Ki-ras mutations are an early event and correlate with tumor stage in transplacentally-induced murine lung tumors

A previous study from this laboratory demonstrated that treatment of pregnant mice with 3-methylcholanthrene (MC) caused lung tumors in the offspring at 1 year after birth, the incidence of which correlated with fetal inducibility of Cyp1a1. Analysis by PCR amplification and allele- specific hybridization (ASO) of paraffin-embedded tumors generated from that study revealed the presence of point mutations in exon 1 of the Ki- ras gene. This work has now been expanded by PCR amplification and ASO analysis of 31 additional lesions. Point mutations were found in 37 of the 47 (79%) lesions analyzed in this and the previous study, the majority of which were G-->T transversions in the first or second base of codon 12. The mutational spectrum appeared to be dependent on the relative stage of differentiation of the lesion, as both the incidence of mutation and type of mutation produced correlated with malignant progression. Mutations occurred in 60% of the hyperplasias, 80% of the adenomas and 100% of the adenocarcinomas. In the lesions with mutations, GLY12-->CYS12 transversions occurred in 100% of the hyperplasias, 42% of the adenomas and 14% of the adenocarcinomas. The GLY12-->VAL12 transversions occurred in none of the hyperplasias, 42% of the adenomas and 57% of the adenocarcinomas. The remaining mutations, which consisted of ASP12 transitions and ARG13 transversions, occurred only in adenomas (17%) and adenocarcinomas (29%). Between this study and our previous analyses, the identity of the mutations obtained by ASO were confirmed by sequence analysis of eight of the 37 lesions that harbored mutations at the Ki-ras gene locus. There were no differences in the type or incidence of mutations relative to the metabolic phenotype or sex of the mice. These data suggest that mutational activation of the Ki-ras gene locus is an early event in transplacental lung tumorigenesis, and that the type of mutations produced by exposure to chemical carcinogens can influence the carcinogenic potential of the tumor. This may have prognostic significance in determining the malignant progression of the neoplasm.      

Immunological factors in milk from Brazilian mothers delivering small-for-date term neonates

Breast milk samples from three groups of Brazilian women were evaluated: G1, mothers delivering term babies of low birth weight (n=16); G2, mothers delivering preterm babies of appropriate birth weight (n = 20); G3, mothers delivering term babies of appropriate birth weight ( n = 30). Milk samples were obtained at 48 h and on the 7th, 15th, 30th and 60th days after delivery and they were analyzed for lysozyme and total IgA levels and for the presence of specific antibodies against Poliovirus types I, II, III, Rotavirus, Herpes simplex virus, Varicella zoster and Cytomegalovirus. The groups were not statistically different in relation to mother's age, parity, type of delivery or socio-economic levels. IgA levels were higher in both low-birth-weight groups (G1 & G2) compared to the control group (G3) throughout the study period. Lysozyme levels decreased up to the 15th day, increasing thereafter up to the 60th day in all groups. Specific antibodies were detected throughout the study period, with no differences among groups. We conclude that breast milk composition of mothers delivering low-birth-weight babies (G1 & G2) was similar despite the different gestational ages.     

Methylene blue derivatives--suitable photoantimicrobials for blood product disinfection?

Photodynamic antimicrobial agents based on the well-established phenothiazinium biological stain methylene blue offer a simple method for the inactivation or destruction of pathogens contained in donated blood and blood products. The technique is currently concentrated on viruses and the disinfective procedure can be carried out in blood bags using basic low-power light sources. Pathogens of the bacterial, yeast and protozoal classes are also susceptible to phenothiaziniums. The photoantimicrobial mode of action is usually via oxidative damage to cellular components, either due to redox reactions between the agent and a biomolecular target or by the action of reactive oxygen species generated in situ by photodynamic action. The targeting of various microbial species is discussed in relation to the physicochemical make-up of the photosensitizers, and future directions are suggested.     

