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Biomedical subjects

J Carles

Publications and source records attributed to J Carles.

At least 55 records · Page 3Linked to original sources

Ultrastructure of human liver grafts preserved with UW solution. Comparison between patients with low and high postoperative transaminases levels.

We studied the morphology of sinusoidal cells on 21 human liver grafts prior to harvesting, at the end of the preservation period in UW solution, and after complete revascularization. The mean cold ischemic period was 11 h 34 min. Immediate follow-up was uneventful in 20 of these cases; 13 showed a mean peak of postoperative transaminases below 1,300 IU/L (group A), and 7 above 1,500 IU/L (group B). In the case of one patient (group C) steatosis was severe (50%) and there was serious postoperative dysfunction (transaminases 18,000 IU/L). Biopsies were perfusion-fixed by the transparenchymal route to ensure satisfactory ultrastructural results. In group A, some sinusoidal endothelial cells presented signs of activation at the end of the preservation period, and even more after revascularization. Kupffer cells also presented signs of activation particularly after reperfusion. Signs of endothelial cell damage with gaps and partial rupture of the plasmic membrane were also observed, particularly after revascularization in areas which contained numerous inflammatory cells adhering to the wall. The sinusoidal pole of hepatocytes was occasionally damaged, with the formation of blebs. In group B, adhesion of inflammatory cells to the sinusoidal wall was increased. Furthermore, in some areas with endothelial cell damage, neutrophils and platelets infiltrated the Disse space, and hepatocytes were increasingly damaged. In the case of patient C, the most obvious signs after reperfusion were hepatocyte drop out and death but there was no evidence of any concomitant sinusoidal cell damage. It would appear that even in cases where immediate follow-up is eventful, endothelial and Kupffer cells show signs of activation. This can be associated with signs of microcirculatory disturbances as was seen in 4 cases in group B. In the only case of severe steatosis that we studied, the essential sign was death of hepatocytes.

Adenosine↗

Pontine myelinolysis following liver transplantation: a report of two cases.

Two cases of central pontine myelinolysis (CPM) following orthotopic liver transplantation (OLT) are reported. Several months after the onset of this neurological syndrome, the two patients are still alive but with severe neurological sequelae. Some patients undergoing emergency OLT present a high risk of CPM because of pre-existing malnutrition, encephalopathy, and hepatic insufficiency. All of these are associated with an inevitable abrupt rise in sodium serum concentration due to intraoperative compensation of blood losses with high-sodium content blood products. Whenever the renal capacity to excrete sodium is impaired by the surgical procedure, continuous intraoperative venovenous hemofiltration is recommended.

Adult↗

Neuroendocrine differentiation as a prognostic factor in non-small cell lung cancer.

The prognostic value of clinical and pathological factors in 97 patients with non-small cell lung cancer (NSCLC), were analyzed through immunohistochemical methods. The impact on response rate and survival of age, Karnofsky performance status (PS), sex, NSCLC subtype and grade, extent of disease, objective chemotherapy response, LDH values, metastatic sites involved and immunohistochemical markers of neuroendocrine differentiation (neuron specific enolase (NSE), synaptophysin (Sy 38), chromogranin (Chr A) and Leu-7) were analyzed. Median age was 61 years and seven patients were women. Histologically, 58 had squamous cell carcinoma, 28 adenocarcinoma and 11 large cell undifferentiated carcinoma. One patient had Stage II, 35 Stage IIIa, 19 Stage IIIb and 42 Stage IV. Six patients achieved complete response, 18 partial response, 34 stable disease and 39 progressive disease. NSE was negative in 54.3% of cases as was Sy 38 (77.4%), Chr A (97.8%) and Leu-7 (95.8%). We have found correlation between neuroendocrine differentiation and absence of P-Glycoprotein expression; patients included in this subset had a higher response rate but no evidence of longer survival. The univariate analysis showed that four parameters had significant adverse effect on survival: non-responders, poor PS, abnormal LDH value and absence of NSE expression. Multivariate analysis showed that the best combination of independent prognostic factors in predicting survival was: PS and NSE expression by immunohistochemical methods.

Adult↗

[Estimation of liver volume as a function of the individual's morphology].

Computed tomography using transversal scanning, may be usefull in the determination of liver volume. The aim of this study is to evaluate this technique in living subjects and to determine a relationship between liver volume and morphological body surface area and other morphological criteria. In a series of 25 patients, liver volume was computed from the body surface area, using a mathematical function. This method allow a quick and accurate determination of the liver volume which could be used in liver transplantation for a better matching between donor liver and recipient.

Anthropometry↗

[Efficacy and tolerance of imipenem/cilastatin in the adjuvant treatment of surgery for peritonitis in patients over the age of 70 years].

