Proposal of a 2-tier histologic grading system for canine cutaneous mast cell tumors to more accurately predict biological behavior.

Currently, prognostic and therapeutic determinations for canine cutaneous mast cell tumors (MCTs) are primarily based on histologic grade. However, the use of different grading systems by veterinary pathologists and institutional modifications make the prognostic value of histologic grading highly questionable. To evaluate the consistency of microscopic grading among veterinary pathologists and the prognostic significance of the Patnaik grading system, 95 cutaneous MCTs from 95 dogs were graded in a blinded study by 28 veterinary pathologists from 16 institutions. Concordance among veterinary pathologists was 75% for the diagnosis of grade 3 MCTs and less than 64% for the diagnosis of grade 1 and 2 MCTs. To improve concordance among pathologists and to provide better prognostic significance, a 2-tier histologic grading system was devised. The diagnosis of high-grade MCTs is based on the presence of any one of the following criteria: at least 7 mitotic figures in 10 high-power fields (hpf); at least 3 multinucleated (3 or more nuclei) cells in 10 hpf; at least 3 bizarre nuclei in 10 hpf; karyomegaly (ie, nuclear diameters of at least 10% of neoplastic cells vary by at least two-fold). Fields with the highest mitotic activity or with the highest degree of anisokaryosis were selected to assess the different parameters. According to the novel grading system, high-grade MCTs were significantly associated with shorter time to metastasis or new tumor development, and with shorter survival time. The median survival time was less than 4 months for high-grade MCTs but more than 2 years for low-grade MCTs.

The berger inquiry: an impact assessment process.

The Mackenzie Valley Pipeline Inquiry, conducted by the Honorable Mr. Justice T. R. Berger, undertook to explore thoroughly the issues surrounding the building of a northern pipeline. In doing so, the Inquiry provided a forum for the interplay of the technical and environmental issues with very personalized social and cultural concerns. As a process, it reached out beyond the direct participants: it became one in which all Canadians, north and south, participated. It touched some of Canada's deepest concerns-concerns about energy policy, resource allocation, the price and priority of industrial development, cultural sovereignty, and self-definition. These have become national concerns, not just regional. And so, no matter what the final decision is about the pipeline, the Inquiry will have a profound and lasting national influence.

The effects of ingesting a carbohydrate-electrolyte beverage 15 minutes prior to high-intensity exercise performance.

The aim of this study was to examine the effect of ingesting a commercially available carbohydrate-electrolyte (CHO-E) solution on strenuous exercise performance. Ten apparently healthy male volunteers (Mean +/- SD; age 20 +/- 2 yrs; height 178 +/- 7 cm; body mass 77 +/- 10 kg; estimated VO(2 max) 56 +/- 3 ml x kg(-1) x min(-1) completed three experimental trials in random order separated by a minimum of 7 days. For each trial, subjects consumed (8 ml x kg(-1) body mass) either a CHO-E solution (6% carbohydrate, 50 mg Na/500 ml), a non-CHO-E placebo, or no fluid, 15 minutes prior to exercise. The exercise involved intermittent shuttle (20 m apart) running for 1 hr followed by an incremental shuttle running test to exhaustion. Subjects displayed longer exercise times when the CHO-E solution was ingested compared with placebo or no fluid groups (exercise time to exhaustion - CHO-E 649 +/- 95 s, vs. placebo 601 +/- 83 s, vs. no fluid 593 +/- 107 s, P < 0.05). There was a main effect for time for specific gravity of urine (P < 0.05 vs. postexercise, pooled data) and body mass (P < 0.05 vs. postexercise, pooled data). The main finding from this investigation indicates that drinking a CHO-E solution 15 minutes prior to exercise improves performance. This study has practical implications for those sports where drinking during activity is restricted.

A review of one year of British Armed Forces mental health hospital admissions.

