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Biomedical subjects

G Uhlschmid

Publications and source records attributed to G Uhlschmid.

At least 19 recordsLinked to original sources

Morphological and functional changes in canine kidneys following extracorporeal shock-wave treatment.

Extracorporeal shock-wave lithotripsy (ESWL) has rapidly become established worldwide as a routine method for treatment of nephro- and ureterolithiasis. Although initial studies showed no tissue-damaging effect by the shock waves, we found, in an animal experiment using canine kidneys, that the ESWL-induced damage to the renal parenchyma is more marked than originally assumed. The damage is limited to the area that was focused on, and heals relatively rapidly by connective tissue encapsulation with final cicatrisation without any further residual effects being observed up to the present. This parenchymal damage is probably also the cause of the macrohematuria that is always observed during therapy. The resulting tissue damage is not extensive enough to cause a demonstrable reduction of function as measured by the usual methods (serum creatinine, creatinine clearance, isotopy renography, i.v. urography). In serum we observed a transient decrease of calcium, an immediate increase of lactate-dehydrogenase, transaminases (SGOT and SGPT) and a delayed increase of alkaline phosphates. Creatinine, blood urea nitrogen, sodium, potassium and amylase remained within normal limits. In urine, a decrease of creatinine and an increase of glucose excretion were noted. We believe that these changes represent a relatively mild and transient damage of renal cells and do not reflect the occasionally heavy morphological changes observed after shock-wave exposure. The main clinical complication is the large subcapsular hematoma which, according to the present knowledge, could well result from a lesion of the larger peripheral vessels. Damage to other organs such as subserous colonic and small bowel hematomata are to be expected although they do not lead to clinical symptoms.

Animals

[Experimental aortic aneurysm with endovascular technique].

We created a simple experimental aneurysm by a minimal operative trauma performing the balloon-dilatation and the rupture of the abdominal aorta of animals. The aorta of minipigs was dilated under angiographic control until the rupture became visible. The abdominal aorta and its branches were mapped out and measured. The angiographics were calculated using a planimetric device. The dilatation of the aorta was increased up to 3.5 times the initial diameter when rupture occurred. The microscopical examination showed lesions in all three layers of the vessel only at the rupture site and some focal lesions of the tunica intima. This one-step procedure of producing an experimental aneurysm is done using a low operative trauma and allows testing of endovascular systems using only one anaesthetic.

Aneurysm, Ruptured

[The effect of rejection crises and immunosuppressive therapy on the lymphocyte subpopulations of patients after kidney transplantation].

The lymphocyte subsets in the peripheral blood were examined 3 times a week in 17 patients receiving a cadaveric renal allograft using 2-color flow cytometry and several combinations of monoclonal antibodies. Patients who experienced a rejection crisis (n = 12) had a significantly higher CD4/CD8-ratio (2.72 +/- 1.26 mean +/- SD) than patients with stable graft function (1.76 +/- 1.33, p less than 0.05). 9/12 patients showed 0-3 days prior to the rejection episode an increase of the CD4/CD8- ratio (greater than or equal to 0.5) and/or a high ratio (greater than or equal to 2.5) with a decrease following antirejection therapy. The activation markers HLA-DR and IL-2 receptor on T cells were increased only during 3/12 rejection episodes. Patients with rejections resistant to prednisone pulse therapy (n = 6) had significantly more lymphocytes/mm3 in the peripheral blood (1111.7 +/- 597.5) than successfully treated patients (n = 6, 336.7 +/- 196.0, p less than 0.02). Antirejection therapy with prednisone pulses and/or antithymocyte globuline resulted in a significant decrease of T lymphocytes (CD3+) with a selective reduction of T helper/inducer cells (CD4+). 6 months after renal transplantation the patients had a higher percentage of suppressor/cytotoxic cells (CD8+) compared to the pretransplant values (26.3 +/- 10.9% vs 17.7 +/- 6.2%, p less than 0.02) and blood donors (16.3 +/- 6.2%, p less than 0.01). Furthermore the percentage of T helper cells (CD4+/CD28-) was significantly higher and the T suppressor-inducer cells (CD4+/CD28+) were significantly lower compared to the controls. Serial flow cytometric determinations of lymphocyte subsets in renal allograft recipients may be helpful in some cases although rejection episodes could not be predicted in the individual patient.