Eighty eight patients over the age of 70 years, suffering from peritonitis, were treated with imipenem/cilastatin single-agent therapy as a complement to surgery. The recommended dosage was 30 mg/kg/day and could be increased up to 50 mg/kg/day, without exceeding four grams per day, administered by four infusions per day. Seventy three patients (32 males, 41 females) with a mean, age of eighty years and suffering from peritonitis due to perforation, were evaluated. One half of patients presented one or several risk factors on inclusion into the study, one third received ventilatory assistance and 28.5% presented with shock. The perforation was situated in the stomach and duodenum (N = 24), biliary tract (N = 8), small intestine (N = 3), caecum (N = 10) and colon or sigmoid (N = 28). The infection was polymicrobial in 57.4% of cases. Blood cultures were positive in seven patients and cultures remained sterile in seven patients. A clinical success was obtained in sixty four patients (87%): fifty-six patients were cured and eight were improved. Six patients died as a result of infection (mortality: 8.2%) and three were not improved. No failure was due to development of an imipenem-resistant organism. These results confirm the efficacy of imipenem/cilastatin single-agent therapy as a complement to surgery for severe intra-abdominal infections in this high-risk elderly population.

Aged↗

[Experience with 150 subcutaneous venous reservoirs for venous access and infusion for the treatment of adult patients with oncologic and hematologic disorders and acquired immunodeficiency syndrome].

BACKGROUND: In the present study the year experience of a multidisciplinary team (oncologic, unit for the acquired immunodeficiency syndrome, and surgery) with the use of a new method of central intravenous administration of medication such as that of subcutaneous venous reservoirs (SVR) is reviewed. METHODS: The subcutaneous injection capsules were implanted as a venous access in 150 surgical procedures in 146 patients from October 1985 to April 1991 with a total follow up of 29.190 days and a mean length of 251 days for SVR. Sixty-two percent (94 implantations) of the SVR were implanted in the out patient clinic, 20% (30 patients) were admitted for placement of the reservoir although this was only indicated in the first two years of the series, 13% (20 patients) during hospitalization for the base disease and only 4% (6 patients) were specifically admitted for surgical preparation (plasma, platelets, and others). SVR were used for chemotherapy (124 cases, 82%), repeated transfusions (6 cases, 4%) and chronic medication (acquired immunodeficiency syndrome, infections) (30 patients, 20%). Forty-two percent permitted chemotherapy administration by continual transfusion on an out patient regime. RESULTS: A series of mechanical complications (3 cases, 2%), septic (9 episodes in 7 patients, 5%) and thrombotic (8 of the catheter) (5%) and 4 of the central veins (2%) were observed. In the present series the rate of infections (5%) (0.072 episodes of bacteremia per 100 days/patient) and thrombosis (3%) was very low due to a strict protocol of maintenance and control by the medical team and hospital staff. The need for radiologic control during surgery is emphasized although, as demonstrated in the present review, the technique of localization by a cath-finder (external detector) permits greater speed with the same security. CONCLUSIONS: The degree of patient satisfaction and the minimum incidence of serious complications in determined risk groups (neutropenia, acquired immunodeficiency syndrome) demonstrates that subcutaneous venous reservoirs (SVR) constitute an excellent method as a chronic venous access. The SVR present a lower rate of complications if compared with any historic series of external vascular catheterization.

Acquired Immunodeficiency Syndrome↗

Phase II feasibility study of high dose epirubicin plus etoposide and cisplatin (HDEEC) regimen in small cell lung cancer.

Seventeen patients with small cell lung cancer entered a phase II trial testing the feasibility of adding high dose epirubicin (100-120 mg/m2, day 1) in combination with etoposide (60-80 mg/m2, days 1-5) and cisplatin (70 mg/m2, day 1) courses repeated every three weeks. Complete responders received thoracic (40 Gy) and prophylactic cranial (30 Gy) irradiation. Sixteen patients were evaluable for response and toxicity. Myelosuppression was the dose-limiting side effect. Neutropenic fever was observed in eight patients (53%) and stomatitis in six (40%). No patient had a greater than 14% decline in the cardiac ejection fraction. Strict adherence to the dose-schedule designed was impossible as doses were trimmed and delayed in 30% of instances. The overall objective response rate was 81% (95% confidence limits, 62% to 100%), in limited disease there were complete remissions in 57%. With a 16 months median follow-up, overall median survival was 13 months. This study was unable to prove the feasibility of epirubicin escalation when added to etoposide-cisplatin combination, hampering the dose-intensification Norton-Simon model test.

Antineoplastic Combined Chemotherapy Protocols↗

Phase I study of mitonafide in 120 hour continuous infusion in non-small cell lung cancer.