OBJECTIVES: The paper provides a review of one year of military Mental Health (MH) hospital admissions. This includes an exploration into demographic trends, differences in clinical opinion and how information gained is used to improve the service and ensure appropriate, cost effective care in the optimum environment. METHODS: The sample group is entitled military MH hospital admissions from 1 April 2005 to 31 March 2006. Data was collected on questionnaires with SPSS used for the management and analysis of the quantitative data, with the information exposed to descriptive and inferential statistical analysis. RESULTS: There were 344 admissions. The paper contains a detailed review of a number of variables. Depression was the most common diagnosis resulting in 112 (33%) hospital admissions and Post Traumatic Stress Disorder accounted for 23 (7%). There were statistically significant differences that may be attributable to gender with more women admitted with depression and more men with alcohol related disorders. The average length of stay was 21 days, with 48% of patients discharged within 3 weeks. 45% of all returns included significant events reporting that highlighted written evidence of good and poor practice. CONCLUSION: This study is part of an extensive monitoring programme of military MH hospital admissions. Depression is the most common MH problem leading to hospital admission. The results indicate that Service-personnel have access to a highly responsive service that provides brief assessment and treatment within a safe therapeutic environment. 45% of returns included significant event information that resulted in policy changes, leading to improved patient care and a better interface with the NHS. Bench-marking, both internally between military Departments of Community Mental Health and externally have improved visibility and self awareness leading to better GP induction programmes, PHC educational seminars and the establishment of MH web-pages. The Armed Forces need an effective MH service that is accessible, readily available, non-stigmatised and which positively advocates a duty of care. The results highlight the importance of further studies regarding depression to ensure that the Armed Forces are in a better position to maximise the use of MH resources.

Variation by body mass index and age in waist-to-hip ratio associations with glycemic status in an aboriginal population at risk for type 2 diabetes in British Columbia, Canada.

BACKGROUND: It is unclear whether obesity and age modify or confound relations between abdominal adiposity and metabolic risk factors for type 2 diabetes. OBJECTIVE: Our objective was assess the consistency of relations between abdominal adiposity and glycemic variables across discrete categories of obesity and age. DESIGN: We performed a stratified analysis of prevalence data from a rural screening initiative in British Columbia, Canada. Subjects were Salishan Indians, all healthy relatives of individuals with type 2 diabetes [n = 151; age: 18-80 y; body mass index (BMI, in kg/m2): 17.0-48.2]. We measured waist-to-hip ratio (WHR) (2 categories); insulin, glycated hemoglobin (Hb A1c), and 2-h glucose concentrations (2 categories); and BMI (4 categories). BMI and age-specific odds ratios (ORs) and 95% CIs were calculated. RESULTS: WHR-glycemic variable relations were not consistent across BMI and age strata. Risks associated with high WHR were: for persons with BMIs from 25 to 29, elevated insulin (OR: 6.71; 95% CI: 1.41, 34.11) and Hb A1c (OR: 16.23; 95% CI: 2.04, 101.73) concentrations; for persons aged 18-34 y, elevated insulin concentrations [OR: indeterminate (+infinity); 95% CI: 1.89, +infinity]; and, for persons aged 35-49 y, elevated Hb A1c (OR: +infinity; 95% CI: 3.17, +infinity) and 2-h glucose (OR: 9.15; 95% CI: 1.74, 59.91) concentrations. CONCLUSIONS: WHR discriminates risk of type 2 diabetes in overweight but not obese individuals. Abdominal adiposity is associated with elevated insulin concentrations in younger age groups and with impaired glucose control in middle-aged groups, suggesting metabolic staging by age on a continuum from insulin resistance to impaired glucose tolerance.

Trazodone overdose: four years of experience from voluntary reports.

The details of 88 cases involving trazodone overdose, either alone or in combination with other drugs, have been forwarded to the manufacturer by reporting physicians since trazodone was made available in March 1982. In 73 of these cases, recovery was uneventful; in 6 cases unexpected complications developed. Nine deaths occurred in patients who had taken trazodone in combination with other drugs and/or alcohol. These case reports are supplemented by data from the American Association of Poison Control Centers and the National Institute on Drug Abuse. Of 206 reported overdose exposures to trazodone, no deaths were recorded. For comparison, 2263 reported tricyclic and tetracyclic overdoses resulted in 16 deaths, and 125 reported monoamine oxidase inhibitor overdoses produced 3 fatalities. When taken alone in overdose, trazodone appears to have limited toxicity. Nevertheless, treatment should be monitored closely in patients who present with a history of seizures or who suffer from cardiovascular or respiratory disease.

