Adrenal hemorrhage secondary to metastasis from lung cancer

The adrenals are common metastatic sites for lung cancers as well as a number of other primary cancers. Usually these metastases are asymptomatic. Hemorrhagic adrenal metastases from lung cancer are extremely rare. Only 5 prior reports of hemorrhagic adrenal metastases from lung cancer have appeared in the English literature. We report a case of spontaneous, massive, adrenal hemorrhage secondary to metastatic lung cancer in a 62-year-old patient. In lung cancer, patients with sudden onset of pain in the flank or back in association with anemia and hypotension, adrenal hemorrhage secondary to metastatic disease should be considered in the differential diagnosis. Computed tomography scans and magnetic resonance imaging aid in confirming the diagnosis.     

Clinical trial of the intradermal administration of hepatitis B vaccine produced at the Department of Medical Research, Myanmar

A total of 280 apparently healthy volunteers were screened for hepatitis B (HB) markers out of which 49 subjects (17.5%) were positive for HB surface antigen (HBsAg) and 82 (29.3%) were positive for antibody to HBsAg (anti-HBs). Three doses of DMR-HB vaccine, 0.15 ml per dose were administered to 95 subjects, who were serologically negative for both HB markers. The vaccination was given by the intradermal route on the flexor surface of the left forearm, at 1 month intervals according to the 0, 1 and 2 months schedule. The subjects were carefully monitored to record any adverse reaction of the vaccine. Blood specimen was collected from each subject, 1 month after the second and third vaccinations, to determine the anti-HBs antibody response to the vaccine. The study results showed that local pain was the only side effect noted and protective antibodies (anti-HBs) were detected in 69 (72.6%) of the vaccinees after the second dose of the vaccine and 89 (93.6%) after the third dose of the vaccine. Thus the intradermal route, which would require approximately one-seventh of the standard dose, would be suitable for use in certain groups such as high risk adults, when the cost of the vaccine is the inhibiting factor for routine or mass vaccination.     

Treatment of spasticity in a spinal cord-injured patient with intrathecal morphine due to intrathecal baclofen tolerance--a case report and review of literature

STUDY DESIGN: Case report. OBJECTIVE: To report treatment of spasticity in a spinal cord-injured person with intrathecal morphine after the person developed tolerance to intrathecal baclofen. METHOD: Spasticity in a 36-year-old man with T6 complete paraplegia was treated with increasing doses of intrathecal baclofen. When he developed tolerance to intrathecal baclofen, he was given continuous infusion of morphine intrathecally. SETTING: Regional Spinal Injuries Centre, UK. RESULTS: Spasticity was adequately controlled by intrathecal morphine. CONCLUSION: In spinal cord-injured patients with severe spasticity, who become tolerant to intrathecal baclofen, treatment with intrathecal morphine may be useful.     

Phenoxybenzamine treatment is insufficient to prevent spasm in the radial artery: the effect of other vasodilators

OBJECTIVES: After its reintroduction as an arterial graft in coronary artery surgery, the radial artery is now established as an alternative arterial conduit, with good early and midterm patency. However, because of the concern about its vasospasticity, numerous vasodilator strategies have been used. Recently the use of the irreversible alpha-adrenergic antagonist phenoxybenzamine has been proposed. Although this treatment is effective in eliminating the vasoconstriction mediated by noradrenaline, the contribution of other circulating vasoconstrictors to vasospasm could be as important. This study investigates the response of radial arteries treated with phenoxybenzamine to vasoconstrictor stimuli and possible preventative strategies. METHODS: In vitro, sections of radial artery, pretreated with phenoxybenzamine after harvesting, were stimulated with maximal concentrations of the vasoconstrictors noradrenaline, vasopressin, angiotensin II, KCl, and endothelin-1. In matched segments of artery, vasoconstrictor responses were recorded in the presence of diltiazem, glyceryl trinitrate, and papaverine and compared with phenoxybenzamine-treated samples. RESULTS: Phenoxybenzamine-treated radial artery failed to respond to noradrenaline but did respond to vasopressin, angiotensin II, endothelin-1, and KCl. Diltiazem was largely ineffective against contractile stimuli apart from KCl. Glyceryl trinitrate and papaverine significantly reduced responses to all of the vasoconstrictors tested. CONCLUSION: In phenoxybenzamine-treated sections of radial artery, circulating vasoconstrictor agonists may still contribute to the induction of spasm. Additional vasodilator strategies may be required to completely prevent vasospasm.     

Pharmacogenomics of cancer chemopreventive isothiocyanate compound sulforaphane in the intestinal polyps of ApcMin/+ mice

Sulforaphane (SFN) is an isothiocyanate that is present in widely consumed vegetables. Previous studies have shown that SFN is effective in preventing carcinogenesis induced by carcinogens in rodents. Recently it was found that SFN could also suppress the growth of intestinal polyps in the ApcMin/+ mouse. In the present study, the acute effect of SFN on the gene expression profile in small intestinal polyps of ApcMin/+ mice using Affymetrix microarray was performed. SFN is a strong inducer for phase II drug metabolizing enzymes, which is believed to contribute to its chemopreventive properties. However, the results show that genes involved in apoptosis, cell growth and maintenance rather than the predicted phase II genes were modulated. The proapoptotic genes including MBD4, TNFR-7 and TNF (ligand)-11 were up-regulated while pro-survival genes including cyclin-D2, integrin-beta1 and Wnt-9A were down-regulated. Interestingly, two genes potentially involved in colorectal carcinogenesis, 15-LOX and COX-2 were found to be increased and decreased, respectively. In conclusion, the results show, for the first time, that chemopreventive agents such as SFN regulate different set of genes involving apoptosis, cell growth/maintenance and inflammation in the small intestinal polyps of ApcMin/+ mice, which could contribute to the overall chemopreventive pharmacological effects.     

Toxicogenomics in Drug Discovery and Drug Development: Potential Applications and Future Challenges

Abstract Despite the massive investments made by pharmaceutical companies on drug research and development, the number of new drug approvals has remained stagnant in the past decades. It is well known that developing safe and effective new drugs is a long, difficult, and expensive process. While the cost of developing new drugs is increasing rapidly, withdrawals of drugs from the marketplace due to adverse drug reactions (ADR) and/or toxicity is increasing concurrently. The recent advent of high-throughput in silico (computer softwares) and in vitro (cell cultures) screenings have somewhat alleviated some, but not all, of these challenges by providing an efficient and effective way for developing safer and better drugs. This emerging technology, known as toxicogenomics, has great potential to facilitate the development of methodologies that could predict the long-term toxic effects of compounds using relatively short-term bioassays. This review is aimed at discussing the potential applications and future challenges of toxicogenomics in drug discovery and drug development.