Search PubMed⌕ Search

Biomedical subjects

R Adam

Publications and source records attributed to R Adam.

At least 73 records · Page 4Linked to original sources

[Liver transplantation in the treatment strategy of portal hypertension].

We reviewed 1000 consecutive liver transplants over a 10 year period with special attention to a pre-transplant history of portal hypertension revealed by variceal hemorrhage. Of 730 primary transplanted patients with chronic liver disease 186 (26%) experienced variceal bleeding prior to transplantation of which 130 (70%) required interventional therapy to palliate the bleeding. Sclerotherapy was performed in 93 (50%), surgical portal diversion in 27 (15%) and TIPSS in 10 (5%) patients. Moderate to severe liver dysfunction accounted for 91% of the patients with bleeding complications. The impact of both bleeding and treatment modality utilized in the pre-transplant period was analyzed in a way to integrate liver transplantation into the multimodality treatment of portal hypertension. The overall survival for all patients was 76% at five years. Previous history of variceal bleeding did not affect the outcome of patients following liver transplantation. The patients treated by initial sclerotherapy demonstrated no difference with either graft or patient survival. The patients who had TIPSS to control hemorrhage had lower, but insignificant, graft and patient survival. The group of patients with variceal hemorrhage who had prior surgical shunt did, however, demonstrate a significant increased survival of 96% when compared to the non-shunted group which had a 73% survival (p < 0.007). The strategy in treating these potential transplant patients is critical to the success of the subsequent transplant.

Adult↗

A phase I-II trial of five-day continuous intravenous infusion of 5-fluorouracil delivered at circadian rhythm modulated rate in patients with metastatic colorectal cancer.

The toxicity of 5-fluorouracil (5-FU) was decreased by two to eight-fold if this drug was injected in mice near the middle of the day (rest span) rather than in the middle of the night (activity span). If the rhythm in 5-FU toxicity is linked to the sleep-wakefulness endogenous circadian cycle across species, the least toxic time in man would correspond to 4.00 hours at night. The availability of a single-reservoir programmable-in-time external ambulatory pump (Chronopump, Autosyringe, Hooksett, USA) allowed us to perform a first test of this hypothesis. Five-FU was infused for 5 consecutive days, via an implanted venous access port, with peak drug delivery at 4.00 hours and no infusion from 18.00 to 22.00 hours. Each course was repeated after a free interval of 16 days. Intrapatient dose escalation was planned from 4 to 9 g/m2/course (800 to 1800 mg/m2/day x 5 days) if toxicity was less than grade 2 according to the World Health Organization (W.H.O.). Thirty-five patients with metastatic colorectal cancer were treated; 15 (41%) had received previous therapy, 22 (63%) had W.H.O. performance status of 2 or greater, and 19 (54%) had two or more sites involved. Grade 2 or greater toxicity was encountered in less than 5% of the courses, indicating an adequate control of toxicity via dose adjustment. Oral mucositis, diarrhea, and/or hand-foot syndrome limited dose escalation, and their incidence was dose dependent. Median maximal tolerated dose was 7.5 mg/m2/course in 30 patients assessed for this endpoint.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

An experimental approach for dynamic rat liver observation in vivo and ex vivo by 31P localized MR spectroscopy for follow-up of liver status at different steps of orthotopic transplantation--a feasibility study.

An experimental approach was evaluated to perform a follow-up of rat liver transplantation by 31P spectroscopy. The approach is based on the use of an implanted surface coil attached to the liver and inductively coupled to the receiver/transmitter line by an external coupling loop. Spatial localization to the liver was performed by selective excitation and dephasing of spins in a slice between the implanted and the coupling coil, the slice being positioned on a proton image acquired prior to spectroscopy. Characteristics of the protocol were established on a phantom and in vivo on non-transplanted rat livers indicating good localization and high signal-to-noise ratio. Preliminary results obtained on transplanted livers revealed a relation between evolution of the 31P spectrum and animal survival. As shown in separate experiments, the same technique also enabled easy acquisition of the 31P profile of livers stored at 4 degrees C in University of Wisconsin solution. Therefore, the experimental approach described here opens up the possibility of measuring changes of the 31P profile on the same liver during the whole transplantation procedure, i.e., in the donor, during preservation and after transplantation, and comparing evolution of spectra with transplantation outcome.