Adult

Post-transplant diabetes mellitus in renal allograft recipients: a matched-pair control study.

The incidence of post-transplant diabetes mellitus was evaluated retrospectively in 901 consecutive renal transplant recipients. Thirty-two (3.6%) patients developed diabetes mellitus requiring drug therapy. 18 of 32 became hyperglycaemic within 3 months of transplantation. Post-transplant diabetes mellitus occurred in 24 of 628 (3.8%) patients treated with conventional therapy consisting in azathioprine and prednisone, and in 8 of 273 (2.9%) patients receiving cyclosporin A (CsA) in addition (triple therapy). To identify predisposing factors 32 non-diabetic patients matched for age, sex, number of graft, immunosuppressive protocol, and graft function at onset of diabetes were used as case controls. Thirteen of 32 patients with diabetes mellitus and 5 of 32 control patients had abnormal glucose tolerance pretransplant (P less than 0.025). HLA-B8 was significantly more frequent in patients with post-transplant diabetes mellitus than in control patients (9 of 29 vs 2 of 31, P less than 0.02). Twelve (38%) patients became diabetic during or immediately after anti-rejection therapy with intravenous pulse prednisone. Four diabetic patients experienced chronic pancreatitis pre-transplant. Family history of diabetes mellitus, bodyweight, number of rejection episodes, and immunosuppressive drug doses were similar in both groups. Actuarial patient and graft survival was not significantly different in diabetic patients and controls, although 10-year data tended to be better in controls. Thus, post-transplant diabetes mellitus was not a frequent complication in patients sometimes predisposed by an impaired glucose tolerance pre-transplant and was triggered by pulse prednisone therapy in 38%.

Adult

Injection of microspheres into pancreatic arteries causes acute hemorrhagic pancreatitis in the rat: a new animal model.

Alterations in the vascular bed of the pancreas or disturbances of the blood coagulation system are mostly considered to be sequelae of acute pancreatitis, but it seems that impairment of the pancreatic blood supply can per se lead to acute hemorrhagic pancreatitis. To test this hypothesis with a new animal model, we injected 20 microns polystyrene microspheres retrogradely into the distal splenic artery of rats, thus incompletely blocking blood perfusion in the splenic portion of the pancreas. Eight of eight rats (100%) subjected to microsphere injection developed acute hemorrhagic pancreatitis by 27 h after surgery, when they were killed, but none of the six sham-operated control animals (0%) showed macroscopic signs of pancreatitis. Blood amylase levels at death were 3,087 +/- 650 I.U./L (mean +/- SEM) and the histologic severity score for pancreatitis was 10.8 +/- 1.0 (mean +/- SEM), whereas in the six control rats amylase levels were 1,375 +/- 158 I.U./L and the histology score was only 1.7 +/- 1.0. The result is, with p less than 0.0005, highly significant (chi 2 analysis) and shows that acute experimental pancreatitis can indeed be induced by partially blocking the arterial blood supply within the organ.

Acute Disease

[Callus distraction by an internal bone transport system in unilateral fixation].

The problem of the treatment of bone defects can be solved by distraction osteogenesis as developed by ILIZAROV. This study shows how the bone transport technique can be adapted to every common external fixator while using a new internal distraction system. In 20 dogs a bone defect of 6 cm was performed at the femur. The femur was stabilized with an unilateral frame. A proximal or distal corticostomized bone fragment (length 2.5 cm) was descended through the bone defect (1 mm day). In 15 dogs a new regeneration of bone was observed. The quality of the regenerated bone depends upon stability of the fixation. In 5 dogs with osteotomy and rapid dislocation of the transported fragment no bone bridging was found.

