Zita Morvay

Peritubular Capillary Damage in Acute Humoral Rejection: An Ultrastructural Study on Human Renal Allografts

The ultrastructural features of peritubular capillary (PC) damage was studied in 12 kidney allografts with acute humoral rejection (AHR). AHR manifested in diffuse linear PC staining for C4d, and histology consistent with Banff grade III in 7 recipients and Banff grade II in 5. Allografts with acute tubular necrosis served as controls. First biopsies (post‐transplantation day 16.2 ± 2.2): The intra‐capillary exudate comprised monocytes (59%), polymorphonuclears (14%), lymphocytes (12%) and not otherwise specified mononuclears (15%). Three patterns of focal PC endothelial injury were observed: lysis, an increased rate of apoptosis and fragmentation. No correlation was found between the respective damage types and the inflammatory cell types or the Banff grades. Controls revealed endothelial swelling, detachment from basement membrane and fragmentation. Follow‐up biopsies: Monocytes transformed into macrophages intra‐luminally. The reparative changes comprised endothelial cytoplasmic protrusions, binucleated endothelial cells and capillary sprouts. Early transplant capillaropathy and transplant glomerulopathy were noted in 2 recipients. Literature data indicate that lysis is mediated by anti‐HLA alloantibodies; apoptosis, demonstrated first in the present study, may be induced by non‐HLA‐type anti‐endothelial antibodies. Fragmentation is caused by ischemia. Ongoing endothelial injury leads to transplant capillaropathy and transplant glomerulopathy, the characteristic lesions of chronic rejection.

Bronchioloalveolar lung cancer: Occurrence, surgical treatment and survival

OBJECTIVE The prevalence of pulmonary adenocarcinoma has risen worldwide. Bronchioloalveolar carcinoma (BAC) was studied with regard to whether it exhibits a similar tendency, and its typical features were analysed. METHODS Between 1992 and 2001, 278 lung resections were carried out for adenocarcinoma. Of these, 67 (24.1%) proved to involve BAC. Whereas BAC accounted for 6.9% of the cases in 1992, in 2001 the proportion was 46.9%. There were 37 men (55.2%) and 30 women (44.7%); the average age was 60.5 years. 58.2% of them had no complaints. Of the 26 non-smokers, 69.2% were women; of the 41 smokers, 29.2% were women. In consequence of the tumour, 49 lobectomies, three bilobectomies, six pneumonectomies and nine wedge resections were performed. RESULTS The surgical mortality was 1.6%. The pathology revealed that 26 (38.8%) tumours were in stage I/A. In 15 cases (22.4%), tuberculosis (TB) could be revealed besides the BAC: by skin tests in four cases, by CT in three cases, by case history in four cases, and by pathology in four cases. For the overall group of 67 patients, the 5-year survival rate was 61.9%, and the mean survival time was 75.7 months. The 5-year survival rate among the women (74%) was significantly better than that among the men (37%) (P=0.030). There was no significant difference in survival with regard to the multiple BAC (85%). The 5-year survival rate was significantly worse in the mixed BAC group (20%) than in the non-mucinous (62.7%) and in mucinous (59%) group. The overall 5-year survival rate among the smokers and TB patients was 61 and 79%, respectively, which is higher than that among the non-smokers (47%) and non-TB patients (56%). The survival rate for the wedge resection cases was 37%, which was lower than that for the cases involving major resections (60%) (P=0.939). CONCLUSION BAC has a favourable survival, particularly in women. In spite of this, resection smaller than lobectomy is recommended only as a compromise. A multiple appearance does not imply a worse survival. The best survival rate was found in the non-mucinous BAC among the histological groups. TB seems to be frequent among BAC patients.

Surgical intervention for pulmonary tuberculosis: analysis of indications and perioperative data relating to diagnostic and therapeutic resections

OBJECTIVE To analyze the data on patients operated on for pulmonary tuberculosis (TB) with (Group I) or without (Group II) a correct TB diagnosis and preoperative anti-TB treatment. METHODS Between 1980 and 1997, 144 resections for TB (Groups I+II) were performed. The 80 patients in Group I underwent therapeutic resections: 32 cases involved recurrent cavities or tuberculomas, three involved post-TB bronchiectasis, 13 involved progression of cavities or tuberculomas, and 32 involved persistent tuberculomas after 6 months of anti-TB therapy. The 64 patients in Group II were operated on for a suspicion of malignancy in 49 cases, for cavitary lesions with haemophthysis in six cases, for multiple lesions in seven cases, and for recurrent hydrothorax in two cases. RESULTS Groups I and II included 0 and five pneumonectomies, 32 and 29 lobectomies, 48 and 20 wedge resections, 0 and nine videothoracoscopic biopsies, and 0 and one hilar lymphadenectomy, respectively. In Groups I and II, the mean duration of postoperative hospitalization was 13.2 and 10.4 days, and the frequency of postoperative pneumothorax was 11.25 and 4.6%, respectively. The incidence of bronchopleural fistula was 1.25 and 0%, the mortality was 0 and 3.1%, and the morbidity was 53.7 and 35.9% in Groups I and II, respectively. Two patients with active disease died in Group II. Pathology demonstrated that the frequency of acid-fast bacilli in Groups I and II was 40 and 25%, respectively. CONCLUSIONS Patients without a correct preoperative TB diagnosis underwent more extensive parenchyma resection. Postoperative complications increased when acid-fast bacilli were present. The lack of preoperative anti-TB treatment did not involve a higher risk of minor complications, but death occurred only in this group.