Animals↗

A magnetic resonance study of the effect of nutritional status on cold-preserved murine liver.

BACKGROUND/AIMS: Clinical and experimental studies suggest a link between nutritional status and the recovery of hepatic function after hypoxic and hypothermic insults. This study aimed at determining the metabolic pathways involved in such recovery as a function of nutrition. METHODS: Livers from fed and fasted mice were perfused with oxygenated Krebs'-Henseleit buffer (RBKB). After depletion of glycogen, 31P and 13C nuclear magnetic resonance spectra were acquired. Livers were flushed with University of Wisconsin solution and stored at 4 degrees C for 0, 24, or 48 hours. At reperfusion with RBKB, recovery of nucleoside triphosphates (NTP) was followed up. After 45 minutes, [3-13C]alanine was added and substrate consumption and metabolic products assessed. RESULTS: Livers from fed animals recovered more NTP at reperfusion both after 24 hours (85% +/- 11% vs. 67% +/- 7%; P < 0.01) and 48 hours (61% +/- 10% vs. 36% +/- 10%; P < 0.01, respectively) of cold storage. Gluconeogenesis as reflected by [3-13C]alanine consumption was also higher from fed animals. Hepatic glycogen before preservation was low in both groups. Livers from fasted animals contained increased triglyceride levels, but these did not contribute to NTP production at reperfusion. CONCLUSIONS: Livers from fed mice show an improved recovery after cold ischemia. Glycogen levels are low in these organs, and NTP synthesis must be from substrates other than fatty acids.

Adenosine↗

Advanced trauma life support program increases emergency room application of trauma resuscitative procedures in a developing country.

Over a 9-year period (July 1981-December 1985--pre-ATLS period; January 1986-June 1990--post-ATLS period), the hospital charts of 813 trauma patients with ISS > or = 16 were reviewed (n = 413, pre-ATLS and n = 400, post-ATLS) in order to assess the impact of the ATLS program. The frequency of endotracheal intubation (ET), nasogastric tube insertion (NG), intravenous access (i.v.), Foley catheterization of the bladder (Foley) and chest tube insertion (CT) were compared by Pearson Chi-square analysis. Overall, pre-ATLS vs. post-ATLS frequencies (%) were 83.5 vs. 65.3 for ET, 97.3 vs. 98.0 for i.v., 74.6 vs. 96.3 for Foley, 68.3 vs. 91.3 for NG, and 18.4 vs. 47.0 for CT. In the emergency room these frequencies (%) were 26.1 vs. 36.4 for ET, 98.8 vs. 98.7 for i.v., 11.0 vs. 97.1 for Foley, 3.2 vs. 95.9 for NG, and 3.9 vs. 95.2 for CT. The differences in the application of these life saving procedures between the pre-ATLS and post-ATLS periods were statistically significant (p < 0.05) except i.v. access, which showed no difference between the pre-ATLS and post-ATLS groups. Of the patients with severe chest injuries (AIS > or = 3) 87.7% had chest tubes post ATLS (94.4% in ER) compared with 48.1% pre ATLS (3.2% in ER). These differences were associated with significant improvement in trauma patient outcome post ATLS. We conclude that the frequency of lifesaving interventions, particularly in the ER, was increased post ATLS.(ABSTRACT TRUNCATED AT 250 WORDS)

Catheterization, Peripheral↗

Cognitive and attitudinal impact of the Advanced Trauma Life Support program in a developing country.

