A reversed-phase high-performance liquid chromatographic assay for the determination of N-acetylcysteine in aqueous formulations

A stability-indicating assay is described for the determination of N-acetylcysteine in aqueous pharmaceutical formulations. The sample is diluted to an appropriate concentration with dilute aqueous orthophosphoric acid. An aliquot of the solution, containing added l-tyrosine as an internal standard, is chromatographed using a 10-mum C(18) stationary phase with dilute orthophosphoric acid (pH 2.0) containing 0.5% w/v of sodium perchlorate as the mobile phase. The assay, which has a relative standard deviation of about 0.8%, can also be used as a test for related impurities in N-acetylcysteine. It is also suitable for determining the N-acetylcysteine content of the drug substance.     

The management of hypertension in Canada: a review of current guidelines, their shortcomings and implications for the future

CLINICIANS ARE EXPOSED to numerous hypertension guidelines. However, their enthusiasm for these guidelines, and the impact of the guidelines, appears modest at best. Barriers to the successful implementation of a guideline can be identified at the level of the clinician, the patient or the practice setting; however, the shortcomings of the guidelines themselves have received little attention. In this paper, we review the hypertension guidelines that are most commonly encountered by Canadian clinicians: the “1999 Canadian Recommendations for the Management of Hypertension,” “The Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure” in the United States and the “1999 World Health Organization–International Society of Hypertension Guidelines for the Management of Hypertension.” The key points of these guidelines are compared and the shortcomings that may impede their ability to influence practice are discussed. The main implications for future guideline developers are outlined.     

Vaccine Hesitancy During the COVID-19 Pandemic: A Latent Class Analysis of Middle-Aged and Older US Adults

Journal of Community Health - It is important to distinguish between apprehensions that lead to vaccine rejection and those that do not. In this study, we (1) identifed latent classes of...     

Pre-irradiation chemotherapy in children with high-grade astrocytoma: Tumor response to two cycles of the ‘8-drugs-in-1-day’ regimen

SummaryPurpose This study was undertaken to evaluate the radiographie response to two cycles of chemotherapy prior to irradiation in newly diagnosed children with high-grade astrocytomas.Patients and methods. One hundred and thirty children less than 21 years of age with newly-diagnosed highgrade astrocytoma were treated with the eight-drugs-in-one-day chemotherapy regimen as part of a phase III multi-institutional Childrens Cancer Group (CCG) trial. Computerized Tomographic (CT) or Magnetic Resonance Image (MRI) scans, obtained after two cycles of chemotherapy had been administered, were compared with post-operative scans to determine treatment response. Scans were evaluated by institutional radiologists, and were reviewed centrally by a single neuroradiologist.Results Of 79 patients with evaluable post-operative residual tumor on CT or MRI scans, 26 (33%) were determined on institutional evaluation to have had an objective response. However, central review of scans documented responses on only 14/79 (18%). A significantly higher response rate on central review was observed for those children 36 months of age or less at study entry than for older children (33% v 11%; p < 0.001). However, a higher disease progression rate was also observed for those children 36 months of age or less than for older children (21% v 2.6%; p < 0.001).Conclusion In this study, the largest yet reported in newly-diagnosed children with high-grade astrocytomas, the chemotherapy regimen has activity in younger children. The differences in response rates reported by institutional and central review highlight the difficulties inherent in assessing response to brain tumor therapy. However, the study does demonstrate the consistent ability of radiologists to identify disease progression within the institutional and central reviews.     

Alpha-fetoprotein and beta-human chorionic gonadotropin: their clinical significance as tumour markers

Tumour markers can aid in areas such as diagnosis, surveillance of recurrence, staging and prognosis. This article focuses on 2 tumour markers, alpha-fetoprotein (AFP) and beta-human chorionic gonadotropin (HCG). These tumour markers have been examined for their utility as prognostic indicators in 2 different manners. First, the marker level at diagnosis has been studied to determine if it is prognostic of outcome presumably because of its relation to tumour bulk or to the biological nature of the tumour. A more recent trend has been to investigate tumour marker decline. The finding of a delayed rate of decline suggests a poorer response of the malignancy to chemotherapy. The major focus of the article will be on marker decline of AFP and HCG as prognostic tools in peripheral and central nervous system (CNS) germ cell tumours (GCTs) and hepatic tumours (hepatoblastoma and hepatocellular carcinoma). The articles reviewed here suggest that HCG and AFP can correlate with survival if examined in specific ways, and could potentially be used to tailor treatment for individual patients. One group of authors presents data on patients with GCTs suggesting that satisfactory marker regression is an independent prognostic factor for survival. In a study of hepatoblastoma, data demonstrate that both the magnitude and rate of decline are associated with survival. Marker decline studies in hepatocellular carcinoma do not exist and marker levels at diagnosis do not appear to have a role in potential therapeutic changes. However, data on fucosylated subtype of AFP, Lens culinaris agglutinin A reactive AFP, has shown prognostic significance in hepatocellular carcinoma. The data for CNS GCTs are limited and studies examining serial cerebrospinal fluid HCG/AFP are ongoing. In some diseases, issues relating to timing of marker sampling when examining marker decline need to be studied in greater detail. Hopefully, marker decline studies can be duplicated in the other diseases, to document a potential role in determining outcome. Further studies are needed to test the ability to alter therapy in attempts to improve survival while decreasing toxicity to patients.     

Unusual dynamics of killing of cultured lewis lung cells by the DNA-intercalating antitumour agentN-[2-(dimethylamino)ethyl]acridine-4-carboxamide

Summary The cytotoxicity ofN-[2-(dimethylamino)ethyl]acridine-4-carboxamide (AC; NSC 601 316), a new experimental DNA-intercalating antitumour drug, against a cultured Lewis lung adenocarcinoma cell line was compared with that of the DNA-intercalating antitumour drug amsacrine. In contrast to amsacrine, AC demonstrated self-inhibition of cytotoxicity following short (3–9 h) incubation periods and exponential killing (with a shoulder) after long (24–72 h) periods of incubation. The difference between these drugs was best demonstrated using a constant concentration x time (CxT) exposure (AC, 12 mol h l^–1; amsacrine, 3 mol h l^–1). In contrast to amsacrine, AC was minimally effective over exposure periods of 1 h and maximally effective over intermediate periods (4–6 h). The results suggest the possibility of designing AC administration protocols that maximise the drug's cytotoxicity towards solid tumours, which, because of diffusion barriers, are subjected to longer drug exposures than are well-vascularised tumours.Supported by the Auckland Division of the Cancer Society of New Zealand and by the Health Research Council of New Zealand     

Conservation of absolute foveal area in New World monkeys. A constraint on eye size and conformation

The foveal specializations of five New World monkeys, the marmoset, Callithrix jacchus; the golden-handed tamarin, Saguinus midas niger; the squirrel monkey, Saimiri ustius; the capuchin monkey, Cebus apella; and the howler monkey, Alouatta caraya were compared. Although retinal area varies by over a factor of two in these monkeys, the area of the fovea does not covary with retinal area and remains approximately the same absolute size, as measured by the dimensions of the high density region of cones, or the rod-free region. This constancy in foveal size also holds for rhesus monkeys and humans, bringing the variation in retinal area to a factor of five. Alouatta caraya is unusual, distinguished by a very high central cone density and a small rod-free zone. Physiological constraints that might limit foveal area over a wide range of eye sizes are considered.