[Laparoscopic-assisted colonoscopic polypectomy--indications and results]. / Laparoskopisch-koloskopische Rendezvousverfahren--Indikationen und Ergebnisse.

OBJECTIVE: Endoscopic treatment of large, sessile or awkward localized polyps, especially in the colon sigmoideum or the coecum holds the risk of colonic perforation. For these cases the combined colonoscopic-laparoscopic approach is described in this publication as an alternative procedure. PATIENTS AND METHODS: Since 1995 23 patients (male 11, female 12, age 70.7 +/- 12.0 years) were treated by laparoscopic-assisted colonoscopic polypectomy. Thirteen polyps were localized in the colon descendens or sigmoideum, seven in the cecum and one in the right respectively the left colonic flecture. Under general anesthesia and modified lithotomy position laparoscopy with occlusion of the colon or terminal ileum was followed by colonoscopy. After endoscopic localization the polyp was removed under laparoscopic visualization. During this procedure the colonic wall was stabilized, interfering adhesions were cut and coagulation- induced lesions of the wall were laparoscopically sutured if needed. RESULTS: In 17 patients the endoscopic polypectomy could be performed laparoscopically-assisted. In two patients the polypectomy was done by colotomy and in two others by segmental colonic resection due to the volume of the polyp. In two patients with histologically verified carcinoma laparoscopic-assisted left hemicolectomy was performed secondarily. Intra- or perioperative complications did not occur. CONCLUSION: Laparoscopic-assisted colonoscopic polypectomy is a new minimal-invasive therapeutical approach in selected cases with large, sessile or arkward localized polyps. The endoscopic procedure is possible also in polyps which should be treated by colotomy or segmental resection in the past. The additional discomfort for the patients due to laparoscopy is minimal.

C57BL/6J-T-associated sex reversal in mice is caused by reduced expression of a Mus domesticus Sry allele.

C57BL/6J-T-associated sex reversal (B6-TAS) in XY mice results in ovarian development and involves (1) hemizygosity for Tas, a gene located in the region of Chromosome 17 deleted in T(hp) and T(Orl), (2) homozygosity for one or more B6-derived autosomal genes, and (3) the presence of the AKR Y chromosome. Here we report results from experiments designed to investigate the Y chromosome component of this sex reversal. Testis development was restored in B6 T(Orl)/+ XY(AKR) mice carrying a Mus musculus Sry transgene. In addition, two functionally different classes of M. domesticus Sry alleles were identified among eight standard and two wild-derived inbred strains. One class, which includes AKR, did not initiate normal testis development in B6 T(Orl)/+ XY mice, whereas the other did. DNA sequence analysis of the Sry ORF and a 5' 800-bp segment divided these inbred strains into the same groups. Finally, we found that Sry is transcribed in B6 T(Orl)/+ XY(AKR) fetal gonads but at a reduced level. These results pinpoint Sry as the Y-linked component of B6-TAS. We hypothesize that the inability of specific M. domesticus Sry alleles to initiate normal testis development in B6 T(Orl)/+ XY(AKR) mice results from a biologically insufficient level of Sry expression, allowing the ovarian development pathway to proceed.

Evidence that Sry is expressed in pre-Sertoli cells and Sertoli and granulosa cells have a common precursor.

The expression of Sry in the undifferentiated, bipotential genital ridges of mammalian XY fetuses initiates testis development and is hypothesized to do so by directing supporting cell precursors to develop as Sertoli cells and not as granulosa cells. To directly test this hypothesis, transgenic mice expressing EGFP under the control of the Sry promoter were produced. After establishing that the transgene was expressed in fetal gonads similarly to endogenous Sry, the spatial and temporal expression of the Sry-EGFP transgene was investigated in developing gonads by using confocal microscopy and immunofluorescent histochemistry. This analysis indicated: (1) Sry is first expressed in cells located centrally in the genital ridge and then later in cells located at the cranial and caudal poles, (2) Sry is expressed exclusively in pre-Sertoli cells in the urogenital ridge, and (3) Sertoli and granulosa cells develop from a common precursor. These results support the hypothesis that Sry initiates testis differentiation by directing the development of supporting cell precursors as Sertoli rather than granulosa cells. Furthermore, the Sry expression pattern explains the nonrandom distribution of testicular and ovarian tissue in mammalian ovotestes.

Conversion from cyclosporine A to tacrolimus after kidney transplantation due to hyperlipidemia.

