Intra-amniotic endotoxin induces lung maturation by direct effects on the developing respiratory tract in preterm sheep

OBJECTIVE: Our purpose was to determine whether improved preterm lung function caused by intraamniotic endotoxin treatment requires endotoxin entry into the respiratory tract. STUDY DESIGN: We assessed lung inflammation 2 days after intra-amniotic endotoxin (10 mg, Escherichia coli 055:B5) or saline solution in preterm lambs (123 days' gestation) that had undergone surgery to isolate the gastrointestinal or respiratory systems from the amniotic sac. In other sheep longer-term effects were assessed 7 days after we isolated the fetal respiratory tract and gave endotoxin or saline solution directly to the lungs or into the amniotic sac. We measured pulmonary inflammation, lung function, and surfactant 1 week after treatment (approximately 125 days). RESULTS: Pulmonary inflammation was present after intra-amniotic endotoxin only if there was communication between the respiratory tract and the amniotic sac. Lung function was improved and surfactant was increased only in preterm lambs that received direct pulmonary endotoxin. CONCLUSION: Endotoxin causes functional improvement of the preterm lung by direct effects on the developing respiratory system.     

Fluconazole attenuates lung injury and mortality in a rat peritonitis model

Objective Acute lung injury following peritonitis constitutes an enigmatic clinical problem with no specific therapy. Recently, immunomodulators such as azole compounds have been shown to attenuate shock-related tissue injury. The present investigation was undertaken to study the effect of fluconazole on acute lung injury and survival following faecal peritonitis in rats.Subjects Male Wistar rats weighing 225–235 g.Design and setting Faecal peritonitis (Fp) was produced in four groups of adult male Wistar rats by intraperitoneal administration of non-sterile faecal suspension (1:1 w/v saline). A fifth group of rats was given sterile faecal material (SFM), which served as control.Interventions Rats in Fp groups were given fluconazole in doses of 0 mg/kg, 3 mg/kg, 10 mg/kg, and 30 mg/kg by gavage 30 min before induction of peritonitis. The control animals received an equal volume of distilled water.Measurements and results Survival over a period of 72 h, oxidative stress, neutrophil activity, and lung injury were measured. This study showed a 90% survival in the fluconazole-treated group compared to only 20% survival in untreated rats (P<0.008 log-rank test). The lungs of animals with Fp showed massive pathological changes including intraalveolar oedema, fibrosis, and mixed inflammatory cell infiltrate. These changes were dose-dependently attenuated by fluconazole. Enhanced oxidative stress (P<0.001) and neutrophil activity in the peritoneal fluid and lung (P<0.001) in Fp animals was dose-dependently reduced by fluconazole.Conclusion This study clearly suggests the role of neutrophils in Fp-induced tissue injury/mortality, which may be dose-dependently, attenuated by fluconazole.     

The role of human glandular kallikrein 2 for prediction of pathologically organ confined prostate cancer

BACKGROUND: In recent studies serum levels of human glandular kallikrein 2 (hK2) demonstrated significant differences in pathologically organ-confined versus non-organ-confined prostate cancer (PCa). In this study we investigated whether hK2 adds independent information when considered together with traditionally used parameters to predict organ confined (pT2a/b) PCa. METHODS: Serum levels of hK2, total and free prostate-specific antigens (PSA) were obtained one day before radical prostatectomy in 245 consecutive men. These were included with clinical stage and biopsy Gleason grade into univariate analysis and multivariate logistic regression models. RESULTS: pT2a/b PCa was found in n = 148 patients. In univariate analysis all preoperative parameters demonstrated significant association with the presence of pT2a/b PCa. Using multivariate logistic regression model hK2 (P = 0.022), clinical stage (P < 0.0001), and Gleason grade (P < 0.0001) were independent predictors of pT2a/b PCa whereas PSA (P = 0.3) was not. In bootstrap corrected logistic regression based nomograms the addition of hK2 density marginally enhanced predictive accuracy when PSA, PSA density, clinical stage, and Gleason grade were considered (AUC = 0.879 without hK2 density and 0.883 with hK2 density). CONCLUSIONS: hK2 and hK2 density could independently predict pT2a/b PCa. However, improvement in predictive accuracy was marginal when nomograms based on traditional variables were complemented with this serum marker.     

