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Biomedical subjects

F Harder

Publications and source records attributed to F Harder.

At least 91 records · Page 5Linked to original sources
PubMed1996

Comparison of cyclosporin A absorption from LCT and MCT solutions following intrajejunal administration in conscious dogs.

Absorption from the intestine of cyclosporin A (CsA), dissolved in either a medium-chain (MCT) or a long-chain triglyceride (LCT) solution, was investigated in a chronic dog model. Following intrajejunal administration of 20 mg of CsA/kg of body weight, absorption, judged by the portalvenous appearance of CsA, was determined by measuring whole blood CsA concentrations in the portalvenous and arterial blood and the portalvenous flow. Appearance of CsA from LCT commenced earlier and attained significantly higher mean peak values (+/- SEM) in the portalvenous blood (2557 +/- 436 ng/mL) than from MCT (274 +/- 80 ng/mL). Portalvenous concentrations of CsA were always higher than arterial concentrations for both LCT and MCT, suggesting that CsA is transported by portalvenous blood following uptake from the gut. Absorption of CsA, measured over 300 min, was 10 times higher with LCT (9.96 +/- 2.00%) than with MCT (0.95 +/- 0.21%). This significant difference is believed to result from the formation of mixed micelles which occurs during digestion of LCT but not MCT.

Animals↗
PubMed1996

Splenectomy as an adjuvant measure in the treatment of severe aplastic anaemia.

The role of splenectomy in aplastic anaemia (AA) is controversial. The hazards of operating on a severely pancytopenic patient, the fear of compromising the patient's immune function, and the improvement of non-surgical treatment have made splenectomy unpopular in this disease. We have evaluated positive and adverse effects of splenectomy in 80 patients with severe aplastic anaemia (SAA) treated with antilymphocyte globulin (ALG) (group A), using 52 nonsplenectomized ALG patients as controls (group B). All patients survived the operation. Nonfatal complications of surgery occurred in 10 (12.5%). Splenectomy induced a significant increase of peripheral blood neutrophils, reticulocytes and platelets within 2 weeks, followed by a continuous increase of all values over the following weeks. 28/132 patients (21%) developed a late clonal disorder of haemopoiesis, paroxysmal nocturnal haemoglobinuria (PNH) or myelodysplastic syndrome (MDS), or both. Their incidence was identical in groups A and B. 13/28 (59%) died, 10/17 (59%) in group A and 3/11 (27%) in group B (not significant (n.s.)). Overall probability of survival at 18 years after ALG was 51+/-6% for group A and 61+/-7% for group B (n.s.). We conclude that splenectomy in AA is safe. It induces an immediate increase of peripheral blood counts and, thereafter, a continuous improvement of haemopoiesis. It does not increase the incidence of late clonal complications but has a borderline effect on mortality from these disorders. Splenectomy should be reconsidered in selective nontransplanted patients who have prolonged transfusion requirements despite otherwise optimal treatment.

Adolescent↗
PubMed1996

Effects of verapamil on skeletal muscle function following ischemia and reperfusion.

Verapamil (VRP) improves ischemic tolerance of different organs including brain, kidney, liver and heart. We report here on the effects of preischemic VRP treatment on skeletal muscle function following 3 h of tourniquet ischemia and 2 h of reperfusion using a rodent model. Postischemic and contralateral limbs were evaluated. Fast (musculi peronei)- and slow-twitch muscles (musculus soleus) of both limbs were excised and electrically stimulated in vitro. VRP pretreatment was found to significantly decrease tetanic peak tension of both contralateral nonischemic m. soleus and mm. peronei. Furthermore, VRP improved fatigability of slow-twitch muscles of both ischemic and contralateral limbs [increase of fatigue index from 0.04 +/- 0.009 (0 mg/kg) to 0.10 +/- 0.019 (4 mg/kg)], but not of fast-twitch muscles. These data indicate that the effects of VRP on postischemic skeletal muscle function depend on fiber composition.

Animals↗
PubMed1996

Ischemic preconditioning improves post-ischemic skeletal muscle function.