Serum immunoreactive trypsin concentrations in infectious and non-infectious illnesses and in juvenile diabetes.

Serum immunoreactive trypsin (SIT) concentrations were measured in 244 patients with infectious illnesses and in 281 children with diabetes of recent onset. Results were compared with reference ranges established in 107 patients with non-infectious, non-diabetic illnesses, in whom SIT concentrations were found to increase with advancing age. Reduced or undetectable concentrations of SIT were associated with diabetes in children and with a few cases of severe childhood infection. Increased SIT concentrations were associated with virologically confirmed cases of infection with mumps and Coxsackie B virus infection, and with clinical diagnoses of mumps, PUO, and meningitis in children, and with Bornholm disease, cardiac infection, and respiratory infection in adults. It is suggested that silent invasion of the exocrine pancreas with elevation of the SIT concentration may accompany infection by Coxsackie B, mumps, and, possibly, other viruses.

Serum immunoreactive trypsin concentrations in diabetic children.

Serum immunoreactive trypsin (SIT) concentrations measured in 616 children with diabetes of recent onset were low, in both boys and girls, in comparison with reference ranges established in patients with non-diabetic, non-infectious illnesses. The mean SIT concentration was 60% of the mean reference level in children tested within three weeks of the onset of diabetes, and about 40% in patients tested six months after the onset of diabetes. Very low SIT levels were found in about 10% of patients, most of whom had no measurable SIT by the assay procedure employed. These very low SIT concentrations were more frequent in older children aged 6-15 years, and in children tested at about 5-6 months after onset. Repeat tests on some of the children showed that the very low SIT levels were generally present for only a limited period.

A comparative study of viruses associated with acute haemorrhagic conjunctivitis.

Seven representative isolates from six outbreaks of acute haemorrhagic conjunctivitis were shown to have the characteristics of enteroviruses. Two viruses differed from the remaining five isolates in producing paralysis in suckling mice and being resistant to 2-hydroxybenzyl-benzimidazole. These two viruses were also closely related antigenically and distinct from the other five viruses which were serologically similar to each other. Neither group of viruses was inhibited by antisera to the known enteroviruses and they probably represent two new enterovirus types one related to the Coxsackie A viruses and the other to the echoviruses.

No evidence for linkage of schizophrenia to DXS7 at chromosome Xp11.

There have been claims that a gene on the X chromosome may contribute to susceptibility to schizophrenia. Crow (1988) initially proposed that such a gene might lie in the pseudoautosomal region, but when evidence that weakened this hypothesis accumulated, he proposed that a susceptibility locus might be present elsewhere on the sex chromosomes instead. DeLisi et al. (1994) found a small nonsignificant positive lod score between the marker DXS7 and schizophrenia, but other failed to replicate this finding. Another study reported by Crow and DeLisi's group was also weakly positive for this marker (Dann et al., 1997). This locus was then investigated in a collaborative study by Laval et al. (1997), which produced a nonparametric lod score of 2.44. Using a sample of 17 pedigrees from Britain and Iceland, we have also tested the hypothesis of linkage between DXS7 and schizophrenia. The 17 families were selected from a larger sample on the basis of an absence of male-to-male transmission for schizophrenia. These families were originally selected for having multiple cases of schizophrenia within them and for having no cases of bipolar affective disorder. We genotyped subjects for a marker at DXS7 and performed classical lod score and model-free linkage analysis using broad and narrow definitions of affection with schizophrenia. We found strongly negative lod scores and no evidence for linkage using model-free analysis. Therefore, this study does not support the hypothesis of linkage of schizophrenia to DXS7, and the evidence for a susceptibility locus on this part of the X chromosome is weakened.

Distribution and function of multiple anion transporter proteins in brain tumor cell lines in relation to glucose transport.

