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S Jonas

Publications and source records attributed to S Jonas.

At least 109 records · Page 6Linked to original sources

Prophylactic use of low-dose urodilatin for prevention of renal impairment following liver transplantation: a randomized placebo-controlled study.

Many therapeutic measures have been employed to prevent or at least ameliorate postoperative renal impairment following liver transplantation. Recent clinical phase II studies have demonstrated that the new natriuretic peptide urodilatin has beneficial effects on renal function following heart and liver transplantation. The present study reports the first prospective randomized placebo-controlled trial of prophylactic urodilatin administration following liver transplantation. Seventy consecutive recipients of primary liver transplants were included in the study following randomization, and 33 patients continuously received urodilatin at a dose of 20 ng/kg/min for 7 d. The remaining 37 patients received a placebo infusion for the same time period. The course of serum creatinine and urea did not differ between the two groups nor did the daily urine production. However, the urodilatin group showed a higher preoperative median serum creatinine and a significant reduction on days 1 and 2, whereas this observation was not made in the placebo group. Furthermore, less furosemide was administered to the patients in the urodilatin group during the first 2 d. The incidence of postoperative hemodialysis and the number of treatments did not differ between the groups either (urodilatin group 4, vs. placebo group 6 and 22 for both groups, respectively). Side effects of the urodilatin therapy were not detected. The prophylactic low-dose urodilatin administration resulted in a trend towards amelioration of the renal function, but did not result in significant differences between the two experimental groups. Further studies, using higher doses, will be required to define the value of urodilatin for prevention of renal impairment after liver transplantation.

Adolescent↗

[Extent of resection in surgical therapy of central bile duct carcinomas].

The introduction of a radical procedure, the extended bile-duct resection, into the surgical treatment of hilar cholangiocarcinoma significantly increased the rate of curative resections (92% versus 62% after partial hepatic resection; p < 0.05). A comparable effect with respect to survival figures after curative resections did not become evident. Therefore, the true potential of this extended surgical procedure remains to be established.

Adult↗

Indications for tacrolimus anti-rejection therapy in liver allograft recipients.

We reviewed our experience with conversion to Tacrolimus after 600 liver transplantations, performed from September 1988 to March 1995. Conversion to Tacrolimus as an anti-rejection therapy was implemented in 78 patients because of chronic ductopenic rejection (n = 9), early chronic rejection (n = 5), OKT3-resistant cellular rejection (n = 12), steroid-resistant cellular rejection (n = 30), late-onset cellular rejection (n = 10), cellular rejection in patients suffering from cyclosporin malabsorption (n = 5) and uncomplicated cellular rejection (n = 7). Control of rejection was achieved in 72 of 78 patients (92%); 6 patients (18%) were non-responsive. Patient and graft survival were 82% and 77%, respectively. Fourteen patients died almost exclusively from opportunistic infections. Out of the six patients who did not respond to Tacrolimus treatment, four underwent successful retransplantation and two died from infections associated with a poor graft function. Overall, graft loss with or without patient death occurred in 6 of 9 patients undergoing chronic rejection, in 3 of 12 patients with OKT3-resistant cellular rejection, in 6 of 30 patients suffering from steroid-resistant cellular rejection and in one patient each suffering from late-onset or uncomplicated cellular rejection. In severe steroid-resistant cellular rejection, successful Tacrolimus rescue therapy corresponded to a significantly lower preconversion total serum bilirubin when compared to failures (9.9 +/- 6.8 mg% vs. 22.2 +/- 7.3 mg%, P < 0.05). Conversion to Tacrolimus was a reliable treatment option in liver allograft rejection. However, failures occurred in the OKT3- and steroid-resistant cellular rejection groups, and only in a subgroup of patients suffering from chronic rejection was a permanent benefit observed. Implementation of a conversion early in the course of a rejection episode may result in a further improved outcome. Predictive parameters, e.g. the total serum bilirubin in steroid-resistant cellular rejection, are still needed to select those patients who would profit rather from a retransplantation.

Adult↗

Incidence and outcome of arterial complications after orthotopic liver transplantation.

Arterial complications can be a major factor in morbidity and mortality after orthotopic liver transplantation (OLT), as they may cause graft failure, sepsis and complications of the biliary tract. From September 1988 to December 1994, 571 OLT were performed in 529 patients. The follow-up period ranged from 8 to 83 months. Actuarial 1-, 3- and 5-year survival figures were 91%, 87% and 85%, respectively. In 12 cases (2.1%) complications of the arterial anastomoses were observed. Early arterial complications occurred in eight cases from various causes, while late arterial complications were exclusively thromboses and developed in four patients 8, 12, 26 and 37 months after surgery, respectively. The main clinical course in patients with arterial thromboses was septic cholangitis with destruction of the biliary tree. Although 70% of the grafts with arterial thrombosis were lost, 30% could, at least temporarily, be salvaged by other treatment options. Provided adequate treatment is carried out, arterial complications do not affect overall patient survival.