CalcDose: a software for drug dosage conversion using metabolically active mass of animals

This Visual Basic computer program has been developed for drug dosage conversions using metabolically active mass (MAM) of the animals. The two body weights (one with known dosage and the other, for which the dosage has to be calculated) and the known dosage are entered in the respective input boxes and the appropriate units are selected using the option buttons. The program displays the report in the form of both the animals' body weights and the respective dosages in milligram per kilogram body weight as well as the total actual doses in milligrams. The object oriented layout, flexible data entry and comprehensive report format render the CalcDose software a convenient and handy tool for dosage conversions.     

Differential immunogenicity of HLA mismatches: HLA-A2 versus HLA-A28

The immunogenicity of human leukocyte antigen (HLA)-A2 versus HLA-A28 was analyzed by antibody production, cytotoxic T-lymphocyte (CTL) induction, and graft survival. We observed that an HLA-A2 mismatched child in HLA-A28 women leads to HLA-A2 specific antibodies in 32% of the women (n=31), whereas in the case of an HLA-A28 child and HLA-A2 women (n=30), no HLA-A28 specific antibodies were found ( P<0.002). Also, the CTL precursor frequencies were significantly lower against HLA-A28 compared with CTLp frequencies against HLA-A2 ( P=0.012). Finally, the kidney graft survival was slightly better in HLA-A2 positive recipients transplanted with HLA-A28 mismatches. We can conclude that single HLA-A28 mismatches are less immunogenic in HLA-A2 individuals compared with single HLA-A2 mismatches in HLA-A28 individuals, which is probably because the mismatched epitopes on the HLA-A2 molecule are unique epitopes, whereas the mismatched epitopes on HLA-A28 are shared by other HLA-A and HLA-B molecules.     

Merkel cell carcinoma: report of seven cases

Merkel cell carcinoma (MCC) is an infrequent, highly malignant, primary skin tumor derived from neuroendocrine cells. Most MCCs occur in elderly individuals, on sun-exposed areas of the body, with the head and neck being the most common sites. We present 7 patients (2 male and 5 female, age 45-80 years) suffering from MCC and treated between 1993 and 2000. All tumors were located on the head and neck and varied from 0.9 to 2.3 cm in size. Five of the patients had stage II disease, 1 patient had stage Ia disease and 1 patient had stage III disease. Six of the patients had positive regional lymph nodes. All patients had local excision of the tumor. Six of them also had lymph node dissection and in 5 of them a superficial parotidectomy was performed. Five patients received adjuvant radiotherapy and 3 of them also received chemotherapy. Local and cervical lymph node recurrence was observed in only 1 patient. Metastases occurred in 5 patients. One patient died within 10 days for other reasons. The patient with the stage III tumor had a survival of 7 months. The other 5 patients had survivals varying from 15 to 54 months. MCC is a skin tumor with very poor prognosis and high recurrence and metastatic rates. Its treatment is still under discussion. Radical excision of the tumor is the main method of treatment. Selective lymph node dissection is suggested. Superficial parotidectomy seems necessary, especially if the tumor is on the auricle. Adjuvant radio- and chemotherapy may extend survival in case of small-size tumors.     

The problem of predicting food intake during the period of adaptation to a new food: a model