The anion transport, "band 3," family of proteins in mammalian brain performs the same functions as that of erythroid band 3. These functions are anion transport, ankyrin binding, and generation of senescent cell antigen, an aging antigen that terminates the life of cells. The presence of 5-7 band 3 related proteins in brain tissue was suggested by the reaction of antibodies to synthetic peptides of erythroid band 3 with a number of bands in immunoblots. Since there are a number of different cell types in brain, tissue cultures of neural cell types were examined to determine whether multiple band 3 related proteins are present in each cell type or whether several band 3 related proteins are present in each cell type. The tumor cell lines exhibit anion transport and are inhibited by the anion transport inhibitors 4,4'-diisothiocyano-2,2' disulfonic acid (DIDS), phenylglyoxal, and furosemide. Glucose transport is inhibited by cytochalasin B and the anion transport inhibitor, phenylglyoxal, in these cell lines, but not by 4,4'-diisothiocyano-2,2' disulfonic acid. Furosemide gave partial inhibition of most, but not all, cell lines. Since phenylglyoxal inhibits anion transport by binding to an arginine near the transport site, inhibition of glucose transport by phenylglyoxal suggests that an arginine lies in the substrate binding site. The number of cytochalasin B and DIDS binding sites was quantitated on cell lines as an approximation of the number of glucose transporter and anion transporter sites, respectively.

Posttranslational changes in band 3 in adult and aging brain following treatment with ergoloid mesylates, comparison to changes observed in Alzheimer's disease.

Band 3, the most heavily used anion transport system in vertebrates, ages as cells and tissues age. Posttranslational changes in band 3 in adult and aging brain were investigated following treatment with ergoloid mesylates and compared to changes observed in Alzheimer's disease (AD). The study was conducted in a double blind fashion and was decoded only after the study was completed. The following posttranslational changes in brain band 3 occur with age: increased breakdown of band 3; decreased phosphorylation; and decreased anion transport. Autoantibodies to senescent cell antigen (SCA) synthetic peptides residue 538-554 and 812-827 increase with age, but antibodies to the former peptide are significantly reduced in ergoloid mesylate treated old mice. This is a critical transport region of band 3. Results showed the aged/altered band 3 increased in Alzheimer's disease (AD) as determined by quantitative antibody binding. Ergoloid mesylates altered the age-related posttranslational changes as follows: the observed age-related decrease in brain band 3 was partially reversed and anion transport was increased. This is consistent with the data indicating decreased autoantibodies to a critical anion transport segment of band 3. Aging appears to result in damage to a critical transport region of the anion transporter which is reflected by decreased anion transport, increased breakdown, alteration of the molecule itself, and an increase in autoantibodies to the region. Ergoloid mesylates seem to protect against this damage.

Effectiveness of community-directed diabetes prevention and control in a rural Aboriginal population in British Columbia, Canada.

This report presents the process and summative evaluation results from a community-based diabetes prevention and control project implemented in response to the increasing prevalence and impact of non-insulin-dependent diabetes mellitus (NIDDM) in the Canadian Aboriginal population. The 24-month project targeted the registered Indian population in British Columbia's rural Okanagan region. A participatory approach was used to plan strategies by which diabetes could be addressed in ways acceptable and meaningful to the intervention community. The strategies emphasised a combination of changing behaviours and changing environments. The project was quasi-experimental. A single intervention community was matched to two comparison communities. Workers in the intervention community conducted interviews of individuals with or at risk for diabetes during a seven-month pre-intervention phase (n = 59). Qualitative analyses were conducted to yield strategies for intervention. Implementation began in the eighth month of the project. Trend measurements of diabetes risk factors were obtained for 'high-risk' cohorts (persons with or at familial risk for NIDDM) (n = 105). Cohorts were tracked over a 16-month intervention phase, with measurements at baseline, the midpoint and completion of the study. Cross-sectional population surveys of diabetes risk factors were conducted at baseline and the end of the intervention phase (n = 295). Surveys of community systems were conducted three times. The project yielded few changes in quantifiable outcomes. Activation of the intervention community was insufficient to enable individual and collective change through dissemination of quality interventions for diabetes prevention and control. Theory and previous research were not sufficiently integrated with information from pre-intervention interviews. Interacting with these limitations were the short planning and intervention phases, just 8 and 16 months, respectively. The level of penetration of the interventions mounted was too limited to be effective. Attention to process is warranted and to the feasibility of achieving effects within 24 months.

Biochemical changes induced by Coxsackie B4 virus in short-term culture of mouse pancreatic islets.

