Modulation of anaphylactic histamine release by calcium channel agonists and antagonists

Calcium antagonists have been reported to exert protective effects in hypersensitivity reactions in man and animals. However, their effect on anaphylactic histamine release is highly variable and controversial. In the present paper we evaluate the effect of calcium entry blockers and BAY K 8644 on the response to specific antigen in isolated hearts taken from actively sensitized guinea-pigs and from isolated rat and guinea-pig mast cells, actively or passively sensitized. Verapamil, diltiazem, nifedipine and prenylamine dose-dependently decreased anaphylactic histamine release in isolated actively sensitized guinea-pig mast cells. BAY K 8644 was found to be ineffective. In isolated, passively sensitized rat mast cells, verapamil showed a highly signficant inhibitory effect, while prenylamine (10^–4 M) was able to evoke a histamine releasing effect. In cardiac anaphylaxis verapamil, diltiazem, prenylamine, but not nifedipine, were active in reducing the release of histamine without modifying the antigen-induced arrhythmias and positive chronotropic and inotropic effects.     

Nitric oxide modulates cardiac and mast cell anaphylaxis

Anaphylaxis in the isolated guinea-pig heart was associated with a sudden release of histamine with a long-lasting release of nitrite (NO ₂ ^– ), an oxidation product of NO.N ^G-monomethyl-l-arginine (MeArg, 300 M) increased the severity of cardiac anaphylaxis, as shown by the decrease in the coronary flow and by a prolonged duration of antigen-induced arrhythmias. Concomitantly, MeArg increased the release of histamine while decreasing the release of nitrite. Sodium nitroprusside (NaNP, 10^–5–10^–4 M) reduced the severity of cardiac anaphylaxis by increasing coronary flow and shortening the duration of antigen-induced arrhythmias. Concomitantly, NaNP decreased the release of histamine while increasing the release of nitrite. In mast cells isolated from actively sensitized guinea-pigs, the release of histamine elicited by specific antigen was increased by MeArg and decreased by NaNP.In conclusion, endogenous and exogenous NO antagonizes the effect of vasoconstrictor mediators released after antigen challenge and plays a protective role in anaphylactic reactions in vitro,     

Stimulation and resection of Vidian nerve in patients with chronic hypertrophic non-allergic rhinitis: effect on histamine content in nasal mucosa

Parasympathetic innervation of nasal mucosa plays an important role in the pathogenesis of chronic hypertrophic non-allergic rhinitis (C.H.N.A.R.). The present study investigated the effect of Vidian nerve stimulation and resection on the histamine contents and on the morphological pattern in mucosal samples of patients with C.H.N.A.R. Vidian nerve stimulation determines a significant decrease in histamine content in the samples examined; microscopical observations showed significant variations in the glandular, stromal and vascular components.The changes indicate an enhanced secretory activity, intensive vasodilatation and active degranulation of mast cells, which were significantly decreased in number in the samples obtained after 90 sec of stimulation.The neurectomy of the Vidian nerve resolves quite completely the clinical symptomatology and in parallel decreases the mucosal histamine contents, which are increased in patients with C.H.N.A.R. before the operation in comparison with the normal controls.     

Prognostic significance of cyclooxygenase-2 pathway and angiogenesis in head and neck squamous cell carcinoma

