoclonal↗

[Breast preserving therapy of breast carcinoma: analysis of over 1,300 patients treated in the Basel region].

From 1977 to 1994 a total of 1329 breast cancer patients have been treated with breast conserving surgery in the region of Basel. This analysis is based on 832 patients treated from 1977 to 1990 according to a prospective treatment protocol, which was adjusted only once (1985). In comparison with the most known international publications this analysis represents one of the greatest homogeneous series of breast conserving treatment. We observe an overall 5-year survival of 91% and a 10-year survival rate of 77%. 94% of the women remain locally recurrence free at 5 years and 86% at 10 years respectively. At 5 years, freedom of local recurrence totals to 97% in patients without (pN0) and to 89% in patients with tumor involvement of the axillary lymph nodes (pN+) (p = 0.00008), as well as to 96% for pT1 and 91% for pT2-tumors (p = 0.08328). In our analysis the R0-resection significantly influences local recurrence free survival.

Adult↗

[Minimal invasive surgery in breast carcinoma].

The presence or absence of involved axillary lymph nodes is the single best predictor of survival of breast cancer, and important treatment decisions are based on it. For staging purpose as well as for local control a level I and II dissection is recommended. In order to lower the morbidity of axillary lymph node dissection less invasive treatment modalities have been evaluated. Beside the sentinel lymph node biopsy another new method is discussed: the endoscopic axillary lymph node dissection. After liposuction of the axillary fat the lymph nodes of level I and II are removed by endoscopy. With this technique enough lymph node can be removed which allows a sufficient staging as well as local control. This technique is not to be recommended for general use unless long term results have proven its value.

Adult↗

Ileocecal interposition--functional outcome.

Surgery of rectal cancer aims at providing satisfactory quality of life early postoperatively. Low postoperative morbidity and good defecation quality early after rectal reconstruction by means of a reservoir construction are essential conditions for a good quality of life. The clinical results show, that the ileocecal interposition is feasible with a low morbidity and that the majority of patients experience good to excellent defecation quality.

Aged↗

[Kidney transplantation from living donors].

Because of the severe shortage of cadaver organs, the transplantation of living donated organs from related and also from unrelated donors has been suggested; graft survival is similar or better than with cadaver kidneys. Therefore, kidneys from living donors are a large and valuable source for transplantation which help increase the pool of organs and thus decrease the time spent waiting for organ transplantation.

Adult↗

Cytotoxic T-lymphocyte responses against mutated p21 ras peptides: an analysis of specific T-cell-receptor gene usage.

Generation of cytotoxic-T-lymphocyte (CTL) responses against mutated ras peptides from peripheral-blood mononuclear cells (PBMC) was attempted in a group of HLA-A2.1+ healthy donors. Bulk PBMC cultures were stimulated in vitro with a mixture of peptides encompassing 12 Gly --> Val, 61 Gln --> Lys or 61 Gln --> Leu ras mutations and displaying HLA-A2.1 binding motifs, selected by a computer program. A promiscuous tetanus toxoid peptide was also added. Weekly thereafter, PBMC were re-stimulated with peptide pulsed autologous Epstein-Barr virus (EBV)-transformed B cells. After 8 rounds of re-stimulation, reproducible cytotoxic activity against peptide-pulsed target cells was detectable in one donor. The CTL line recognized 2 nonamers encompassing ras 61 Gln --> Leu mutation. Killing was mediated by CD8+ T cells displaying alphabeta TCR and was inhibited by anti-HLA-A2.1 monoclonal antibodies. No killing of tumor cells expressing the specific mutation could be observed. More than 60 CTL clones were generated. Fine specificity studies revealed effective, though differing cytotoxic activity against both 53-LDILDTAGL-61 and 55-ILDTAGLEE-63, but not against 54-DILDTAGLE-62 mutated peptides, in all but one of the clones. None was able to exert effective cytotoxic activity against tumor cells expressing the specific mutation. T-cell-receptor (TCR) usage was then analyzed phenotypically, by reverse-transcription-polymerase-chain-reaction (RT-PCR) and by sequence analysis. This study revealed the monoclonal nature of the CTL response against mutated nonamers, with TCR expressing Vbeta14 gene product in combination with, Jbeta2.7 and Cbeta2.

Amino Acid Sequence↗

Ischemic preconditioning--a new concept in orthopedic and reconstructive surgery.

The duration of tourniquet-induced ischemia during orthopedic and reconstructive surgery is limited by the risk of ischemia and reperfusion injury to skeletal muscle. This study evaluated the potential of ischemic preconditioning (short periods of ischemia with intermittent reperfusion) to improve skeletal muscle function after ischemia and reperfusion in a rodent model. Preconditioning was found to improve force, contractility, and performance and to decrease fatigue of skeletal muscle. In contrast, energy-rich phosphates, measured concurrently, were not affected by preconditioning, suggesting mechanisms other than energy preservation to be involved. In summary, preconditioning may enable prolongation of orthopedic and reconstructive procedures.

Animals↗

[Ischemic preconditioning in surgery of extremities: experimental studies].

Ischemic preconditioning (IP), using one or more brief periods of ischemia, each followed by a short reperfusion phase, improves tolerance of subsequent sustained ischemia in different organs. The aim of this experimental study was to evaluate the effects of IP on postischemic function in skeletal muscle. Right hindlimbs of anesthetized rats were pretreated with three cycles each of 10 min of ischemia and 10 min of reperfusion (n = 12). Non-preconditioned animals (n = 12) served as controls. These hindlimbs were then subjected to 3 h of ischemia and 2 h of reperfusion. IP resulted in a significant increase in postischemic skeletal muscle force (240 +/- 47 mN vs 409 +/- 63 mN), force-time integral (1081 +/- 242 mN*s vs 2546 +/- 481 mN*s) and endurance (29.6 +/- 3.4 s vs 48.0 +/- 5.0 s). These data support the potential of IP to reduce postischemic skeletal muscle damage in surgery of the extremities using tourniquet ischemia. The concept deserves clinical evaluation.

Animals↗

Nitric oxide-independent inhibitory effects of L-arginine analog NG-monomethy-L-arginine on the generation of interleukin-2 activated cytotoxic activity in humans.

Nitric oxide (NO) derived intracellularly from L-arginine (Arg) is indispensable for optimalgeneration of lymphokine-activated killer (LAK) cell activity in rodents. Still unclear, however, is its role in humans. To address this question human peripheral blood mononuclear cells (PBMC) from healthy donors were cultured in L-arginine free medium supplemented with recombinant interleukin-2 (rIL-2) and in the presence of exogenous L-arginine analog NG-monomethyl-L-arginine (NMMA), a specific inhibitor of the NO synthetic pathway. Cultured PBMC were tested for cytotoxic activity, proliferative capacity, and expression of phenotypic and activation markers (CD3, CD4, CD8, CD16, CD56 and CD25). Culture supernatants were assayed for nitrite (NO2-) and tumor necrosis factor-alpha (TNF-alpha) production. We found that NMMA inhibits the generation of optimal LAK cell activity when no exogenous Arg is supplied. Similar effects were also observed on proliferation, expression of IL-2 receptor induced upon rIL-2 stimulation and on TNF-alpha production. Sodium nitroprusside (SNP), used as a source of exogenous NO could not overcome this effect of NMMA on LAK cell activity. NO2- production was virtually undetectable in culture supernatants. Thus, NMMA affects in an NO-independent manner rlL-2 induced LAK activity in human PBMC.

Journal Article↗