ENDOSCOPIC NASOBILIARY DRAINAGE: CURRENT INDICATIONS AND EVALUATION OF THE PRODUCTS

Endoscopic nasobiliary drainage (ENBD) is a well established mode of biliary decompression. Although ENBD is certainly an uncomfortable procedure with the potential risk of spontaneous dislocation or removal of the drainage catheter by disoriented patients, it has several advantages over endoscopic biliary drainage (EBD) using an indwelling stent. The current indications for ENBD are: (i) temporary drainage to treat obstructive jaundice and cholangitis caused by malignant or benign biliary stricture; (ii) urgent drainage to treat suppurative cholangitis primarily caused by common bile duct stones; (iii) temporary drainage after stone removal in patients with suspected incomplete clearance and/or with cholangitis; and (iv) biliary leaks that occur primarily after surgery, as well as other indications. Different types of nasobiliary catheters are currently available that have been designed with various diameters, shapes, and materials. However, the current catheters are not considered by most endoscopists to be sufficient. Further improvements are needed to achieve better drainage and better maneuverability.     

Clinical significance of associated nodular lesions of the adrenal in patients with aldosteronoma

Thirty-seven patients with primary aldosteronism were treated by unilateral total adrenalectomy during a 7-year period (1981–1987). The 37 patients were classified into 3 groups on the basis of adrenal pathology: unilateral solitary adenoma, 23 cases (group 1); unilateral adenomas, 3 cases (group 2); and adenoma with multiple macro- or microscopic nodules, 11 cases (group 3). The preoperative conditions of the patients (age, duration of hypertension, plasma renin activity, plasma aldosterone concentration, and serum potassium concentration), postoperative sequential changes of hormone levels, and outcome of hypertension were compared among the groups in order to determine whether the differences of adrenal pathology would affect the postoperative course. The preoperative parameters excluding age at surgery did not differ significantly among the 3 groups. The mean age in group 3, however, was slightly higher than in groups 1 and 2 (47.8 versus 42.8 versus 42.7 years). Postoperative hormonal changes were also similar, particularly in groups 1 and 3, staying within the normal range throughout the follow-up period (mean, 31 months; range, 3–86 months). However, postoperative improvement of hypertension showed marked differences, being significantl retarded in patients with multinodular lesions (group 3), about half of whom remained hypertensive even after 1 year. Nodular lesions other than adenoma(s) were, therefore, thought not to contribute to hormonal excess but to result from intractable hypertension.

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Resumen Treinta y siete pacientes con aldosteronismo primario fueron tratados mediante adrenalectomía total unilateral en un período de 7 años (1981–1987). Los 37 pacientes fueron clasificados en 3 grupos con base en la patología adrenal: adenoma solitario unilateral, 23 casos (grupo I); adenomas unilaterales, 3 casos (grupo 2); y adenoma con múltiples macro-o micronódulos, 11 casos (grupo 3). Las condiciones preoperatorias de los pacientes (edad, duración de la hipertensión, actividad de renina plasmática, concentración plasmática de aldosterona, y concentración sérica de potasio), los cambios postoperatorios secuenciales en los niveles hormonales, y el resultado de la hipertensión fueron comparados en los 3 grupos, con el objeto de determinar si las diferencias en la patología adrenal podrían afectar la evolución postoperatoria. Los parámetros preoperatorios, excluyendo la edad en el momento de la cirugía, no diferieron significativamente en los 3 grupos. La edad promedio en el grupo 3, sin embargo, fue ligeramente superior en los grupos 1 y 2 (47.8 versus 42.8 versus 42.7 años).Los cambios hormonales postoperatorios también fueron similares, particularmente en los grupos 1 y 3, manteniéndose dentro del rango normal a través del seguimiento (promedio, 31 meses; rango, 3–86). Sin embargo, la mejoría postoperatoria de la hipertensión exhibió diferencias marcadas, con aparación significativamente tardía en pacientes con lesiones nodulares (grupo 3); aproximadamente la mitad de éstos permanecieron hipertensos aún después de un año. Por consiguiente, se piensa que las lesiones nodulares diferentes del adenoma(s) no contribuyen al exceso hormonal sino que resultan de la hipertensión intratable.