Prostaglandins play a critical role in tumor development and growth by regulating numerous biologic processes, including tumor angiogenesis, with clear prognostic and therapeutic implications. The aim of this study was to investigate the prognostic relevance of cyclooxygenase-2 (COX-2) pathway activation in head and neck squamous cell carcinoma (HNSCC). COX-2 activity was analyzed in 52 consecutive patients by assessing protein expression and prostaglandin E(2) (PgE(2)) levels and was then correlated to vascular endothelial growth factor (VEGF) expression and tumor angiogenesis. We evaluated the prognostic impact of these parameters by Kaplan-Meier and Cox survival analysis. COX-2 expression by tumor cells was closely correlated to VEGF expression and to tumor vascularization. According to Kaplan-Meier analysis, patients with COX-2 tumor overexpression and with higher PgE(2) tumor levels had significantly shorter overall survival estimates (P = 0.022 and P = 0.033, respectively). Analogously, patients with more-vascularized tumors had worse survival than those with less-vascularized cancers (P = 0.032). Cox multivariate analysis demonstrated that the most significant prognostic factors were presence of lymph node metastasis, tumor vascularization, COX-2 protein expression, and PgE(2) tumor levels. This study demonstrates a close correlation between COX-2 pathway, VEGF expression, and tumor angiogenesis in HNSCC. In addition, COX-2 overexpression and higher tumor vascularization appear to predict a shorter survival in patients with head and neck cancer.     

p53 Immunoreactivity in inflammatory and neoplastic diseases of the uterine cervix

Immunoreactivity for the tumour suppressor gene product p53 is commonly found in many different human malignancies and few premalignant lesions. Data on cervical neoplasms, however, are still lacking. We retrospectively investigated p53 immunoreactivity in 92 lesions of the uterine cervix, including 44 cases of chronic cervicitis, 29 squamous intraepithelial lesions (SILs), and 19 invasive carcinomas. p53 immunoreactivity confined to the basal cell layer, was detected in 74 per cent of cases showing chronic cervicitis and in all cases with low-grade SILs. Conversely, suprabasal and/or diffuse p53 immunoreactivity was exclusively demonstrated in 25 per cent of high-grade SILs and in 74 per cent of invasive carcinomas. The results of this investigation document a high prevalence of p53-immunoreactive malignant tumours of the uterine cervix. In high-grade SILs, p53-immunoreactive cells paralleled the height of involvement by dysplastic changes within the squamous epithelium. A prolonged half-life of the protein is the most likely explanation for the occurrence of p53 immunoreactivity in neoplastic cells. The unexpected finding of p53-immunoreactive cells in inflammatory lesions, though possibly related to an increased proliferation rate of the basal cell compartment, requires further study and underlines the need for a careful approach to p53 immunocytochemistry.     

Surgical treatment of portal hypertension in schistosomiasis

Patients with mansonic schistosomiasis and portal hypertension are usually young, with good liver functional reserve, huge splenomegaly, and hypersplenism detectable only by alterations seen in laboratory tests. Patients who are not operated on do not develop portosystemic encephalopathy (PSE). Angiographic alterations are characteristic and totally different from those observed in patients with liver atrophy or cirrhosis. Digestive tract hemorrhage is the most severe complication. The patient with schistosomiasis is, therefore, a good model for the study of the consequences caused by the surgical treatment of portal hypertension. The evaluation, however, of results published in the literature regarding schistosomiasis is practically impossible. In a review of 130 publications referring to 4,516 surgically treated patients, the absence of prospective or retrospective studies with adequate controls was observed, and only 3.2% of the patients were followed for 5 years. According to available data, a total of 29 different surgical techniques has been employed, 81.6% of which are represented by simple splenectomy, esophagogastric devascularization (EGDS), and splenorenal shunt (SRS). Splenectomy was the surgical procedure showing the highest rate of recurrent hemorrhage (54.3%), and the portocaval shunt had the highest PSE incidence (60%). Portosystemic encephalopathy incidence after SRS was 29%. Thus, in view of a lack of objective information, in 1977 our group started a prospective, randomized study comparing the results of the surgical procedures most widely used in our country: selective portal decompression (SPD), EGDS, and SRS. The randomization was interrupted after 94 patients had been operated on (32 SRS, 30 SPD, and 32 EGDS) because of a highly significant PSE incidence in the SRS group. Preliminary results as of January, 1984, refer to an average follow-up period of 53 months (minimum 29, maximum 77 months). In the SRS group, the late mortality rate was 18.7%, and the incidence of PSE was 31.2%. Among the patients included in this group, 18.7% had arterial hypertension. In the SPD group, late mortality occurred in 10% of the cases, and PSE in 13.3%, while a mild hyperbilirubinemia was seen in 43.3% of patients. Recurrent hemorrhage and ascites had an approximately similar incidence in the 3 groups.

