Pharmacokinetics of orally administered norethisterone enanthate in rabbit, monkey, and women

Norethisterone enanthate (NET-En), an established intramuscular long-acting contraceptive agent, has previously been shown to be effective in inhibiting fertility in two rodent species even 4 days after oral ingestion. Pharmacokinetics of NET and NET-En were studied after oral and intramuscular doses in two animal species and a few women. The results suggest that the NET-En was absorbed within a day in all the species after oral dose. The estimates of relative bioavailability ranged from 13 to 51% in rabbits, monkeys, and women. The elimination half-life was 5–10 days. The presence of the active component, NET, in the circulation over the experimental period of 15 days suggests that NET-En could be useful as a long-acting oral pill. The suppression of progesterone levels during the luteal phase of menstrual cycle in women also supports this finding.     

Heroin-Induces Differential Protein Expression by Normal Human Astrocytes (NHA)

Heroin use is postulated to act as a cofactor in the neuropathogenesis of human immunodeficiency virus (HIV-1) infection. Astrocytes, integral components of the CNS, are reported to be susceptible to HIV-1 infection. Upon activation, astrocytes release a number of immunoregulatory products or modulate the expression of a number of proteins that foster the immunopathogenesis of HIV-1 infection. However, the role of heroin on HIV-1 infectivity and the expression of the proteome of normal human astrocytes (NHA) have not been elucidated. We hypothesize that heroin modulates the expression of a number of proteins by NHA that foster the neuoropathogenesis of HIV-1 infection. We utilized LTR amplification and the p24 antigen assay to quantitate the effect of heroin on HIV-1 infectivity while difference gel electrophoresis (DIGE) combined with protein identification through high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) to analyze the effects of heroin on the proteomic profile of NHA. Results demonstrate that heroin potentiates HIV-1 replication in NHA. Furthermore, heroin significantly increased protein expression levels for protein kinase C (PKC), reticulocalbin 1 precursor, reticulocalbin 1, tyrosine 3-monooxgenase/tryptophan 5-monooxgenase activation protein, chloride intracellular channel 1, cathepsin D preproprotein, galectin 1 and myosin light chain alkali. Heroin also significantly decreased protein expression for proliferating cell nuclear antigen, proteasome beta 6 subunit, tropomyosin 3, laminin receptor 1, tubulin alpha 6, vimentin, EF hand domain family member D2, Tumor protein D54 (hD54), ATP synthase, H+ transporting, mitochondrial F1 complex and ribosomal protein S14. Identification of unique, heroin-induced proteins may help to develop novel markers for diagnostic, preventative and therapeutic targeting in heroin using subjects.     

Association of the renin-sodium profile with the risk of myocardial infarction in patients with hypertension.

BACKGROUND. To test the prognostic value of plasma renin activity prospectively, we determined the pretreatment renin-sodium profile of 1717 subjects with mild-to-moderate hypertension (mean age, 53 years; 36 percent white; 67 percent men) in a systematic work-site treatment program. METHODS. Renin profiles, obtained by plotting plasma renin activity against the urinary excretion of sodium, were classified as high (12 percent of the subjects), normal (56 percent), and low (32 percent), and there were expected variations according to age, sex, and race. Modified stepped-care treatment for hypertension, prescribed without reference to the renin profile, was similar in the three renin groups. RESULTS. Mean (+/- SD) blood pressure at entry was 151 +/- 19/100 +/- 10 mm Hg in the subjects with a high renin profile, 151 +/- 19/97 +/- 10 mm Hg in those with a normal profile, and 151 +/- 20/96 +/- 11 mm Hg in those with a low profile. During 8.3 years of follow-up, there were 27 myocardial infarctions. As adjusted for age, sex, and race, the incidence of myocardial infarction per 1000 person-years was 14.7 among the subjects with a high renin profile, 5.6 among those with a normal profile, and 2.8 among those with a low profile (rate ratio for high vs. low, 5.3; 95 percent confidence interval, 3.4 to 8.3). The rate of mortality from all causes was 9.3 in the high-profile group, 5.3 in the normal-profile group, and 3.9 in the low-profile group. The independent association of a high renin profile with myocardial infarction (but not with stroke or noncardiovascular events) was affirmed by Cox analyses (rate ratio for high vs. normal plus low, 3.2; 95 percent confidence interval, 1.2 to 8.4) after adjustment for race, sex, age at entry, serum cholesterol level, smoking status, electrocardiographic evidence of left ventricular hypertrophy, blood glucose level, body-mass index, history of cardiovascular disease or treatment, blood pressure, and use of beta-blockers. CONCLUSIONS. In the study population, whose blood pressure before and during treatment was in a narrow range, and after other cardiovascular risk factors had been considered, the renin profile before treatment remained independently associated with the subsequent risk of myocardial infarction.     

