Search PubMed⌕ Search

Biomedical subjects

J Jeekel

Publications and source records attributed to J Jeekel.

At least 109 records · Page 6Linked to original sources
PubMed1991

Treatment perspectives in locally advanced unresectable pancreatic cancer.

Locally advanced unresectable pancreatic cancer is sometimes encountered without manifest distant metastases. Twenty patients with histologically proven unresectable pancreatic cancer without distant metastases were treated with radiotherapy and 5-fluorouracil (5-FU). Radiotherapy consisted of 50 Gy external upper abdomen radiation in two courses, concomitant with intravenous 5-FU 375 mg/m2 given as a bolus injection 4-6h before radiation on the first 4 days of each treatment course. The treatment protocol was completed in 18 patients without complications. The median survival time was 10 months which compares favourably with a 3-5 months median survival time when treatment is withheld. Nine patients (45 per cent) were alive at 1 year, two patients at 2, 3 and 4 years. A second-look operation was performed in four patients 6, 11, 12 and 22 months after completion of radiotherapy. In two patients the tumour could be resected. It appears that treatment with radiotherapy and 5-FU may benefit patients with locally advanced unresectable pancreatic cancer.

Combined Modality Therapy↗
PubMed1991

En bloc resection of colon carcinoma adherent to other organs: an efficacious treatment?

From 1977 to 1984, 56 patients with colon cancer adherent to other organs were operated upon. Twenty-three (41 percent) underwent palliative treatment without resection. The mean survival in this group was 6 months. The results of en bloc resection were evaluated in 33 patients (59 percent) with colon carcinoma and tumor growth in adjacent organs. Pathologic staging was based on Dukes' (Astler and Coller) classification. Dukes' B carcinoma was shown in 15 patients. Dukes' C in 14 patients, and Dukes' D in four patients. The 4-year survival rate was as follows: Dukes' B, 47 percent; Dukes' C, 29 percent; and Dukes' D, 0 percent. The 4-year survival rate for the whole group was 33 percent. The postoperative morbidity and mortality were 6 percent and 3 percent, respectively. Colon cancer with involvement of adjacent structures should not be regarded as an incurable Dukes' D carcinoma; en bloc resection is indicated and can be performed with acceptable morbidity and mortality.

Carcinoma↗
PubMed1991

Total orthotopic allogeneic small bowel transplantation in rats: effect of allograft irradiation combined with cyclosporine-A therapy.

Rejection and graft versus host disease are prominent features in small bowel allotransplantation in rats. Cyclosporine treatment of the recipient and irradiation of the donor were used to circumvent these phenomena in the WAG to brown Norway rat model. Irradiation of the donor with five or 10 Gy did prevent graft versus host disease but resulted in a more vigorous rejection of small bowel allografts in untreated recipients (mean (SEM) survival times of 11.5 (0.4) (n = 8) and 7.5 (0.9) (n = 11) days respectively, versus 16.6 (2.6) days (n = 17), p less than 0.01). Cyclosporine treatment of the recipient (25 mg/kg on days 0, 1, 2, 4, and 6 after transplantation) led to a mean (SEM) survival time of 38.3 (8.5) days (n = 10); 20% of the animals developed graft versus host disease. Combined with 5 Gy donor pretreatment, a similar survival was obtained without occurrence of graft versus host disease. However, cyclosporine treatment combined with 10 Gy led to a significant shortening of graft survival (23.1 (6.8) days, n = 9). These results suggest that although irradiation is very effective in preventing graft versus host disease, high dosages may accelerate rejection either by making the graft more vulnerable to rejection or by completely removing the immuno-suppressive effect of graft versus host disease.

Animals↗
PubMed1991

Extracorporeal shock wave lithotripsy of pancreatic duct stones.

Chronic calcifying pancreatitis presents a major clinical problem, often requiring extensive surgery. Extracorporeal shock wave lithotripsy (ESWL) offers a new therapeutic option. We applied ESWL after endoscopic sphincterotomy of the pancreatic orifice in eight patients with impacted pancreatic duct stones. An electromagnetic lithotriptor (Siemens Lithostar, Erlangen, FRG) was used. Patients were treated in prone position under fluoroscopic control. A mean of 6,813 shock waves (range 1,500-10,000) was delivered in one or two sessions. Disintegration of stones was achieved in 6/8 patients, initial relief of pain in 7/8 patients, and total clearance of the pancreatic duct in 3/8 patients. One patient had an exacerbation of her pancreatitis one day after ESWL, which resolved rapidly with medical treatment. No other complications were observed. Four of five patients with fragmented stones had no abdominal complaints at follow-up (mean 17 months, range 3-27). Three patients in whom ESWL was not completely successful (two without and one with partial fragmentation) underwent an operation according to Puestow. Two of them still have abdominal complaints after surgery. From these data, we conclude that ESWL of pancreatic duct stones is a promising new alternative for surgery, when endoscopic stone extraction fails.