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Resumen Los pacientes con esquistosomiasis mansónica e hipertensión portal generalmente son jóvenes con buena reserva funcional hepática, enorme esplenomegalia e hipersplenismo detectable solamente por las pruebas de laboratorio. Los pacientes nó operados no desarrollan encefalopatia portosistémica (EPS). Los cambios angiográficos son característicos y totalmente diferentes de los que se presentan en pacientes con cirrosis y atrofia hepática. La complicación más grave es la hemorragia digestiva. Por consiguiente, el paciente con esquistosomiasis es un buen modelo para el estudio de las consecuencias que se derivan del tratamiento quirúrgico de la hipertensión portal. Sinembargo, la evaluación de los resultados en la esquistosomiasis que han sido publicados en la literatura es prácticamente imposible. En una revisión de 130 publicaciones relativas a 4516 pacientes operados, se pudo comprobar ausencia de estudios prospectivos o retrospectivos con controles adecuados, y apenas el 3.2% de los casos fué seguido por 5 años. De acuerdo con los datos disponibles, se empleó un total de 29 técnicas quirúrgicas diferentes, 81.6% de los cuales estuvo representado por simple esplenectomía, devascularización esofagogástrica (DEG) y shunt espleno-renal (SER). La esplenectomía fué el procedimiento quirúrgico que tuvo la más alta incidencia de hemorragia recurrente (54.3%) y el shunt portacava la más alta incidencia de EPS (60%). La incidencia de EPS después de SER fué de 29%.Por consiguiente, en vista de la ausencia de información objetiva, nuestro grupo inición en 1977 un estudio prospectivo y aleatorizado para comparar los resultados de los procedimientos quirúrgicos mayormente utilizados en nuestro país: descompresión portal selectiva (DPS), DEG y SER. La aleatorización fué interrumpida después de haber operado los primeros 94 pacientes (32 SER, 30 DPS y 32 DEG) debido a una muy significativa incidencia de la EPS en el grupo con SER. Los resultados preliminares (enero de 1984) se refieren a un período promedio de seguimiento de 53 meses (mínimo 29, máximo 77 meses). En el grupo de SER la mortalidad tardía fué de 18.7% y la incidencia de EPS fué de 31.2%.El 18.7% de los pacientes incluidos en este grupo exhibió hipertensión arterial. En el grupo de DPS la mortalidad tardía fué de 10% y la incidencia de EPS de 13.3%; se observó hiperbilirrubinemia leve en 43.3% de los pacientes. La incidencia de hemorragia recurrente y de ascitis fué aproximadamente igual en los tres grupos.

