Doppler ultrasonographic and scintigraphic assessment of an auxiliary heterotopic liver transplantation with portal vein arterialization in pigs.

OBJECTIVE: Our aim was to evaluate liver graft integrity and function using scintigraphy and ultrasonography in a porcine model of auxiliary heterotopic liver transplantation with portal vein arterialization (AHLT-PVA). MATERIALS AND METHODS: Using Doppler ultrasonography we evaluated eight AHLT-PVA by parenchymal echogenicity, portal and arterial anatomy, and portal and biliary system flow. Two types of scintigraphy were performed: microaggregated human albumin colloid scintigraphy and diisopropyl iminodiacetic acid (DISIDA) scintigraphy, both labeled with 99mTc. RESULTS: The animals were distributed into two groups. The first group consisted of three animals with clinical suspicion of graft dysfunction, in which the ultrasonographic study revealed areas of parenchymal destructuring. In the scintigraphic study, heterogenous uptake was observed; there was no uptake in one animal. Necropsy of these three animals revealed areas of graft necrosis. The second group consisted of five animals with good clinical evolutions, in which the ultrasonographic study showed portal dilation, portal flow with arterial spiculations, and homogenous echogenicity of the hepatic parenchyma. The scintigraphic study revealed homogenous uptake by the graft and an elimination speed of the hepatobiliary agent similar to that of the native liver. CONCLUSIONS: An heterogenous echostructure of the graft provided a sign of poor prognosis indicating necrosis in the same way as heterogenous uptake or nonuptake of radioisotope upon scintigraphy. Scintigraphy is a good method to evaluate biliary function and bile elimination. In an AHLT-PVA, the main ultrasound findings derived from arterialization were dilation of the portal system and portal flow with arterial spiculations.

Prevention of hyperacute rejection in a model of orthotopic liver xenotransplantation from pig to baboon using polytransgenic pig livers (CD55, CD59, and H-transferase).

INTRODUCTION: The search for alternative sources for transplant organs leads us to the search for animals as an inexhaustible source of organs. The objective of this study was to analyze whether livers from polytransgenic pigs expressing the human complement regulatory proteins CD55 (hDAF), CD59, and alfa alpha1,2-fucosyltransferase (H-transferase), protected against hyperacute rejection after orthotopic liver xenotransplantation to a baboon and also to study pig liver function in a nonhuman primate. MATERIALS AND METHODS: Nine liver transplants from pig to baboon were divided into two groups: a control group (n = 4) of genetically unmodified pigs and an experimental group (n = 5) of pigs transgenic for CD55, CD59, and H-transferase as donors. All the donating piglets obtained through hysterectomy were maintained in specific pathogen-free conditions. The selection of transgenic pig donors followed demonstration of transgene expression using monoclonal antibodies (antiCD55, antiCD59) and immunohistological studies on liver biopsies. RESULTS: All animals in the control group developed hyperacute rejection with survival rates less than 16 hours without function of transplanted livers. In the experimental group none of the animals suffered hyperacute rejection. Survival in this group was between 13 and 24 hours. The livers were functional, producing bile and maintaining above 35% prothrombin activity. Only in one case was there primary dysfunction of the xenograft. CONCLUSION: Polytransgenic livers for complement regulatory proteins prevent hyperacute rejection when xenotransplanted into a baboon.

Glomangiosarcoma of the hypothenar eminence: a case report.

Glomangiosarcoma is an exceptionally rare soft tissue tumor. It tends to appear as a painful nodule located in the subcutaneous tissue. There are only two cases described on the hand before instead of the benign glomus tumor is usually located at this level. Histochemically the glomangiosarcoma shows features that remind a benign glomus tumor, except for the malignant glomus tumor arising de novo. This neoplasm is considered a low grade malignant tumor with tendency to local recurrence, though metastasis have been reported. We report the case of a 36 year-old -woman with a glomangiosarcoma in a glomus tumor in the hypotenar eminence. The treatment was a local complete excision and there was no signs of recurrence after 18 months.

Life-supporting human complement regulator decay accelerating factor transgenic pig liver xenograft maintains the metabolic function and coagulation in the nonhuman primate for up to 8 days.

