Fracture behaviour of zirconia FPDs substructures

Summary The purpose of this study was to evaluate the occurrence of superficial flaws after machining and to identify fracture initiation and propagation in three‐unit heat‐treated machined fixed partial dentures (FPDs) substructures made of hot isostatic pressed (HIPed) yttria‐stabilized tetragonal zirconia polycrystal (Y‐TZP) after loaded to fracture. Four three‐unit HIPed Y‐TZP‐based FPDs substructures were examined. To evaluate the occurrence of superficial flaws after machining, the surfaces were studied utilizing a fluorescent penetrant method. After static loading to fracture, characteristic fracture features on both mating halves of the fractured specimens were studied using a stereomicroscope and a scanning electron microscope. Grinding grooves were clearly visible on the surfaces of the machined FPDs substructures, but no other flaws could be seen with the fluorescent penetrant method. After loading to fracture, the characteristic fracture features of arrest lines, compression curl, fracture mirror, fracture origin, hackle and twist hackle were detected. These findings indicated that the decisive fracture was initiated at the gingival embrasure of the pontic in association with a grinding groove. Thus, in three‐unit heat‐treated machined HIPed Y‐TZP FPDs substructures, with the shape studied in this study, the gingival embrasure of the pontic seems to be a weak area providing a location for tensile stresses when they are occlusally loaded. In this area, fracture initiation may be located to a grinding groove.     

Nutrition in the elderly hospital patient Nottingham studies

Forty percent of elderly hospital admissions in the UK are undernourished, half severely so. Most continue to lose weight in hospital. not only because of disease, but also because of failure to identify and treat malnutrition and due to shortcomings in hospital food provision, upon which most patients depend for their nutritional care. Our studies have shown that more than 40% of food set before patients is left, and therefore wasted. This means that elderly patients are taking less than 70% of their energy (30-35 kcal/kg/day), and protein (1 dram/kg/day) requirements. Catering strategies, such as provision of smaller volume, high energy and protein density meals with snacks and, if necessary, proprietary oral supplements, have been shown not only to improve nutritional status of patients, but to result in improved clinical outcome. Our work has shown a relationship between malnutrition and loss of thermoregulation, which is reversed by appropriate feeding. We have also described the beneficial effects of overnight nasogastric tube feeding in undernourished patients with fractured femur. Like others, we have used a percutaneous endoscopic gastrostomy in the management of elderly patients with cerebrovascular and motor neurone disease, and have published audits of outcome in this field.     

Concurrent chemoradiation in advanced cervical cancer

The pelvis is the predominant site of failure following radical radiotherapy (RT) for locally advanced cervical cancer. We report the results of phase I-II studies on 200 patients with bulky (greater than or equal to 5 cm) carcinoma of the cervix. Patients were treated between 1981 and 1988 on sequential protocols of concurrent chemoradiation to establish an acceptable treatment regimen. RT with daily or partially hyperfractionated pelvic (n = 154) or pelvic plus paraaortic (n = 46) fields was given by continuous (n = 154) or split course (n = 46) regimens. Infusional fluorouracil (5-FU) in a dose of 1 g/m2/day was given on the first and last 4 days of a 5-week course of continuous RT, or with both halves of split course RT. Seventy-eight patients received bolus mitomycin C (Mit-C), 6 mg/m2, once or twice with the start of the 5-FU infusion. The median external RT dose was 46 Gy (range 40 to 65 Gy) followed in 90% (n = 181) by a single intracavitary application of 40 Gy using a linear source of cesium-137. Median follow up is 2.5 years (range 0.6 to 6.9 years) and is sufficient to reliably estimate late toxicities. Acute toxicities were transient oral mucositis (13), RT interruption for enteritis (7), febrile neutropenia (3), and thrombocytopenic tumor bleed (1). Serious late toxicities resulted in death in 3 patients and occurred in bladder in 6 and in bowel in 25, including 8 patients with tumor recurrence. The incidence of late bowel toxicity correlated with the specific therapy given and decreased with each successive protocol. On logistic regression the only treatment variable showing a statistically significant effect on complications was the use of Mit-C (P = 0.0053). Pelvic RT and 5-FU alone produced fewer complications, only 4/105, than historically seen with standard pelvic RT alone. Three-year pelvic control and survival rates were 85 and 71% respectively in stage Ib/II (n = 100) and 50 and 42% in stage III/IV (n = 100). Encouraged by these results and decreased toxicity, we have begun a phase III study to determine whether the addition of concurrent 5-FU to continuous partially hyperfractionated pelvic RT improves local control and survival.     

