mdm2 deletion does not alter growth characteristics of p53-deficient embryo fibroblasts.

The mdm2 gene encodes a protein that is necessary for the negative regulation of p53 function in vivo. Deletion of the mdm2 gene in mice results in early embryonic death while concomitant mdm2 and p53 deletion results in viable offspring. The viability of these mice prompted us to ask if MDM2 had an important growth regulatory function independent of p53. We established mouse embryo fibroblasts null for both p53 and mdm2 and compared them with p53-null fibroblasts. The cells did not differ in their growth rates or their ability to bypass a G1 arrest. Both cell lines formed colonies efficiently when plated at low density and showed a similar degree of genetic instability. Thus, the analysis of several growth parameters indicated no difference between p53-null and p53/mdm2-null cell lines.

Fibrinolytic activity in laparoscopic cholecystectomy.

The aim of this study was to examine the fibrinolytic activity in laparoscopic cholecystectomy (LC) to determine whether changes occur that might indicate a greater risk of thrombosis. The study was carried out in 20 patients who had undergone laparoscopic surgery for cholelithiasis without complications. The average age was 59.4 years (34-77 years). Seventy-five percent were women. The mean operating time was 70 minutes (35-120 minutes). Pneumoperitoneum at 14 mm Hg was maintained in all patients, and they were in 30 degrees reverse Trendelenburg position. Postoperative mobilization was obtained before 24 hours, and patients were discharged 48 hours after surgery. The control group was composed of 12 patients, evenly distributed by age, sex, and length of surgery, who had undergone Bassini herniorrhaphy without complications or relapses. The following hemostatic parameters were studied: plasma fibrinolytic activity (PFA), euglobulin fibrinolytic activity (EFA), tissue-type plasminogen activator (t-PA), fast-acting plasminogen activator inhibitor-1 (PAI-1), and D-dimer (D-D). Samples were obtained at the following times: (1) under basal conditions the day before surgery, (2) preoperatively, (3) at the end of surgery, (4) 24 hours after surgery, and (5) on the seventh day following surgery. No patient had clinical manifestations of thromboembolic disease immediately after surgery or during an average follow-up period of 16 months (range 15-18 months). Analysis of the results of global fibrinolysis showed that fibrinolytic activity was enhanced only in the postoperative period (third sample) of the LC patients. The fraction of euglobulins enhances fibrinolytic activity in both groups in the third sample with regard to the other determinations; the LC patients showed a higher degree of significance (p<0.005). A significant increase of postoperative t-PA in both groups was found, being more significant in the LC group (p<0.005). In the PAI-1 values, no significant differences existed between either determinations or groups. A significant increase in D-dimer (p<0.05) occurred in the immediate postoperative period (third sample) and 24 hours later (fourth sample), returning to normal basal values on the seventh day. No significant differences were found between the two groups. These results seem to indicate that LC produces an increase in the fibrinolytic activity in plasma as a result of the liberation of tissue plasminogen activator from the venous endothelium, which could indicate hypocoagulability during the immediate postoperative period and, therefore, signify less thrombotic risk for patients undergoing this procedure.

Non heart beating donors. Succesfully expanding the donor's pool.

OBJECTIVES: Expand the donors pool is one of the most hastening problems among transplant coordination teams all over the world. Our Hospital outlined thirteen years ago a specific policy to increase donors pool with non-heart-beating-donors program. METHODS: We have developed an specific program, called "code 9" to get donors from "previously healthy" people who die of sudden or unexpected death. Madrid has one of the best emergency medical services all over the world, with response time under eight minutes, and being able to perform all kind of advanced life support maneuvers in situ and during transfer to hospital. RESULTS: From 1989 we have reported the goodness of the program and the excellence of the organs transplanted. In Madrid, one of the most active communities in Spain in organ donors procurement, 33% of donors comes from this program. Organs and tissues obtained are of same or better quality than those obtained from encephalic death donors. CONCLUSIONS: Non-heart beating programs are a good option to increase donors pool.

[Acute cholecystitis: an evaluation of the factors that determine the start of surgical treatment]. / Colecistitis aguda: valoración de los factores que condicionan el inicio del tratamiento quirúrgico.