As more than 90% of renal grafts retain their function 1 year after renal transplantation, side effects of immunosuppressive therapy gain more and more importance. In a randomised prospective study, we investigated the effects of conversion from cyclosporine A to tacrolimus due to hyperlipidemia in recipients of renal allografts. Fifty-seven patients with stable graft function treated with cyclosporine were randomly assigned to conversion to tacrolimus or continuation of their current therapy and followed for 1 year. Twenty-seven patients were switched and 30 patients remained on cyclosporine A. Cholesterol levels decreased significantly in the tacrolimus group as compared to controls in the intent to treat analysis. When only those patients were evaluated who received cyclosporine or tacrolimus during the whole study, statistical significance was even more pronounced. Triglyceride levels decreased in the tacrolimus group, whereas they increased in controls. Creatinine levels remained stable and no acute rejection was observed. A switch to tacrolimus is a safe alternative in cases of hyperlipidemia after renal transplantation.

Related function of mouse SOX3, SOX9, and SRY HMG domains assayed by male sex determination.

Sox genes encode proteins related to each other, and to the sex determining gene Sry, by the presence of a DNA binding motif known as the HMG domain. Although HMG domains can bind to related DNA sequences, Sox gene products may achieve target gene specificity by binding to preferred target sequences or by interacting with specific partner proteins. To assess their functional similarities, we replaced the HMG box of Sry with the HMG box of Sox3 or Sox9 and tested whether these constructs caused sex reversal in XX mice. Our results indicate that such chimeric transgenes can functionally replace Sry and elicit development of testis cords, male patterns of gene expression, and elaboration of male secondary sexual characteristics. This implies that chimeric SRY proteins with SOX HMG domains can bind to and regulate SRY target genes and that potential SRY partner factor interactions are not disrupted by HMG domain substitutions. genesis 28:111-124, 2000.

Defective mesonephric cell migration is associated with abnormal testis cord development in C57BL/6J XY(Mus domesticus) mice.

During the critical period of mouse sex determination, mesenchymal cells migrate from the mesonephros into the adjacent developing testis. This process is thought to initiate cord development and is dependent on Sry. The presence of Sry, however, does not always guarantee normal testis development. For example, transfer of certain Mus domesticus-derived Y chromosomes, i.e., M. domesticus Sry alleles, onto the C57BL/6J (B6) inbred mouse strain results in abnormal testis development. We tested the hypothesis that mesonephric cell migration was impaired in three cases representing a range of aberrant testis development: B6 XY(AKR), B6 XY(POS), and (BXD-21 x B6-Y(POS))F1 XY(POS). In each case, mesonephric cell migration was abnormal. Furthermore, the timing, extent, and position of migrating cells in vitro and cord development in vivo were coincident, supporting the hypothesis that mesonephric cells are critical for cord development. Additional experiments indicated that aberrant testis development results from the inability of Sry(M. domesticus) to initiate normal cell migration, but that downstream signal transduction mechanisms are intact. These experiments provide new insight into the mechanism of C57BL/6J-Y(M. domesticus) sex reversal. We present a model incorporating these findings as they relate to mammalian sex determination.

Migration of mesonephric cells into the mammalian gonad depends on Sry.

In mammals, the primary step in male sex determination is the initiation of testis development which depends on the expression of the Y-linked testis determining gene, Sry. The mechanisms by which Sry controls this process are unknown. Studies showed that cell migration from the adjacent mesonephros only occurs into XY gonads; however, it was not known whether this effect depended on Sry, another Y-linked gene, or the presence of one versus two X chromosomes. Here we provide genetic proof that Sry is the only Y-linked gene necessary for cell migration into the gonad. Cell migration from the mesonephros into the differentiating gonad is consistently associated with Sty's presence and with testis cord formation, suggesting that cell migration plays a critical role in the initiation of testis cord development. The induction of cell migration represents the earliest signaling pathway yet assigned to Sry.

Do urinary tract infections trigger chronic kidney transplant rejection in man?