Primary pulmonary adenoid cystic carcinoma: report of a case diagnosed by fine-needle aspiration cytology

Adenoid cystic carcinoma of the lower respiratory tract is an uncommon tumor that can arise in the mainstem bronchus and often presents as an endobronchial mass lesion causing bronchial obstruction with post obstructive atelectasis and pneumonia. Exfoliative cytology is seldom useful in the diagnosis of primary bronchial adenoid cystic carcinoma, because these neoplasms usually have a submucosal location with often intact mucosa. Since most endobronchial adenoid cystic carcinomas are endoscopically visible, bronchoscope-guided fine-needle aspiration constitutes an excellent approach to establish a pathologic diagnosis. The fine-needle aspiration cytology of primary pulmonary adenoid cystic carcinoma has been rarely described. We report a case of primary adenoid cystic carcinoma of the lung having characteristic cytologic features and correlate with computed tomography, bronchoscopic, and histological findings. Bronchoscope-guided aspiration cytology provided a conclusive diagnosis of adenoid cystic carcinoma, which was further corroborated by histology in the pneumonectomy specimen. Diagn. Cytopathol. 2004;30:51-56.     

The extent of resection influences outcome following hepatectomy for colorectal liver metastases.

BACKGROUND: The acceptable indications for liver resection in patients with colorectal metastases have increased significantly in the last decade. It is thus becoming more difficult to ascertain the limitations for selection as the boundaries have been greatly extended. This has resulted in not only more extensive resections, but more atypical and bilobar resections. The aim of this study was to compare the outcome of patients undergoing different extent of liver resection in a specialist unit. METHODS: All patients undergoing liver resection for colorectal metastases at the Royal Infirmary of Edinburgh between October 1988 and April 2001 were reviewed. Patients were allocated into one of three groups: standard group, extended group, and segmental group. Patient information was collected from a prospectively completed database. RESULTS: One hundred and thirty-seven patients had liver resections for colorectal metastases during the study period. There were 69 standard hepatectomies, 41 extended resections and 27 segmental resections. CEA level was significantly lower in the segmental group(p = 0.012). There was a significant difference between the groups in terms of median operating time (p < 0.0001, Kruskal-Wallis test), operative blood loss (p = 0.006, Kruskal-Wallis test) and post-operative stay ( p = 0.036, Kruskal-Wallis test). Major post-operative complications were similar between standard and extended resections but less following segmental resection (p = 0.050. Predicted median survival was 51 months following standard resection, 23 months following extended resection and 59 months after segmental resection ( p = 0.037, log rank test), however, there was no difference between the three groups for actual 5-year survival (p = 0.662, Pearson chi-square test). CONCLUSION: Morbidity and mortality rates were comparable with other previous studies as was overall survival, although survival in patients undergoing extended resections was reduced. There was an acceptable level of morbidity and mortality for all three groups. Patients undergoing segmental resection had fewer complications, shorter length of stay, and the longest median survival suggesting adequate oncological clearance. Segmental resection has a role for favourably placed tumour deposits if oncological clearance can be ensured. Extended liver resections have a role for selected patients with bilobar colorectal metastases or large solitary deposits close to the hepatic vein confluence.