Degradation of Paclitaxel and Related Compounds in Aqueous Solutions III: Degradation Under Acidic pH Conditions and Overall Kinetics

Paclitaxel and related taxanes are complex molecules with numerous hydrolysable ester groups, possible epimerization at the 7‐position, and possessing a strained oxetane ring, a possible site for acid‐catalyzed cleavage. Presented here is the stability of paclitaxel, 10‐deacetylbaccatin III, baccatin III, and N‐benzoyl‐3‐phenylisoserine ethyl ester in aqueous solution over a pH range of 1–5 at various temperatures. Analysis of various samples was by HPLC–UV and LC–MS. Baccatin III, 10‐deacetylbaccatin III, and N‐benzoyl‐3‐phenylisoserine ethyl ester were found to undergo acid catalysis since pH‐rate profiles all followed a first‐order dependency in hydrogen ion concentration. No evidence of any epimerization was noted at acidic pH values. Baccatin III and 10‐deacetylbaccatin III showed similar degradation rates with possible products being possible dehydration around the 13‐hydroxy group and cleavage of the oxetane ring. Cleavage of the 10‐acetyl group of baccatin III was a minor initial pathway. N‐Benzoyl‐3‐phenylisoserine ethyl ester degraded significantly slower than both 10‐deacetylbaccatin III and baccatin III. At pH 2, paclitaxel degraded at a rate between that of N‐benzoyl‐3‐phenylisoserine ethyl ester and 10‐deacetylbaccatin III. The pH of maximum stability for all compounds appeared to be around pH 4. © 2009 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 99: 1288–1298, 2010     

A prospective study of tobacco use and multiple myeloma: evidence against an association

The relationship between the use of cigarettes and other tobacco products and the risk of multiple myeloma was examined in a cohort of nearly 250,000 American veterans followed prospectively for 26 years. Compared with men who had never used tobacco, the risk of death from myeloma was not increased among current (relative risk [RR]=0.9, 95 percent confidence interval [CI]=0.8–1.2) or former (RR=1.0, CI=0.8–1.3) cigarette smokers, nor among users of chewing tobacco or snuff (RR=1.0, CI=0.4–2.3). Risk was only slightly and nonsignificantly increased among pipe or cigar smokers (RR=1.2, CI=0.9–1.5). There was no indication of increasing risk with amount of tobacco used or earlier age at first use. With over 90 percent power to detect a 30 percent increased risk of this tumor occuring among current cigarette smokers, this study provides the strongest evidence to date against an association of cigarette smoking with multiple myeloma.Epidemiology and Biometry Program, Division of Cancer Etiology, National Cancer Institute. Westat, Inc. Rockville, MD. National Cancer Institute, 6130 Executive Blvd, Room 418, Rockville, MD 20892, USA.     

Testicular regression syndrome. A case report

Testicular regression syndrome occurred in a 20-year-old, white, phenotypic female with a 46,XY karyotype. The basal levels of serum gonadotropins were elevated, while the testosterone was in the normal range. Estrogens were undetectable. At laparotomy no gonadal rudiments or müllerian or wolffian derivatives were found. The logical diagnosis was late embryonic testicular regression with a specific testicular insult 62-63 days after fertilization.     

Ninety-one Cases of Breast Cancer and Chronic Lymphoproliferative Neoplasm: A Retrospective Review of a Population at High Risk for Multiple Malignancies

Abstract: We performed a retrospective analysis of clinical course of 91 patients who developed both breast cancer and a chronic lymphoproliferative neoplasm and were seen at the M. D. Anderson Cancer Center between January 1, 1970 and December 30, 1991. The sample included 24 individuals who developed lymphoproliferative neoplasm first (Group A), 22 individuals with concurrent diagnosis of both malignancies (Group B), and 45 individuals who developed breast cancer first (Group C). The median time to diagnosis of secondary breast cancer and lymphoproliferative neoplasm was 66 months (range, 7–459) and 65 months (range, 0–334), respectively. A higher proportion of Group B lymphomas were low-grade (77% vs. 47% [Group A] vs. 37% [Group C] p = 0.009). Prior occurrence of either one of these malignancies did not affect the disease-specific survival from the second malignancy. However, continuing mortality from the first malignancy appeared to contribute to a poor overall survival following second malignancy. Group A included 8 patients who developed breast cancer following radiation therapy for Hodgkin's disease after a mean interval of 18 (± 4.3) years. Three of these individuals had coexisting ductal and lobular histology (vs. none of the individuals in Groups B and C, p = 0.02). Another interesting finding was the high incidence of multiple additional malignancies in this patient population. A total of 29 additional neoplasms occurred in 21 (23%) of the 91 study subjects. These malignancies involved a wide variety of organ sites and could not be attributed to the therapy for either the breast cancer or the lymphoma in most cases. The data suggest that individuals who develop both breast cancer and a lymphoproliferative neoplasm are at a high risk for multiple malignancies. Close surveillance of such individuals for additional malignancies and further studies to understand the molecular basis of this predisposition are warranted.?     