PURPOSE: Urinary tract infections are frequent after kidney transplantation but little is known about the impact on long-term survival. As chronic rejection is the major cause of graft loss in the long term, we retrospectively analyzed the role of urinary tract infections in this process. MATERIALS AND METHODS: We included in the study all adult patients who received kidney transplants at our unit between 1972 and 1991, which ensured followup of at least 5 years, and we focused on the relationship between urinary tract infections and the incidence of chronic rejection episodes. To analyze the influence of urinary tract infections on chronic rejection patients were separated into those in whom biopsy proved chronic rejection developed within the first 5 years after transplantation (chronic rejection group 225) and those without apparent signs of chronic rejection during that period (control group 351). The correlation between urinary tract infections per year and the incidence of chronic rejection was analyzed. RESULTS: Patients with chronic rejection had more urinary tract infections per year than controls. In the first year after transplantation both groups had the highest incidence of urinary tract infections but thereafter the rate of urinary tract infections per year declined. However, the incidence consistently remained higher in the chronic rejection group. This difference reached significance by year 3 after transplantation. Furthermore, a high rate of urinary tract infections correlated with an early onset of chronic rejection. CONCLUSIONS: Urinary tract infections are an important risk factor for the onset of chronic rejection, and early and intense treatment is critical.

[Surgical management of ruptured abdominal aortic aneurysm--diagnosis, risk factors and prognosis]. / Chirurgische Versorgung des rupturierten Bauchaortenaneurysmas--Diagnose, Risikofaktoren und Prognose.

It has been observed that the number of emergency operations for ruptured abdominal aortic aneurysms (AAA) is still high, as is the corresponding mortality. With the aim to determine how pre-clinical as well as clinical factors affect survival of patients with perforated AAA, we examined the course of patients admitted with perforated AAA in the last six years. Retrospectively we assessed the following documented parameters: patient's age, pre-clinical interval between onset of symptoms and hospitalization, the preoperative circulatory situation, hospital resuscitation period before surgery, the duration of aortic cross-clamping and the need of intraoperative blood transfusions in relation to the hospital mortality. In the period between 1.1.1990-31.12.1995, 39 patients with ruptured abdominal aortic aneurysms were operated on emergency basis in the Department of General Surgery of the University of Essen. There were 36 men and 3 women. The average age was 69.1 years. 25 patients (64%) died on admission, 4 of them intraoperatively. The most relevant observed prognostic factors were the preoperative circulatory status (systolic blood pressure p < 0.0001; hemoglobin p < 0.01) as well as the intraoperative blood transfusion requirement (p < 0.01) In view of the high mortality associated with surgical treatment of ruptured AAA and with the difficulty to decisively influence the relevant prognostic factors, early elective surgery of asymptomatic patients with AAA is highly recommended.

Prevalence of diverticulosis and incidence of bowel perforation after kidney transplantation in patients with polycystic kidney disease.

Sigmoid perforation due to diverticulitis is a life-threatening complication in the postoperative course of allogenic kidney transplantation. The incidence of diverticulosis is especially high among patients with autosomal dominant polycystic kidney disease (ADPKD). Thus, those who undergo allogenic kidney transplantation represent a high-risk group. The aim of this study was to evaluate the prevalence of diverticulosis in ADPKD patients awaiting renal transplantation and the incidence of bowel perforation following allogenic kidney transplantation due to ADPKD. Within the group of 1128 patients who underwent transplantation between January 1974 and January 1990, there were 46 patients (4.07%) whose indication for transplantation was ADPKD. There was one patient who developed a sigmoid perforation under postoperative immunosuppression. Surgical treatment was a discontinuity resection of the sigmoid (Hartmann's procedure). The postoperative course was favorable, the bowel continuity has already been restored, and the graft is still functioning well. Fifteen of the 28 (53.5%) ADPKD patients awaiting transplantation had colon diverticulosis (12 male and 3 female patients). No case of bowel perforation has thus far been observed in 15 of these patients who have undergone transplantation. A sigmoid resection was necessary in one patient due to diverticulitis without perforation. We did not find a higher prevalence of diverticulosis in patients with ADPKD, nor did we see a higher incidence of sigmoid perforation during post-transplant immunosuppression in this study.

Metabolic factors have a major impact on kidney allograft survival.