BACKGROUND: It is not known whether the pig liver is capable of functioning efficiently when transplanted into a primate, neither is there experience in transplanting a liver from a transgenic pigs expressing the human complement regulator human complement regulator decay accelerating factor (h-DAF) into a baboon. The objective of this study was to determine whether the porcine liver would support the metabolic functions of non-human primates and to establish the effect of hDAF expression in the prevention of hyperacute rejection of porcine livers transplanted into primates. METHODS: Five orthotopic liver xenotransplants from pig to baboon were carried out: three from unmodified pigs and two using livers from h-DAF transgenic pigs. FINDINGS: The three control animals transplanted with livers from unmodified pigs survived for less than 12 hr. Baboons transplanted with livers from h-DAF transgenic pigs survived for 4 and 8 days. Hyperacute rejection was not detected in the baboons transplanted with hDAF transgenic pig livers; however, it was demonstrated in the three transplants from unmodified pigs. Baboons transplanted with livers from h-DAF transgenic pigs were extubated at postoperative day 1 and were awake and able to eat and drink. In the recipients of hDAF transgenic pig livers the clotting parameters reached nearly normal levels at day 2 after transplantation and remained normal up to the end of the experiments. In these hDAF liver recipients, porcine fibrinogen was first detected in the baboon plasma 2 hr postreperfusion, and was present up to the end of the experiments. One animal was euthanized at day 8 after development of sepsis and coagulopathy, the other animal arrested at day 4, after an episode of vomiting and aspiration. The postmortem examination of the hDAF transgenic liver xenografts did not demonstrate rejection. INTERPRETATION: The livers from h-DAF transgenic pigs did not undergo hyperacute rejection after orthotopic xenotransplantation in baboons. When HAR is abrogated, the porcine liver maintains sufficient coagulation and protein levels in the baboon up to 8 days after OLT.

Anthropometric, computed tomography and fat cell data in an obese population: relationship with insulin, leptin, tumor necrosis factor-alpha, sex hormone-binding globulin and sex hormones.

OBJECTIVE: To correlate anthropometric, computed tomography and fat cell data from abdominal regions with the levels of serum insulin, C-peptide, leptin, tumor necrosis factor-alpha (TNF-alpha), testosterone, 17beta-estradiol, androstenedione, dehydroepiandrosterone sulphate (DHEA-S) and sex hormone-binding globulin (SHBG). DESIGN AND METHODS: The sample consisted of 84 obese patients (29 men, 22 premenopausal women and 33 postmenopausal women) who had undergone abdominal surgery. Weight, height, percentage of body fat by skinfolds, waist, hip and thigh circumferences, sagittal and coronal diameters, visceral and subcutaneous area, serum hormones and fat cell data were studied. RESULTS AND CONCLUSIONS: Premenopausal women showed the lowest values in most abdominal distribution parameters, although, depending on the waist circumference criteria at the umbilicus level perimeter (W1) or midway between lower rib margin and iliac crest perimeter (W2), the population was classified differently, as gynoid or android. Although there were no differences in fat cell size between genders, gynoid women had smaller and more numerous fat cells than the android type. Perivisceral fat cell size was significantly smaller than subcutaneous fat cell size. In women, central obesity was significantly correlated with an increase in serum insulin, leptin, TNF-alpha, testosterone and androstenedione levels, and a decrease in 17beta-estradiol and DHEA-S, while in men significant correlations were positive with insulin and negative with testosterone and androstenedione. Fat cell size was positively correlated with serum levels of leptin, insulin, DHEA-S, androstenedione and inversely correlated with SHBG. These data indicate that hormones seem to interact not only with body fat distribution but also with fat cell size. This interaction differs between genders and between the different abdominal adipose tissue regions.

Duodenogastric reflux quantification in peptic ulcer surgery: comparison between different surgical techniques.