The authors studied 100 acute cholecystitis treated between 1984 and 1990. In 71.4% of the cases it was associated with gallstones and 28.6% were primary acalculous cholecystitis. Two percent were postoperative. 77 patients underwent surgery. 14.3% needed an emergency operation due to acute abdominal syndrome and sepsis. In the remaining patients, the surgical procedure was performed days or weeks later according to the course of the disease, the surgeons criteria, and family and social-labour conditions. Based on these criteria, 31.7% had surgery during the first week, 23.8% in the second and 44.5% in the third or later. Cholecystectomy was the surgical procedure performed in 98.7% of the cases. Morbidity rate was 11.6% and mortality 3.9%. Analysis of morpho-clinical grades has been done in relation with the type of cholecystitis, the clinical symptoms and the course of the disease. Finally the different factors used to argue for an early or delayed surgical treatment are discussed.

[Carcinoma in a long-standing Zenker's diverticulum]. / Carcinoma en divertículo de Zenker de larga evolución.

The authors report a case of carcinoma arising in a longstanding Zenker's diverticulum, in a 66 years old man that refused surgical treatment for 25 years. Three months prior to his admission to our hospital, an exacerbation of his dysphagia, which became severe, was observed; and so was regurgitation, with passage to the airway during swallowing or when asleep. The esophagram showed the diverticulum without images suggestive of neoplasm, and with spilling of barium into the tracheobronchial tree. Esophagoscopy was refused by the patient. After surgical diverticulectomy, a thickened area in the inferior portion of the diverticular body was observed, which was histologically reported as a squamous cell carcinoma with pearl formation, involving only the diverticular wall. Complementary radiotherapy with TCT was administered over the esophagus, mediastinum and supraclavicular lymphatic areas, with a total dose of 5000 Cgy. Concomitant chemotherapy with Mitomycin and 5-Fluorouracil was administered. After a 2 year follow-up, the patient is completely asymptomatic. We discuss etiopathogenic factors, clinical manifestations, diagnostic procedures, and therapeutic possibilities.

[Risk factors of peptic ulcer hemorrhage]. / Estudio de factores de riesgo de la hemorragia por úlcera péptica.

A retrospective analysis is made of the risk factors in 229 patients admitted to hospital with hemorrhage from peptic ulcer. The factors that have been studied are: 1) age. 2) type of ulcer lesion. 3) associated disease. 4) antiinflammatory intake. 5) prior ulcer symptoms. 6) intensity and outcome of the bleeding episode. 7) endoscopic findings. 8) treatment modality. 9) mortality. The analysis of these factors tries to establish, by means of the square chi test with Yates correction, the possible relations between the factors, to determine which ones will have a pronostic value. From the results obtained we conclude that the factors with the highest pronostic importance are: 1) With respect to the severity of the bleeding episode, antiinflammatory intake and duodenal location of the ulcer lesion. 2) With respect to the need for urgent surgical treatment, antiinflammatory intake and prior ulcer symptoms. 3) With respect to mortality, severity, persistence and recurrence of bleeding, and the need for urgent surgical treatment. Finally, it is important to mention the absence of pronostic value, with respect to mortality, of advanced age and the endoscopic findings of active and/or recent bleeding.

[Blood gastrin changes in the late postoperative period after proximal gastric vagotomy]. / Alteraciones de la gastrinemia en el postoperatorio tardío tras vagotomía gástrica proximal.

Changes in serum gastrin levels in the late postoperative period have been studied in 24 patients with non-stenotic duodenal ulcer who underwent proximal gastric vagotomy. Twenty healthy volunteers were used as a control group. Serum gastrin levels were determined under basal conditions and after a high protein meal stimulation. Both measurements were done in the preoperative, early postoperative (12th day) and late postoperative periods (X = 5.5 yrs.). Regarding basal serum gastrin levels, the results show mean values of 46.2 pg/ml in the preoperative, 61.6 pg/ml in the early postoperative, 73.9 pg/ml in the late postoperative and 51 pg/ml in the control group. Early and late postoperative period values show statistical significant differences when compared with preoperative values (p < 0.05), but not with the control group ones. Stimulated gastrin levels show mean values of 75.7 pg/ml in the preoperative, 99.1 pg/ml in the early postoperative, 134.1 pg/ml in the late postoperative and 73.4 pg/ml in the control group. Late postoperative values show statistical significant differences when compared with preoperative and early postoperative values (p < 0.05), and also when compared with the control group (p < 0.05). Possible causes and the physiopathological effects of these variations are discussed.