BACKGROUND: At the present time, late graft loss is the major cause of kidney failure after transplantation. However, the influence of metabolic factors on this process is ill-defined. METHODS: To identify the impact of lipid metabolism, glucose metabolism, and blood pressure and their prognostic value for graft survival, data for all recipients of a kidney allograft with a potential graft survival of >15 years and a minimum graft survival of 1 month were analyzed retrospectively. Recipients of kidney grafts functioning more than 15 years (n=32) were compared with those with a graft function of less than 10 years (n=152, controls) and evaluated in a multivariate analysis. RESULTS: Low levels of serum cholesterol, triglycerides, and glucose, before and after transplantation, were accompanied by a prolonged graft survival. Prognostic factors for early graft failure included serum triglycerides >300 mg/dl, cholesterol >250 mg/dl before transplantation, serum creatinine >4.0 mg/dl 1 month after transplantation, and donor age above 45 or less than 10 years. Additionally, systolic and, particularly, diastolic blood pressure was lower in the group with a prolonged graft function as compared with controls immediately before and after transplantation. In addition, the incidence of primary graft function was lower and the incidence of acute rejection episodes higher in controls. Cold and warm ischemic time, body mass index, recipient age, and gender did not differ significantly. CONCLUSIONS: Our data suggest that metabolic parameters play an important role in the process of late graft loss after kidney transplantation.

Rescue therapy with tacrolimus in simultaneous pancreas/kidney transplantation.

Tacrolimus has been effective both in primary and rescue therapy following steroid and OKT3-resistant acute rejection in liver and kidney transplantation. Due to the effects of tacrolimus on glucose metabolism, there has been concern about its use in simultaneous pancreas/kidney transplantation. We report on the results of six patients (three female, three male, age 35.2 +/- 7.3 years) converted from cyclosporin A to tacrolimus following simultaneous pancreas/kidney transplantation in steroid-resistant acute rejection. Tacrolimus was induced 2.8 +/- 1.7 months (range 1-4.8 months) after transplantation; follow-up was 3-18 months. Following conversion, creatinine levels declined in all patients [3.5 +/- 1.2 mg/dl before conversion, 3.0 +/- 1.9 mg/dl (n = 6) at three months, 1.4 +/- 0.1 mg/ dl at 1 year (n = 3)]. Before conversion, fasting blood glucose levels averaged 154 +/- 33 mg/dl, with three patients receiving insulin. Three months later no patient required insulin, the mean glucose level being 107 +/- 23 mg/dl (n = 6); at 1 year it was 92 +/- 9 mg/dl (n = 3). One patient lost his pancreatic graft after 4 months due to a mycotic aneurysm. We conclude that conversion to tacrolimus is a safe and effective treatment in cases of steroid-resistant rejections following pancreas/ kidney transplantation.

[Crossectomy in ascending superficial thrombophlebitis of the leg veins]. / Die Crossektomie bei aszendierender oberflächlicher Thrombophlebitis der Beinvenen.

Ascending thrombophlebitis of the superficial leg veins is known to propagate into the deep leg veins and to embolize. In a prospective study we followed up 44 patients with sonographically diagnosed ascending thrombophlebitis into the deep veins (V. saphena magna n = 40, V. saphena parva n = 4). In 15 of 44 cases (34%) thrombosis of the crossing veins was found intraoperatively and 6 of 44 crossings were filled with floating thrombi into the deep vein lumina (14%). Among complications of treatment (11.4%) recurrence of thrombi in the ligated superficial residual vein stump was seen in 2 of 44 cases. One of these patients suffered a symptomatic, non-fulminant pulmonary embolism. The other patient developed a femoral vein thrombosis. 1 patient had an abscess and 1 a seroma of the groin. In 11% of all cases ascending thrombophlebitis diagnosed duplex sonographically was not effective in preventing propagation of thrombi into the deep veins thromboembolism remains a complication of ascending thrombophlebitis.

DNA sequence analysis of Sry alleles (subgenus Mus) implicates misregulation as the cause of C57BL/6J-Y(POS) sex reversal and defines the SRY functional unit.

The Sry (sex determining region, Y chromosome) open reading frame from mice representing four species of the genus Mus was sequenced in an effort to understand the conditional dysfunction of some M. domesticus Sry alleles when present on the C57BL/6J inbred strain genetic background and to delimit the functionally important protein regions. Twenty-two Sry alleles were sequenced, most from wild-derived Y chromosomes, including 11 M. domesticus alleles, seven M. musculus alleles and two alleles each from the related species M. spicilegus and M. spretus. We found that the HMG domain (high mobility group DNA binding domain) and the unique regions are well conserved, while the glutamine repeat cluster (GRC) region is quite variable. No correlation was found between the predicted protein isoforms and the ability of a Sry allele to allow differentiation of ovarian tissue when on the C57BL/6J genetic background, strongly suggesting that the cause of this sex reversal is not the Sry protein itself, but rather the regulation of SRY expression. Furthermore, our interspecies sequence analysis provides compelling evidence that the M. musculus and M. domesticus SRY functional domain is contained in the first 143 amino acids, which includes the HMG domain and adjacent unique region (UR-2).