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Résumé Trente-sept patients ayant un hyperaldostéronisme primaire ont eu une surrénalectomie totale unilatérale entre 1981 et 1987. Ces 37 patients ont été classés en 3 groupes selon la pathologie surrénalienne: adénome solitaire unilatéral, 23 cas (groupe 1); adénome unilatéral, 3 cas (groupe 2); et adénome avec nodules micro ou macroscopiques multiples, 11 cas (groupe 3). On a comparé les données préopératoires (âge, durée de l'hypertension, activité rénine plasmatique, concentration d'aldostérone plasmatique et kaliémie), les changements hormonaux postopératoires, et l'évolution de l'hypertension afin de déterminer si des différences de pathologie surrénalienne peuvent influencer l'évolution postopératoire. Les paramètres préopératoires (excepté l'âge) ne différaient pas de façon significative parmi les 3 groupes. L'âge moyen était plus élevé dans le groupe 3 que dans les groupes 1 et 2 (47.8 versus 42.8 versus 42.7 ans).Les variations hormonales postopératoires étaient également similaires, surtout dans les groupes 1 et 3, restant dans les limites de la normale pendant la période de suivi (moyenne, 31 mois; extrêmes, 3 à 86 mois). Cependant l'amélioration de l'hypertension postopératoire était différente, retardée de façon significative chez les patients ayant des lésions multinodulaires (groupe 3), la moitié d'entre eux restant hypertendus après un an. Les lésions nodulaires, étant donné que les adénomes ne donnent pas d'hypersécrétion hormonale, peuvent traduire plutôt une hypertension prolongée.

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Presented at the International Association of Endocrine Surgeons in Toronto, Ontario, Canada, September, 1989.     

Ontogeny of behavioral sensitization to cocaine

The ontogeny of the behavioral effects of acute cocaine administration and behavioral sensitization to cocaine in rat pups was investigated. Acute behavior stimulating effects of cocaine were observed in pups as young as 7 postnatal days (PND) old, although they needed a higher dose of cocaine than adult rats to evoke the same motor effects. An adult dose-response curve pattern of stereotypy and locomotion to acute cocaine treatment was observed at PND 21, and of rearing at PND 28. Rats aged PND 7, 14, 21, 28, and 56 received repeated injections of saline or cocaine (15 mg/kg) twice a day for 5 consecutive days. After a 3-week period of abstinence, sensitization to a challenge dose of cocaine was assessed. Cocaine-induced stereotyped behavior was enhanced significantly only in rats in which cocaine pretreatment was initiated on PND 21, 28, and 56, but not earlier on PND 7 and 14. Adult female rats given repeated cocaine injections on PND 56–60 showed significantly greater sensitization than males, but no such sex difference was observed in pups given cocaine repeatedly on PND 21–25 or 28–32. These results show clearly that cocaine-induced behavioral sensitization in rats occurred only when subchronic cocaine administration was commenced on PND 21 or later.     

HMG-CoA reductase inhibitor cerivastatin prolonged rat cardiac allograft survival by blocking intercellular signals.

BACKGROUND: The development of atherosclerotic cardiovascular complications caused by hyperlipidemia is a common and serious problem for long-term survivors of organ transplantation. However, adhesion molecules such as intercellular adhesion molecule (ICAM)-1 and lymphocyte function-associated antigen (LFA)-1 are involved in allograft rejection, possibly by providing costimulatory signals. 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor cerivastatin has been shown to suppress ICAM-1 expression in acute inflammatory responses. METHODS: In this study, we evaluated the immunosuppressive effects of cerivastatin in rat cardiac allografts. The hearts of Fischer rats were transplanted heterotopically into Lewis rats. Cerivastatin (2 mg/kg) was administrated intraperitoneally to recipients for 7 consecutive days from the day before transplantation. RESULTS: Graft survival in the cerivastatin-treated group (n = 8) was significantly longer than in controls (n = 10) (24.6 +/- 2.2 days vs 10.2 +/- 1.3 days, p < 0.05). Mixed lymphocyte reaction (MLR) showed that on Day 8 after grafting, the proliferative response of alloreactive T cells against F344 alloantigen in cerivastatin-treated rats was significantly more suppressed than in Lewis rats. The Interleukin-2 concentration of supernatant in MLR cultures in the cerivastatin-treated group was lower than in the control group. Immunohistochemical analysis showed that the percentage of CD4-positive cells to infiltrating mononuclear cells was less prominent in the cerivastatin-treated group (9.8% +/- 2.2%) than in the control group (20.9% +/- 3.2%). CONCLUSIONS: The HMG-CoA reductase inhibitor cerivastatin effectively suppressed acute graft rejection, possibly by blocking intercellular signals via ICAM/LFA-1, and cerivastatin may be a candidate for treating patients with hyperlipidemia who undergo organ transplantation.     

Techniques for difficult cases of laparoscopic cholecystectomy

Our basic techniques for the management of difficult cases of laparoscopic cholecystectomy (LC) are presented in this article. If access to Calot's triangle cannot be gained safely, dissection should be started at the fundus or body of the gallbladder (GB), rather than the neck (fundus-first method). In cases with a short and wide cystic duct, a transfixing suture should be applied for ligation instead of clipping. EndoGIA is useful for ligating and transecting this case to avoid a subsequent stricture caused by normal method of ligation. Intraoperative cholangiography should be performed near the neck of the GB in cases in which orientation is lost during dissection. More dissection should be performed in the direction of the junction of the bile ducts after orientation is regained. In cases with GB filled with stones accompanied by severe fibrosis, part of the GB is incised to remove the stones and expose the lumen of the GB. Confluence stones can be removed by placing an incision on the GB side of the junction of the duct. The incised part is closed with suture. A cystic tube (C-tube) is placed in the common bile duct through the cystic duct for decompression. In more difficult cases in which dissection cannot be started safely at any location, the body and the fundus of the GB are excised, and a drain is placed at the neck of the GB. Dissection can be carried out from the main surgeon's or the assistant's side depending on the situation, and cooperation between the two surgeons is mandatory to achieve safe LC in difficult cases. When performing the LC, one must have a low threshold for converting to open surgery if injuries cannot be managed safely.     

