Recurrent malignant pilomatrixoma invading the cranial cavity: Improved local control with adjuvant radiation.

We report the case of a 41-year-old mentally retarded male with recurrent pilomatrix carcinoma of the occipital region which invaded the occipital bone, left cerebellum and left temporal lobe. At his initial presentation the patient had a craniotomy and subtotal excision of the lesion with positive margins. He received no adjuvant therapy. After an early intracranial recurrence he had subtotal debulking and was referred for external beam radiotherapy. At 27 months follow-up after adjuvant external beam radiotherapy the intracranial component has not progressed and the patient remains clinically well.

Novel primers for the amplification of nuclear DNA introns in the entomopathogenic nematode Heterorhabditis bacteriophora and their cross-amplification in seven other Heterorhabditis species.

We describe 24 novel primers that amplify intron regions in housekeeping and structural genes of Heterorhabditis bacteriophora. The cross-amplification potential of these primers in seven other Heterorhabditis species was determined. The results obtained showed interspecific nucleotide, length and splice site variability in the sequenced introns and for one gene, an intron gain was observed. These primers will be useful tools for studying population genetics, genetic diversity and intron DNA evolution within the genus Heterorhabditis and other genera of rhabditid nematodes.

Ovarian cancer--the need for change in service delivery in Northern Ireland.

This paper provides local data on the provision of services for patients diagnosed with ovarian cancer in 1996 prior to the reorganisation of cancer services. It documents a service for 140 patients provided by 80 consultant teams and illustrates the need for reorganisation to meet the evidence base already in existence for improvement in survival and will serve as a baseline for future audits in this area.

Lung cancer survival in Northern Ireland.

Lung cancer causes more deaths than any other cancer in Northern Ireland. Survival, and factors which could influence survival, were examined for the 4,458 patients diagnosed with lung cancer from 1992 to 1996. Overall five-year relative survival was low, but better for females (9%) than males (7%). Survival improved each year although this could not be attributed to treatment changes. Survival was better for men under 65 years, than older men (p<0.01), while survival from non-small cell type lung cancer was better than small cell (p<0.001). The proportion of patients having bronchoscopy and CT scan increased over the study period. Although the proportion of patients receiving surgery or radiotherapy remained unchanged over the period there was an increase in the proportion receiving chemotherapy (8.7% vs. 9.4%, P<0.05). Survival rates, although slightly better than in the rest of the United Kingdom, were poorer than in several other countries, including the Republic of Ireland and the United States of America. High mortality rates from lung cancer and, at best, modest improvements in survival, point to the need for increased efforts to reduce levels of lung cancer by tackling the main cause, smoking.

Mortality in Barrett's oesophagus: results from a population based study.

BACKGROUND: Patients with Barrett's oesophagus have an increased risk of oesophageal adenocarcinoma but this cancer only accounts for a small proportion of deaths in these patients. Other causes of death are reportedly raised in this group. We examined cause specific mortality among individuals in a population based Barrett's oesophagus register. METHODS: We constructed a register of all patients diagnosed with columnar mucosa (including specialised intestinal metaplasia) of the oesophagus within Northern Ireland between 1993 and 1999. Deaths occurring within this cohort until 31 December 2000 were identified and mortality rates were compared with the general population. RESULTS: Overall mortality was not raised in Barrett's patients. During 7413 person years of follow up in 2373 patients there were 253 deaths (standardised mortality ratio (SMR) 96 (95% confidence interval (CI) 84-107)). Mortality from oesophageal cancer was raised in patients with specialised intestinal metaplasia (SMR 774 (95% CI 317-1231)) but only 4.7% of patients died from this cancer. Mortality from stroke (SMR 65 (95% CI 37-93)) was significantly lower than the general population while mortality from non-cancerous digestive system diseases was significantly higher (SMR 211 (95% CI 111-311)). Mortality rates from all other causes were similar to those of the general population. CONCLUSIONS: This study demonstrates that the overall mortality rate in patients with Barrett's oesophagus is closely similar to that of the general population. Oesophageal cancer mortality was raised but is an uncommon cause of death in these patients who also appear to have a reduced risk of death from stroke.

Biochemical changes induced by hypomagnesaemia in lactating cows and ewes.