[Differential diagnostic evaluation of a dysfunctional kidney transplant by magnetic resonance tomography]. / Differentialdiagnostische Abklärung des dysfunktionellen Nierentransplantats durch die Kernspintomographie.

Immediate diagnosis of rejection is essential for the prognosis of a renal transplant. To differentiate between rejection and acute tubular necrosis, 48 examinations (31 patients) were evaluated by Magnetic Resonance Imagining and Duplex Doppler ultrasound, and compared to the clinical outcome and histology. Sensitivity of MRI and Duplex Doppler was 82% (14/17), specificity was 77% (24/31) and 84% (26/31), respectively. Even when the results of both methods matched well, due to the extensive financial and technical efforts MRI may only be used as an additional tool for diagnosis.

[The effect of donor and recipient ages on the results of kidney transplantation]. / Einfluss von Spender- und Empfängeralter auf die Ergebnisse der Nierentransplantation.

In a retrospective study of 814 patients (349 women, 465 men) who had received their first kidney transplant, early function rate as well as transplant and patient survival rates were determined in relation to age (up to 50 years: 530; 51-55 years: 140; 56-60 years: 83; over 60 years: 61). The same rates were also grouped by donor age (> 16 years, 68 patients; 16-40 years, 387; 41-50 years, 165; 51-60 years, 144; over 60 years, 50). The 5-year transplant function rate fell significantly with increasing donor age (P = 0.0001) from 78% (16-40 years) to 47% (over 60 years). For the same age groups the proportion of transplants which never resumed their function rose from 8 to 28%. Age of recipient had no influence on early function and 5-year transplant function rates. Thus, regardless of the recipient's age, higher donor age is an independent risk factor for early and late results after transplantation.

HLA-DP antibodies in patients awaiting renal transplantation.

Sera from 505 patients awaiting renal transplantation with known panel-reactive cytotoxic antibody (PRA) status were tested for HLA-DP antibodies of the IgG class by means of the monoclonal antibody immobilization of leukocyte antigens (MAILA) technique. The overall incidence of HLA-DP antibodies was 7.3%. A positive HLA-DP antibody status correlated only weakly (r = 0.23) with a positive cytotoxic antibody status. After retrospective analysis, patients with HLA-DP antibodies prior to retransplantation revealed a significantly (P < 0.025) higher graft function rate than HLA-DP-negative patients. One patient was found to possess IgG HLA-DP autoantibodies prior to transplantation; thus far, his graft has been functioning for more than 2 years.

[The effect of obesity on outcome of kidney transplantation]. / Der Einfluss der Adipositas auf die Ergebnisse der Nierentransplantation.

BACKGROUND AND AIM: Obesity is a risk factor for postoperative complications in surgery. In a retrospective study we investigated the course of body weight during the waiting period and the first postoperative year and the influence of obesity on graft function. PATIENTS AND METHOD: The medical records of 334 adult patients undergoing cadaveric kidney transplantation between 1986 and 1992 were reviewed. Immunosuppression was performed with cyclosporine and prednisone. For all patients the Broca index was calculated with the relative body weight by the formula: body weight/Broca index x 100 (% BI). Obesity was defined as relative body weight > or = 120% BI. RESULTS: At the time of the indication for kidney transplantation 15.3% of the patients were obese. Only 12 of these 51 obese patients reduced their body weight below 120% BI until transplantation, whereas 25 patients increased weight in excess of 120% BI. Thus the number of obese patients raised to 19.2% by the time of transplantation. The graft survival in the obese group was significantly lower than in the nonobese group. This difference appeared already in the first half year after transplantation being constant in the following time. The resulting 1-year graft survival was 82.8% and 91.4% respectively (p < 0.05). During the first year 59 patients more became obese, the percentage of obese raised up to 36.0%. One year after transplantation there was no longer significant difference of graft survival rate in the further follow-up between obese and nonobese patients. CONCLUSION: Our findings show, that obesity is an important risk factor for early graft loss. Therefore all participating physicians assume a great responsibility for the pre-operative treatment during the waiting time.