BACKGROUND: We quantified duodenogastric reflux with 6-hour continuous intravenous infusion of technetium 99m-labeled hepatoiminodiacetic acid (99mTc-HIDA) and subsequent quantification in gastric juice. METHODS: For this purpose, 50 patients were studied who had undergone surgery on the stomach with different surgical techniques: bilateral vagotomy plus Heineke-Mikulicz pyloroplasty, bilateral truncal vagotomy plus anterior pylorectomy, proximal gastric vagotomy, antrectomy and Billroth I reconstruction, and antrectomy and Billroth II reconstruction, comparing them with 10 healthy subjects used as a control group. We also studied the existing correlation between the rates of reflux determined by 99mTc-HIDA and those of total bile acids in gastric juice. RESULTS AND CONCLUSIONS: Patients who underwent gastric surgery had significantly greater quantities of duodenogastric reflux (p < 0.001) than had the control group. When the groups undergoing gastric surgery were compared, the patients who underwent resection showed higher reflux rates (p < 0.001) than did the patients who did not undergo resection. We found no differences among the groups of patients who did or did not undergo resection. We also found a highly significant correlation (p < 0.001) between the concentrations of 99mTc-HIDA and bile acids in gastric juice.

Hyperthermia-induced seizures alter the levels of methionine-enkephalin in immature rat brain.

The effects of hyperthermia induced seizures on the amount of Methionine-enkephalin (Met-E) in 15 day rat pups were examined. Animals exposed to an ambient temperature of 40 degrees C showed a gradual increase in body temperature reaching a maximum of 40.6 +/- 0.2 degrees C; at this time all of the animals had seizures. Elevated brain Met-E concentration was observed immediately after seizures. When the animals were exposed for 30 min to 27 degrees C environment maintained their normal body temperature throughout the experiments and no seizures were observed. The brain Met-E levels in this group were significantly lower than those observed in the animals exposed to 40 degrees C environment. These experiments suggest that enkephalinergic system may play a role in hyperthermia-induced seizures in the rat pups.

Prenatal stress alters the hypothalamic levels of methionine-enkephalin in pup rats.

We examined hypothalamic Methionine-enkephalin levels in offspring (postnatal day 10) from stressed female rats in different period of gestation: Group 1, restraint stress day 2 through 6; group 2, restraint stress day 7 through 11; group 3, restraint stress day 12 through day 16 and group 4, restraint stress day 2 through day 16. The hypothalamic levels of Methionine-enkephalin (134.37 +/- 6.19 pg/mg) in the offspring of stressed females from day 2 to day 6 of gestation were significantly (p < 0.001) higher than that obtained in the control group (100.66 +/- 10.13 pg/mg). Similar results were obtained in groups 2 and 3. However, in rat pups from females stressed during 15 days of gestation (group 4) the hypothalamic levels of Methionine-enkephalin (96.5 +/- 6.33 pg/mg) were similar to that obtained in the control group (101.5 +/- 5.15 pg/mg). These results suggest that acute prenatal stress alters the endogenous opioid activity in offspring with possible resultant effects on developmental processes.

Pituitary-adrenocortical response to acute and chronic administration of U-50,488H in the rat.

K-opioid substances have been shown to stimulate and/or depress the HPA activity. The objective of this study was to determine the effects of the acute and chronic administration of U-50,488H, a k-opioid receptor agonist, on the pituitary-adrenocortical activity in the rat. The acute administration of U-50,488H (25 mg/kg i.p.) produced a hypothermic effect and an increase in plasma levels of B-END-LI and cortisol, effects which were prevented by naloxone (3 mg/kg s.c.). Chronic administration of U-50,488H twice a day for 4 days resulted in a decrease in basal plasma levels of B-END-LI and cortisol and in the development of tolerance to its neuroendocrine and hypothermic effects. In rats made tolerant to U-50,488H, naloxone precipitated hypothermia (which is an index of opiate dependence in rats), whereas no changes in plasma B-END-LI and cortisol levels were seen. These data suggest that k receptors may be involved in the regulation of pituitary-adrenocortical activity in physiological conditions and during opiate abuse. On the other hand, U-50,488H induced only negligible dependence in rats, which was not morphine-like.

Plasma beta-endorphin and cortisol levels in morphine-tolerant rats and in naloxone-induced withdrawal.