Adult↗
PubMed1991

Treatment with rIFN-gamma has no effect on cardiac allograft rejection.

The effect of recombinant rat interferon-gamma (rRIFN-gamma) on allograft rejection was studied in two rat heart transplantation models. Recipients were treated with rRIFN-gamma by intraperitoneal or intravenous injection, either by bolus or continuous infusion. Treatment was started after transplantation and continued during a period ranging from 4 to 10 days; dosages varied from 2.5 x 10(2) U/kg/day to 3 x 10(6) U/kg/day. Controls were infused with PBS. Treatment with rRIFN-gamma had no effect on allograft survival, irrespective of the route of administration, the dosage used or the duration of treatment. Higher dosages of rRIFN-gamma induced serious morbidity and mortality. In conclusion, systemic treatment of cardiac allograft recipients with rRIFN-gamma has no effect on graft rejection and is associated with serious toxicity and mortality when high dosages are used.

Animals↗
PubMed1991

Local treatment of liver metastases with recombinant tumour necrosis factor (rTNF): a phase one study.

Fifteen patients with therapy-resistant liver metastases were treated in a phase-I study with recombinant human TNF (rTNF). The rTNF was injected into one liver metastasis by ultrasound guidance, using a 50 microgram escalating dose schedule (3 patients/dosage) ranging from 100-350 micrograms/injection. Influenza-like symptoms like fever, chills, nausea and vomiting were the main clinical side effects. Two patients, treated concomitantly with rTNF and morphine, showed mild hypotension. Other toxicities, as reported after systemic use of rTNF, such as decrease in leukocyte and platelet counts, renal or liver toxicity were not observed. In eight patients growth arrest was observed in rTNF-treated metastases, whereas non-injected lesions showed growth progression. The maximum tolerated dose by this route of administration is greater than 350 micrograms/injection. Based on these observations it is concluded that the toxicity of rTNF injected into liver metastases by sonographic control is transient and mild and that intratumoural administration of rTNF might play a role in local tumour control.

Adult↗
PubMed1991

The influence of blood loss on tumour growth: effect and mechanism in an experimental model.

Retrospective studies have provided indirect evidence that allogeneic blood transfusion may adversely influence the prognosis of cancer patients. This effect may be prevented by using autologous blood transfusions. However, this involves preoperative donation of blood, the consequences of which are still unknown. The aim of the present study was to investigate the possible effects of blood loss on tumour growth and on NK-cell activity. An artificial lung metastasis model was used in the BN rat from which 20 per cent of the blood volume was taken at different time intervals. The results showed that blood loss, one day prior to tumour challenge, had a profound stimulating effect on tumour growth. After blood loss, the number of lung metastases was doubled as compared to controls. This tumour-promoting effect could be prevented by an immediate plasma transfusion, but not by evoking a normal haemoglobin level after blood loss by pretreatment with recombinant erythropoietin (rEpo). The NK-cell activity of spleen cells was significantly depressed, 24 hours after blood loss. At a 50:1-lymphocyte-to-target cell ratio, the NK-cell activity dropped from 25.3 per cent in controls to 9.3 per cent in experimental animals. Since NK-cells are assumed to play a role in the clearance of tumour cells from the circulation, the enhanced tumour growth observed after blood loss might be caused by this depression.

Animals↗
PubMed1990

[The treatment of recurrent inguinal hernia].

Between 1980 and 1987 a total of 163 patients were operated for unilateral recurrent inguinal hernia in the University Hospital Dijkzigt. Various factors were analysed statistically with the log rank test for their prognostic value to predict repeat recurrence. Lower repeat recurrence rates were found with increase of age (p = 0.05) and time passed since the previous hernia operation (p = 0.001). Using the actuarial method of analysis the total cumulative repeat recurrence rate after five years was 23%.

Actuarial Analysis↗
PubMed1990

Meta-analysis of randomized, controlled clinical trials of antibiotic prophylaxis in biliary tract surgery.