Adolescent↗

Liver graft-transmitted glioblastoma multiforme. A case report and experience with 13 multiorgan donors suffering from primary cerebral neoplasia.

The transmission of donor-related malignancies by organ transplantation is a rather rare event. There has only been one report on the development of a brain tumor metastasis in liver transplantation. From September 1988 to January 1993, 342 donor hepatectomies with subsequent transplantation were performed at our center. The main donor diagnoses included subarachnoidal bleeding (n = 128; 37.4%), isolated head injury (n = 114; 33.3%), multiple injuries (n = 55; 16.1%), primary cerebral neoplasia (n = 13; 3.8%), and other (n = 32; 9.4%). Primary cerebral neoplasia included glioblastoma (n = 4), meningioma (n = 3), astrocytoma (n = 2), angioma (n = 2), neurocytoma (n = 1), and ependymoma (n = 1). In the group of donors suffering from primary cerebral neoplasia, procured organs other than the liver included kidneys (n = 20), combined kidneys and pancreata (n = 1), pancreata (n = 2), hearts (n = 8), combined hearts and lungs (n = 1), and single lungs (n = 1). Follow-up of the respective graft recipients ranged from 28 to 68 months (median 43 months). Recurrent malignancy was observed once, in a liver graft recipient. The donor, a 48-year-old female, had undergone surgical resection of an intracerebral multiform glioblastoma and died 4 months later of a relapse in the brain stem. The 28-year-old female recipient had undergone transplantation for an autoimmune-hepatitic cirrhosis. Four months later, histopathological examination of an intraperitoneal and intrahepatic mass revealed a poorly differentiated, small-cell pleomorphic cancer, identified as a glioma metastasis by S100- and glial fibrillary acidic protein immunohistochemical staining. The patient died 6 months post-transplantation. On autopsy, no further neoplastic lesions were detected. Our review adds a second reported case of a liver graft-transmitted brain tumor to the literature and the fourth donor-related malignancy after hepatic transplantation in general.

Adult↗

Conversion to tacrolimus after liver transplantation.

We have reviewed our experience with conversion to tacrolimus after 435 liver transplantations. Tacrolimus was administered as a rescue agent in 33 patients until October 1993. Indications for rescue therapy were: cholestatic forms of severe, steroid-resistant cellular rejection (n = 8), OKT3-resistant cellular rejections (n = 6), cellular rejections in patients suffering from cyclosporin malabsorption (n = 4), late onset cellular rejections (n = 4), early chronic rejections (n = 3), and chronic vascular or ductopenic rejections (n = 8). Response was evident in 29 of the 33 patients (88%), whereas 4 patients (12%) were nonresponsive. Patient and graft survival were 76% and 70%, respectively. Graft loss with or without patient death occurred in three of eight patients suffering from severe, steroid-resistant cellular rejection, in two of six patients with OKT3-resistant cellular rejections, and in five of eight patients undergoing chronic rejection. In severe steroid-resistant cellular rejection, successful tacrolimus rescue therapy corresponded to a significantly lower total serum bilirubin than unsuccessful therapy (12.0 +/- 5.6 mg% vs 29.7 +/- 5.9 mg%, P < 0.05). We conclude that tacrolimus rescue therapy is a safe and efficient alternative for high-risk cases that do not respond to conservative treatment. In severe, steroid-resistant cellular rejection and in chronic ductopenic rejection, conversion to tacrolimus is beneficial only in a limited number of cases. A predictive parameter, which total serum bilirubin may prove to be in severe, steroid-resistant cellular rejection, is needed to select those cases that might benefit more from retransplantation than from conversion to tacrolimus.

Adult↗

Exhaled nitric oxide in childhood asthma.

UNLABELLED: Endogenous synthesis of nitric oxide (NO) and its presence in exhaled air was observed in various species including humans. Particularly high levels were found in adults with bronchial asthma, possibly because of the underlying pulmonary inflammatory activity. We studied oral and nasal exhaled NO by chemiluminescence in 47 children aged between 6 and 10 years. Thirty children had bronchial asthma, 17 were healthy controls. In asthmatic children oral exhaled NO was 13.4 +/- 1.4 parts per billion (ppb) (mean +/- SEM), nasal exhaled NO was 21.7 +/- 1.5 ppb. In healthy controls oral exhaled NO was 7.2 +/0 1.0 ppb, nasal exhaled NO was 18.2 +/- 22 ppb. Oral exhaled NO was significantly higher in asthmatic children compared to healthy controls (P = 0.0017). Nasal exhaled NO did not differ significantly in the two groups. There was a significant negative correlation between oral exhaled NO and forced expiratory volume in 1 s (FeV1). No significant correlation between oral or nasal exhaled NO and other markers of obstructive lung function impairment, oral minute ventilation, the body mass index and the presence of upper respiratory tract infection could be found. CONCLUSION: Children with bronchial asthma have significantly higher levels of orally exhaled nitric oxide than healthy controls.