Animals

[Does extracorporeal shock wave lithotripsy injure the female reproductive tract?].

Female reproductive tract lies near the distal ureter where extracorporeal shock wave lithotripsy (ESWL) of calculi is performed. The question whether ESWL may induce morphological changes in ovary, tube or uterus should be investigated in animal experiments. The female reproductive system of 28 Wistar rats was exposed to 600 or 1200 shock waves. After 24 hours or 35 days the animals were sacrificed and examined by light microscopy and scanning electron microscopy (SEM). Acute after ESWL 2/14 rats revealed minimal subcapsular bleeding in the ovaries. SEM showed a desquamation of superficial cells and a loss in microvilli. In long-term groups there was no morphological lesion. Besides the correlation between healthy and atretic follicles were unchanged. In animal experiment no sign of long lasting changes in female reproductive tract after ESWL could be observed.

Animals

[Do shock waves damage the kidney? Morphologic and functional changes of the kidney following exposure to shock waves].

The introduction of extracorporeal shockwave lithotripsy (ESWL) as a routine procedure has brought about a dramatic change in the therapy of urolithiasis. More than 500,000 patients have been treated successfully. Although a tissue damaging effect of the shock wave on the kidney was regarded as non-existent, phenomena such as hematuria during ESWL treatment and subsequent subcapsular hematomas suggest the possibility of damage in the region of the renal parenchyma by the shockwave itself. To investigate this possibility canine kidneys were examined histologically at different intervals after shockwave exposure. Extensive histological changes such as hemorrhage and sometimes direct tubular damage were found, with scar formation after three months. These changes are limited to the areas exposed to ESWL treatment.

Animals

Cyclosporine A impairs wound healing of ureterocystoneostomy in rats. Scanning electron microscopic examination.

The effect of cyclosporine A (CsA), an immunosuppressive agent used in transplantation, on wound healing following microsurgical neoimplantation of a ureter in the bladder of 63 SIV ZUR rats was examined morphologically using the light and scanning electron microscopes and functionally by radiography. Following ureterocystoneostomy (UCN) on the right side, the animals in Group I (control group) received 1.0 ml CsA solvent (0.1 g ethanol and 0.3 g intralipid) per day. Group II received 12.5 mg/kg/day CsA and Group III 17.5 mg/kg/day CsA. All drugs were administered i.p. A third of the animals in each group were reoperated 7, 14 or 28 days after UCN. At these time intervals, there were no radiologically demonstrable differences in the operated side. Examination under the scanning electron microscope indicated delayed restitution of epithelium in the bladder for rats which had received CsA as compared to the control group. In the area of the UCN, CsA caused dose-independent retardation of the regenerative hyperplasia associated with wound healing (Group I: max. 7 days after UCN: Group II and Group III, max. 14 days after UCN). Hyperplastic areas had ropy microridges and uniform short microvilli. Where the hyperplasia exhibited nodular and papillary formation, also histologically more evident under CsA, occasional epithelial cells had pleomorphic microvilli on their luminal surface. Unlike other known premalignant changes of this kind, the frequent occurrence of pleomorphic microvilli under CsA was reversible. In general, CsA led to dose-unrelated protraction of UCN wound healing with no lasting functional disturbance in rats.

Animals

[Experimental pancreatic duct occlusion with polyurethane].

Pancreatic transplantation requires an effective method to manage exocrine secretion. A new technique to eliminate the exocrine function of the pancreas by obstruction of the duct with polyurethane was investigated in terms of function, outcome and morphology. Polyurethane is an alcoholic solution of block copolymers with the property of polymerizing within 5-10 min. In this study the in-situ pancreatic tail model in dogs was utilized, the pancreatic duct was cannulated and injected with 2-3 ml of polyurethane. As a result, complete atrophy and fibrosclerosis of the exocrine tissue was obtained leaving islets well vascularized and functioning for the entire experimental periods. All animals remained normoglycemic and showed normal K-values. Amylase levels were found to be maximally elevated at 24 h and returned to normal within 2 weeks after duct occlusion. Insulin, glucagon and somatostatin levels remained normal. Because of its ability to effect a complete occlusion of the pancreatic ducts with subsequent atrophy of the exocrine gland and without notable disturbance of endocrine function, we feel that polyurethane solution is superior to previously used materials for this purpose.

