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Biomedical subjects

H G Gooszen

Publications and source records attributed to H G Gooszen.

At least 91 records · Page 5Linked to original sources

Insulinotropic effects of cholecystokinin, gastric inhibitory polypeptide and glucagon-like peptide-1 during perifusion of short-term cultured canine isolated islets.

Recent metabolic studies suggest that the incretin effect of gut hormones may account for most of the circulating insulin during mild postprandial hyperglycemia after transplantation of isolated islets. As yet, however, insulinotropic effects of pharmacological rather than physiological levels of the incretin candidates cholecystokinin-33 (CCK-33), gastric inhibitory polypeptide (GIP), and glucagon-like peptide-1 (GLP-1) on isolated perifused islets have been reported. We examined the insulinotropic effects of these peptides during perifusion of canine isolated islets. Exploration of beta-cell sensitivity in our model with graded 0.1-10 nM doses of CCK-33 and GIP at a 7.5 mM glucose level demonstrated insulinotropic effects from the lowest level. We, therefore, focused on the (near-) physiological effects of both CCK-33 (20 pM), GIP (500 pM), and GLP-1 (100 pM) during perifusion at a 2.5, 7.5, and 10 mM glucose level. No effects of CCK-33 were observed. GIP enhanced insulin release 1.1- and 1.2-fold, at the 7.5 and 10 mM glucose level, respectively. GLP-1 stimulated insulin output from the 2.5 mM glucose level; and a maximum, 2-fold, increase of insulin output was observed from the 7.5 mM glucose level. Thus, isolated perifused islets do respond to near-physiological beta-cell stimulation with gut hormones, and both GIP and GLP-1 may contribute to a hyperglycemia-enhanced activation of the enteroinsular axis after transplantation of isolated islets.

Animals↗

Human complement activation via the alternative pathway on porcine endothelium initiated by IgA antibodies.

The role of the classical pathway (CP) and the alternative pathway (AP) of complement activation in hyperacute xenograft rejection remains a matter of considerable debate. In addition, it is unknown whether IgG and IgA antibodies activate complement, although these antibodies have been found in hyperacutely rejected xenografts. This study was initiated to assess a possible role of the AP of complement activation in a pig-to-human transplantation model using fresh human sera and isolated antibodies with cultured porcine endothelial cells (PEC) as targets. IgM, IgG, monomeric IgA, and dimeric IgA (dIgA) antibodies with reactivity toward PEC as determined by ELISA were isolated from pooled normal human sera. Serum from patients with agammaglobulinemia was used as a source of human complement. C3 and C4 deposition on nonfixed PEC during CP (1% serum) or AP activation (10% serum with MgEGTA) was analyzed using an ELISA. Complement-mediated PEC lysis was tested in a 51Cr release assay. Using normal human sera as the source of antibodies and complement, C3 and C4 deposition was already found after 10 min of incubation in the CP, whereas an increasing amount of C3 was found in the AP. During AP activation, no C4 deposition was observed, indicating that CP activation did not contribute to the observed AP-mediated C3 deposition. Moreover, dIgA antibodies caused deposition of C3 and not C4. Purified IgM and dIgA antibodies (1 mg/ml) in the presence of 10% agammaglobulinemic serum showed a mean specific PEC lysis of 31% and 28%, respectively. Agammaglobulinemic serum alone or with IgG or monomeric IgA antibodies had no detectable lytic activity. In conclusion, dIgA antibodies might play an additional role in pig-to-human xenograft rejection by activating human complement via the AP.

Acute Disease↗

Effect of blood group and HLA matching on pancreas graft survival with the use of UW solution.

Pancreas graft survival is influenced by various donor and recipient factors. Factors that have posed serious problems to pancreas transplantation have included the limited cold ischemia time, early graft thrombosis, and rejection. A limited cold ischemia time not only causes problems in terms of logistics but also implies limitations with regard to HLA matching and organ exchange. Between August 1988 and August 1989 we performed a prospective, nonrandomized European multicenter study to evaluate the effect of University of Wisconsin (UW) solution on pancreas graft survival. In addition, donor and recipient factors were collected and their influence on graft survival analyzed. Overall pancreas graft survival at 1 and 4 years was 67% and 59%, respectively (n = 62). When only simultaneous pancreas and kidney transplants were included, the graft survival was 70% and 63% at 1 and 4 years, respectively. The incidence of pancreas graft thrombosis was 8%. Cold ischemia time was not found to significantly influence pancreas graft survival even when it exceeded 12 h. Factors that did were HLA-DR matching, simultaneous pancreas and kidney transplantation versus pancreas transplantation alone, and ABO blood group matching. We feel that the use of UW solution for pancreas preservation has contributed to improved pancreas graft survival and has reduced early graft thrombosis despite much longer cold ischemia times of over 12 h. Given this and the significant effect of HLA and blood group matching, we conclude that more attention should be paid to preoperative matching and organ exchange in order to further improve pancreas graft survival.