Mitonafide is the lead compound of a new series of antitumor drugs, the 3-Nitronaphthalimides, which have shown antineoplastic activity in vitro as well as in vivo. This phase I Mitonafide study in non-small cell lung cancer using a 120-hour continuous infusion (120 h. C.I.) schedule of administration was designed to deliver the maximum amount of drug while avoiding the risk of central nervous system (CNS) toxicity, previously observed in studies with daily short (1 hour) administration schedules. Twenty patients were treated at doses ranging from 107-200 mg/m2 x 120 h. C.I. Dose-limiting toxicity with this schedule of administration was leukopenia. Other toxicities were mild or not relevant. No CNS toxicity was observed. The recommended dose for phase II C.I. Mitonafide studies is 170 mg/m2 x 120 h. C.I. in previously untreated patients. Plasma level monitoring is recommended.

Aged↗

Comparison of three protracted antiemetic regimens for the control of delayed emesis in cisplatin-treated patients.

Antiemetic activity of three protracted regimens for the control of cisplatin-evoked delayed emesis was explored. 63 patients were randomly assigned to receive one of three protracted antiemetic schedules over 4 days. Group C patients received dexamethasone 8 mg twice daily on days 2 and 3, then 4 mg twice daily on days 4 and 5; in group B, alizapride 2.5 mg/kg four times daily on days 2-5 plus dexamethasone as in group C was administered; and in group A, metoclopramide 0.5 mg/kg four times daily on days 2-5 plus dexamethasone was given at the same dose-schedule as in groups C and B. Complete protection from delayed vomiting was achieved in 44% of group C, 30% of B and 70% of group A (P = 0.02). Mild side-effects were noted in all three groups. A higher complete protection for delayed emesis was obtained in metoclopramide-dexamethasone-treated patients. Neither of the regimens used in the protection of delayed emesis controlled late nausea.

Adult↗

A phase II study of days 1 and 8 cisplatin and recombinant alpha-2B interferon in advanced non-small cell lung cancer.

Preclinical data from studies of human lung cancer xenografts suggest that the cytotoxic effects of cisplatin are enhanced by alpha-interferon. To verify the above observations, the authors initiated a Phase II trial in advanced non-small cell lung cancer (NSCLC). Cisplatin was given at 100 mg/m2 during a 28-day cycle in a divided day 1 and day 8 schedule. Starting on day 1, alpha-2B interferon was administered intramuscularly at a dose of 5 million units three times a week continuously for a minimum of 2 months. Between January 1989 and September 1989, 30 patients were evaluated for response and toxicity. According to the staging system proposed by Mountain, 20 patients had Stage IV disease, 7 had Stage IIIB disease, and 3 had Stage IIIA disease. Expression of neuron-specific enolase (NSE) and Leu-7 was immunohistochemically investigated to evaluate possible relationship to treatment response. The response rate was 13.3% (95% confidence interval [CI]: 1.2% to 25%). The four responders showed positivity for NSE, and two of them were positive for Leu-7. An average of three cycles was given. The mean dose intensity administered was 83% of the projected dose for cisplatin and 92% of the projected dose for alpha-2B interferon. A standard scale was used to assess interferon toxicity. Hematologic, renal, and systemic side effects were not significant. In advanced NSCLC the addition of alpha-2B interferon did not increase the cisplatin-induced response rate. Further studies should be performed to determine the real value of chemotherapy response in tumors showing positive immunoreactivity for neural markers such as NSE and Leu-7.

Adult↗

Sequential combination of methotrexate (MTX), 5-fluorouracil (FU), and high-dose folinic acid (FA) in advanced colorectal cancer: double biochemical modulation?

Thirty evaluable patients were treated with methotrexate (MTX) 200 mg/m2, i.v. infusion over 60 minutes, 24 hours prior to the administration of 5-fluorouracil 600 mg/m2, and folinic acid 200 mg/m2, i.v. infusion over 60 minutes, every 2 weeks. A partial or complete response was achieved in 12 patients (40%), and disease stable in 10 patients (33%). Median actuarial survival was 18 months. Side effects, which were within acceptable limits, included 11 cases of stomatitis (5 Grade 3), 3 cases of leukopenia (Grade 2) and 12 cases of mild nausea and vomiting. We conclude that the present combination is active in metastatic colorectal cancer with mild toxicity. These results are being confirmed and a randomized trial is being carried out to prove that this combination holds therapeutic advantage.

Adenocarcinoma↗

Randomized trial for the control of acute vomiting in cisplatin-treated patients: high-dose metoclopramide with dexamethasone and lorazepam as adjuncts versus high-dose alizapride plus dexamethasone and lorazepam. Study of the incidence of delayed emesis.

This study investigated the antiemetic activity of two different acute antiemesis regimens in patients receiving cisplatin-based chemotherapy. Seventy-four patients were treated with high-dose metoclopramide, dexamethasone and lorazepam (MDL) and 71 patients received high-dose alizapride, dexamethasone and lorazepam (ADL). Complete protection from vomiting was 50% in MDL-treated patients as compared with 30% in the ADL arm (p = 0.04). Incidence of delayed emesis was assessed in the first 82 patients accrued for the 120 h postcisplatin, being 69 and 60% in MDL and ADL, respectively.

Antiemetics↗