An ultrasonographic method for the evaluation of dexmedetomidine on micturition in intact rats

We describe a simple, noninvasive, nontraumatic, and reproducible ultrasonographic method to determine the effect of the alpha 2-adrenoceptor agonist dexmedetomidine in anesthetic dose (300 micrograms/kg subcutaneously) on the micturition reflex in intact rats. The bladder volumes were estimated by an ellipsoid equation. To validate the reliability of the method, an in vitro model assessment also was performed. The mean difference between estimated and instilled volumes were 27.3 microL (-21.61, 76.23). The highly significant correlation (r = 0.98, p < .001) indicates that the ultrasonography with the equation is a reliable tool. After the dexmedetomidine administration to intact rats, urine dribbling occurred at 30 +/- 4.8 min. The volume threshold for urination was 2100 +/- 100 microL. Although dribbling of the urine was observed almost continuously, significant differences were not observed between bladder volumes obtained at any time (from 10 to 100 min). This study indicates that the alpha 2-adrenoceptor agonist dexmedetomidine inhibits the micturition reflex in intact rats. The method described, which is both noninvasive and nonpainful, may therefore be widely used to quantify in small animals pharmacological effects on the urinary bladder.

Long-lasting, distinct changes in central opioid receptor and urinary bladder functions in models of schizophrenia in rats

Ketamine treatments and social isolation of rats reflect certain features of schizophrenia, among them altered pain sensitivity. To study the underlying mechanisms of these phenomena, rats were either housed individually or grouped for 33 days after weaning, and treated with either ketamine or saline for 14 days. After one month re-socialization, the urinary bladder capacity by ultrasound examination in the anesthetized animals, and changes of μ-opioid receptors by saturation binding experiments using a specific μ-opioid agonist [(3)H]DAMGO were determined. G-protein signaling was investigated in DAMGO-stimulated [(35)S]GTPγS functional assays. Ketamine treatment significantly decreased the bladder volume and isolation decreased the receptor density in cortical membranes. Among all groups, the only change in binding affinity was an increase induced by social isolation in the cortex. G-protein signaling was significantly decreased by either ketamine or social isolation in this tissue. Ketamine treatment, but not housing, significantly increased μ-opioid receptor densities in hippocampal membranes. Both ketamine and isolation increased the efficacy, while the potency of signaling was decreased by any treatment. Ketamine increased the receptor density and G-protein activation; while isolation decreased the efficacy of G-protein signaling in hippocampal membranes. The changes in the co-treated group were similar to those of the isolated animals in most tests. The distinct changes of opioid receptor functioning in different areas of the CNS may, at least partially, explain the augmented nociceptive threshold and morphine potency observed in these animals. Changes in the relative urinary bladder suggest a detrusor hyperreflexia, another sign of schizophrenia.

Chronic pancreatitis. Evidence based management guidelines of the Hungarian Pancreatic Study Group

Chronic pancreatitis is an inflammatory disease associated with structural and functional damage of the pancreas. In most cases pain, maldigestion and weight loss are the leading symptoms, which significantly worsen the quality of life. Correct diagnosis and differential diagnosis of chronic pancreatitis and treatment of these patients requires up-to-date and evidence based treatment guidelines. The Hungarian Pancreatic Study Group proposed to prepare an evidence based guideline based on the available international guidelines and evidence. The preparatory and consultation task force appointed by the Hungarian Pancreatic Study Group translated and complemented and/or modified the international guidelines if it was necessary. 123 relevant clinical questions in 11 topics were defined. Evidence was classified according to the UpToDate® grading system. The draft of the guidelines were presented and discussed at the consensus meeting in September 12, 2014. All clinical questions were accepted with total or strong agreement. The present guideline is the first evidence based guideline for chronic pancreatitis in Hungary. This guideline provides very important and helpful data for tuition, everyday practice and proper financing of chronic pancreatitis. Therefore, the authors believe that these guidelines will widely become a basic reference in Hungary.