Improvement in trauma patient outcome has been reported after Advanced Training Life Support training (ATLS) in the developing country of Trinidad and Tobago (T & T). The cognitive impact of ATLS training was assessed from pre-ATLS and post-ATLS performance of T & T physicians in multiple choice question tests and comparison with post-ATLS test performance among Nebraska physicians. Overall, improvement between the pre-test and post-test among the T & T physicians was 22.0% +/- 2.0%. All physicians including failures (199 out of 212 passed) improved in their post-test scores. Individual item analysis of the post-test, including the KR-20 determination, varied but the overall performance was similar for both physician groups with the T & T physicians performing slightly better in test 2 (6 of 16 vs. 25 of 100 failures, p < 0.05). Attitudinal impact was assessed through 87 questionnaires from 50 physicians (92% response) and 37 nurses (89% response). Physicians (97.8% compared with 69.7%) were more aware of the ATLS training, and both groups (physicians, 77.3%; nurses, 69.6%) differentiated ATLS-trained physicians based on better resuscitation, more timely and appropriate consultation, greater confidence in trauma management, and improvement in trauma mortality and morbidity; all respondents recommended ATLS training for all emergency room physicians. The demonstrated positive cognitive and attitudinal effects very likely contributed to the improved post-ATLS trauma patient outcome.

Attitude of Health Personnel↗

Improving trauma care in Trinidad and Tobago.

Identification of trauma as a major cause of morbidity and mortality in Trinidad and Tobago prompted the establishment of a training programme aimed at improving trauma care in this developing country. An Advanced Trauma Life Support (ATLS) programme for physicians, funded through the Canadian International Development Agency resulted in a statistically significant improvement of in-hospital trauma patient outcome at the Port-of-Spain General Hospital (observed to expected mortality ratio of 3.16 pre-ATLS compared to 1.94 post-ATLS). A recent analysis of all motor vehicle injuries for a shorter period did not confirm this positive impact of the ATLS programme, primarily because a large number of these patients died in the pre-hospital period. Pre-hospital trauma care therefore required urgent attention to complement the positive in-hospital impact of the ATLS programme. A second training programme (the Pre-Hospital Trauma Life Support or PHTLS) for paramedical personnel was thus instituted in 1990. Over 250 physicians have been trained in the ATLS programme and to date over 100 paramedical personnel have been trained in the PHTLS programme. Attempts have also been made to equip the ambulances with more appropriate resuscitative devices in order to improve pre-hospital care. The combination of the PHTLS and the ATLS programme should result in further improvement in the care of patients sustaining major injuries in Trinidad and Tobago.

Emergency Medical Services↗

PCR detection and typing of genital papillomavirus in a New Brunswick population.

We have used a broad range of primers for HPV detection, using the polymerase chain reaction (PCR) so as to compare PCR typing of HPV with the results of cytological diagnosis in a New Brunswick population referred to the out-patient clinic of the Saint John Regional Hospital. The primers selected were found to be capable of amplification with high efficiency, therefore we did not perform further hybridization analysis for specific identification of HPV types. Amplification of selected fragments for detection of HPV 6, 11, 16, 18, 31 and 33 was obtained from cervical swabs collected from 154 patients. Microscopic examination was performed in duplicate samples and the results compared with the DNA-typing analysis. HPV of any of the above types was detected in 43 out of 154 patients. Among these, 32 patients showed single or multiple infections with "high-risk" HPV strains 16, 18, 31 or 33. Cytologically normal or atypical samples with any of the HPV types tested amounted to 17%, but increased to 56% in patients with CIN I, and to 100% in patients with CIN II or III. Prevalence of "high-risk" types alone increased from 15% and 10%, for normal and atypical cases respectively, to 48% for CIN I, 75% for CIN II and 100% for CIN III. Our results indicate that HPV detection and typing by this simple procedure can be a valuable indicator of cancer progression and thus can help to identify individuals at high risk in pre-malignant stages of the disease.

Base Sequence↗

Ultrastructural hepatic alterations in hamsters and jirds after experimental infection with the liver fluke Opisthorchis viverrini.