In this study all available clinical trials of antibiotic prophylaxis in biliary tract surgery, published from 1965 to 1988, were examined. Results of 42 randomized, controlled trials (4129 patients), in which a group of patients treated with antibiotics was compared with a group of patients not treated with antibiotics, were pooled. Wound infection rates in the control groups range from 3 to 47 per cent and are 15 per cent overall. The overall difference in infection rates is 9 per cent in favour of antibiotic treatment (95 per cent confidence interval 7-11 per cent), while the common odds ratio is 0.30 (95 per cent confidence interval 0.23-0.38). Subgroup meta-analysis showed a significant stronger protective effect in high risk patients, while the timing of wound inspection (i.e. early in hospital or late at follow-up) markedly influenced the treatment effect reported. Comparison of wound infection rates in patients treated with first generation versus second or third generation cephalosporins (11 trials, 1128 patients), as well as single-dose versus multiple-dose regimens (15 trials, 1226 patients) did not reveal any significant effect (P greater than 0.05) in each trial separately as well as in the overall comparison. The results indicate that there is evidence against further use of no-treatment controls and that the choice of treatment regimen can largely be made on the basis of cost.

Anti-Bacterial Agents↗
PubMed1990

The antitumour activity of the interferon inducer bropirimine is partially mediated by endogenous tumour necrosis factor alpha.

Pyrimidinones, like 2-amino-5-bromo-6-phenyl-4-pyrimidinone (bropirimine), are potent immunomodulators. Natural killer cell activity and macrophage cytotoxicity are increased after bropirimine treatment, an effect exerted through induction of cytokines. Up to now, the interferons have been supposed to be the main mediators but we have found that tumour necrosis factor alpha (TNF alpha) can also be an important mediator of the bropirimine antitumour effects. Increased serum levels of TNF alpha were seen in rats after intraperitoneal administration of 200 mg/kg bropirimine on 2 consecutive days. We also found that the tumour-growth-inhibiting effect of the drug on a colon carcinoma in rats could be reduced about 40% by giving the rats rabbit anti-TNF alpha serum just prior to drug treatment. These results indicate that bropirimine can induce the release of TNF alpha in vivo and that this endogenous TNF alpha may be important as far as the antitumour effect of the drug is concerned.

Animals↗
PubMed1990

Rejection prophylaxis with sequential OKT3 and CSA after kidney transplantation.

Sixteen kidney transplant recipients received the IgG2a anti-CD3 monoclonal antibody OKT3 and azathioprine as rejection prophylaxis during the first two postoperative weeks. Concomitant immunosuppression consisted of low dose steroids while cyclosporine A therapy was instituted on day 12. Side effects included fever, bronchospasm, hypotension and diarrhoea. OKT3 caused T cell modulation resulting in CD3 dim+, CD4+ or CD8+, CD5+, WT31- and 11F2- cells. Anti-OKT3 antibodies were found in approximately 50% of the patients. The protocol induced a 100% patient and graft survival and a 81% actuarial freedom of rejection at 18 months. It prevented CsA associated nephrotoxicity in the direct postoperative phase. These beneficial effects outweighed the side effects of OKT3.

Adult↗
PubMed1990

Immunomodulation by recombinant rat interferon-gamma in vivo.

Most studies on the immunomodulating effects of interferon-gamma (IFN-gamma) have been performed in vitro, using recombinant mouse and human IFN-gamma preparations. Recently, recombinant rat IFN-gamma (rRIFN-gamma) became available, enabling extensive studies with this new preparation in vivo. In the present study a LEW rat model was used to determine the efficacy of rRIFN-gamma on immune functions in vivo. LEW rats were treated with rRIFN-gamma by continuous intravenous infusion at a dosage of 1.5 x 10(5) U/kg.h for 2 consecutive days. Twelve hours after cessation of rRIFN-gamma administration immune functions, including NK-cell activity, phagocytosis, and mitogen-induced blastogenesis, were assessed. All experimental animals displayed a marked reduction in the number of peripheral blood and bone marrow cells when compared with controls (p less than 0.005). Assessment of immune functions revealed a significant enhancement of NK-cell activity (p less than 0.001), phagocytosis (p less than 0.05), and mitogen-induced blastogenesis (p less than 0.05). These findings indicate that rRIFN-gamma, when given in high dosages, has a stimulatory effect on various immune functions, which substantiates its important immunological role in vivo.

Animals↗
PubMed1990

Hypervolaemic haemodilution in an anaemic Jehovah's Witness.