A model is described which aims to predict intake immediately following a change from one food to another that is higher in bulk content; it deals with the transition from one 'equilibrium' intake to another. The system considered is an immature pig fed ad libitum on a single homogeneous food, which is balanced for nutrients and contains no toxins so that the first limiting resource is always energy. It is assumed that an animal has a desired rate of food intake (DFI) which is that needed to meet the energy requirements for protein and lipid deposition and for maintenance. DFI may not be achieved if a bulk constraint to intake exists. Where a bulk constraint operates intake is calculated as constrained food intake (CFI) where (where WHC is the water-holding capacity of the food (kg water/kg dry food) and Cwhc is the animal's capacity for WHC (units/kg live weight per d)). Where intake is not constrained it is assumed that genetic potential will be achieved. Potential growth rate is described by the Gompertz growth function. Where intake is constrained, growth will be less than the potential. Constrained growth rate is predicted as where W is pig weight (kg), EI is energy intake (MJ/d), Em is the energy required for maintenance (MJ/d) and eg is the energy required for unit gain (MJ/kg). The value of eg depends on weight and the fattening characteristics of the pig. Actual growth is predicted to be the lesser of potential and constrained growth. To deal with adaptation it is assumed that the time taken to reach equilibrium depends on the difference in WHC values between the previous and current food and that the capacity to consume food bulk is related to the WHC of the current food. It is proposed that the capacity for WHC on the first day on a new food will be equal to the current capacity for WHC on the last day of the previous food. Thus where FI is food intake (kg/d). Thereafter Cwhc will gradually increase over time to a maximum of 0.27 g/kg. The rate of change in Cwhc is made to be the same for all pigs and all foods. The increase in capacity over time is assumed to be linear at the rate of 0.01 units/d. The model was tested using published data. Qualitatively the predictions of the model were in close agreement with the relevant observed data in at least some cases. It is concluded that the underlying theoretical assumptions of the model are reasonable. However, the model fails to predict initial intake when changed to foods high in wheat-bran content and fails to predict the intake of a non-limiting food where compensatory increases in intake and gain occur. The model could be adapted to overcome the first failure by taking into account the time course of digestive efficiency following a change in food. To deal with the second would require a sufficient understanding of the time course of compensatory growth.     

A cohort study on Helicobacter pylori serology before and after induction in the Hellenic Navy

BACKGROUND AND AIMS: To determine whether military personnel are at increased risk of Helicobacter pylori (HP) infection in proportion to their occupation during their national service in the armed forces. MATERIALS AND METHODS: Serum samples were obtained from 142 young male Hellenic Navy recruits (mean age, 23.6 years; range, 20-30 years). The first specimen was obtained during their induction into the Hellenic Navy, and the second was obtained after having served for 8 months in different services within Greece. An enzyme-linked immunosorbent assay was used to detect HP-specific immunoglobulin G antibodies. Statistical analysis was performed using the sign test, logistic regression, and the chi 2 test. RESULTS: The crude seropositivity rate increased from 19.01% to 28.16% (p = 0.007). Of the 115 initially seronegative subjects, 17 (14.8%) seroconverted. The most important predictive variable for seroconversion was deployment in a crowded commission (> 20 subjects) combined with the absence of air conditioning in personnel sleeping quarters (p = 0.03, odds ratio = 3.14). CONCLUSION: Our data suggest that the risk of HP infection increases among 20- to 30-year-old individuals during their national service. Degrading environmental conditions may play a major role in HP transmission between young adults who serve in the armed forces.     

Intra-amniotic corticosteroids for preterm lung maturation in sheep

OBJECTIVE: The purpose of this study was to compare efficacy on fetal lung maturation of intra-amniotic betamethasone or budesonide with the efficacy of maternal intramuscular betamethasone. STUDY DESIGN: Pregnant ewes received intra-amniotic betamethasone (0.5 mg/kg or 2 mg/kg fetal weight), intra-amniotic budesonide (0.5 mg/kg or 2 mg/kg), maternal intramuscular betamethasone (0.5 mg/kg maternal weight), intra-amniotic saline solution, or maternal saline solution. Lambs were delivered 2 or 7 days later, at 124 days of gestation for measurement of respiratory system compliance, ventilatory efficiency index, and surfactant levels. RESULTS: Lung function increased 2 days after maternal betamethasone, intra-amniotic betamethasone (2 mg/kg), and intra-amniotic budesonide (2 mg/kg) administration and 7 days after maternal betamethasone or intra-amniotic budesonide (2.0 mg/kg) administration. Lung function was not improved 7 days after intra-amniotic betamethasone (2.0 mg/kg) administration or 2 days after intra-amniotic betamethasone (0.5 mg/kg) or intra-amniotic budesonide (0.5 mg/kg) administration. Intra-amniotic corticosteroid administration increased fetal death and respiratory morbidity. CONCLUSION: Intra-amniotic corticosteroid administration improved preterm lung function, but the associated morbidity and mortality rates suggest that they are not suitable for clinical use.