Ischemic preconditioning (IP), using one or more brief periods of ischemia before a sustained ischemia, represents a new approach to reduce tourniquet ischemia-induced skeletal muscle damage. The aim of this study was to investigate the effect of IP on skeletal muscle function and high-energy phosphate tissues levels in a rodent model. IP protocols using one, two, or three preconditioning cycles were compared. IP was found to significantly improve force, performance, endurance, and contractility of postischemic skeletal muscle. The efficacy of IP-induced protection was correlated with the number of preconditioning cycles. Preconditioning with three cycles resulted in a more effective protection as compared to one or two cycles. Three cycles of IP significantly improved force (409 +/- 63 versus 240 +/- 47 mN), performance (2546 +/- 481 versus 1081 +/- 242 mN*sec), endurance (46.7 +/- 5.0 versus 29.6 +/- 3.4 sec) and contractility (59.9 +/- 4.2 versus 38.7 +/- 5.1) in postischemic m.extensor dig. long. when compared to nonpreconditioned muscles. In contrast, high-energy phosphate tissue levels remained unchanged after three cycles of preconditioning. Altogether, this study describes, for the first time, the efficacy of IP to improve postischemic muscle function. The respective clinical potential warrants further exploration.

Animals↗
PubMed1996

[laparoscopic cholecystectomy and acute cholecystitis--feasibility and morbidity].

This quality control study was devised to establish, wether laparoscopic cholecystectomy is recommendable for acute cholecystitis. Of 314 prospectively recorded laparoscopic cholecystectomies 59 were done for histologically proven acute cholecystitis within 3 years. 29 cases (49.2%) were converted to open cholecystectomy due to unsatisfactory exposure and recognition of anatomical structures or haemorrhage. Morbidity with laparoscopic cholecystectomy without conversion was 16.6% (5/30 patients), mortality zero. There were no common bile duct injuries. Our results show that, if the operation is performed by an experienced laparoscopic surgeon or under one's supervision, laparoscopic cholecystectomy for acute cholecystitis is safe. A low threshold for converting to open laparotomy must be observed particularly when anatomical structures are not clearly identified.

Acute Disease↗
PubMed1996

[Mesenteric venous thrombosis (MVT): a problem in diagnosis and management].

The mesenterial venous thrombosis is a rare and independent cause of intestinal ischemia. 5 to 15% of all intestinal ischemias are due to venous problems. The lack of specific clinical symptoms and laboratory data often leads to a delayed diagnosis with irreversible intestinal infarction. Only by thorough searching by means of modern diagnostic devices is it possible to make an early diagnosis and treat the ischemic situation timely. Several therapeutical options are at hand. A timely and adequate application of these aids mostly depends on the clinical experience of the medical team as well as on an optimal interdisciplinary collaboration (radiology, hematology, angiology, gastroenterology, surgery). We want to analyze the problems related to diagnostics and management on the basis of 2 cases with different manifestations of a mesenterial venous thrombosis. We ascertain that: (1) the enhanced-CT analysis and/or the duplex-sonography mostly lead to a diagnosis, (2) the prognosis benefits from an immediate heparinization, (3) the request for large-scale intestinal resection, keeping a safety-space, has been replaced by the technique of limited resection, followed by earlier second-look-operations.

Adult↗
PubMed1995

Peptide-specific CTL in tumor infiltrating lymphocytes from metastatic melanomas expressing MART-1/Melan-A, gp100 and Tyrosinase genes: a study in an unselected group of HLA-A2.1-positive patients.

