Reports by anaesthetists to procurators-fiscal: analysis of "anaesthetic deaths" over 10 years in four Scottish teaching hospitals.

Review of 489 "anaesthetic deaths" reported to procurators-fiscal over 10 years disclosed only 30 that were thought to justify such reporting. Most of the remainder occurred in patients so desperately ill at the time of operation that death was expected. Postmortem examinations ordered by the Crown authorities in nearly all cases were probably largely unrewarding and mostly unnecessary. The results suggest that the present regulation on reporting should be revised to focus more attention on the few deaths that occur in patients who have no apparent contraindication to anaesthesia or operation.     

Cure rates of oral contraceptive users and non-users when treated for vulvovaginal candidiasis (moniliasis) with miconazole nitrate 2% vaginal cream

Analysis of the data from a carefully conducted multi-investigator study utilizing 261 subjects with a diagnosis of vulvovaginal candidiasis determined the cure rates in oral contraceptive users as compared to the cure rates in oral contraceptive non-users when treated with miconazole nitrate 2% Vaginal Cream (MONISTAT¹). The criteria for a cure required that subjects have a negative KOH smear, negative NICKERSON'S Medium culture for $\text{Candida}$ species, and complete absence of the signs and symptoms of vulvovaginal candidiasis 30 or more days following the course of therapy. There was no significant difference in the cure rates of the oral contraceptive users when compared to the oral contraceptive non-users. It is concluded that there is no justification for routinely discontinuing oral contraceptive therapy during treatment for vulvovaginal candidiasis with miconazole nitrate 2% Vaginal Cream (MONISTAT).     

Preliminary assessment of the acute toxicity of malathion in animals

Laboratory studies were conducted to acquire information concerning the acute toxicity of malathion in animals under various conditions of exposure. The responses in rabbits and quail exposed to aerosols generated from technical grade malathion (95%) and approximating an ultra-low volume ground spray were compared with those from a 6% malathion/No. 2 fuel oil mixture simulating a high volume spray. Results indicate that technical grade malathion (95%) as an ultra-low volume spray and at effective insecticidal concentrations in particle sizes having a mass median diameter of about 12 µ is relatively nonhazardous compared to the possible toxic fuel oil effects of a 6% malathion/No. 2 fuel oil mixture with a mass median diameter of 25 µ. Based on blood plasma cholinesterase activity analyses, quail were more sensitive to equivalent malathion exposure concentrations than were rabbits. Oral administration of technical grade malathion to rabbits resulted in reduction of plasma and erythrocyte cholinesterase activity at dosages of 120, 300, and 600 mg/kg with death resulting from 1200 mg/kg.The opinions contained herein are those of the authors and should not be construed as official or reflecting the views of the Department of the Army or the Department of Defense. Mention of proprietary products is for the purpose of identification only and does not imply endorsement by the Department of the Army.The experiments reported herein were conducted according to the Guide for the Care and Use of Laboratory Animals (1972) as prepared by the Committee on Revision of the Guide for Laboratory Animal Facilities and Care, of the Institute of Laboratory Animal Resources, National Research Council.     

Differential response of human ovarian cancer cells to induction of apoptosis by vitamin E Succinate and vitamin E analogue, alpha-TEA.

A vitamin E derivative, vitamin E succinate (VES; RRR-alpha-tocopheryl succinate), and a vitamin E analogue, 2,5,7,8-tetramethyl-2R-(4R,8R,12-trimethyltridecyl)chroman-6-yloxy acetic acid (alpha-TEA), induce human breast, prostate, colon, lung, cervical, and endometrial tumor cells in culture to undergo apoptosis but not normal human mammary epithelial cells, immortalized, nontumorigenic breast cells, or normal human prostate epithelial cells. Human ovarian and cervical cancer cell lines are exceptions, with alpha-TEA exhibiting greater proapoptotic effects. Although both VES and alpha-TEA can induce A2780 and subline A2780/cp70 ovarian cancer cells to undergo DNA synthesis arrest within 24 h of treatment, only alpha-TEA is an effective inducer of apoptosis. VES or alpha-TEA treatment of cp70 cells with 5, 10, or 20 microg/ml for 3 days induced 5, 6, and 19% versus 9, 36, and 71% apoptosis, respectively. Colony formation data provide additional evidence that cp70 cells are more sensitive to growth inhibition by alpha-TEA than VES. Differences in stability of the ester-linked succinate moiety of VES versus the ether-linked acetic acid moiety of alpha-TEA were demonstrated by high-performance liquid chromatography analyses that showed alpha-TEA to remain intact, whereas VES was hydrolyzed to the free phenol, RRR-alpha-tocopherol. Pretreatment of cp70 cells with bis-(p-nitrophenyl) phosphate, an esterase inhibitor, before VES treatment, resulted in increased levels of intact VES and apoptosis. Taken together, these data show alpha-TEA to be a potent and stable proapoptotic agent for human ovarian tumor cells and suggest that endogenous ovarian esterases can hydrolyze the succinate moiety of VES, yielding RRR-alpha-tocopherol, an ineffective apoptotic-inducing agent.     

Mouse mammary tumor virus-like gene sequences in breast tumors of Australian and Vietnamese women.

