Controlled organocatalyzed d,l-lactide ring-opening polymerizations: synthesis of low molecular weight oligomers.

A systematic approach to the synthesis of organocatalyzed oligo(d,l-lactide) demonstrates that choice of initiator, catalytic ratio, and reaction time yields well-controlled oligomers. Ring-opening polymerization of d,l-lactide with the initiator α-methyl propargyl alcohol, a secondary alcohol, used in excess of 4-dimethylaminopyridine catalyst mitigates cyclicization, transesterification, and catalyst-initiated side reactions. This approach enables the design of uniform lactide oligomers for controlled release applications, such as delivery systems for drugs, prodrugs, and molecular sensors.

Lack of high-dose radiation mediated prostate cancer promotion and low-dose radiation adaptive response in the TRAMP mouse model.

Cancer of the prostate is a highly prevalent disease with a heterogeneous aetiology and prognosis. Current understanding of the biological mechanisms underlying the responses of prostate tissue to ionizing radiation exposure, including cancer induction, is surprisingly limited for both high- and low-dose exposures. As population exposure to radiation increases, largely through medical imaging, a better understanding of the response of the prostate to radiation exposure is required. Low-dose radiation-induced adaptive responses for increased cancer latency and decreased cancer frequency have been demonstrated in mouse models, largely for hematological cancers. This study examines the effects of high- and low-dose whole-body radiation exposure on prostate cancer development using an autochthonous mouse model of prostate cancer: TRansgenic Adenocarcinoma of the Mouse Prostate (TRAMP). TRAMP mice were exposed to single acute high (2 Gy), low (50 mGy) and repeated low (5 × 50 mGy) doses of X rays to evaluate both the potential prostate cancer promoting effects of high-dose radiation and low-dose adaptive response phenomena in this prostate cancer model. Prostate weights and histopathology were examined to evaluate gross changes in cancer development and, in mice exposed to a single 2 Gy dose, time to palpable tumor was examined. Proliferation (Ki-67), apoptosis, DNA damage (γ-H2AX) and transgene expression (large T-antigen) were examined within TRAMP prostate sections. Neither high- nor low-dose radiation-induced effects on prostate cancer progression were observed for any of the endpoints studied. Lack of observable effects of high- or low-dose radiation exposure suggests that modulation of tumorigenesis in the TRAMP model is largely resistant to such exposures. However, further study is required to better assess the effects of radiation exposure using alternative prostate cancer models that incorporate normal prostate and in those that are not driven by SV40 large T antigen.

Diagnosis of breast microcalcifications: a comparison of stereotactic FNA and core imprint cytology as adjuncts to core biopsy.

Stereotactic core biopsy (CB) using 14-gauge needles was adopted as the standard method of diagnosis of screen-detected breast microcalcifications (MC) at Sir Charles Gairdner Hospital in 1996. Fine needle aspiration (SFNA) was included as an adjunct, to optimise sensitivity and to provide immediate reporting. Recently, core imprint cytology (CI) has been shown to have a high sensitivity in diagnosing malignancy. The aims of this paper were to evaluate the accuracy of SFNA as an adjunct to CB, and whether CI could replace SFNA for immediate reporting in MC. Part A is a retrospective review of CB/SFNA of screen-detected MC from May 1998 to February 2000. A minimum of five cores was performed. SFNA samples were restricted to a maximum of three needle passes. Part B is a prospective study of CI from May to November 2000. In Part A, there were 406 MC in 353 women and 81 carcinomas were proven on excision. The complete sensitivity of CB for a diagnosis of malignancy was 97.5% and of SFNA was 65%. No false-positive diagnoses were made by either method. No extra carcinomas were detected using SFNA. In Part B, CB/CI were performed on 203 MC from 165 women. There were 38 carcinomas and 30 of these (79%) were diagnosed as malignant on CI. No false-positive diagnoses were made. The predictive value of a benign diagnosis was 95%. SFNA had little value as an adjunct to core biopsy in MC. CI promises to be useful in providing same day diagnosis for counselling purposes and for planning future surgery.