Severe hypomagnesaemia was induced in lactating cows and lactating sheep by feeding them magnesium-deficient diets for 17 and 14 days, respectively. Hypomagnesaemia in cows was associated with abnormally high rates of change in the numbers of leucocytes, neutrophils, monocytes and platelets. There were increases in the concentration of iron in the liver of the hypomagnesaemic ewes and in the heart of the hypomagnesaemic cows, which were not associated with a haemolytic process. The percentage of some of the peroxidisable fatty acids was lower in the heart tissue of hypomagnesaemic cows, but the reduction was not associated with significant lipid peroxidation.

Testing of bulk tank milk from Northern Ireland dairy herds for viral RNA and antibody to bovine viral diarrhoea virus.

Bulk tank milk samples collected from 929 Northern Ireland dairy herds were classified according to their geographical location, somatic cell count and milk yield. Each sample was tested by ELISA for antibody levels to bovine viral diarrhoea virus (BVDV) and the herds were assigned to four groups with increasing antibody levels. In nine herds (1 per cent) no antibodies were detectable in the milk samples (group 1) and they were detectable at low levels in the milk from 90 herds (9.7 per cent, group 2), at moderate levels in 369 herds (39.7 per cent, group 3), and at high levels in the remaining 461 herds (49.6 per cent, group 4). The testing of samples from 90 herds in groups 1 and 2 after an interval of 12 months showed that the annual incidence risk for new infections with BVDV was in the range 0.133 to 0.477. There were significant relationships (P < 0.001) between the mean corrected optical density in the ELISA and herd location and somatic cell count, but not yield; the relationship with somatic cell count was linear (P < 0.01). Forty-three group 3 herds and 49 group 4 herds were selected at random and bulk milk samples were tested for BVDV by reverse transcriptase polymerase chain reaction. None of the group 3 herds was positive, but five group 4 herds were positive.

Effect of concentrate feed level in late gestation on subsequent milk yield, milk composition, and fertility of dairy cows.

The effects of level of concentrate feeding in late gestation on feed intake, milk yield, milk composition, and fertility in the subsequent lactation were evaluated in a randomized block design experiment involving 60 cows. Grass silage was offered ad libitum for the last 28 d of gestation either as the sole diet (OC) or supplemented with 5 kg/d of concentrates (5C). Following calving, the cows were offered the same grass silages supplemented with 7 kg/d of concentrates. For treatments OC and 5C, total dry matter intakes were 9.28 and 11.03 kg/d of dry matter, respectively, during the last 4 wk of gestation. During wk 1 to 12 of the subsequent lactation, treatment 5C increased milk fat concentration but did not alter feed intake, milk yield, or protein concentration relative to treatment OC. Treatment 5C increased the interval to first progesterone rise and the number of services per conception relative to treatment OC. Cow parity, BF depth assessed at d 28 before parturition, and treatment provided the best fit relationships for the yields of fat and fat plus protein (R2 relationships = 0.65 and 0.64, respectively) during wk 1 to 4 of lactation. It was concluded that, other than milk fat concentration, supplementation with additional concentrates in late gestation did not alter milk yield or composition and dairy cow fertility. Furthermore, despite the very large differences in cow characteristics at d 28 before parturition, there was no evidence of any interaction between treatment and specific cow characteristics on animal performance in the first 12 wk of lactation.

Postmortem biochemical markers of experimentally induced hypomagnesaemic tetany in cattle.

Severe hypomagnesaemia and tetany were induced in 10 lactating cows by feeding them semi-synthetic low magnesium diets and the animals were used to study the stability of postmortem markers of hypomagnesaemic tetany. There were significant relationships between the concentrations of magnesium in either cerebrospinal fluid (CSF) or plasma and either aqueous or vitreous humour. The onset of hypomagnesamic tetany was also associated with low magnesium concentrations in plasma, CSF and aqueous and vitreous humour. Magnesium concentrations less than 0.25 mmol/litre in fresh aqueous humour may be indicative of severe hypomagnesaemia and possible tetany in lactating cows, but the concentration of magnesium in aqueous humour was unstable postmortem. The concentration of magnesium in vitreous humour was relatively stable and a concentration of less than 0.55 mmol/litre could be used as a diagnostic marker of tetany in cattle for up to at least 48 hours postmortem, at ambient temperatures typical of Northern Ireland.

