Marijuana components suppress induction and cytolytic function of murine cytotoxic T cells in vitro and in vivo.

Killer lymphocytes play a major role in host defense against tumors and infectious diseases. Previously, we reported that delta-9-tetrahydrocannabinol (THC) and II-hydroxy-delta-9-tetrahydrocannabinol (II-hydroxy-THC) suppressed the cytolytic activity of cultured natural killer (NK) cells. Also, we showed that the drugs appeared to be affecting a stage in the killing process subsequent to the binding of the killer cell to the target cell. In the present report, we have extended these studies to an examination of the effect of cannabinoids on the activity of cytotoxic T lymphocytes (CTLs). The cytolytic activity of CTLs generated by cocultivation with either allospecific stimulators or TNP-modified-self stimulators were suppressed by both THC and II-hydroxy-THC treatment. Allospecific CTLs generated in vivo were also inhibited by an in vitro exposure to either THC or II-hydroxy-THC, and the sensitivity of these cells to drug effects appeared to be greater than the sensitivity of the in vitro generated CTLs. Suppression of cytolytic function by THC and II-hydroxy-THC was maximal after a 4-h drug treatment, suggesting that the drug effects were inducible and therefore required a finite period of time to develop maximally. As seen in previous studies involving NK cells, drug treatment of mature CTLs appears to have little effect on the binding capacity of these cells for the target. However, the maximal killing capacity of the cells and the frequency of CTLs were significantly reduced by drug treatment. In addition to suppressing the cytolytic activity of mature effector CTLs, we also show that drug treatment inhibits both the proliferation of lymphocytes responding to an allogeneic stimulus and the maturation of these lymphocytes to mature CTLs. Similarly, CTL activity developing in vivo could be inhibited by THC injection. These results suggest that CTLs are inhibited by cannabinoids by at least two mechanisms. First, the cytolytic activity of mature killers is suppressed at some point beyond the binding to the target cell. Second, the cannabinoids appear to suppress the normal development of these mature effector cells from less mature precursor cells.     

All five digits of the hands of fetuses with Down syndrome are short.

OBJECTIVE: To compare mid-gestation sonographic measurements of all five digits of the hands of fetuses with Down syndrome with those of normal controls. METHODS: Twenty-nine fetuses between 17 and 26 weeks' gestation which had been confirmed by karyotyping to have Down syndrome were included in this prospective study. Each fetus was scanned once and the digits of only one hand were measured. Measurements were compared with those of 302 previously reported normal controls matched for gestational age. All measurements were expressed in multiples of the gestation-specific normal median (MoM) for each digit. RESULTS: Compared to 1 MoM for the length of Digits 1 to 5 from the normal population, the respective values in the Down syndrome digits were: 0.94, 0.85, 0.92, 0.88 and 0.85 MoM, representing values significantly lower than normal (P < 0.05; t-test). CONCLUSIONS: All five digits of the hands of fetuses with Down syndrome are shorter than are those of euploid fetuses. Integration of fetal digit measurement into the antenatal assessment of selected high-risk cases may be of value although confirmation of our findings should be obtained before this measurement is incorporated into Down syndrome screening in the general population.     

Effect of anti-PcrV antibody in a murine chronic airway Pseudomonas aeruginosa infection model.

Pseudomonas aeruginosa is one of the most important pathogens in patients with chronic airway conditions, such as cystic fibrosis and diffuse panbronchiolitis. Type III secretion system-mediated virulence factors contribute to the lung damage in chronic P. aeruginosa infection. The effects of the anti-PcrV immunoglobulin (Ig)G, which blocks the type III secretion system, were evaluated in a mouse model of chronic P. aeruginosa infection. On bacteriological examination, anti-PcrV IgG showed no bactericidal effects. On bronchoalveolar lavage fluid (BALF) analysis, total cell number and neutrophil ratios in the anti-PcrV IgG-treated groups were lower than those in the control group. In addition, macrophage inflammatory protein-2, tumour necrosis factor-alpha, and interleukin-beta concentrations in BALF were lower in the anti-PcrV IgG-treated groups when compared with controls. Plasma anti-PcrV IgG titre was elevated after administration of anti-PcrV IgG. Although plasma titre decreased gradually, a significant concentration was maintained during the experimental period. These data suggest that anti-PcrV immunoglobulin G reduces the inflammatory reaction caused by chronic Pseudomonas aeruginosa respiratory infection and may be useful in treating respiratory diseases.     

Detection of extrapulmonary lesions with integrated PET/CT in the staging of lung cancer.

The aim of the present study was to assess retrospectively the additional value of positron emission tomography (PET)/computed tomography (CT) in the detection of unexpected extrapulmonary lesions in the staging of patients with a malignant pulmonary lesion in comparison with CT and PET used alone. A total of 217 patients with a pathologically proven lung tumour underwent PET/CT. CT, PET and PET/CT were evaluated in the detection of extrapulmonary lesions. These abnormalities were compared with the final diagnosis obtained from the medical records and statistical analysis was carried out. In total, 108 lesions were clinically detected. PET/CT showed a sensitivity, specificity, positive and negative predictive values and accuracy of 100, 81, 71, 100 and 87%, respectively, for the detection of extrapulmonary lesions and 92, 98, 89, 98 and 97%, respectively, for the detection of malignant extrapulmonary lesions. PET/CT was significantly better than CT and PET used alone. Conventional staging work-up has a poor sensitivity in detecting second primary cancers or unexpected metastases. The detection of malignant extrapulmonary lesions is necessary for correct tumour staging. By combining both metabolic and anatomical information, positron emission tomography/computed tomography is able to depict more unexpected extrapulmonary lesions than computed tomography and positron emission tomography used alone, and positron emission tomography/computed tomography provides more additional information of malignancy or benignancy of lesions detected with one of the two imaging modalities alone.     

Chirurgische Behandlung benigner Läsionen und Strikturen der Gallenwege

Benign strictures of the biliary ducts are treated surgically in 90% of cases. Usually they are caused by trauma to the choledochous duct during gallbladder operations. Younger patients are frequently affected and, particularly if the strictures go untreated, can suffer from secondary complications such as cholangitis or secondary biliary cirrhosis with the serious dangers of portal hypertension and even hepatic failure and death. Although immediate treatment by end-to-end anastomosis has sometimes been described, this method is reasonable only for smooth cuts to the choledochous duct. Good long-term results have been achieved in 86% of cases with Roux-en-Y hepaticojejunostomy. In general, the best way to avoid complications is the all-important surgical maxim of correct indication for the primary operation. The best course is to limit the decision for surgery to symptomatic gallstones.