Isolated mouse pancreatic islets were infected in vitro with two strains of Coxsackie B4 virus--a tissue culture-adapted strain and a mouse pancreas-adapted strain. Within 48 h of infection changes had occurred in the biochemical activities of islets infected with the mouse pancreas-adapted strain of virus. Basal insulin release was increased two-fold in these islets, while glucose-induced insulin secretion remained unchanged. Insulin biosynthesis was greatly reduced at a stimulatory concentration of glucose (20 mM), thus leading to a reduced insulin content in these islets. These effects are of importance because they demonstrate that certain strains of Coxsackie B4 virus, like encephalomyocarditis virus, may selectively alter beta-cell function in vitro.

The effect of maternal fluid intake on breast milk supply: a pilot study.

To examine the effect of increased and decreased fluids on breast milk supply, a pilot study using a cross-over design with 10 mother-infant pairs was completed. Baseline measures of milk supply were determined over a 3-day period of normal fluid intake based on body weight. Subjects were studied over 3-day periods when fluid intake was alternately 50% more and 50% less than normal level. Milk supply was calculated by averaging breast milk intake, determined by test weighing the infants with electronic scales, and milk yield, measured either by total breast expression with an electric breast pump or a combination of expression and test weighing. Although milk supply decreased with decreased fluids and increased with increased fluids, this change was not statistically significant. Recommendations for further research include replication using subjects' usual fluid intake as a baseline and replication using mothers suspected of insufficient milk syndrome.

Use of the thyrotropin releasing hormone stimulation test to diagnose mild hyperthyroidism in cats.

We evaluated serum T4 and T3 concentrations before and after administration of thyrotropin releasing hormone (TRH) in 35 cats with mild to moderate hyperthyroidism, 15 cats with nonthyroidal disease, and 31 clinically normal cats. The TRH stimulation test was performed by collecting blood for serum T4 and T3 determinations before and 4 hours after IV administration of 0.1 mg/kg TRH. Mean basal serum thyroid hormone concentrations in hyperthyroid cats were significantly (P < .05) higher than concentrations in normal cats and in those with nonthyroidal disease, but there was considerable overlap among the 3 groups. After administration of TRH, mean serum T4 concentrations increased significantly in all groups of cats, whereas mean T3 concentrations increased significantly in normal cats and in those with nonthyroidal disease, but not in cats with hyperthyroidism. The absolute difference between mean basal and TRH-stimulated serum concentrations of T4 in cats with hyperthyroidism (10.7 nmol/L) was significantly lower than the difference in the cats with nonthyroidal disease (20.0 nmol/L) and in clinically normal cats (28.3 nmol/L), but there was considerable overlap in values among groups. The mean value for relative change in serum T4 concentration after TRH was significantly lower in cats with hyperthyroidism (18.9%) than in those with nonthyroidal disease (110.0%) and in clinically normal cats (130.2%). Serum T4 concentrations increased by > 50% in all normal cats and cats with nonthyroidal disease, whereas only 4 (11.4%) of the 35 hyperthyroid cats had an increase of > 50% after TRH administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Triiodothyronine (T3) suppression test. An aid in the diagnosis of mild hyperthyroidism in cats.

The purpose of this study was to develop a T3 suppression test to help in the diagnosis of mild hyperthyroidism in cats. We evaluated the response in circulating T4 concentrations to exogenous T3 (liothyronine) administration in 44 clinically normal cats, 77 cats with hyperthyroidism, and 22 cats with nonthyroidal disease. The test was performed by first collecting blood samples for basal serum T4 and T3 determinations, administering liothyronine at an oral dosage of 25 micrograms three times daily for seven doses, and, on the morning of the third day, again collecting serum samples for T4 and T3 determinations 2 to 4 hours after the seventh dose of liothyronine. The mean basal serum concentrations of T4 (53.1 nmol/L) and T3 (1.8 nmol/L) were significantly higher in the cats with hyperthyroidism than in the normal cats (T4 = 25.3 nmol/L, T3 = 1.3 nmol/L) and the cats with nonthyroidal disease (T4 = 29.5 nmol/L, T3 = 1.4 nmol/L); however, there was a great deal of overlap of basal values between the three groups of cats. Of the 77 cats with mild hyperthyroidism, 41 (53%) had serum T4 values and 55 (71%) had T3 values that were within the established normal ranges. After administration of liothyronine, mean serum T4 concentrations fell much more markedly in the normal cats and the cats with nonthyroidal disease than in the hyperthyroid cats.(ABSTRACT TRUNCATED AT 250 WORDS)

Fathers of breastfed infants: postponing and types of involvement.

