The effects of oral 4-hydroxyandrostenedione on peripheral aromatisation in post-menopausal breast cancer patients

This study investigated the influence of the aromatase inhibitor 4-hydroxyandrostenedione (4OHA, formestane), given orally, on peripheral aromatase activity and plasma oestradiol (E ₂) levels in post-menopausal women with advanced breast cancer. The aim was to establish whether an optimal dose could be identified that had a pharmacological effectiveness comparable with that of parenteral 4OHA. A total of 13 post-menopausal women were studied before treatment and after a minimum of 4 weeks on treatment with one or more of the following doses: 125 mg once daily (od), 125 mg b.i.d. (bd) and 250 mg od. In all, seven aromatase studied were performed at 125 mg od; four, at 125 mg bd; and ten, at 250 mg od. Three patients were studied at all doses. E₂ was measured concurrently and was available at all dose increments for seven patients. Given at doses of 125 mg od, 125 mg bd and 250 mg od, treatment with formestane inhibited in vivo aromatisation by 62.3%±9.5%, 70.0%±5.1% and 57.3%±5.3%, respectively (mean±SEM). Corresponding values for plasma E₂ suppression were 30.7%±6.5%, 43.4%±4.5% and 42.9%±6.7%, respectively. Thus, apart from a somewhat better suppression of plasma E₂ levels by the two higher doses as compared with 125 mg od, no significant difference in the degree of aromatase inhibition or plasma E₂ suppression was observed. The suppression of E₂ by oral 4OHA at 125 mg bd or 250 mg od approaches that achieved by the recommended parenteral schedule of 250 mg fortnightly, but inhibition of aromatase at this dose was substantially inferior. The findings are consistent with a hypothesis that 4OHA given orally may cause substantial plasma oestrogen suppression during part of the day, but neither the od nor the bd regimens investigated in the present study were capable of producing optimal aromatase inhibition.     

Mechanical Analysis of Atherosclerotic Plaques Based on Optical Coherence Tomography

Finite element analysis is a powerful tool for investigating the biomechanics of atherosclerosis and has thereby provided an improved understanding of acute myocardial infarction. Structural analysis of arterial walls is traditionally performed using geometry contours derived from histology. In this paper we demonstrate the first use of a new imaging technique, optical coherence tomography (OCT), as a basis for finite element analysis. There are two primary benefits of OCT relative to histology: 1) imaging is performed without excessive tissue handling, providing a more realistic geometry than histology and avoiding structural artifacts common to histologic processing, and 2) OCT imaging can be performed in vivo, making it possible to study disease progression and the effect of therapeutic treatments in animal models and living patients. Patterns of mechanical stress and strain distributions computed from finite element analysis based on OCT were compared with those from modeling based on "gold standard" histology. Our results indicate that vascular structure and composition determined by OCT provides an adequate basis for investigating the biomechanical factors relevant to atherosclerosis and acute myocardial infarction.     

The Schizosaccharomyces pomberfc3 + gene encodes a homologue of the human hRFC36 and Saccharomyces cerevisiae Rfc3 subunits of replication factor C

In the yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe replication factor C (RF-C) plays key roles both in chromosomal DNA replication and in DNA replication checkpoint function. At the replication fork, the five-subunit RF-C complex functions to load the trimeric polymerase accessory factor PCNA onto DNA. PCNA then acts as a sliding clamp, tethering Pol δ to the DNA to maximise its processivity. Here we describe the cloning of the S. pomberfc3 ⁺ gene, encoding a homologue of the S. cerevisiae Rfc3 and human hRFC36 proteins. The 1026 bp rfc3 ⁺ ORF is interrupted by five introns, ranging in size from 49 to 165 bp. The spliced ORF is predicted to encode a 342 amino-acid protein that is approximately 50% identical at the amino acid sequence level to the S. cerevisiae Rfc3 and human hRFC36 proteins. As expected, S. pomberfc3 ⁺ is an essential gene, with rfc3Δ cells being defective for DNA replication. Loss of rfc3 ⁺ function can be rescued by heterologous expression of either the S. cerevisiae Rfc3 or human hRFC36 proteins in S. pombe. Received: 15 October 1999     