Animals

Morphological changes in canine kidneys following extra-corporeal shock wave treatment.

Extracorporal shock wave lithotripsy has rapidly become established world wide as a routine method for treatment of nephro- and ureterolithiasis. Although initial studies showed no tissue damaging effect by the shock waves, we found in an animal experiment using canine kidneys, the ESWL induced damage to the renal parenchyma is more marked than originally assumed. The damage is limited to the area that was focused on, and heals relatively rapidly by connective tissue encapsulation with final cicatrisation without any further residual effects being observed until now. This parenchymal damage is probably also the cause of the macrohaematuria that is always observed during therapy. The resulting tissue damage is not extensive enough to cause demonstrable reduction of function as measured by the usual methods (serum creatinine, creatinine clearance, isotopy renography, i/v-urography). The main clinical complication is the large subcapsular haematoma which, according to present knowledge, could well result from a lesion of the larger peripheral vessels. Damage to other organs such as subserous colonic and small bowel haematomata are to be expected although they do not lead to clinical symptoms.

Animals

Intracolonic migration of a pacemaker generator.

Following pacemaker implantation, a 75-year-old male developed a low grade infection of the generator pocket. Utilizing the same generator, several relocations of the generator were made with the result that eventually the pacemaker, eroding the muscular planes, found his way into the ascending colon. Healing could be achieved only after removing the whole pacemaker system. The authors' current policy in case of pacemaker infection is also reported.

Aged

Influence of various prostaglandin synthesis inhibitors on DMH-induced rat colon cancer.

To evaluate the influence of inhibitors of prostaglandin synthesis on the incidence of DMH-induced colon cancer, 90 male Sprague-Dawley rats were randomly assigned to: indomethacin 20 mg per liter drinking water, meclofenamate 50 mg per liter drinking water, or normal drinking water (control group). Dimethylhydrazine was given by weekly subcutaneous injections (20 mg/kg body weight) during the first 20 weeks. Thirty-two weeks after the start of treatment and carcinogen exposure, the animals were killed and examined for the number, size, location, and spread of intestinal tumors. Colon cancer incidence was significantly lower in animals receiving indomethacin (56 per cent) compared with the control group (88 per cent) and with the meclofenamate group (90 per cent) (P less than 0.005). The corresponding figures for tumors in the small intestine were 31, 46, and 35 per cent, respectively. The tumors in indomethacin-treated animals did not differ in number, size, location, or spread from tumors of the other groups, suggesting that indomethacin might influence the carcinogenic process itself, rather than the natural course of the established disease. We conclude that indomethacin significantly reduces the incidence of large-bowel cancer in this animal model and that this observation may have some potential for future chemopreventive studies in human high-risk groups (e.g. ulcerative colitis, familial polyposis).

1,2-Dimethylhydrazine

On the pathogenesis of pancreatic ascites.

The pancreatic ascites of 2 patients and the drainage fluid collected adjacent to the pancreas postoperatively of 1 of them were analyzed for protein composition and enzyme activity. We did not find a proteolytic activity, especially enzymatically active trypsin and chymotrypsin in these fluids. Immunoreactive (inactive) trypsin was, however, present in rather high concentrations. The drainage fluid changed from an inflammatory exudate to a fluid similar in composition to pancreatic juice later on. Our results indicate that pancreatic ascites consist of a combination of enzyme-rich pancreatic fluid and protein-rich exudate from the inflamed pancreas. No evidence of peritonitis or of proteolytic activity capable of inducing peritonitis was found.

Adult