Carriage of Haemophilus influenzae and Streptococcus pneumoniae in healthy Chinese and Vietnamese children in Hong Kong

Nasopharyngeal carriage of Haemophilus influenzae and Streptococcus pneumoniae was studied in 621 healthy Chinese children and 300 healthy Vietnamese children aged from 2 months to 5 years in Hong Kong. The carriage rate of H, influenzae type b in Vietnamese children was 1.3% (CI 0.04-2.63%); it was zero in Chinese. The carriage rate of non-typable H. influenzae was 5.8% (CI 1.4-7.6%) in Chinese and 65.4% (CI 58.9-69.8%) in Vietnamese. The carriage rates of S. pneumoniae were 10.8% (CI 8.3-13.2%) and 55.7% (CI 50.1-61.3%) in Chinese and Vietnamese children, respectively. Univariate and multivariate logistic regression analyses were performed to search for factors associated with differences in carriage rates of both H. influenzae and S. pneumoniae between Chinese and Vietnamese children. Although older age, smaller living area and parental smoking were associated with higher carriage rates, these could not explain the remarkably low carriage rates of both bacteria in Chinese children.     

Epidemiology of premenstrual symptoms in a nonclinical sample. I. Prevalence, natural history and help-seeking behavior

A stratified sample of 996 nursing school graduates from 1963 to 1984 was surveyed by mail regarding menstrual cycle characteristics. The 730 respondents reported an 87% overall lifetime prevalence of premenstrual symptoms. When the symptoms were categorized according to severity, only 3.2% of the respondents reported severe symptoms. Symptomatic women used diet change (24.6%), exercise (41.8%) and vitamins (18.9%) as self-help measures. Seventeen percent sought advice from a physician. Drug use was common; 22% were using a drug for symptoms at the time of the survey. Despite the common use of treatment, few women reported a significant work impairment. These findings support the conclusion that premenstrual symptoms are common but do not usually interfere with functioning.     

Genetic Engineering and Medical Ethics

In the introduction I express the need of introducing the point of view of Ethics when we are dealing with problems of science, technology, and especially medicine. In the first part of my presentation I deal with the problem of the value of human life, coming to the conclusion that human life might not be completely absolute, but is extremely important and “ceteris paribus” should be respected, and the problem of when it starts. Some of the main arguments are discussed. In this connection the question of abortion is briefly discussed. In the second part I deal with some problems related to human reproduction. Most people will be willing to support programmes for treating individuals with genetic disease; but at the same time the dangers of increasing depersonalization of the reproductive process are pointed out. In the third part I take up the problem of In Vitro Fertilisation. IVF has certainly brought benefits to some couples suffering from infertility, but at the same time it has raised quite a few human and moral problems. Is it permissible to fertilise an egg with a donor sperm, replacing the embryo in the womb? What about fertilising a donor egg with the husband's sperm? Is it acceptable to store or freeze embryos for future use? Is it moral to implant such an embryo in a woman who has no genetic relationship with the embryo? Is it moral to use surrogate mothers? Is it moral for ‘spare’ embryos to be killed or used as tissue for research? At the end I stress the need of dialogue between life sciences and ethics.     

Concurrent radiation and chemotherapy for carcinoma of the cervix recurrent after radical surgery

Results of salvage therapy in patients with carcinoma of the cervix, recurrent after primary surgery, have been dismal even when disease was apparently confined to the pelvis. Further surgery or radiation therapy cured only some with central pelvic disease alone who had recurred at intervals longer than 6 months after primary therapy. To try to improve the results of salvage therapy, we used a combination of concurrent chemotherapy, 5-Fluorouracil with or without Mitomycin-C, and radiation therapy. Seventeen patients were treated. Recurrent disease was present in the pelvis or pelvis and paraaortic nodes after radical surgery for Stage IB carcinoma of the cervix. Eight of seventeen (47%) are alive, disease-free, 21 to 58 months after therapy. Seven of the eight had biopsy proven recurrence. Five of eight had recurred within 9 months of primary surgery and 7/8 had a component of pelvic side wall disease. Thus the survivors had unfavorable prognostic features. Nevertheless, the use of concurrent radiation and chemotherapy produced an exceptionally high proportion of sustained complete remissions and possible cures.     