Peptide specificity of cultured tumor-infiltrating lymphocytes (TIL) was systematically investigated in a group of HLA-A2.1+ metastatic melanoma patients consecutively referred to our department for surgical treatment. Seven samples from 6 patients were studied. All surgical specimens showed evidence of gp 100, MART-1/Melan-A and Tyrosinase gene expression as detectable by reverse PCR (rPCR). Cultured TIL from 2 patients displayed cytotoxic activity against autologous or HLA-matched EBV-transformed cells previously pulsed with MART-1/Melan-A27-35 peptide. In contrast, no CTL activity against gp100(280-288) or tyrosinase1-9 peptides could be observed. TIL were then repeatedly stimulated in vitro with the same peptides. After 6 restimulation courses at weekly intervals, specific recognition of gp100(280-288) and MART-1/Melan-A peptides was detectable in 3 and 5 TIL populations, respectively. In one case Tyrosinase1-9-specific CTL could be demonstrated. Two TIL populations from metastases resected from a melanoma patient at 6 months' distance showed a different peptide specificity pattern, and no specific CTL could be generated from simultaneously sampled peripheral blood mononuclear cells (PBMC). All peptide-specific CTL populations also displayed significant cytotoxic activity against HLA-A2.1 matched melanoma cell lines expressing the antigens under investigation. Our data indicate that CTL specific for MART-Melan-A27-35, gp100(280-288) or Tyrosinase1-9 peptides could be expanded with varying frequency from TIL derived from 4 out of 6 HLA-A2.1+ patients whose tumors expressed the genes encoding these tumor-associated antigens (TAA).

Adult↗
PubMed1995

[Laparoscopic adrenalectomy in pheochromocytoma].

Standard adrenalectomy for pheochromocytoma was until recently performed via the transperitoneal open approach. The disadvantage of the open procedure is a more painful and longer recovery. With good surgical experience in laparoscopic techniques and in endocrine surgery, laparoscopic adrenalectomy can be performed safely without complications. The advantage of the laparoscopic technique is excellent vision of the operative field with magnification even of very small vessels. The first two cases of laparoscopic right adrenalectomy at our institution are described.

Adrenal Gland Neoplasms↗
PubMed1995

Identification and intracellular location of MAGE-3 gene product.

The human MAGE-3 gene encodes a melanoma antigenic epitope recognized by specific cytotoxic T lymphocytes, but its gene product has not been identified thus far. We produced a recombinant MAGE-3 gene product by expression cloning of the entire reading frame in the context of a fusion protein characterized by a 10-histidine tail, allowing purification by metal chelation on a nickel Sepharose column. The semipurified product was used to generate MAGE-3-specific monoclonal antibodies. One reagent could identify by immunoblotting the native MAGE-3 gene product as a M(r) 48,000 protein in lysates of cell lines showing evidence of MAGE-3 gene expression. No apparent cross-reactivity with recombinant or native MAGE-1 gene product was observed. Immunohistochemistry shows that, closely resembling the MAGE-1 gene product, MAGE-3 is a cytoplasmic protein.

Animals↗
PubMed1995

[Sphincter-conserving surgery in tumors of the middle and distal rectum: methods, indications and limitations].

The purpose of this review is to summarize new developments in the surgical treatment of benign and malignant tumors of the rectum, focusing on oncological requirements and postoperative functional aspects which affect the quality of life. One of the developments is the transanal endoscopic microsurgical (TEM) approach to resection of adenomas and low risk early cancers in the rectum. Another focus is total rectum resection with colo-anal reconstruction with a colon pouch. This procedure reconstructs anorectal anatomy and provides nearly normal function. The reconstruction exists in two forms, (a) the colon-J-pouch and (b) the ileocecal interposition pouch (cecum pouch), which was developed at our institution. The review includes 33 consecutive patients with a rectum tumor. Standardized tumor-specific and functional staging determines which technique is used. 12 patients were operated on using the transanal endoscopic approach, 3 patients had a posterior proctotomy, another patient a transanal local excision and 17 patients total rectum resection with colon pouch reconstruction as described above.

Aged↗
PubMed1995

Expression of HLA-DR in granulocytes of polytraumatized patients treated with recombinant human granulocyte macrophage-colony-stimulating factor.

MHC class II determinants are the restriction elements involved in antigen-specific activation of helper T lymphocytes and interaction with CD4 molecules. They are typically expressed on a limited number of cell types, mostly endowed with antigen-presenting capacity. Recently, expression of HLA-DR has been detected on granulocytes stimulated "in vitro" with GM-CSF. However, no evidence of "in vivo" expression in humans has been presented so far. We report here that class II determinant expression is detectable in vivo on peripheral blood granulocytes of polytraumatized patients upon intravenous administration of rhGM-CSF. Expression of these molecules appears to be an early effect of rhGM-CSF treatment, independent from endotoxemia or endogenous production of IL-6 or TNF-alpha, and rapidly declining upon discontinuation of therapy. Thus, this treatment might increase the number of cells potentially capable of presenting class-II-restricted antigens in these patients.