The relationship between morphine tolerance and pituitary-adrenocortical activity was examined. In rats made tolerant to morphine by implantation of morphine-containing pellets, there was a significant reduction in plasma levels of beta-endorphin-like immunoreactivity (beta-END-LI), whereas no significant changes in cortisol levels were seen. Naloxone treatment induced an increase in plasma beta-END-LI and cortisol levels in morphine-tolerant animals. Additionally, acute morphine administration induced an increase in plasma levels of beta-END-LI and cortisol, an effect which was prevented by naloxone. These results are consistent with an increased release of pro-opiomelanocortin-derived peptides after acute morphine and with a decreased release of these peptides in tolerant rats, and suggest that opioid peptides play an important role in the regulation of pituitary-adrenocortical function.

The beta-endorphin response to prenatal stress during postnatal development in the rat.

We examined the hypothalamic beta-endorphin (B-END) levels in offspring (postnatal day 10) from stressed female rats in different period of gestation: group 1, restraint stress from day 2 to 6; group 2, from day 7 to 11 and group 3, from day 2 to 16. The hypothalamic levels of B-END in the offspring from group 1 were significantly (P < 0.001) higher to that obtained in the control. Similar results were obtained in the group 2. However, in rat pups from female stressed during 15 days of gestation hypothalamic levels of B-END were similar to control group.

Catecholaminergic activity and 3',5'-cyclic adenosine monophosphate levels in heart right ventricle after naloxone induced withdrawal.

This study evaluated the adaptive changes in noradrenergic neurons and the concomitant production of cAMP during morphine dependence and withdrawal in the right ventricle of the rat. Rats were made dependent on morphine by morphine pellet implantation for 7 days. On the day of sacrifice animals received an acute injection of saline or naloxone (1 mg/kg s.c.) and were decapitated 30 min later. Pretreatment with propranolol 15 min prior to naloxone was conducted to evaluate the possible implication of beta-adrenoceptors. The contents of noradrenaline and dopamine and their metabolites were examined. After naloxone administration to morphine-dependent rats (withdrawal) there was a pronounced increase in the content of normetanephrine and 3,4-dihydroxyphenylacetic acid and increased noradrenaline and dopamine turnover. In addition cAMP levels were increased after naloxone administration to morphine-treated rats. Propranolol did not block the hyperactivity of catecholaminergic neurons or the enhancement of cAMP observed in the heart during withdrawal. The present results indicate that heart catecholaminergic neurons play a significant role in the alterations in heart functions during morphine abstinence syndrome and suggest that those alterations are mediated through cAMP.

The positive feedback of estradiol on gonadotropin secretion in women with perimenopausal dysfunctional uterine bleeding.

The functionality of the hypothalamic-pituitary-ovarian axis was explored in 27 women with perimenopausal dysfunctional uterine bleeding. The positive feedback effect of estradiol on LH and FSH was studied by the estrogen challenge test, which was performed by a single i.m. injection of estradiol benzoate. An early decline of both LH and FSH was followed by an increase of LH, mainly due to the cases in which the estrogen test was positive. FSH remained low through the whole period tested. The results were compared with those found in 5 normal menstruating women. The frequency of positive estrogen tests, defined by an acute estradiol-induced discharge of LH, was lower in the perimenopausal patients (P less than 0.025). The results of the tests used in our study showed an impairment of the positive feedback system in the perimenopausal-dysfunctional-bleeding group.

Changes in small intestinal motility in acute physical stress--an experimental study.

The objectives of the present study were: 1) to describe the modifications in motility of the small intestine in response to situations of acute physical stress during fasting and post-prandial periods. 2) To analyse the possible involvement of the adrenergic and beta-endorphinergic systems in these modifications. For this we used a total of 60 dogs. The motility of the small intestine was recorded using electromyography techniques (monopolar electrodes) and manometric techniques (submucous microballoons). Plasma levels of beta-endorphin and catecholamines were determined before and after the stimulus. We show that physical stress applied in phases I or II of the fasting period induced a significant increase in the percentage of slow waves followed by the action potential for 1 minute in the three locations of the intestine studied (duodenum, angle of Treitz and proximal part of the jejunum), lasting from 8 to 12 minutes (p less than 0.001). When it is applied during the early post-prandial period it is responsible for a significant decrease in the percentage of slow waves followed by the action potential for 1 minute for a period of 6 to 11 minutes (p less than 0.001). The administration of adrenergic blockers prevents the effect of hypomotility caused by acute physical stress (p less than 0.001), whereas the administration of naloxone favors this hypomotility effect (p less than 0.001). Acute physical stress, on being applied during the late post-prandial period increases the percentage of slow waves followed by the action potential for 1 minute for a period of 8 minutes (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