Simple color tests based on an alanyl peptidase reaction which differentiate Listeria monocytogenes from other Listeria species.

The hydrolysis of DL-alanine-beta-naphthylamide and D-alanine-p-nitroanilide for identification of Listeria spp. has been studied with 227 cultures. All species of Listeria, except L. monocytogenes, hydrolyzed these substrates. The reactions were detected by simple chromogenic reactions and could substitute for the CAMP test.     

Reliability of IL Monarch ion-selective electrode module for sodium, potassium, and chloride measurements

We evaluated the IL Monarch random-access centrifugal analyzer for measurement of Na+, K+, and Cl- by an indirect potentiometric method. For different concentrations of control material, the total precision (CV) ranged between 0.82% and 1.14% for the three electrolytes; linearity was acceptable within a range of 103 to 215 mmol/L for Na+, 1.6-15.25 mmol/L for K+, and 80-173 mmol/L for Cl-. Data correlated well with those by flame photometry for Na+ and K+ and with those by coulometry for Cl-, both for various biological materials--sera, urines, dialysis fluids--and commercial control materials from various producers. Stability of the potentiometric signal was acceptable: daily variations were 0.2 mV for Na+, 0.05 mV for K+, and 0.03 mV for Cl-. Accordingly, we conclude that the system supplies reproducible and accurate results while being easy to use and requiring little maintenance. The use of indirect potentiometry offers results consistent with those obtained with traditional methods, and easily interpretable by clinical staff. However, better information about the actual ion activity in the tested sample for certain pathologies such as hyperlipemia and dysproteinemia could be obtained by methods involving direct potentiometry.     

In vitro activity of ceftriaxone and other cephalosporins against 602 clinical isolates of staphylococci from geographically diverse medical centers

The in vitro activity of ceftriaxone and six additional antimicrobial agents (ceftizoxime, cefoperazone, cefuroxime, fleroxacin, ciprofloxacin, and trimethoprim/sulfamethoxazole) was assessed or 602 recent clinical isolates of staphylococci from six geographically distinct medical centers in North America. All seven antimicrobial agents were active (90–100% of strains susceptible) against oxacillin-susceptible (OS) strains of Staphylococcus aureus (OSSA) and coagulase-negative staphylococci (OSCNS) but had limited activity against oxacillin resistant (OR) staphylococci. Our assessment of the in vitro antistaphylococcal activity of ceftriaxone against contemporary isolates of Staphylococcus aureus and coagulase-negative staphylococci indicates that the activity versus OS staphylococci has not changed over the past decade despite widespread use of the drug. It appears that these agents will continue to be useful for empiric therapy in those centers in which OR strains are uncommon.Corresponding author.     

Laser instrumentation for intra-abdominal microlaser gynecologic surgery

With proper laser instrumentation, the gynecologic microlaser surgeon enhances his ability to accomplish intra-abdominal fertility-promoting procedures in a safe and efficient manner.     

Contributions of parental alcoholism, prenatal substance exposure, and genetic transmission to child ADHD risk: a female twin study

BACKGROUND: Genetic influences have been shown to play a major role in determining the risk of attention-deficit hyperactivity disorder (ADHD). In addition, prenatal exposure to nicotine and/or alcohol has also been suggested to increase risk of the disorder. Little attention, however, has been directed to investigating the roles of genetic transmission and prenatal exposure simultaneously. METHOD: Diagnostic telephone interview data from parents of Missouri adolescent female twin pairs born during 1975-1985 were analyzed. Logistic regression models were fitted to interview data from a total of 1936 twin pairs (1091 MZ and 845 DZ pairs) to determine the relative contributions of parental smoking and drinking behavior (both during and outside of pregnancy) as risk factors for DSM-IV ADHD. Structural equation models were fitted to determine the extent of residual genetic and environmental influences on ADHD risk while controlling for effects of prenatal and parental predictors on risk. RESULTS: ADHD was more likely to be diagnosed in girls whose mothers or fathers were alcohol dependent, whose mothers reported heavy alcohol use during pregnancy, and in those with low birth weight. Controlling for other risk factors, risk was not significantly increased in those whose mothers smoked during pregnancy. After allowing for effects of prenatal and childhood predictors, 86% of the residual variance in ADHD risk was attributable to genetic effects and 14% to non-shared environmental influences. CONCLUSIONS: Prenatal and parental risk factors may not be important mediators of influences on risk with much of the association between these variables and ADHD appearing to be indirect.