Adult↗
PubMed1995

Parathyroidectomy in primary hyperparathyroidism: preoperative localization and routine biopsy of unaltered glands are not necessary.

BACKGROUND: An assessment was made of operative risk and outcome after parathyroidectomy for primary hyperparathyroidism. METHODS: A retrospective study was conducted in a single center university hospital in Switzerland. The 173 patients (130 women and 43 men) ranged from 17 to 89 years of age (mean, 62.0 years). No routine preoperative localization methods were used for primary neck exploration. Parathyroidectomy was performed under general anesthesia. No routine use was made of intraoperative biopsy of glands whose macroscopic appearance was normal. The 173 patients underwent 179 operations (170 primary and 9 secondary interventions). Resection of a single gland was performed in 127 cases (73.4%) and of two glands in 36 cases (20.8%). Subtotal parathyroidectomy (3 1/2 glands) was performed in 10 cases (5.8%). RESULTS: Of 170 patients with primary intervention, 164 (96.5%) were normocalcemic after operation. Six of 170 patients (3.5%) underwent early reexploration. Three additional patients underwent late secondary procedures. These nine secondary operations were successful in seven patients (78%). At follow-up (mean, 24.7 months after operation) normocalcemia was noted in 163 of 171 patients (95.3%). Persistent and recurrent hyperparathyroidism occurred in 1.2% and 3.5% of patients, respectively. Permanent postoperative hypoparathyroidism was noted in 4% (six of seven patients underwent a subtotal parathyroidectomy for multiglandular hyperplasia). Operative morbidity and mortality were 2.3% and 0.6%, respectively. CONCLUSIONS: Our surgical strategy for treatment of primary hyperparathyroidism has proved to be safe with a favorable outcome in more than 95% of patients. This was possible without the routine use of preoperative localization studies and intraoperative biopsy of macroscopically normal glands. Routine biopsy of normal-appearing glands seems to be unnecessary and may increase the risk of hypoparathyroidism.

Adolescent↗
PubMed1995

[Small bowel injuries in blunt abdominal trauma--a diagnostic problem!].

AIMS: Injuries of the small bowel following a blunt abdominal trauma are rare (incidence 6%). The diagnosis is difficult and therefore often missed. The aim of this paper is to acquire an useful diagnostic sequence of our own results in comparison to the literature. METHODS: The diagnostic procedures and the time of the final diagnosis of 13 patients with this rare injury have been retrospectively analysed. RESULTS: Two of these 13 patients died in the emergency room. Five of the remaining 11 patients had signs of peritonitis at the first examination. These were confirmed by findings either in peritoneal lavage (3), ultrasound (1) or X-ray (1). Patients without signs of peritonitis revealed no pathological signs at the first examination with these diagnostic tools. Correct diagnosis was achieved on 7/11 patients within 24 hours. The diagnosis of small bowel injury was confirmed by the rest of the patients (n = 4) after an average of 11 days after trauma. DISCUSSION/CONCLUSION: Initial assessment with diagnostic tools as ultrasound, peritoneal lavage or X-ray is poor. Therefore repetitive controls (Nowadays by ultrasound) are indicated. The CT is a valuable tool to detect an organ lesion in hemodynamic stable patients with positive proof of liquid in the ultrasound. Today the value of the diagnostic laparoscopy is not established. It should be considered that a local ischemia due to the blunt trauma can cause a delayed perforation.

Abdomen↗
PubMed1995

Tyrosine kinase-dependent and -independent events induced by interleukin-2 stimulation: interleukin-2-mediated NO production required for the induction of lymphokine-activated killer cell activity in rat splenocytes is tyrosine kinase independent.