[Mycobacterial infections: yield of bacillary microscopy in different clinical samples (1975-1988)]. / Infecciones por micobacterias: rendimiento de la baciloscopia en diferentes muestras clínicas (1975-1988).

BACKGROUND: The yield of microscopy examination as a quick diagnostic test in several pulmonary and nonpulmonary samples referred to the mycobacterial laboratory of a general hospital is reviewed. METHODS: During a 14-year period (1975-1988), 113,836 biological products were investigated. In 9,972 a positive culture for mycobacteria was obtained. For the microscopy examination the auramin technique was used; if positive, acid-alcohol resistance was confirmed by overstaining with the Ziehl-Neelsen technique. The culture was used as the reference method. RESULTS: Microscopic examination was positive in 34% of samples with a positive culture, being 39% for Mycobacterium tuberculosis and 10% for environmental mycobacteria. The overall specificity was 99%, the positive predictive value was 91% and the negative predictive value was 94%. In pleuropulmonary samples the sensitivity ranged from 48% in sputum and 2% in pleural biopsy, with specificity higher than 99%. In nonpulmonary samples, sensitivity, specificity and positive and negative predictive values varied with the type of sample. The false positive rate (positive microscopy with negative culture) was 0.3, and it was shown that 80% of these patients had received previous therapy. In organic fluids (pleural, peritoneal, cerebrospinal), the sensitivity was not greater than 13%. CONCLUSIONS: Sputum, bronchoaspirate and bronchoalveolar lavage were better for the diagnosis of tuberculosis than gastric aspirate. Approximately 1 in each positive microscopy examinations corresponded to environmental mycobacteria. In some nonpulmonary samples with high sensitivity the positive predictive value was low. 80% of the false positive results corresponded to previously treated patients.

[The effect of a race 4 hours in duration on the production of beta-endorphin and adrenocorticotropic hormone]. / Efecto de una carrera de cuatro horas de duración sobre la producción de betaendorfina y hormona adrenocorticotropa.

BACKGROUND: Physiological hormone adaptation to a prolonged and submaximum exercise is not well known. The present study was designed to evaluate changes in plasma levels of beta-endorphin and ACTH before and after a 4 hour pedestrian race. SUBJECTS AND METHOD: Fourteen amateur athletes enrolled in a 4-hour race were studied. Beta-endorphin and ACTH determinations were performed (double antibody IRMA) 10 minutes before and after the race. Simultaneously, heart rate and blood pressure were registered. RESULTS: After the race beta-endorphin level increased 2.8 times with respect to basal values (X [DE]) (42.2 [20,5] VS 14.9 [5.1] pM/I; p < 0.0001), and ACTH level increased 3.5 times (110.8 [72.9] vs 31.4 [14.2] pg/ml; p < 0.0001). There was a positive correlation between the increase of beta-endorphin and ACTH and the distance covered by each athlete (r = 0.617, p < 0.001 and r = 0.533, p < 0.05, respectively), and between the increase of basal and post-race values of both hormones (r = 0.935; p < 0.001). CONCLUSION: Prolonged and submaximum exercise provokes beta-endorphin and ACTH increase, and is related to the amount of performed exercise. There is a positive correlation between the increase of plasma levels of both hormones. Therefore, exercise amount could be one of the main modulator mechanism of beta-endorphin and ACTH release.

[Isolation of M. tuberculosis in abdominal specimens]. / Aislamiento de M. tuberculosis en muestras de origen abdominal.