Changes in the hepatocytes of male hamsters (Mesocricetus auratus) and jirds (Meriones unguiculatus) at 220 days after experimental infection with the liver fluke Opisthorchis viverrini were studied by light and electron microscopy. The hepatocytes of the control group were characterized by an intracellular compartmentation. A globular nucleus was located centrally. The main features of the perinuclear zone were the cisternae of the rough endoplasmic reticulum (RER) and interjacent mitochondria, lysosomes, and peroxisomes. The peripheral cell region was dominated by glycogen fields and scattered lipid droplets, which were surrounded by anastomosing tubules of the smooth endoplasmic reticulum (SER). An immense proliferation of the SER was striking in the hepatocytes of animals infected with O. viverrini. Coincidentally, the intracellular compartmentation disappeared. Glycogen rosettes, RER, lysosomes, and lipid droplets were distributed irregularly all over the cell, the latter being observed more frequently than in control animals. The nuclei showed lobe-like protrusions and were enlarged. The mitochondria were often dumbbell-shaped and showed pathologic degenerations up to lysis. Our results resemble those of numerous investigations concerning hepatocellular alterations caused by N-nitroso compounds. Therefore, these observations suggest a synergistic effect for trematode infection and N-nitroso compounds in the pathogenesis of opisthorchiasis. The cellular alterations observed in the hepatocytes of Opisthorchis-infected animals together with the accumulation of intermediate filaments seen in the adjacent bile-duct epithelia and in the epithelium of the gall-bladder seem to indicate a disturbance of the cell metabolism and might be related to a neoplastic transformation.

Animals↗

Circadian rhythm-modulated chemotherapy with high-dose 5-fluorouracil: a pilot study in patients with pancreatic adenocarcinoma.

From November 1986 to April 1989, 16 patients with advanced measurable pancreatic carcinoma were involved in a pilot phase I-II study. 5-Fluorouracil was given every 3 weeks by 5-day continuous chronomodulated venous infusion (CMVI) with peak 5-FU delivery at 4 a.m. Intrapatient dose escalation started at 1200 mg/m2/day up to 1600 mg/m2/day in the absence of grade III (WHO) toxicity. Mucositis and diarrhoea were dose limiting in the 131 cycles given. Three partial responses (21%) and 5 stable diseases were seen in the 14 patients with measurable disease. Dose intensity after three or after six courses (1800 mg/m2/week) was significantly correlated with time to progression (Pearson r = 0.64; P < 0.004). These results, although modest, support a multicentre phase II trial with 5-FU CMVI.

Adenocarcinoma↗

Liver resection versus transplantation for hepatocellular carcinoma in cirrhotic patients.

OBJECTIVE: Currently, there is considerable controversy about the place of transplantation in the treatment of hepatocellular carcinoma (HCC). This study compared resection to transplantation in cirrhotic patients with HCC in order to determine reasonable indications of each treatment. SUMMARY BACKGROUND DATA: The usual procedure is to resect when feasible and to transplant in other cases. METHODS: Three-year survival with and without recurrence was analyzed in 60 patients who underwent resection and 60 who underwent transplantation. Several prognostic factors, such as size, number of nodules, portal thrombus, and histologic form, were studied. RESULTS: In terms of overall survival rates, resection and transplantation yield the same results (50% vs. 47%, respectively, at 3 years). For transplantation, however, the rate for survival without recurrence is better than that for resection (46% vs. 27%, respectively; p < 0.05). In the case of small uninodular or binodular tumors (< 3 cm), transplantation has much better results than resection (survival without recurrence, 83% vs. 18%, respectively; p < 0.001). However, it seems that a group of patients with high risk of recurrence after transplantation can be determined (diffuse form, more than two nodules > 3 cm, or presence of portal thrombus). CONCLUSIONS: The best indication for transplantation seems to be patients with small and uninodular or binodular tumors; until now, these patients were considered to be the best candidates for resection. Patients undergoing transplantation for unresectable, large, multinodular or diffuse tumors seem to represent bad indications for transplantation. These results could help define reasonable indications for transplantation in an era with a shortage of liver grafts.

Carcinoma, Hepatocellular↗