We report the effects of acute hypervolaemic haemodilution, induced before operation, on haemodynamics and systemic oxygenation. Major surgery in an anaemic Jehovah's Witness patient was facilitated with this technique. Some hours after operation, a perioperative decrease in haemoglobin concentration of less than 5% was observed, in spite of a blood loss of nearly 50% of the calculated blood volume.

Adult↗
PubMed1990

Moderate effect of preoperative blood transfusions on pancreas allograft survival in rats and dogs.

Treatment of type I diabetes by early pancreas transplantation requires the availability of a safe and effective transplantation technique. With the currently available immunosuppressive drugs it is difficult to obtain long-term pancreatic allograft survival. In this respect pancreas grafts compare unfavorably with heart or kidney grafts. Using a relatively simple and safe subcutaneous transplantation technique we investigated the effect of blood transfusions combined with low-dose immunosuppressive drugs in rats and dogs in order to attain an immunosuppressive schedule of low toxicity. Subcutaneous pancreas transplantation appeared to be a feasible technique, with long-term graft survival in syngeneically transplanted rats and autotransplanted dogs. Only a moderate prolongation of pancreatic allograft survival by blood transfusions was demonstrated in both models. In rats one or three preoperative donor-specific blood transfusions significantly prolonged pancreas graft survival to 23 +/- 15 and 29 +/- 15 days, respectively, compared with 12 +/- 2 days in untreated controls. Low-dose cyclosporine (15 mg/kg on the day of operation) led to improved graft survival in nontransfused recipients (17 +/- 4 days), however, this treatment could not further prolong graft survival in transfused animals (34 +/- 20 days). In dogs, treated postoperatively with azathioprine and prednisolone, three preoperative third-party blood transfusions led to 29 +/- 19 days of pancreas graft survival, which was not significantly different from nontransfused controls (17 +/- 5 days). These results indicate that, in rats as well in dogs, pancreatic allografts are less sensitive to the immunomodulating effect of blood transfusions than heart and kidney grafts.

Animals↗
PubMed1990

The limited efficacy of cyclosporine in preventing rejection and graft-versus-host disease in orthotopic small bowel transplantation in rats.

The effect of different schedules of cyclosporine treatment on the survival of small bowel allografts was studied in rats. The administration of a short course of CsA (15 mg/kg on days 0, 1, 2, 4, and 6) had no beneficial effect on graft-vs.-host disease and survival time of the recipient compared with untreated controls. CsA, 25 mg/kg for 1 or 2 weeks prolonged survival significantly (38.3 +/- 3.8 and 42.5 +/- 2.7 vs. 16.6 +/- 2.7, P less than 0.01). When combined with maintenance therapy, 15 mg/kg of CsA 3 times weekly until day 100, only 7 of 30 rats survived more than 100 days. In addition, GVHD was not consistently abrogated in these groups. Only high doses of CsA (25 mg/kg on days 0-6, 15 mg/kg on days 7-13, followed by maintenance therapy) could prevent the onset of GVHD, although the survival time of the transplants was not prolonged compared with untreated controls due to a toxic side effect of CsA on the transplants. It can be concluded that CsA used as monotherapy is ineffective in consistently ameliorating GVHD and rejection in the WAG-BN rat model. This model exhibits at least some of the immunological problems seen in large animal models and can be useful in studying combinations of immunosuppressive drugs or methods that may be applicable to small bowel transplantation in man.

Animals↗
PubMed1990

Eicosanoid profile of healing colon anastomosis and peritoneal macrophages in the rat.

Because intraperitoneal administration of prostaglandin E2 (PGE2) has a negative influence on the healing of colonic anastomosis, the production of eicosanoid products in the healing rat colon after resection and anastomosis was studied using high performance liquid chromatography. Normal colonic tissue metabolizes small amounts of arachidonic acid into cyclo-oxygenase and lipoxygenase products. After construction of an anastomosis, however, there is increased production of lipoxygenase products, while cyclooxygenase activity remains low. Increased amounts of PGE2 and other cyclo-oxygenase products are not produced after anastomosis of the colon and probably do not play a major role in uncomplicated healing of the large intestine in the rat. During the first eight days of repair in the anastomosed colonic tissue, a statistically significant increase in 12-hydroxyeicosatetraenoic acid (12-HETE) production was found compared with control colon tissue (p = 0.001). At the same time peritoneal macrophages from these rats showed increased 12-HETE production. Eicosanoid synthesis of peritoneal macrophages resembled eicosanoid synthesis of anastomosed colon taken from the same rat indicating that 12-HETE, in particular, may be of macrophage origin.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