Asthma↗

Identification of carcinoembryonic antigen-producing cells circulating in the blood of patients with colorectal carcinoma by reverse transcriptase polymerase chain reaction.

BACKGROUND: Application of the reverse transcriptase polymerase chain reaction (RT-PCR) to identification of circulating tumour cells in colorectal cancer. AIMS: To assess whether circulating malignant cells in patients with colorectal liver metastasis could be identified by RT-PCR recognition of mRNA coding for the tumour marker carcinoembryonic antigen (CEA). PATIENTS: A total of 31 with colorectal liver metastases and 22 no-cancer controls. METHODS: Specific cDNA primers for CEA transcripts were used to apply RT-PCR to tissue biopsy specimens, colon carcinoma cell lines, and peripheral blood samples from patients with colorectal liver metastases. A strongly CEA-expressive HT115 colorectal carcinoma cell line was used to spike blood samples from no-cancer control subjects. RESULTS: The limit for detection of CEA cDNA by Southern blotting using HT115 cells was 50 cells per 14 ml of spiked blood. There was a significant difference (p = 0.007) in RT-PCR positive expression between patients with liver metastasis (26/31) compared with controls (5/22). There was no significant relation between the prevalence of CEA cDNA amplification and serum CEA level or metastasis volume in patients with liver metastasis. CONCLUSIONS: This is the first study to suggest that identification of circulating colorectal cancer cells using RT-PCR for detection of CEA cDNA is feasible.

Biomarkers, Tumor↗

Evaluating neuroprotective agents for clinical anti-ischemic benefit using neurological and neuropsychological changes after cardiac surgery under cardiopulmonary bypass. Methodological strategies and results of a double-blind, placebo-controlled trial of GM1 ganglioside.

BACKGROUND AND PURPOSE: Many neuroprotective agents (NPAs) are effective in acute experimental cerebral ischemia in animals. None have proven effective in human stroke trials. Even short treatment delays cause substantial efficacy loss. Cardiac surgery under cardiopulmonary bypass (CS-CPB) causes cerebral ischemia with cognitive impairment at a predeterminable time point and should permit efficient screening of NPAs for stroke benefit. We sought to develop sensitive methods to assess dysfunction from CS-CPB in a double-blind trial of the NPA GM1 ganglioside. METHODS: Eighteen GM1 and 11 Control patients received GM1 300 mg or placebo, two doses intravenously, before nonemergency CS-CPB. Independent examiners administered structured neurological examinations and neuropsychological test batteries at Baseline and 1 day (Acute Postop; neurological only), 1 week (Early F/U), and > or = 6 months (Long-term F/U) postoperatively; using defined procedures they employed ordinal Clinical Change Scores (CCSs) to quantify neurological cerebral, neurological noncerebral, and neuropsychological performance changes. Several methods to analyze CCSs and neuropsychological test score changes were evaluated. RESULTS: The most sensitive indicators were the mean Acute Postop Neurologist's CCS-Cerebral (P < 10(-5)) and the mean Early F/U Neuropsychologist's CCS (P < .01), with statistically nonsignificant differences favoring GM1. No significant mean changes in Neurologist's CCS-Noncerebral or any Long-term F/U CCSs occurred. CCS distributions and neuropsychological test score mean changes showed similar temporal patterns, with less sensitivity to change. When, as usual in prior CS-CPB studies, impairment was defined by neuropsychological test score declines (increases ignored), results were spurious. CONCLUSIONS: The strokelike cerebral dysfunction (maximal acutely, with eventual recovery) that occurs after CS-CPB is useful to screen NPAs for clinical efficacy. CCSs based on detailed neurological examination and neuropsychological testing are sensitive measures; refinement of this approach should enhance the efficiency of the CS-CPB model. Further testing of GM1 is warranted.

Adult↗

[Early endotoxin tolerance--a preventive concept against infection].

After induction of early-phase endotoxin tolerance in a porcine endotoxin shock model over a period of 3-4 days a highly significant survival-time extension (p < or = 0.0001) was achieved. The protective effect of the unspecific tolerant state led to a significant enhancement of cardiorespiratory parameters during the continuous endotoxin challenge. However, the level of tolerance is relative and can be overcome by increasing the endotoxin challenge dose.

Animals↗

Prophylactic pharmacologic neuroprotection against focal cerebral ischemia.