Possible relationship between low birth weight and magnesium status: from the standpoint of "fetal origin" hypothesis.

Magnesium deficiency in pregnant women is frequently seen because of inadequate or low intake of magnesium. Magnesium deficiency during pregnancy can induce not only maternal and fetal nutritional problems, but also consequences that might last in offspring throughout life. Many epidemiological studies have shown that restricted fetal growth, i.e. intrauterine growth retardation (IUGR), is associated with an increased risk of insulin resistance in adult life. We previously postulated that the intracellular magnesium of cord blood platelets is lower in the small for gestational age group than in the appropriate for gestational age group, suggesting that intrauterine magnesium deficiency may result in IUGR. Taken together, intrauterine magnesium deficiency in the fetus may lead to or program the insulin resistance after birth. We hypothesize that intrauterine magnesium deficiency may induce a metabolic syndrome in later life. Prospective studies will further clarify whether infants with IUGR induced by magnesium deficiency are at higher risk for metabolic syndromes in childhood or adulthood.     

Surgical technique of experimental lung transplantation in rabbits.

BACKGROUND: Although rabbits have often been used as an experimental model for the analysis of lung preservation, there are no reports of long-term survival after rabbit lung allotransplantation. The purpose of this study was to establish a lung allotransplantation model for the evaluation of acute lung rejection in the rabbit and to investigate the transplantation techniques in the rabbit. METHODS: Left unilateral lung allotransplantations were performed in 10 pairs of Japanese white male rabbits, weighing from 2.8 to 3.7 kg. Rabbits were divided into two groups. Group A rabbits (n=5) received Cyclosporine A (CsA) (20 mg/kg/day) orally for 5 days postoperatively, while Group B rabbits (n=5) received no CsA. All rabbits were sacrificed at the fifth postoperative day for histological examinations. RESULTS: Anastomoses of the pulmonary vein were achieved by using the atrial cuff technique. Satisfied blood flow was obtained in all arterial and venous anastomosis sites. Bronchial anastomosis was also well healed and all rabbits could maintain adequate spontaneous ventilation. In Group A, histopathology revealed that three cases were grade A0, one was grade A1 and the other was A2. In Group B, three cases lived for five days, and histopathology showed two cases were grade A2 and one case was grade A3. CONCLUSION: We established a left unilateral lung allotransplantation model in the rabbit and observed suppression of acute rejection of the transplanted lung by CsA. This study suggests that the rabbit is also an experimental model suited for the analysis of lung preservation as well as lung allotransplant rejection.     

Studies on FK482. II. Synthesis and structure-activity relationships of 7 beta-[(Z)-2-(2-aminothiazol-4-yl)-2-substituted acetamido]-3-vinyl-3-cephem-4-carboxylic acid derivatives

Various 7 beta-[2-(2-aminothiazol-4-yl)-2-substituted acetamido]-3-vinyl-3-cephem-4-carboxylic acid derivatives (Ia--e, IIa--g) were synthesized in order to find a new orally active cephalosporin improving the antibacterial activity of cefixime (CFIX) against Staphylococcus aureus. These derivatives include three types of alpha-substituted 2-(2-aminothiazol-4-yl)acetyl side chain; i) mono or non substituted acetyl moiety, ii) carboxyalkoxyimino acetyl moiety, iii) phosphonomethoxyimino and hydroxyimino acetyl moiety. Their structure-activity relationships and urinary recoveries in rats were studied. As a result, the compound with a hydroxyimino acetyl side chain (IIg, FK482) showed good oral absorption and excellent antibacterial activity against both gram-positive and gram-negative bacteria and was selected as a candidate for clinical trial.     

Inhibition of IgE formation in mice by glycoproteins from corn silk

The inhibitory effects of glycoproteins separated from a hot water extract of corn silk (U-CSE) on the formation of IgE antibodies after primarily and secondarily challenged responses with dinitrophenyl (DNP)-ovalbumin (OVA) antigen in mice were investigated using the passive cutaneous anaphylaxis (PCA) test. When U-CSE was given intranasally or intraperitoneally the day before primary immunization, IgE antibody production was strongly inhibited. Furthermore, it was found that new formation of IgE antibodies was readily inhibited by U-CSE administration in mice with high levels of IgE after primary immunization. It was also found that U-CSE markedly suppressed IgE antibody formation in secondarily challenged responses with the antigen. U-CSE may be clinically applicable to type I allergic diseases.