Effects of maternal exercise on fetal activity in late gestation.

In order to test the effects of maternal exercise in late gestation on fetal biophysical activities as measured by fetal breathing, shoulder movement, and kick response, these parameters were monitored by ultrasound in ten healthy pregnant women at 35 weeks of gestation before and after 20 minutes of aerobic dance and before and after 20 minutes of rest. A randomized crossover design between exercise (sequence A) and rest (sequence B) that used each pregnant woman as her own control was used in this study. Cumulative means for each fetal activity were compared. Results indicated a significant decrease in fetal breathing after maternal exercise and no significant change in shoulder movements or kick response.

National audit on the practice and training in breech deliveries in the United Kingdom.

OBJECTIVE: To assess training in breech delivery in the United Kingdom at the level of registrar. METHOD: Three hundred and nineteen registrars in obstetrics and gynecology in the United Kingdom replied to a postal questionnaire. RESULTS: The various indications of cesarean section in breech presentation answered by respondents were: pre-term labor, pelvimetric measurement of inlet/outlet less than 11.5 cm, primigravida, no spontaneous labor, estimated fetal weight less than 2.5 kg or more than 3.5 kg, non-progression of labor in active phase, non-delivery after one hour of active pushing in second stage. A total of 190 respondents (60%) felt that they had been given sufficient training in vaginal breech delivery but only 125 respondents (39%) had the training in the United Kingdom. CONCLUSION: There is a high rate of cesarean section in breech presentation due to inadequate training of junior staff in vaginal breech delivery.

Covalent binding of acetaldehyde to proteins: participation of lysine residues.

The results of this study demonstrate that lysine is the major amino acid participating in the binding of acetaldehyde to proteins. The formation of both stable and unstable acetaldehyde-albumin adducts was shown to occur via the reaction of acetaldehyde with lysine residues. This conclusion was based on the following experimental evidence: (a) the ratio of stable to unstable adducts of bovine serum albumin was similar to that observed for polylysine; (b) acetylation of albumin markedly reduced acetaldehyde binding; (c) the radio-activity profiles (obtained by high-performance liquid chromatographic analysis) of [14C]acetaldehyde modified amino acids hydrolyzed from total and stable adducts of albumin were nearly identical to those of polylysine or alpha-t-boc-lysine. Analysis of stable adducts of albumin indicated two major modified lysine residues; one residue was much more acidic and the other more basic than unmodified lysine. Unstable adducts were shown to be Schiff bases since NaBH4 treatment resulted in the formation of N-ethyllysine residues. The reducing agents, NaCNBH3 and ascorbic acid, both increased stable adduct formation via increased binding to lysine residues; however, a different elution profile of modified lysine residues was observed for these reducing agents. NaCNBH3 increased the formation of N-ethyllysine residues exclusively, whereas ascorbate increased the formation of the acidic adduct of lysine and also caused the formation of an additional modified lysine residue which was present only in the ascorbate-treated polypeptides. In addition to their detection by radioactivity measurements, the acetaldehyde-lysine adducts could also be detected by the fluorescence of their ophthalaldehyde derivatives.(ABSTRACT TRUNCATED AT 250 WORDS)

The Isaacs Endometrial Cell Sampler. An evaluation in 100 patients with postmenopausal bleeding.

The Curity Isaacs Endometrial Cell Sampler was used to obtain cytologic material from 100 consecutive patients presenting with postmenopausal bleeding. It was followed by uterine curettage to obtain material for histology. Satisfactory endometrial aspiration smears were obtained from 92 patients, whereas curettage yielded endometrial tissue in only 48. Of 17 patients with histologic confirmation of malignancy, 7 had smears diagnosed as showing malignancy, and 7 had smears showing hyperplastic changes; 3 of the aspiration smears were judged to be unsatisfactory for cytologic evaluation. All the carcinomas were found in the hyperplastic, malignant or unsatisfactory smears. This technique is worthy of further study.