Adenosine↗

Endosonography of the anal sphincter after ileal pouch-anal anastomosis. Relation with anal manometry and fecal continence.

PURPOSE: The aim of the present study was to visualize supposed defects of the internal anal sphincter after ileal pouch-anal anastomosis (IPAA) by anal endosonography and to relate these findings with anal manometry and fecal continence. METHODS: We investigated 23 patients, visualized the sphincter complex by anal endosonography, and quantified the anatomic changes of the sphincter. Anal resting and squeezing pressures as well as length of the anal canal were determined by anal manometry. Continence was objectively scored by an observer not involved in treatment of patients and subjectively by patients themselves. RESULTS: At anal endosonography, the mean thickness of the internal anal sphincter was 1.16 mm (95 percent confidence interval, 0.98-1.33), which is significantly less than in normal volunteers. Tapering of the internal anal sphincter only occurred in six patients (of whom two had a gap in the internal sphincter). In 17 patients endosonography showed a thin internal anal sphincter without essential variation in thickness over the complete circumference. Approximately eight weeks after ileostomy closure following IPAA, maximum resting pressure (MRP) and length of the anal canal appeared to be significantly decreased compared with values before IPAA (P = 0.001 and 0.002, respectively). These differences were less striking (P = 0.05 and 0.04, respectively) when measured six or more months after ileostomy closure. The extent of reduction of the MRP and thickness of the internal anal sphincter were not correlated with grade of continence or with subjectively scored continence. CONCLUSIONS: IPAA leads to a reduction of thickness of the internal anal sphincter and reduction of the MRP. Tapering or gaps in the internal anal sphincter are probably caused by direct trauma to this sphincter because of mucosectomy, whereas in cases of circular reduction of thickness of the internal anal sphincter without tapering or gaps, direct trauma is an unlikely explanation; this reduction is probably caused by denervation. IPAA compromises continence to a variable degree in 18 of 23 patients. No correlations were found between the extent of reduction of the MRP and the extent of reduction in internal anal sphincter thickness or between these two parameters and objectively or subjectively scored continence. Difficulties in obtaining reliable information on continence may be a causal factor. A striking discrepancy was noticed among objective, scored disturbances in continence, and overall satisfaction concerning level of continence by patients themselves.

Adenomatous Polyposis Coli↗

A prospective study on the effect of the Belsey Mark IV 270-degree fundoplication on lower esophageal sphincter characteristics and esophageal body motility.

The effect of the Belsey Mark IV operation on lower esophageal sphincter characteristics and esophageal body motor function was prospectively studied in 38 patients who underwent successful operation (relief of symptoms, healing of esophagitis; group I) and 8 who had surgical failure (group II). Mean follow-up was 3 years (0.5 to 8 years). Only in group I a rise in basal lower esophageal sphincter pressure (from 8.3 +/- 0.8 mm Hg to 14.5 +/- 0.5 mm Hg, p < 0.001), total sphincter length (from 2.7 +/- 0.1 cm to 3.4 +/- 0.1 cm, p < 0.001), and the intraabdominal sphincter segment (1.3 +/- 0.1 cm to 2.3 +/- 0.1 cm, p < 0.001) with a reduction of the intrathoracic segment (from 1.5 +/- 0.1 cm to 1.1 +/- 0.1 cm, p < 0.05) was recorded. Preoperative and postoperative lower esophageal sphincter pressure and length values showed a large overlap. Antireflux operation had no effect on peristaltic amplitude, velocity, and duration, irrespective of the outcome of operation. One of five patients with incomplete swallow-induced lower esophageal sphincter relaxation had moderate dysphagia. Successful operation by 270-degree fundoplication is accompanied by a significant increase in lower esophageal sphincter pressure and length and does not affect esophageal body motor function.

Adult↗

Perioperative blood transfusion does not prevent recurrence in Crohn's disease. A pooled analysis.