Postmortem biochemical markers of experimentally induced hypomagnesaemic tetany in sheep.

Hypomagnesaemic tetany was induced in non-lactating and lactating ewes by feeding them semi-synthetic low magnesium diets containing additional potassium chloride and citric acid. Aqueous and vitreous humour were sampled from one eye at the time of death (fresh) and from the second eye after the head had been stored at ambient temperature for 24 hours (24-hour). There were significant relationships between the concentrations of magnesium in cerebrospinal fluid and plasma and its concentrations in fresh aqueous humour and fresh vitreous humour. Magnesium concentrations of < 0.33 mmol/litre in fresh aqueous humour and < 0.50 mmol/litre in 24-hour aqueous humour were associated with severe hypomagnesaemia and tetany. However, the concentration of magnesium in aqueous humour is relatively unstable and, unless the time of death was known accurately, its interpretation would be difficult. Magnesium concentrations of < 0.60 mmol/litre in fresh vitreous humour and < 0.65 mmol/litre in 24-hour vitreous humour were associated with severe hypomagnesaemia and tetany in adult sheep. The concentration of magnesium in vitreous humour was relatively stable for up to 48 hours postmortem.

Effects of supplementation of dairy cattle with fish oil on silage intake, milk yield and milk composition.

The effects of level of fish oil inclusion in the diet on grass silage intake, and milk yield and composition of dairy cows offered either 5 or 10 kg concentrates/d were evaluated in a ten treatment, partly balanced, changeover design experiment involving 50 cows in early lactation. Concentrates were prepared to provide 0, 150, 300 or 450 g fish oil/cow per d or 300 g fish oil/cow per d from a premix when each animal was offered 5 kg/d. The fish oil was predominantly from herring and mackerel caught in the North Atlantic while the fish oil premix was obtained from a commercial source and used palm kernel expeller as a carrier. Increasing fish oil supplementation decreased silage dry matter intake and the concentrations of milk fat and protein, and increased milk yield and diet digestibility. There were significant interactions between concentrate feed level and level of fish oil for silage intake and milk yield. Other than for the concentrations of milk fat and protein, and 20:4n-6 fatty acids, the source of fish oil did not affect forage intake or animal performance. Fish oil supplementation also decreased the concentrations of milk protein by 0.9 g/kg for each 100 g increase in fish oil supplementation, the depression being similar at each level of concentrate feeding. Supplementing the feed of dairy cows with 450 g fish oil/cow per d decreased the concentration of milk fat by 15 g/kg. This study also showed that feeding dairy cattle with fish oil is an efficient method of increasing eicosapentaenoic acid in the human diet through transfer into milk.

Stillbirth/perinatal weak calf syndrome: a study of calves infected with Leptospira.

Leptospiral infection has been reported in calves which were either stillborn or dead from perinatal weak calf syndrome; 356 such calves were examined for evidence of associations between leptospiral infection and macroscopic, histological and microbiological findings, and the parity of the dam. Calves in which leptospiral antigen was detected in the placenta were significantly lighter by an average of 6 to 10 kg than calves with no antigen in the placenta. Calves infected with Leptospira were more likely to be infected by Actinomyces pyogenes or Bacillus species. No other significant associations were detected. The adrenal gland, lung and placenta were the most useful organs to examine for leptospiral antigen. The placenta was the only antigen-positive tissue 8.9 per cent of the calves submitted with their placenta.

Automation of environmental ELISAs.

ELISAs for pesticides and herbicides in environmental and agricultural samples are becoming very important in screening applications [1-3]. Traditional chromatographic methods are expensive and results need long turnaround times, making them incompatible with rapid on-site decision making. ELISA methods have been shown to meet or exceed the performance of gas chromatography-they offer rapid low-cost analysis, thereby increasing the frequency of sampling and enhancing data quality. Automated ELISA workstations allow the full benefit of these kits to be realized. Sample preparation, reagent pipetting, incubation, and photometric evaluation can be performed without user intervention. Reliability is increased through the elimination of operator error, better accuracy and precision, and often higher speed. Much larger batch sizes are possible and these systems can provide sample tracking with report generation for documentation requirements. In this paper the manual procedures and ELISA methods are compared and some critical aspects of automating these ELISA kits are discussed.