The isolation of mycobacteria in abdominal specimens during a 10 years period is presented. Twenty-three clinical cases have been reviewed; patients were divided in three groups: 1) Peritoneal and intestinal tuberculosis. 2) Pulmonary tuberculosis with isolation of M. tuberculosis in feces, and 3) Miliary tuberculosis. We emphasize the low yielding of bacilloscopy, the low number of colonies in cultures and the importance of the microbiological study of abdominal specimens in the confirmatory diagnosis. The predominant symptoms of peritoneal tuberculosis were abdominal pain and distention and fever. The study of the ascitic fluid showed in most of the cases lymphocytic exudate and the pathological study of biopsies showed granulomas with caseous necrosis. Three patients had another associated abdominal disease. Isolation of M. tuberculosis in feces does not invariably mean the presence of intestinal tuberculosis. We confirm the frequent association of disseminated tuberculosis and HIV1 infection.

[Moraxella (Branhamella) catarrhalis: its isolation in the respiratory secretions of adult patients]. / Moraxella (Branhamella) catarrhalis: aislamiento en secreciones respiratorias de pacientes adultos.

OBJECTIVE: We have designed a retrospective study in order to know the clinical significance of the isolation of Moraxella (Branhamella) catarrhalis (MC) in respiratory specimens of adult hospitalized patients. METHODS: We performed a Gram stain and culture on blood-agar, MacConkey media and quantitative culture in chocolate-agar to all respiratory samples. In patients with a clinical diagnosis of pneumonia BCYE-alpha was added. During 2 years (1992-1993) MC was isolated in respiratory specimens from 52 patients. We revised the clinical history of all these patients. RESULTS: MC was isolated in 60 respiratory specimens (sputum and/or tracheobronchial aspirates) from 52 patients. The Gram stain showed gram-negative cocci in 77% and gram-positive cocci in 17% of the cases. MC grew in pure culture in 28 specimens (46.6%). In 23% of cases MC was isolated with Streptococcus pneumoniae and in 21% with Haemophilus influenzae. Fifty-two stocks (86.6%) produced beta-lactamase. Twelve patients had a clinical diagnosis of pneumonia, 8 of them had an underlying chronic respiratory disease. Other 24 patients with an underlying chronic respiratory disease had a bronchial infection as a cause of exacerbation of their respiratory disease. Seven patients without an underlying chronic respiratory disease had a clinical episode of acute bronchitis. Finally, in 9 patients the isolation of MC was considered a colonization. CONCLUSIONS: In 17% cases MC was identified as a gram-positive cocci in the Gram stain, which may cause false diagnosis. The etiological importance of MC in episodes of acute exacerbation of patients with an underlying chronic respiratory disease is high.

[The stability of solid food labeled with different radiopharmaceuticals for studying gastric emptying]. / Estabilidad de alimento sólido marcado con diferentes radiofármacos para vaciamiento gástrico.

OBJECTIVE: Sulfur colloid 99mTc-SC, the radiopharmaceutical of choice for solid gastric emptying studies, is not available in our country. It has led us to assess the solid binding stability of seven alternative radiopharmaceuticals that could present adequate fixation to it a priori. MATERIALS AND METHOD: The stability of labelled solid food with seven colloidal 99mTc-radiopharmaceuticals of different sizes and nature (MAA, tin colloid, rhenium sulphide macrocolloid, albumin microcolloid, sulfur nanocolloid, albumin nanocolloid and rhenium sulfur nanocolloid) has been studied by measuring their dissociated activity after two hours digestion in simulated gastric fluid (kept 120' in agitation, in HCl 0.1 M at 37). The survey also assesses radiopharmaceutical labelling stability after two hours digestion in identical conditions by measuring their radiochemical purity in ITLC. RESULTS: In these conditions, MAA, rhenium sulphide macrocolloid, albumin microcolloid and albumin microcolloid present the best behaviour, with an activity linked to food over 90 % of the previously fixed activity. CONCLUSIONS: According to the results, there is no relationship between the radiopharmaceutical size and nature and the stability of its binding to the solid food. Because rhenium sulphide macrocolloid is no longer manufactured and the other three radiopharmaceuticals which have a binding stability to the solid food over 90 % do not include digestive explorations amongst their indications, nowadays, there is a serious legal limitation to carry out this type of studies in our country.