The effect of perioperative blood transfusion on the recurrence of Crohn's disease is controversial. Various studies have suggested that perioperative blood transfusions reduce the risk of recurrence; others have failed to find a protective effect. Since all the studies are based on relatively small numbers, we performed a pooled analysis. We contacted the senior authors of seven previously published studies and asked for the original data. Four authors provided their data. The pooled database included 622 patients with a primary and complete resection of macroscopic disease. Recurrence was defined as the need for repeat surgery for disease control. Kaplan-Meier life table analysis was performed. Of the study sample, 366 cases (59%) were female. Disease distribution was as follows: small bowel (47%), small/large bowel (35%), and large bowel only (18%). Three hundred thirty-one patients (53%) received blood in the perioperative period. Mean follow-up was 72.8 months. For the overall sample, the 5-year recurrence rates were 26.9% for the transfused group and 25.2% for the nontransfused (p = 0.456). When the data were stratified by age, gender, disease location, and length of resection, no difference in 5-year recurrence rates between transfused and nontransfused cases could be detected. In this pooled analysis of four retrospective studies on the effect of blood transfusions on the risk of recurrence in Crohn's disease, we were unable to document a protective effect.

Adolescent↗

[Surgical strategy in acute or elective sigmoid resection in The Netherlands; survey based on a marketing model].

OBJECTIVE: To gain insight into the operative strategies used by Dutch surgeons for complicated diverticulitis and sigmoid carcinoma, and into the influence of patient risk factors and surgeon's experience on the preferred operative strategy. DESIGN: Descriptive. METHOD: A questionnaire was sent to all 148 members of the Dutch Society of Gastrointestinal Surgery, concerning 32 fictitious patients with sigmoid pathology. It was based on conjoint-analysis, a model used in marketing research. This model analyses qualities that make a product preferable to another product of the same product group. The operative choices were: resection with Hartmann's procedure, resection with primary anastomosis after on-table lavage, or with primary anastomosis only, or no primary resection but diverting stoma only, or some personal technique. The survey focused on experience of the surgeons with the operative procedures, and on treatment choices in four fictitious cases frequently encountered in general surgery. RESULTS: There was little agreement concerning the preferred surgical option for treatment of complicated diverticular disease or sigmoid carcinoma. With the exception of one fictitious young, electively operated 'ideal' patient (resection with primary anastomosis) there is hardly any consensus among the surgeons with respect to preferred treatment. CONCLUSIONS: Reasons to depart from the conceptually optimal treatment (resection and anastomosis) in complicated cases (from the point of view of the surgeon or the patient), and absence of agreement on responsible other treatment could be differences in appraisal of the importance of several risk factors, or differences in acquired decision making strategies. The literature offers no answer to the question which techniques should be preferred under various circumstances.

Adult↗

Antibody-dependent cell-mediated cytotoxicity against porcine endothelium induced by a majority of human sera.

Preformed natural antibodies seem to play a predominant role in hyperacute xenograft rejection. The potential of these antibodies in antibody-dependent cell-mediated rejection has not been elucidated, yet. This study was performed to assess a possible role of human antibodies in antibody-dependent cell-mediated cytotoxicity (ADCC) in pig to human transplantation using cultured porcine endothelial cells (PEC). Sera from 100 healthy blood donors were used to determine their ability to lyse PEC in a 51Cr release assay using human PBMC as effector cells. To reveal the underlying mechanism of the observed lysis, binding of human IgM, IgA, and IgG (IgG1, IgG2, IgG3, and IgG4) antibodies and F(ab')2 fragments to PEC was studied. Sixty-four percent of the sera showed a positive ADCC with 12-56% specific lysis of PEC using 1/16 diluted serum. Blocking of FcRIII (CD16) on effector cells did prevent PEC lysis. Most sera contained IgM, IgG, and IgA antibodies to PEC. IgG F(ab')2 fragments isolated from these sera specifically recognized PEC antigens without displaying ADCC activity. With regard to IgG subclass distribution of these antibodies, all sera contained IgG antibodies reacting with PEC, whereas most sera showed binding of IgG1 or IgG3 antibodies to PEC. No binding of IgG4 antibodies to PEC was found. Binding of total IgG, IgG1, IgG2, or IgG3 antibodies to PEC was not directly correlated with serum cytotoxicity. In conclusion, most human sera have the ability to lyse PEC through non-complement-fixing IgG antibodies via binding to FcRIII (CD16) on killer cells. Thus, human IgG antibodies may contribute to porcine xenograft rejection. The in vivo consequences of the predominant recognition of PEC antigens by IgG2 and IgA antibodies remain to be studied.

Adult↗

Impact of donor-related variables on islet isolation outcome in dogs.