[Determination of basal and stimulated blood gastrin in duodenal ulcer]. / Valoración de la gastrinemia basal y estimulada en la úlcera duodenal.

Serum gastrin levels were measured under basal conditions and after hyperproteic meal stimulation in 24 patients with non-stenotic duodenal ulcer, 78% of them were males with a mean age of 36.4 years. Results were compared with those obtained in 20 volunteers. Basal gastrin levels in patients with duodenal ulcer 46.2 +/- 17.5 pg/ml did not show any significant statistical differences when compared with those in the control group (51.01 +/- 28.1 pg/ml). After meal stimulation gastrin levels at different time intervals, were similar in patients with duodenal ulcer and in the control group. We conclude that serum gastrin does not seem to play a relevant pathogenic role in the development of duodenal ulcer; its measurement is of no value as a biological marker of duodenal ulcer disease.

[Anatomopathologic changes in the distal esophagus following proximal gastric vagotomy. Experimental study]. / Cambios anatomo-patológicos en el esófago distal tras la vagotomía gástrica proximal. Estudio experimental.

In order to determine the causes of postvagotomy dysphagia, we examined microscopic changes in the lower esophagus after a proximal gastric vagotomy. Forty dogs were divided into 4 groups (n = 10). Group I was used as control. In group II, the effect of denervation was studied by means of transthoracic vagotomy. In group III, the effect of mechanical traction of the lower esophagus was studied, without denervation or surgical manoeuvres. In group IV, the effect of denervation, esophageal traction and the surgical manoeuvres, of proximal gastric vagotomy was examined. No periesophageal hematomas or fibrosis was found. Degenerative nerve phenomena were found with no significant differences in the three groups. In groups III and IV, lesions of the esophageal muscular layer were observed, without significant differences. Chronic inflammatory changes and fibrosis were also encountered being more intense and significantly more frequent in group IV. We conclude that the surgical manoeuvers necessary to obtain denervation of the cardioesophageal function during proximal gastric vagotomy, could be responsible for the appearance of post-vagotomy dysphagia.

Laboratory evaluation of the effect of prophylaxis for thromboembolism with fractionated heparin in patients undergoing laparoscopic cholecystectomy.

OBJECTIVE: We studied the effect of prophylaxis for thromboembolism with low-molecular-weight heparin (LMWH) during hospitalization on the biological hemostasis system in patients who had undergone laparoscopic cholecystectomy. METHODS: This was a prospective paired cohort study without a control group (i.e., a before-after study). The subjects were 20 patients operated on laparoscopically for uncomplicated cholelithiasis. All patients received LMWH 2 h before the operation and 24 h after the first dose. Mean duration of surgery was 70 min. Pneumoperitoneum was accomplished at 14 mmHg, and all patients were operated on in the inverted Trendelenberg position (30 degrees). Patients were mobilized within 24 h, and were discharged within 48 h after surgery. As parameters of hemostasis we studied anti-Xa factor activity (anti-Xa), antithrombin III (AT III), partial active thromboplastin time (PTT) and fibrinogen. Samples were taken for laboratory analyses under basal conditions the day before the operation (first determination), 1 h after the first preoperative dose of LMWH was given (second), at the end of the operation (third), 24 h after surgery (fourth), and on postoperative day 7 (fifth). RESULTS: Mean basal values of all parameters were within the normal range. Mean anti-Xa activity was significantly higher in the second and third determinations than in the first and fifth measurements (p < 0.05). Mean PTT was significantly elevated on the second determination and decreased thereafter; however, none of the results differed significantly from the normal value. Mean AT III was significantly lower in the third determination in comparison with the first and fifth measurements. Fibrinogen was significantly higher in the fourth and fifth determinations than in the second and third measurements. Among all parameters and sampling times, the only values outside the normal range were anti-Xa activity on the second, third and fourth determinations. CONCLUSIONS: Plasma anti-Xa factor activity was increased preoperatively, and remained elevated for 24 h after surgery, returning to basal values on postoperative day 7. Partial thromboplastin time was slightly prolonged after the first dose of LMWH, indicating good antithrombotic action.

[The role of olanzapine in Parkinsonian dopaminergic psychosis]. / Papel de la olanzapina en la psicosis dopaminérgica parkinsoniana.