Nitric oxide (NO) has recently been shown to be an indispensable co-factor in the generation of lymphokine-activated killer (LAK) cells induced by interleukin-2 (IL-2). Upon stimulation with IL-2, cells endowed with specific receptors undergo phosphorylation of substrates mediated by protein tyrosine kinases (PTK). In this work we utilized a well-characterized PTK inhibitor, genistein (GEN), to address the role of PTK on NO-dependent LAK cell generation. The effects of GEN were tested on the expression of the inducible NO synthase (iNOS) gene, proliferation, generation of cytotoxic activity and production of NO upon IL-2 stimulation of rat splenocytes. We report here that GEN displays profound inhibitory effects on recombinant (r)IL-2 induced proliferation and on LAK cell generation, while only marginally affecting NO production, measured as NO2-. In contrast, a specific inhibitor of the NO synthetic pathway (NG-monomethyl-L-arginine; NMMA) blocked generation of LAK cells and NO production without affecting cell proliferation. If added directly to the cytotoxicity tests, GEN exerted minor inhibitory effects, not exceeding 25% of control tests, while NMMA was completely ineffective. Sodium nitroprusside (SNP), a non-enzymatic NO-releasing substance, restored LAK cell generation in cultures performed in the presence of NMMA, but not in those performed in the presence of GEN. These results indicate that IL-2-induced NO production is a PTK-independent event. IL-2-stimulated LAK cell generation obligatorily requires the concurrent activation of PTK dependent and independent signal transduction pathways.

Animals↗
PubMed1995

[Local treatment of breast carcinoma: when is breast-saving therapy not indicated?].

Conservative treatment of breast cancer is now an accepted oncological procedure. It further allows a good functional and cosmetic result. This treatment needs more skills and time than mastectomy, as it does not only include a surgical excision but also a postoperative local radiotherapy and a sometimes difficult follow-up during many years. The contraindications for conservative breast cancer therapy are numerous and depend on factors as tumor, patient and radiotherapy. As more than 1100 patients have been treated since 1977 in our area at a single radiooncological center by a breast conserving procedure. We have confirmed or defined criteria which lead to a good local tumor control as well as to good functional and cosmetic results.

Breast Neoplasms↗
PubMed1995

[Functional and morphological results of transplantation of vascularized knee joints in a dog model--a preliminary report].

Functional and morphological results of transplantation (n = 3) and replantation (n = 4) of vascularised total knee joints were compared in a canine model. Follow up time was 6 months. All vascular anastomoses remained patent and all osteotomies healed. Replanted animals displayed normal static weight bearing in contrast to the transplant recipients, which showed reduced weight bearing after 6 months compared to preoperative values. Mild to moderate signs of chronic allograft rejection were detected in all transplanted animals. Functional results were correlated with morphological outcome demonstrating the relevance of adequate control of rejection.

Animals↗
PubMed1994

MAGE-1 gene product is a cytoplasmic protein.

MAGE-1 gene encodes a human melanoma antigen, recognized by syngeneic cytotoxic T lymphocytes (CTL). MAGE-1 transcripts are also detectable in breast cancers, in non-small-cell lung carcinomas and in central nervous system tumors. In order to identify, in cellular preparations, the protein encompassing the antigenic peptide, we generated a panel of monoclonal antibodies (MAbs) against the MAGE-1 gene product by using, as immunogen, a full-length recombinant preparation (rMAGE-1), obtained through expression cloning of the relevant gene in E. coli. Four reagents were obtained recognizing both rMAGE-1 and the 46-kDa native protein in cell lines expressing MAGE-1 mRNA. No positivity could be detected in MAGE-1-mRNA-negative melanoma lines. No surface labelling of MAGE-1-positive cell lines could be observed. In contrast, on permeabilization of MZ2 melanoma cells, all 4 MAbs induced efficient staining, as detected by cytofluorography. Fluorescence microscopy shows that MAGE-1 gene product is a cytoplasmic protein clustered in paranuclear organelle-like structures. Thus, MAGE-1 protein location closely resembles that of P91A and P198 murine-tumor antigens.

Animals↗