Clinical human islet transplantation programmes are considerably hampered by the variability of islet isolation outcome. The effects of the islet content of the pancreas and other donor-related variables on isolation outcome have not been evaluated systematically so far--either in large animals, or in man. We studied the impact of interindividual differences in age, body weight and pancreatic islet content on the outcome of collagenase isolation of islets from the splenic pancreas of beagle dogs (n = 31). The islet volume of the splenic pancreas amounted to a mean (+/- SEM) 15.7 +/- 0.9 microliters per gramme pancreas, and varied three-fold (from 8.4 to 27.3 microliters). Isolated islet yield was 7.6 +/- 0.7 microliters/g and varied nine-fold (1.8-16.3 microliters). Animals also varied in age eight-fold (8-67 months) and body weight two-fold (8.6-18.3 kg). Differences in body weight and age explained 60% of variance in the fractional islet volume of the pancreas and 50% of the variance in islet yield (p < 0.001). Fractional islet volume of the splenic pancreas also explained 50% of the variance in islet yield (p < 0.001). We conclude that the outcome of islet isolation may be predictable after controlling for the variable islet content of pancreases, and other donor-related variables, and suggest that similar studies should be done in man.

Aging↗

Anterior rectocele: assessment with radiographic defecography, dynamic magnetic resonance imaging, and physical examination.

PURPOSE: The aim of this study was to devise a measuring method for an anterior rectocele on standardized defecographies and magnetic resonance images (MRI) to quantify anterior rectocele and to test whether this could substantiate clinical decision making for operative treatment for anterior rectocele. METHODS: Quantitative analysis by the measuring method as proposed was compared with qualitative scores on defecographies and MRI from the same patients. Thirty-eight patients with symptoms compatible with an anterior rectocele were subjected to physical examination in the left decubitis position and supine position and to defecography. Findings on defecography were compared with findings on physical examination. Thirteen patients were examined before and after surgical correction of the anterior rectocele for a total of 51 qualitative and quantitative examinations. The group of operated patients was analyzed for treatment results. Nineteen controls were included. RESULTS: Sixty-six radiographs of 33 defecographies were qualified in three grading classes and quantified with the proposed method by two observers. The mean measured value of the anterior rectocele in the three subjective grading classes is significantly different (P < 0.001). Anterior rectoceles qualified as severe had a measured value of 20 mm or more in 96 percent of the radiographs. Lower gradings were never > 20 mm. On MRI severe anterior rectoceles were not scored and measured values did not correlate with qualitative scores. When findings on physical examination were compared with defecographic measurement, the coefficient of correlation (r) between the radiologic assessment and clinical examination in the left decubitis position is r = 0.87, for the examination in the supine position, r = 0.77. All 15 cases scored as severe anterior rectocele in the left decubitis position had a measured anterior rectocele of > or = 20 mm. In the 13 cases that received surgery, there was a significant reduction of the anterior rectocele (P < 0.001) and clinical improvement. Patients with small or moderate anterior rectocele on physical examination with a size > or = 20 mm on defecography were cured by surgical correction. None of the controls had an anterior rectocele on physical examination or an anterior rectocele > or = 20 mm on defecography. CONCLUSIONS: An anterior rectocele with a size of 20 mm or more corresponds with a qualitative score of "severe" on radiographic defecography. Physical examination for anterior rectocele in the left decubitis position corresponds best with quantitative radiographic assessment and anterior rectocele with a size > or = 20 mm on defecography is pathologic. Patients with complaints compatible with anterior rectocele can be assessed in objective and quantitative terms by radiography and can be successfully surgically treated, even if at physical examination the anterior rectocele is not classified as large, provided that dynamic defecography shows an anterior rectocele of > or = 20 mm. The potential of dynamic MRI with regard to anterior rectoceles presently seems absent.

Adult↗

A prospective study of effects of Belsey MK IV antireflux surgery on endoscopic esophagitis, lower esophageal sphincter pressure, and 24-hr pH measurements. Relation to symptom improvement.