PURPOSE: There is considerable evidence that the presence of mouse mammary tumor virus (MMTV)-like gene sequences in human breast cancer is highly associated with human breast carcinoma. Previous studies have found MMTV-like gene sequences in 38% of breast cancer tissue from United States women. The prevalence of these sequences in Australian and Vietnamese women has never been reported. EXPERIMENTAL DESIGN: Using PCR and primers that amplify MMTV-like gene sequences, we tested cancerous and benign breast tissue from Caucasian-Australian, Vietnamese-Australian, and Vietnamese women. RESULTS: MMTV-like gene sequences were amplified in 19 of 45 (42.2%) archival breast cancer biopsy tissues from Caucasian-Australian women, but only 1 of 120 (0.8%) and 0 of 41 breast cancer biopsy tissues from Vietnamese and Vietnamese-Australian women, respectively. The same sequences were found in only 2 of 111 (1.8%) and 0 of 60 normal (benign) breast tissue samples from Australian and Vietnamese women, respectively. CONCLUSIONS: MMTV-like gene sequences are found in only some human populations and are rarely found in normal human breast tissue from all populations, suggesting they are not present in the normal human genome and have been acquired.     

Effects of conjugated linoleic acid supplementation on blood lipids and adiposity of rats fed diets rich in saturated versus unsaturated fat

Conjugated linoleic acid (CLA) may decrease adiposity and improve blood lipid profiles under some conditions. The goal of this study was to determine the effects of CLA supplementation on blood lipid profiles and adiposity of rats fed a diet containing a primarily saturated fat versus a diet containing a primarily unsaturated fat. Twenty-eight male Sprague-Dawley rats were randomly assigned to one of four diets containing coconut oil, coconut oil with CLA, corn oil or corn oil with CLA. After 28 days, blood was collected and serum concentrations of total cholesterol (TC), HDL-cholesterol (HDL-C), and triacylglycerols (TG) were assessed. Food intake, body weights, and epididymal fat pads were measured. No significant differences (p>0.05) were noted among groups for amount of food consumed, weight gained, food efficiency ratio or serum TG concentrations. TC concentrations were lower (p<0.05) in the CLA-supplemented rats that were fed coconut oil but not those consuming corn oil. Serum HDL-C was lower (p<0.05) in rats consuming corn oil but was not significantly different (p>0.05) for CLA supplemented groups. Epididymal fat pads weighed significantly more (p<0.05) in the coconut oil fed group compared to the corn oil fed group, but there was no significant difference (p>0.05) between the corn oil and coconut oil + CLA group. Overall, this study suggests that CLA is more beneficial for control of blood lipids and adiposity when supplemented to a diet rich in saturated versus unsaturated fat.     

Regional differences in milk and complementary feeding patterns in infants participating in an international nutritional type 1 diabetes prevention trial

Differences in breastfeeding, other milk feeding and complementary feeding patterns were evaluated in infants at increased genetic risk with and without maternal type 1 diabetes (T1D). The Trial to Reduce IDDM in the Genetically at Risk is an international nutritional primary prevention double‐blinded randomized trial to test whether weaning to extensively hydrolyzed vs. intact cow's milk protein formula will decrease the development of T1D‐associated autoantibodies and T1D. Infant diet was prospectively assessed at two visits and seven telephone interviews between birth and 8 months. Countries were grouped into seven regions: Australia, Canada, Northern Europe, Southern Europe, Central Europe I, Central Europe II and the United States. Newborn infants with a first‐degree relative with T1D and increased human leukocyte antigen‐conferred susceptibility to T1D were recruited. A lower proportion of infants born to mothers with than without T1D were breastfed until 6 months of age in all regions (range, 51% to 60% vs. 70% to 80%). Complementary feeding patterns differed more by region than by maternal T1D. In Northern Europe, a higher proportion of infants consumed vegetables and fruits daily compared with other regions. Consumption of meat was more frequent in all European regions, whereas cereal consumption was most frequent in Southern Europe, Canada and the United States. Maternal T1D status was associated with breastfeeding and other milk feeding patterns similarly across regions but was unrelated to the introduction of complementary foods. Infant feeding patterns differed significantly among regions and were largely inconsistent with current recommended guidelines.     

Increased nasal potential difference and amiloride sensitivity in neonates with cystic fibrosis

Patients with cystic fibrosis (CF) have an increased nasal transepithelial potential difference (PD) which reflects increased sodium absorption across epithelium relatively impermeable to chloride. To evaluate nasal epithelial function in neonates with CF, the PD was recorded and the voltage response to superfusion of 10(-5M) amiloride, an inhibitor of sodium transport, measured between a Ringer perfused bridge on the nasal mucosa and a reference electrode in the subcutaneous space. We studied three neonates with CF with meconium ileus and compared the results with those in 24 term healthy neonates, including one obligate heterozygote for CF, and 27 control neonates with disease. All three CF neonates had raised sweat chloride values (mean 100 mEq/L) at 2 months. The CF neonates had higher PDs (-64.0 +/- 8.4 mV) than those in normal (-24.4 +/- 2.0 mV) or control (-25.8 +/- 2.0 mV) neonates. Superfusion with amiloride induced a 72% reduction in PD in the CF neonates as compared with healthy (37.5 +/- 1.0%) and diseased (36.0 +/- 1.3%) neonates. The PD and amiloride response in CF neonates are similar to those in CF infants (2.24 months), older CF children (greater than 6 years), and CF adults (-64.9 +/- 9.3 mV; 77.7 +/- 1.8%, n = 51). These results suggest that (1) nasal epithelial dysfunction is present in patients with CF shortly after birth, and (2) the nasal PD may be a diagnostic adjunct to the sweat test in the early diagnosis of CF.