Oral ondansetron decreases vomiting after tonsillectomy in children

Vomiting is a common, unpleasant aftermath of tonsillectomy in children. Intraoperative intravenous ondansetron (OND) reduces vomiting after this operation. Our doubleblind, placebocontrolled, randomized investigation studied the effect of the oral form of OND on vomiting after outpatient tonsillectomy in children. We studied 233 healthy children age 2–14 yr undergoing elective tonsillectomy. Subjects were given placebo (PLAC) or OND 0.1 mg · kg^?1 rounded off to the nearest 2 mg one hr before surgery. Anaesthesia was induced with either propofol or halothane/N₂O. Vecuronium 0.1 mg · kg^?1 was administered at the discretion of the anaesthetist. Anaesthesia was maintained with halothane/N₂O, 50 μg · kg^?1 midazolam iv and 1–1.5 mg · kg^?1 codeine im. At the end of surgery, residual neuromuscular blockade was reversed with neostigmine and atropine. All episodes of inhospital emesis were recorded by nursing staff. Rescue antiemetics in the hospital were 1 mg · kg^?1 dimenhydrinate ivfor vomiting × 2 and 50 μg · kg^?1 droperidol iv for vomiting × 4. Parents kept a diary of emesis after discharge. Postoperative pain was treated with morphine, codeine and/or acetaminophen. The two groups were similar with respect to demographic data, induction technique and anaesthesia time. Oral OND (n = 109) reduced postoperative emesis from 54% to 39%, P < 0.05. This effect was most dramatic inhospital, where 10% of the OND-patients and 30% of the PLAC-group vomited, P < 0.05. The OND-subjects required fewer rescue antiemetics, 7% vs 17%, P < 0.05. In conclusion, oral ondansetron decreased the incidence of vomiting after outpatient tonsillectomy in children.     

Preoperative ketorolac increases bleeding after tonsillectomy in children

Purpose

To compare the incidence of vomiting following codeine or ketorolac for tonsillectomy in children.

Methods

We had planned to enrol 240 patients, aged 2–12 yr undergoing elective tonsillectomy into a randomized, single-blind study in University Children’s Hospital. The study was terminated, after 64 patients because interim analysis of the data by a blinded non-study scientist concluded that the patients were at undue risk of excessive perioperative bleeding. After induction of anaesthesia by inhalation with N₂O/halothane or with propofol 2.5?3.5 mg· kg^?1 iv, the children were administered 150 μg· kg^?1 ondansetron and 50 μg · kg^?1 midazolam. Maintenance of anaesthesia was with N₂O and halothane in O₂. Subjects were administered either 1.5 mg · kg^?1 codeine im or 1 mg· kg^?1 ketorolac iv before the commencement of surgery. Intraoperative blood loss was measured with a Baxter Medi-Vac® Universal Critical Measurement Unit. Postoperative management of vomiting and pain was standardized. Vomiting was recorded for 24 hr after anaesthesia. Data were compared with ANOVA, Chi-Square analysis and Fisher Exact Test.

Results

Thirty-five subjects received ketorolac. Demographic data were similar. The incidence of vomiting during the postoperative period was 31% in the codeine-group and 40% in the ketorolac-group. Intraoperative blood losses was 1.3 ± 0.8 ml · kg^?1 after codeine and 2.2 ± 1.9 ml · kg^?1 after ketorolac (mean ± SD) P < 0.05. Five ketorolac-treated patients had bleeding which led to unscheduled admission to hospital, P < 0.05, Exact Test.

Conclusion

Preoperative ketorolac increases perioperative bleeding among children undergoing tonsillectomy without beneficial effects.     

Evidence-Based Strategies for the Treatment of Peritoneal Malignancies during Health Care Resource Restriction: The COVID-19 Pandemic

Background: The COVID-19 pandemic has put enormous pressure on hospital resources, and has affected all aspects of patient care. As operative volumes decrease, cancer surgeries must be triaged and prioritized with careful thought and attention to ensure maximal benefit for the maximum number of patients. Peritoneal malignancies present a unique challenge, as surgical management can be resource intensive, but patients have limited non-surgical treatment options. This review summarizes current data on outcomes and resource utilization to help inform decision-making and case prioritization in times of constrained health care resources. Methods: A rapid literature review was performed, examining surgical and non-surgical outcomes data for peritoneal malignancies. Narrative data synthesis was cross-referenced with relevant societal guidelines. Peritoneal malignancy surgeons and medical oncologists reviewed recommendations to establish a national perspective on case triage and mitigating treatment strategies. Results and Conclusions: Triage of peritoneal malignancies during this time of restricted health care resource is nuanced and requires multidisciplinary discussion with consideration of individual patient factors. Prioritization should be given to patients where delay may compromise resectability of disease, and where alternative treatment options are lacking. Mitigating strategies such as systemic chemotherapy and/or surgical deferral may be utilized with close surveillance for disease stability or progression, which may affect surgical urgency. Unique hospital capacity, and ability to manage the complex post-operative course for these patients must also be considered to ensure patient and system needs are aligned.     

Clinical Utility of the Normative Studies Research Project Test Battery Among Vascular Dementia Patients

The purpose of the present study was to examine the clinical utility of the Normative Studies Research Project test battery for detecting dementia with a known vascular component. The study compared 65 patients who had both suffered a stroke and met the DSM-IV criteria for dementia with 86 older medical patients who were cognitively intact. Multivariate analysis of covariance results demonstrated that these two groups had significantly different means on tests within the battery even after controlling for the influence of demographic variables. Logistic regression results demonstrated positive predictive value of 81.36%, negative predictive value of 85.23%, and an overall correct classification rate of 83.67%.