OBJECTIVE: To examine husbands' experiences of having their wives breastfeed. DESIGN: Qualitative method of grounded theory. SETTING: In-depth interviews by phone at home. PARTICIPANTS: Fourteen middle-class, urban, Canadian fathers of successfully breastfed infants. RESULTS: The fathers reported a disparity in the types of relationships that their children had with each of their parents as a result of breastfeeding. The process that enabled the fathers to accept this perceived difference was labeled postponing. Four fathering styles, which explain the variation in postponing, were found. The phases of postponing include becoming aware of the disparity, simultaneously developing accepting strategies and acknowledging reinforcing factors, and, finally, developing compensating behaviors to increase the fathers' interactions with their infants and promote closer relationships. When weaning occurred, the fathers' relationships with their children changed as the fathers found ways to catch up. CONCLUSIONS: A need exists for realistic education about the realities of breastfeeding for fathers. More outlets for fathers' negative emotions toward breastfeeding need to be found.

Effect of nonthyroidal illness on serum thyroxine concentrations in cats: 494 cases (1988).

We reviewed the medical records of 494 cats with a variety of nonthyroidal diseases in which serum thyroxine (T4) concentration was determined as part of diagnostic evaluation. The cats were grouped by category of disease (ie, renal disease, congestive heart failure, diabetes mellitus, focal neoplasia, systemic neoplasia, hepatopathy, inflammatory bowel disease, inflammatory pulmonary disease, miscellaneous diseases, or undiagnosed disease), degree of illness (ie, mild, moderate, or severe), survival (ie, lived, died, or euthanatized), and presence or absence of a palpable thyroid gland. The mean (+/- SD) serum T4 concentrations in all 10 groups of cats, which ranged from 10.5 +/- 11.1 nmol/L in cats with diabetes mellitus to 18.7 +/- 7.8 nmol/L in cats with focal neoplasia, were significantly (P less than 0.001) lower than those of normal cats (27.0 +/- 10.4 nmol/L). The number of ill cats with low serum T4 concentrations (less than 10 nmol/L) was highest in the cats with diabetes mellitus (59%), hepatopathy (54%), renal failure (48%), and systemic neoplasia (41%). When the serum T4 concentrations in cats with mild, moderate, and severe illness were compared, mean concentrations were progressively lower (21.3 +/- 6.8, 14.8 +/- 8.1, and 6.5 +/- 5.8 nmol/L, respectively) as degree of illness increased. Severity of illness had a more significant (P less than 0.001) effect in lowering serum T4 concentrations than did disease category. Mean serum T4 concentrations in the cats that died (7.8 +/- 9.8 nmol/L) or were euthanatized (10.0 +/- 7.0 nmol/L) were also significantly (P less than 0.001) lower than those of cats that survived (15.2 +/- 8.8 nmol/L).(ABSTRACT TRUNCATED AT 250 WORDS)

Neuroaxonal dystrophy of Rottweiler dogs.

Five Rottweiler dogs were examined because of progressive ataxia of thoracic and pelvic limbs of several months' to 4 years' duration. Hypermetria, especially of the thoracic limbs, and head incoordination and tremors were obvious features in the 3 older dogs. None of the dogs had evidence of weakness or loss of conscious proprioception. An electroencephalogram in 1 severely affected dog was normal. Electromyograms in 2 severely affected dogs were normal except for some positive sharp waves and fibrillation potentials in the interosseus muscles of all 4 feet. Cerebrospinal fluid evaluations of 2 severely affected dogs were normal. A reduced number of sensory nerve endings, compared with age-matched controls, was seen on histologic examination of a conjunctival biopsy specimen in 1 severely affected dog. An antemortem diagnosis of neuroaxonal dystrophy was suspected from the signalment, history, and neurologic examination findings. The diagnosis was confirmed on the basis of microscopic findings in 3 dogs necropsied.