INTRODUCTION: The drug induced psychosis (DIP) that appears in Parkinson s disease (PD) is a frequent complication which is difficult to deal with therapeutically. Treatment is based on lowering the amount of antiparkinson drugs or using classical neuroleptics (haloperidol), which in both cases deteriorates motor function. Recently, antipsychotic drugs have appeared which are called atypical (AA) due to their scarce or null motor effects. METHOD: We carried out a review of the research work that has been published in which one of these AA, olanzapine (OLZ), was used to treat the DIP that appears in PD patients. The results obtained show OLZ to be an effective antipsychotic drug. However, the data on its capacity to deteriorate motor function is contradictory and it has not been possible to pinpoint the reasons why this adverse side effect appears in some patients and not in others. The causes that have been suggested, although they do not account for all the cases, are the use of high doses of OLZ and the prior existence of dementia. Moreover, some cases of OLZ induced agranulocytosis have been detected, although it was thought that this side effect within the AA was exclusive to clozapine. CONCLUSION: Although it is effective as an antipsychotic drug, there exists contradictory data about the capacity of OLZ to deteriorate the state of patients suffering from Parkinson s disease, which means that it does not seem to be the first choice drug in the DIP that appears in PD.

[Bilateral hemifacial spasm: eight personal case reports]. / Espasmo hemifacial bilateral. A propósito de ocho casos.

INTRODUCTION: Hemifacial spasms consist in tonic clonic, involuntary, asymmetrical and asynchronous contractions in the territory innerved by the facial nerve. Several different causes may give rise to this disorder, the most frequent of which are vascular abnormalities in the cerebellopontine angle. Its clinical features and electrophysiological studies are commonly used in diagnosis and its etiological diagnosis is most frequently performed by means of magnetic resonance imaging. Symptoms are treated using local injections of Botulinum toxin Type A in the affected muscles. AIMS: To review our experience in the handling of this pathological condition and to determine the results of employing Botulinum toxin. PATIENTS AND METHODS: We describe the cases of bilateral hemifacial spasms that have been diagnosed in the Virgen Macarena Hospital in Seville and La Fe in Valencia since 1980, as well as the follow up after treatment with Botulinum toxin. RESULTS: We describe eight cases of this pathological condition in which patients were treated with Botulinum toxin, and in all cases there was an improvement in the symptoms. CONCLUSIONS: Treatment with Botulinum toxin is considered to be satisfactory and provides a marked improvement in the patients quality of life.

[Kidney transplantation: the current situation in Portugal, 1989]. / Transplantação renal: o ponto da situação em Portugal, 1989.

The modern treatment of renal failure has been one of the most exciting developments of modern medicine. Within this field the portuguese doctors had a performance that compares with the average developed countries. The number of patients that need haemodialysis and renal transplantation is still increasing. These treatments are very expensive. As the patients would die if not treated, this whole issue is a political concern and a public health problem. We give the demographic outline of this CRF patients group. Dialysis and transplantation should be in balance, with a particular stress on transplantation because it is much less expensive. Shortness of organ supply has been like elsewhere the most important limiting factor of renal transplantation. Some public controversy concerning brain death, permission, and commercial profit from organ donation, has been sometimes deleterious. We review the results of renal transplantation. In 1987 and 1988, 92% of transplanted kidneys had still function after one year. We conclude that our programs in Portugal can expand, on the condition that people keep their acceptance and give their support to transplanting teams.

[Kidney transplant: the current situation in Portugal, 1989]. / Transplantação renal: o ponto da situação em Portugal, 1989.

The modern treatment of renal failure has been one of the most exciting developments of modern medicine. Within this field the portuguese doctors had a performance that compares with the average developed countries. The number of patients that need haemodialysis and renal transplantation is still increasing. These treatments are very expensive. As the patients would die if not treated, this whole issue is a political concern and a public health problem. We give the demographic outline of this CRF patients group. Dialysis and transplantation should be in balance, with a particular stress on transplantation because it is much less expensive. Shortness of organ supply has been like elsewhere the most important limiting factor of renal transplantation. Some public controversy concerning brain death, permission, and commercial profit from organ donation, has been sometimes deleterious. We review the results of renal transplantation. In 1987 and 1988, 92% of transplanted kidneys had still function after one year. We conclude that our programs in Portugal can expand, on the condition that people keep their acceptance and give their support to transplanting teams.