The crucial importance of the earliest possible treatment of ischemic stroke has been stressed. This leads to the concept of prophylactic neuroprotection: long-term administration of neuroprotective agents to people at risk for stroke, so that the effects of focal ischemia are countered from the moment of onset of vascular occlusion. We at NYU (and researchers at several other centers) have been testing possible neuroprotective agents in the cardiopulmonary bypass setting. We believe that by such means we can rapidly and economically screen agents and dose schedules for efficacy. We believe that an agent demonstrably reducing mental impairment after cardiopulmonary bypass suggests that testing such an agent in a prospective manner in people at risk for stroke would be productive, and we propose a sequence for such trials: people during and in the first month after carotid endarterectomy, then postcarotid endarterectomy patients during long-term follow-up, and finally populations at risk for spontaneous stroke in the nonvascular surgery setting.

Age Factors↗

Comparison of FK506- and cyclosporine-based immunosuppression in primary orthotopic liver transplantation. A single center experience.

FK506 has been proven effective for prevention and treatment of liver allograft rejection. Herein, we compare FK506-based immunosuppression with an effective quadruple immunosuppressive regimen, including cyclosporine and antithymocyte globulin. The results of a single center participating in the European multicenter FK506 study are reported, including immunosuppressive efficacy as well as toxicity. One-year patient and graft survival was 96.7% and 90.0% for the CsA group and 90.2% and 88.5% for the FK506 group, which is not statistically different. The incidence and severity of acute rejection episodes during the first postoperative year was similar in both treatment groups with 34.4% and 33.3% for the FK506 and CsA treatment group, respectively. Immunosuppressive potency was better for the FK506 group compared with the CsA group according to the incidence of chronic rejection. Furthermore, 5 patients (8.3%) required conversion to FK506 for immunological reasons, i.e., refractory acute or chronic rejection. The incidence of moderate and severe neurotoxicity during the early postoperative period was higher in the FK506 group (21.3%) compared with the CsA group (11.7%), while the incidence of renal insufficiency and acute renal failure was similar (18.0% and 18.3% for the FK506 and CsA treatment groups, respectively). The incidence of CMV infection was significantly higher under treatment with CsA (25.0%) than with FK506 (6.6%) (P < or = 0.05), while the incidence of pneumonia (13.1% and 13.3%), cholangitis (29.5% and 26.7%), and urinary tract infection (39.3% and 28.3% for the FK506 and CsA treatment groups, respectively) was similar in both treatment groups. However, infection was more serious in some cases treated with FK506, and evolved as the main cause of death in the FK506 treatment group. Therefore, caution should be paid to over immunosuppression and toxicity in FK506-treated patients. Regarding the monitoring of FK506, FK506 plasma level failed to be a reliable indicator, and therefore we recommend measurement of whole blood FK506 levels. Our data indicate that immunosuppressive potency of FK506 is greater than that of CsA, especially concerning the incidence of chronic rejection.

Adolescent↗

Somatostatin receptor subtypes in neuroendocrine tumor cell lines and tumor tissues.

Somatostatin receptor scintigraphy (SRS) is positive in approximately 80% of all patients who have been found to have neuroendocrine (NE) gastroenteropancreatic (GEP) tumors. The reasons for negative results are unclear. The aim of the present study was identification of the specific somatostatin receptor (SSTR) subtypes that are responsible for the in vivo binding of the widely used somatostatin (SST) analogues octreotide and lanreotide in human neuroendocrine gastroenteropancreatic tumors. Ten patients were subjected to SRS with radiolabeled octreotide. Following surgical resection, tumor tissues were analyzed for SSTR subtype mRNA expression by the reverse transcription-polymerase chain reaction (RT-PCR). In addition, SSTR subtype transcripts were investigated by Northern blot analysis and RT-PCR in neuroendocrine tumor cell lines. Expression of SSTR at the protein level was studied by chemical cross-linking experiments. Three patients were negative by SRS. However, RT-PCR revealed most prominently SSTR 2 expression in all tumor specimens. In addition, all tumor tissues analyzed by chemical crosslinking exhibited SST-14 binding sites, indicating that at least some NE tumors were false-negative on SRS.

Animals↗

Mycobacterial infection after liver transplantation.

Tuberculosis occurred in 5 (1.2%) of 462 liver transplant recipients. De novo infection was assumed in 4 patients and a recurrent infection in 1. The clinical courses varied, from asymptomatic open lung tuberculosis to disseminated disease with cerebral tuberculoma and convulsions. Four patients survived with anti-tuberculous triple-drug therapy. Very few cases of tuberculosis after liver transplantation have been reported (4 patients in the medical literature and 5 patients in this paper). However, the incidence, course of infection, and outcome seem to be similar to those of tuberculosis in renal transplant recipients, approximately 150 cases of which are known.

Adolescent↗