A tailored therapy for the metabolic syndrome: the dual peroxisome proliferator-activated receptor-alpha/gamma agonist LY465608 ameliorates insulin resistance and diabetic hyperglycemia while improving cardiovascular risk factors in preclinical models

A novel nonthiazolidinedione dual peroxisome proliferator- activated receptor (PPAR)-alpha/gamma agonist, LY465608, was designed to address the major metabolic disturbances of type 2 diabetes. LY465608 altered PPAR-responsive genes in liver and fat of db/db mice and dose-dependently lowered plasma glucose in hyperglycemic male Zucker diabetic fatty (ZDF) rats, with an ED(50) for glucose normalization of 3.8 mg small middle dot kg(-1) small middle dot day(-1). Metabolic improvements were associated with enhanced insulin sensitivity, as demonstrated in female obese Zucker (fa/fa) rats using both oral glucose tolerance tests and hyperinsulinemic-euglycemic clamps. Further characterization of LY465608 revealed metabolic changes distinct from a selective PPAR-gamma agonist, which were presumably due to the concomitant PPAR-alpha agonism, lower respiratory quotient, and less fat accumulation, despite a similar impact on glycemia in male ZDF rats. In addition to these alterations in diabetic and insulin-resistant animals, LY465608 dose-dependently elevated HDL cholesterol and lowered plasma triglycerides in human apolipoprotein A-I transgenic mice, demonstrating that this compound significantly improves primary cardiovascular risk factors. Overall, these studies demonstrate that LY465608 beneficially impacts multiple facets of type 2 diabetes and associated cardiovascular risk, including those facets involved in the development of micro- and macrovascular complications, which are the major sources for morbidity and mortality in these patients.     

Historical trends of survival among widows and widowers

One of the most consistent findings in social demography is that recently widowed individuals, male or female, have higher rates of mortality than comparable married persons. These results are based generally on contemporary studies in developed nations where life expectancy is high. Because of data limitations, there are few studies available to determine whether these findings also occur when mortality rates were higher. This study uses the Utah Population Database that was developed from extensive family genealogies and now linked to Utah death certificates. These data make it possible to employ life course analysis of four marriage cohorts extending from 1860 through 1904 with mortality follow-up to 1990. This approach is used to compare mortality risks of widowed males and females relative to comparable married individuals. Covariates included in the study are remarriage, as well as religion and number of children ever born; these are all hypothesized to have protective effects on mortality risks for widowed men and women. Analysis of these data indicates that there are significant differences in the mortality risk for widowed men and women, and it is widowed men who have an excess risk of dying in every cohort and nearly every age. A consistent pattern of excess mortality in the comparison of married and widowed women was not observed. There are significant female and male differences in the effect of religion which was treated as a proxy for life style and social support: however, remarriage as a proxy for social support has similar protective effects on the surviving spouse.     

Intranasal or oral immunization of inbred and outbred mice with murine or human rotavirus VP6 proteins protects against viral shedding after challenge with murine rotaviruses

Intranasal (i.n.) administration of an Escherichia coli-expressed chimeric VP6 protein from the EDIM strain of murine rotavirus to adult BALB/c (H-2(d)) mice along with LT(R192G), an attenuated mutant of the mucosal adjuvant E. coli heat-labile toxin, has been found to consistently stimulate ca. 99% reductions in rotavirus shedding after subsequent EDIM challenge. This study was designed to determine the robustness of this protection, i.e. can VP6 immunization consistently protect against shedding in this model, thus, providing an indication of its potential as a vaccine. Intranasal immunization with two 8.8 microg doses of EDIM VP6 and 10 microg of LT(R192G) was found to stimulate 99% reductions in EDIM shedding in four additional strains of inbred mice belonging to three haplotypes, i.e. DBA/2 (H-2(d)), C57BL/6 (H-2(b)), 129 (H-2(b)) and C3H (H-2(k)). Protection stimulated against EDIM antigen shedding following i.n. immunization with VP6 from the human CJN strain was less (P=0.02) than induced by EDIM VP6 (86% versus 99%), but no further loss of protection was observed when the dose of CJN VP6 was reduced 100-fold. Protection against EDIM shedding was also maintained after i.n. immunization of three strains of outbred mice (CF-1, CD-1 and Swiss Webster) with either EDIM or CJN VP6, i.e. EDIM VP6 immunization reduced EDIM shedding by 99% while CJN VP6 immunization produced reductions of 86-96%. Protection stimulated by oral immunization of BALB/c mice with two 8.8 microg doses of either VP6 chimera plus LT(R192G) was not significantly different from that induced by i.n. immunization. Finally, protection found after either oral or i.n. immunization with EDIM or CJN VP6 was no different when the mice were challenged with McN, another strain of murine rotavirus. These results support further evaluation of VP6 as a vaccine.