A prospective study on the effect of the Belsey MK IV operation on esophagitis, lower esophageal sphincter pressure (LESP), and acid reflux as monitored on 24-hr pH recording was conducted to investigate the association between objective changes and the effect of operation on reflux-associated symptoms. Thirty-one patients were included. The effect of surgery on symptoms was recorded in all patients, and 22 patients agreed to undergo endoscopy, manometry, and 24-hr pH recording. Follow-up ranged from three to nine years (mean five years); 87% reported long-lasting improvement (50% free of symptoms, 37% major improvement, no medication needed). The combination of symptomatic improvement and absence of esophagitis was found in 70%. LESP significantly increased [8 +/- 6 mm Hg preoperatively, 14 +/- 5 mm Hg postoperatively (P < 0.001)] to a level above 5 mm Hg in 96% of the patients. No endoscopic esophagitis was found in 17 of 20 patients (85%; P < 0.05) (two patients refused endoscopy). The 24-hr pH monitoring normalized in 11 of the 20 patients (55%) (one registration failed). The operation-induced rise in LESP correlated with improvement on endoscopy (r = 0.51; P < 0.002) and with reduction of reflux parameters (number of episodes with pH < 4: r = 0.64; P < 0.05, percentage of total time pH < 4: r = 0.42; P = 0.07). A rise in LESP must be an important aim of antireflux surgery. The Belsey MK IV does not induce a rise to a level that causes severe dysphagia or bloating, but the trade-off is less control of acid reflux.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Protective effect of blood transfusions on postoperative recurrence of Crohn's disease in parous women.

BACKGROUND: Perioperative blood transfusion (BT) appeared to have adverse effects on survival after surgery for malignant tumors while pretransplantation BT suppressed allograft rejection. Interest grew in the effect of BT on postoperative recurrence of Crohn's disease. STUDY DESIGN AND METHODS: To determine the effect of perioperative BT on the recurrence of Crohn's disease after primary surgery, the medical histories of 148 patients with Crohn's disease, 62 males and 86 females (49 nonparous and 37 parous), were reviewed. Eighty-seven patients received perioperative BT. RESULTS: Overall, perioperative BT showed no effect on recurrence. Patients with Crohn's disease limited to the ileum had a better prognosis with regard to recurrence than did patients with Crohn's disease located in the colon or located in both ileum and colon, but the difference was not significant. Perioperative transfusion seemed to protect against recurrent disease after colon resection, which might be explained by the fact that colon resections, which often necessitate perioperative BT, generally result in a shorter bowel segment at risk for recurrent disease. Overall, parous women showed a worse prognosis than nonparous females and men (p = 0.022). Transfusions had a beneficial effect in parous women (p = 0.068) and, after correction for type of operation, this beneficial effect was significant (p = 0.026). After perioperative BT, parous women had a similar prognosis with respect to recurrent Crohn's disease as nonparous females and men. CONCLUSION: Perioperative BT has a beneficial effect on the postoperative recurrence of Crohn's disease in parous women.

Adolescent↗

Prospective evaluation of 24 hour ambulatory pH metry in Belsey Mark IV antireflux surgery.

This study evaluated the effect of the 270 degrees Belsey Mark IV fundoplication on 24 hour ambulatory pH metry variables. Thirty seven patients with confirmed gastro-oesophageal reflux disease who had a Belsey Mark IV antireflux procedure were evaluated preoperatively and three to six months postoperatively including endoscopy, lower oesophageal sphincter manometry, and 24 hour ambulatory pH metry. In 30 of 37 patients the Belsey Mark IV fundoplication was judged successful based on symptom relief and healing of oesophagitis. In these 30 patients percentage reflux for total, upright, and supine time (median and range) decreased significantly (p < 0.001) from 10.0% (2.7-35.3%), 10.8% (3.2-39.9%), and 6.7 (0.0-33.0%) respectively to 0.5% (0.0-7.4%), 0.6% (0.0-13.7%), and 0.1% (0.0-4.9%) after operation. This decrease in reflux time resulted predominantly from a significant (p < 0.001) reduction in the number of reflux episodes from 98 (23-231) to 14 (0-82) postoperatively. Normalisation of total reflux time (upper limit of normal for time with pH below 4:4%) was found in 89% and normalisation of total and upright and supine reflux in 64% of successfully operated patients with confirmed abnormal acid reflux before operation. A successful antireflux procedure was associated with significant (p < 0.001) increases in lower oesophageal sphincter pressure from 7.8 (0.6) mm Hg to 14.5 (0.7) mm Hg mean (SEM). In seven patients with a failed antireflux operation basal lower oesophageal sphincter pressure did not change significant;y (preoperative value 5.7 (1.3) mm Hg; postoperative value 7.8 (0.8) mm Hg). In these patients reflux time did not decrease after the operation and remained in the abnormal range in all patients. It is concluded that a successful, in contrast with a failed, Belsey Mark IV fundoplication is associated with significant decreases in total, upright, and supine reflux time. Normalisation of pH metry variables is not a prerequisite for successful antireflux surgery. A surgery. A successful 270 degree Belsey Mark IV fundoplication was associated with a significant increase in basal lower oesophageal sphincter pressure, in contrast with the failure group. Restoration of a sufficient lower oesophageal sphincter barrier is an important aim in antireflux surgery.

Adult↗