Radiosensitization of human colorectal tumor cells by 4-nitro-5-sulfonatoimidazoles.

Misonidazole, a clinically-effective 2-nitroimidazole hypoxic cell radiation sensitizer, and 12 4-nitro-5-sulfonatoimidazoles were tested in cultured human SW1116 colorectal adenocarcinoma cells for radiosensitizing efficiency. Octanol-water partition coefficients and HPLC capacity factors were determined for all agents as measurements of lipophilicity, and an excellent correlation was found between the two measurements. Cytotoxicity, in vitro glutathione reactivity, and one-electron reduction potential were also determined for each compound to evaluate potential utility as macromolecularly transported radiosensitizers. Ten members of the set were found to be 40 to 300 times more radiotoxic than misonidazole, but no correlation was found between their radiosensitizing efficiencies and the chemical and physical parameters.

Radiosensitizer conjugation to the carcinoma 19-9 monoclonal antibody.

Misonidazole was covalently conjugated (3-68 mol drug/mol antibody) to 19-9 monoclonal antibody directed against a colorectal carcinoma tumor-associated antigen as a method for targeting radiosensitizing agents. This attachment was accomplished by the mixed anhydride method using the hemisuccinate derivative of misonidazole. Evaluation of conjugates in vitro shows a loss of antibody binding activity with increasing loading levels; however, significant binding activity is retained even at relatively high sensitizer/antibody ratios. This observation was consistent in three binding assays: a competitive radioimmunoassay; an enzyme immunoassay; and an affinity column assay. From these studies, it was concluded that the optimal loading factor for misonidazole-antibody conjugates, when it is used for immunochemotherapy lies between 8 and 15. In vitro release studies indicated that conjugates are hydrolytically stable (t1/2 = 4 days) under physiological conditions.

Macromolecular attachment as a metabolic stabilizer for a labile radiosensitizer.

4-Nitro-5-sulfonylimidazoles represent a class of hypoxic cell radiation sensitizers whose in vitro activity greatly exceeds that of the current clinical standard, misonidazole. However, in vivo studies with these 4,5-disubstituted imidazoles have shown that a rapid reaction with circulating thiols decomposes the agent and compromises its clinical utility. Drug-macromolecule conjugates prepared in this study from poly-L-glutamate, succinylated poly-L-lysine, dextran, and a succinylated polylysine-antibody, all demonstrated protection of the drug from glutathione displacement. 1-Methyl-4-nitro-5-imidazolyl 4-aminophenyl sulfone conjugated to a succinylated poly-L-lysine-antibody was greater than 7 times less reactive than the unbound drug. Polymer transport may offer a useful tumor-delivery mechanism for these highly reactive radiation sensitizers.

The effects of wear, acid etching, and bond removal on human enamel.

A method of marking human enamel so that reduction in enamel thickness by etching, bonding, and wear could be measured to within a range of -2.5 to +3.5 microns for the impression accuracy and to within a range of -1.5 to +3.8 microns for the measurement error, was devised and used to measure the effects of the above factors on enamel. For five unetched surfaces studied in vivo, the 85-day loss of enamel averaged 1.6 microns. For twenty teeth etched and studied in vivo, the etch removed 9.9 microns of enamel and the subsequent loss over 85 days exceeded normal wear by 3.0 microns. The etch produces microporosities up to 50 microns in depth; therefore, the remaining 40 to 45 microns must be filled rather than worn smooth. For twelve teeth subjected to etching, bonding, bracket removal, and "clean up," enamel removed averaged 55.6 microns or approximately the entire thickness of the etch. The surface immediately following the "clean up" and 2 months after "clean up" were clinically and microscopically comparable to an untouched enamel surface.

Antigenic independence of some microbial urate oxidases.

Antisera were prepared to urate oxidase derived from three microbial species, a yeast (Candida utilis), a mold (Aspergillus flavus), and a bacterium (Bacillus fastidious). The antisera inhibited enyme activity to a limited extent. Cross-reaction studies with preparations of the enzyme from these and other species indicated that the microbial enzyme exhibits a high degree of antigenic independence. This appeared to be particularly true of the bacteria studied.