Pediatric pancreatitis. Evidence based management guidelines of the Hungarian Pancreatic Study Group

Pediatric pancreatitis is a rare disease with variable etiology. In the past 10-15 years the incidence of pediatric pancreatitis has been increased. The management of pediatric pancreatitis requires up-to-date and evidence based management guidelines. The Hungarian Pancreatic Study Group proposed to prepare an evidence based guideline based on the available international guidelines and evidences. The preparatory and consultation task force appointed by the Hungarian Pancreatic Study Group translated and complemented and/or modified the international guidelines if it was necessary. In 8 clinical topics (diagnosis; etiology; prognosis; imaging; therapy; biliary tract management; complications; chronic pancreatitis) 50 relevant questions were defined. Evidence was classified according to the UpToDate(®) grading system. The draft of the guidelines was presented and discussed at the consensus meeting on September 12, 2014. All clinical statements were accepted with total (more than 95%) agreement. The present Hungarian Pancreatic Study Group guideline is the first evidence based pediatric pancreatitis guideline in Hungary. The present guideline is the first evidence-based pancreatic cancer guideline in Hungary that provides a solid ground for teaching purposes, offers quick reference for daily patient care in pediatric pancreatitis and guides financing options. The authors strongly believe that these guidelines will become a standard reference for pancreatic cancer treatment in Hungary.

The effects of juvenile capsaicin desensitization in rats: Behavioral impairments

Capsaicin desensitization leads to behavioral changes, some of which are related to schizophrenia, but investigations into these effects have been scarce. The goal of this study was to characterize the consequences of juvenile capsaicin desensitization on different functions: acute and inflammation-induced thermal and mechanical sensitivity, urinary bladder capacity and thermoregulation, and also on the potentially schizophrenia-related impairments in sensory-motor gating, motor activity and cognitive functioning. Male Wistar rats desensitized with increasing doses of subcutaneous capsaicin after weaning were investigated. Heat and mechanical pain sensitivity did not change significantly; however, morphine produced a prolonged decrease in the nociceptive response to inflammation in desensitized animals. Ultrasound examination of the bladder revealed enhanced bladder volume in treated animals. Capsaicin-treated animals had higher body temperature at 22 °C in both dark and light periods, and they also showed prolonged hyperthermia in new environmental circumstances. Warm environment induced a profound impairment of thermoregulation in desensitized animals. The treated animals also showed higher levels of activity during the active phase and at both cool and warm temperatures. The amplitude of the responses to auditory stimuli and prepulse inhibition did not differ between the two groups, but the desensitized animals showed learning impairments in the novel object recognition test. These results suggest that juvenile capsaicin desensitization leads to sustained changes in several functions that may be related to schizophrenia. We propose that capsaicin desensitization, together with other interventions, may lead to an improved chronic animal model of schizophrenia.

Treatment of Subclinical Injuries Detected by Protocol Biopsy Improves the Long-Term Kidney Allograft Function: A Single Center Prospective Randomized Clinical Trial

BACKGROUND The long-term benefit of early treatment of subclinical disorders detected in kidney allografts by protocol biopsy is controversial. We collected 145 protocol biopsies from 113 recipients for comparison with 51 control patients in a single-center, prospective, randomized trial. METHODS Ultrasound-guided biopsies were performed in recipients with stable renal function. Samples were taken at 3 (n=66) and/or 12 months (n=79) after transplantation. The biopsies were evaluated according to the Banff scheme, and patients were treated based on the diagnosis. Changes in glomerular filtration rate (GFR) were compared with 51 patients who were randomized as a control group. RESULTS The findings on 38 samples (29%) were considered to be normal. Based on the pathology findings, such as subclinical acute rejection (n=23), calcineurin inhibitor toxicity (n=28), chronic rejection (n=6), and other specific pathologies (n=23), including polyoma virus nephropathy (n=2), induced treatment among 82 recipients (57%). Significantly better graft function was observed at 3-year follow-up among the biopsy group, compared with controls: GFR = 46.0 ± 13.8 vs 35 ± 15 mL/min (P=.002). The 5-year graft survival was significantly higher in the biopsy (81%) than in the control (55.6%) group (P=.0012). CONCLUSION Early detection and treatment of subclinical pathologies improved graft function and long-term survival. Protocol biopsies were a valuable tool for posttransplantation management.

Liver Abscess Caused by Stenotrophomonas maltophilia: Report of a Case

Abstract.We report the case of a melioidosis-like abscess of the liver caused by Stenotrophomonas (Xanthomonas) maltophilia infection in a Chinese man living in Hungary. Although this appears to be the first documentation of a liver abscess of this origin in a nonimmunocompromised patient, our case report demonstrates that this common facultative pathogen can also cause liver abscess and sepsis. After repeated negative blood cultures, histological examinations of liver biopsies suggested the possibility of chronic melioidosis, but the microbiological examination performed directly on the same specimen identified a Stenotrophomonas maltophilia infection. Surgical drainage was performed and sulphamethoxazole/trimethoprim therapy was commenced, after which the patient recovered fully. The facultative pathogen S. maltophilia, which most often causes nosocomial infections, may cause severe sepsis and liver abscess. We wish to draw attention to the fact that the antibiotic sensitivity of S. maltophilia is not necessarily the same in vivo and in vitro. This can create difficulties in both diagnosis and treatment.