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Résumé Les malades qui accusent une hypertension portale d'origine bilharzienne sont généralement jeunes. Leurs fonctions hépatiques sont bonnes mais ils présentent une splénomégalie très importante et une hypersplénisme qui se manifeste seulement par des altérations des tests biologiques. Lorsqu'ils ne sont pas opérés ils ne présentent pas de manifestations d'encéphalopathie. Les caractères angiographiques sont très particuliers et totalement différents de ceux qui sont observés chez les sujets dont le foie est atrophié ou cirrhotique. L'hémorragie digestive représente la complication la plus sévère. Le malade atteint de bilharziose hépatique est par conséquent un bon modèle d'étude des conséquences provoquées par le traitement chirurgical de l'hypertension portale. Cependant les résultats du traitement publiés dans la littérature sont ininterprétables. Dans une revue de 130 publications concernant 4516 opérations, l'absence d'études prospectives ou rétrospectives bénéficiant d'un contrôle de qualité a été constatée, 3,2% seulement des malades ayant été suivis pendant 5 ans. En tenant compte des données disponibles 29 techniques chirurgicales ont été employées, 81,6% desquelles sont repésentées par les opérations suivantes: splénectomie, devascularisation et anastomose spléno-rénale. La splénectomie a été suivie du taux le plus élevé de récidive hémorragique (54,3%) et l'anastomose portocave du taux le plus important d'encéphalopathie (60%), l'anastomose spléno-rénale n'étant suivie d'encéphalopathie que dans 29% des cas. En raison du défaut d'information objective notre équipe a entrepris en 1977 une étude prospective faite selon la méthode du choix au hasard des 3 techniques chirurgicales les plus employées au Brésil: l'anastomose spléno-rénale, la décompression portale sélective et la dévascularisation. L'étude fut interrompue alors que 94 malades avaient été opérés (32 anastomose spléno-rénales, 30 décompressions portales sélectives et 32 dévascularisations oesophagogastriques) en raison du taux particulièrement élevé de l'encéphalopathie postopératoire. Les résultats de cette étude menée jusqu'en janvier 1984 répondent à une période postopératoire moyenne de 53 mois (minimum 29, maximum 77 mois). Dans le groupe traité par anastomose spléno-rénale le taux de la mortalité tardive fut de 18,7% et celui de l'encéphalopathie de 31,2%. Parmi les malades de ce groupe, 18,7% présentaient une hypertension artérielle. Dans le groupe traité par décompression portale selective le taux de la mortalité tardive fut de 10%, celui de l'encéphalopathie de 13,3%, cependant qu'une hyperbilirubinémie fut constatée chez 43,3% de ces opères. La récidive hémorragique et l'ascite atteignent un taux très voisin pour les trois opérations.

     

Clearing the clouds: Case‐report and review of the literature

In peritoneal dialysis (PD), a cloudy dialysate is an alarming finding. Bacterial peritonitis is the most common cause, however, atypical infections and non‐infectious causes must be considered. A 46‐year‐old man presented with asthenia, paraesthesia, foamy urine and hypertension. Laboratory testing revealed severe azotaemia, anaemia, hyperkalaemia and nephrotic‐range proteinuria. Haemodialysis was started through a central venous catheter. Later, due to patient preference, a Tenckhoff catheter was inserted. Conversion to PD occurred 3 weeks later, during hospitalization for a presumed central line infection. A month later, the patient was hospitalized for neutropenic fever. He was diagnosed an acute parvovirus infection and was discharged under isoniazid for latent tuberculosis. Four months later, the patient presented with fever and a cloudy effluent. Peritoneal fluid (PF) cytology was suggestive of infectious peritonitis, but the symptoms persisted despite antibiotic therapy. Bacterial and mycological cultures were negative. No neoplastic cells were detected. Mycobacterium tuberculosis eventually grew in PF cultures, despite previous negative molecular tests. Directed therapy was then initiated with excellent response. Thus, facing a cloudy effluent, one must consider multiple aetiologies. Diagnosis of peritoneal tuberculosis is hampered by the lack of highly sensitive and specific exams. Here, diagnosis was only possible due to positive mycobacterial cultures.     

Binocular interactions and steady-state VEPs. A study in normal and defective binocular vision (Part II)