Early pregnancy complications: endovaginal sonographic findings correlated with human chorionic gonadotropin levels

Endovaginal sonography results were compared with quantitatively determined human chorionic gonadotropin (hCG) levels in 84 women referred for early pregnancy complications. Of the 27 with normal intrauterine pregnancies, an intrauterine gestational sac was prospectively identified in one of five cases (20%) in which hCG levels were below 500 IU/L (Second International Standard), four of five (80%) with hCG levels of 500-1,000 IU/L, and all 17 with hCG levels above 1,000 IU/L. In comparison, 17 of the 26 women with ectopic pregnancies (65%) had hCG levels greater than 1,000 IU/L, and none of the 26 had an intrauterine gestational sac. Endovaginal sonography demonstrated an adnexal mass and/or a gestational sac-like structure in 16 of the 17 cases (94%) in which hCG levels were above 1,000 IU/L, compared with only three of the nine (33%) with lower hCG levels (P less than .01). These findings indicate that an intrauterine gestational sac should be normally visualized with endovaginal sonography when the hCG level exceeds 1,000 IU/L, and that visualization of an extrauterine gestational sac and/or adnexal mass is significantly more likely in ectopic pregnancies when the hCG level exceeds 1,000 IU/L.     

Misleading high tobramycin plasma concentrations can be caused by skin contamination of fingerprick blood following inhalation of nebulized tobramycin (TOBI): a short report

We observed unexpected high plasma concentrations of tobramycin (48.5 and 28.1 mg/L) in fingerprick blood samples after the nebulization of tobramycin solution for inhalation (tobramycin 300 mg/5 mL, TOBI by 2 young children aged 3 years. To investigate whether dermal contamination could be the source of error, 3 adult volunteers were present during another nebulization by a third child (age 2 years). The volunteers had exposure to tobramycin by handling the nebulizer or the nebule and also by inhalation from holding the child and being in close proximity while TOBI was being administered. Five blood samples by fingerprick and 2 by venipuncture were collected and assayed for tobramycin concentration. On each occasion the site was swabbed with alcohol wipes to mimic standard patient sampling methods. One site was resampled after cleaning of hands with 2% chlorhexidine gluconate and water. Tobramycin concentrations from venipuncture 1-2 hours after nebulization were all <0.2 mg/L except for 1 result of 1.2 mg/L. The tobramycin concentrations from fingerpricks before hand washing varied between 6.8 and 172 mg/L, and after hand washing between 0.3 and 17.6 mg/L. Contamination of fingers with tobramycin is likely to have caused the error in the 2 initial cases and did cause misleadingly elevated levels in the adult volunteers. We caution that therapeutic drug monitoring of nebulized tobramycin should not be done by fingerprick sampling, and care should be taken to avoid contamination of the venipuncture site.     

Extrapulmonary Tuberculosis in Human Immunodificiency Virus Infection

Background

In view of increase in incidence of exptrapulmonary tuberculosis after the epidemic of human immunodeficiency virus infection, the clinical profile of extrapulmonary tuberculosis in patients with HIV infection was studied.

Method

The study population comprised patients of HIV infection with extrapulmonary tuberculosis. Work up included history, clinical examination, sputum for acid fast bacilli, chext X-ray, ultrasonography (USG) abdomen, fine needle aspiration cytology(FNAC), transbronchial needle aspiration (TBNA) and computed tomography of chest.

Results

There were 50 cases, all males with mean age of 35 years. 24(48%) were without pulmonary tuberculosis and 26(52%) had pulmonary tuberculosis. 41(82%) had disseminated disease and 9(18%) involve one site. Fever and weight loss were the most frequent symptoms (79% and 58% respectively) in cases without pulmonary tuberculosis. The most frequent extrapulmonary site was lymph node in 46(92%), followed by spleen in 13(26%), pleura 9(18%), miliary 7(14%) and hepatic 1(2%). The diagnosis was confirmed by invasive methods in 30 out of 50(60%) cases [FNAC in 23(88%), TBNA in 2(25%) and pleural biopsy in 5(55%)].

Conclusion

In HIV infected patients, the most common extrapulmonary site is lymph mode followed by spleen.Key Words: Extrapulmonary TB, HIV Infection