Background: Recent evidence indicates that an index of binocular activity may be found in some properties of steady-state visual evoked potentials (VEPs), such as amplitude facilitation and phase shortening. We evaluated binocular interactions with steady-state VEPs in normal subjects as well as in patients with concomitant strabismus and defective binocular vision. Methods: Steady-state (8-Hz) VEPs to counterphased sinusoidal gratings (1.2 c/deg spatial frequency) of low contrast (3.2%) were recorded in 19 esotropic patients and in 18 age-matched controls. Patients had either anomalous retinal correspondence (ARC, n =10) or suppression (n=9) in casual seeing conditions (striated glasses). In all subjects, both binocular and monocular VEPs displayed a major component at twice the stimulation frequency (second harmonic), whose amplitude and phase were measured. A binocular interaction index was obtained by comparing binocular VEPs (BVEPs) with the sum (vectorial) of the two monocular VEPs (SMVEPs). Results: In normal subjects, BVEPs were larger in amplitude than SMVEPs (facilitation), and shortened in latency (phase). On average, both ARC and suppression patients displayed loss in amplitude facilitation and absence of phase shortening. However, 50% of ARC patients showed clear VEP facilitation. In both ARC and suppression patients, the amplitude ratio BVEP/SMVEP was negatively correlated with the amount of the angle of deviation. Conclusion: These results suggest that losses in amplitude facilitation and phase shortening of binocular steady-state VEPs reflect abnormal binocular interactions associated with different forms of sensorial adaptation in concomitant strabismus.     

A splenic autograft in posttraumatic splenectomies

BACKGROUND AND AIMS: The authors report their experience regarding the use of autologous splenic transplantation in post-traumatic splenectomy unable to be treated using conservative surgery. After reviewing the international literature on the subject, they report a retrospective survey of cases treated from January 1992 to December 1996. METHODS: Owing to the particular logistic location of the hospital in an area with a high density of industry and at the crossroad of major road and rail routes, a total of 56 patients were admitted to the Emergency Ward suffering from abdominal trauma in 4 years. The patients included in this study could not be treated using conservative surgery: the study group included 15 patients aged between 14 and 76 years old. The surgical technique consisted of the graft of sections of splenic pulp in omental pockets, subsequently marked using metal clips. In order to evaluate splenic immunological function a complete hemochromocytometric examination was performed in each patient at the same time as emergency preoperative tests consisting of peripheral blood strip and pitted cells (PC) assay. This was followed by postoperative evaluations at weekly intervals, including platelet count, Howell-Jolly bodies assay (HJb), immunoglobulin M assay and hepatosplenic scintigraphy using erythrocytes marked with 99m-Technetium pertechnetate (99mTc). RESULTS: An adequate functional recovery of splenic tissue was achieved in all patients with partial recovery of hemocatheretic and immunological function. CONCLUSIONS: The authors' clinical experience confirmed the data inferred from animal experiments: the simplicity of the preparation technique and the autologous transplantation of splenic pulp in the absence of major complications confirms the possibility of applying this method in all splenectomies performed under emergency conditions.     

A comparison of skinfold anthropometry and dual-energy X-ray absorptiometry for the evaluation of body fat in cirrhotic patients

BACKGROUND AND AIMS: Skinfold anthropometry has been used to evaluate the nutritional status in cirrhosis. Such estimates are based on the calculations which derive from healthy subjects and may not apply to cirrhotic patients. We aimed to calculate the limits of agreement between Skinfold anthropometry (SA) and dual-energy X-ray absorptiometry (DXA) in estimating body fat in cirrhotics. METHODS: Forty cirrhotic patients were studied by both methods. The limits of agreement were estimated by the Bland and Altman method. RESULTS: Percentage body fat was similar when measured by DXA and SA (29.6 +/- 9.2 vs 28.9 +/- 7.5 %). Body fat mass was also similar (20.3 +/- 8.4 vs 20.3 +/- 7.7 kg). The limits of agreement between DXA and SA measurements were -7.04 (95%CI: -9.55 to -5.2) +8.56 (95%CI: +10.7 to +6.4.) in the assessment of percentage body fat and -5.32 (95%CI: -6.77 to -3.87) +5.24 (95%CI: +3.79 to +6.69) in the assessment of fat mass. CONCLUSION: Percentage body fat can be evaluated by SA or DXA with a difference of less then 5% in the majority of cirrhotic patients without overt fluid retention. This result is important when considering the large applicability of SA.