Prognostic value of histologic grading for feline mammary carcinoma: a retrospective survival analysis.

Feline mammary carcinoma is highly malignant and generally associated with a poor prognosis, although studies suggest the range of survival times in affected cats is broad. Histologic grading of these tumors is achieved using the Elston and Ellis system, originally developed for human breast cancer. In cats, however, classification using this method has variable prognostic value. Therefore, objectives of this study were (1) to evaluate the Elston and Ellis grading system for feline mammary carcinoma in a predominantly spayed population and (2) to determine whether modification of this system or development of a novel system improved the prognostic value of histologic grading. Survey data and histologic features for 108 carcinomas from 97 cats were analyzed with respect to overall survival. Elston and Ellis grading failed to correlate significantly with overall survival. Using multivariable analysis, lymphovascular invasion, nuclear form, and mitotic count each demonstrated independent prognostic significance (P = .008, <.001, and .004, respectively). Modifications of the Elston and Ellis system and a novel grading system were proposed based on these results; all showed significant correlation with overall survival (P < .001). Median survival times were 27, 29, or 31 months for grade I; 14, 12, or 14 months for grade II; and 13, 5, or 8 months for grade III carcinomas using the mitotic-modified Elston and Ellis, the revised Elston and Ellis, or the novel grading system, respectively. Based on this retrospective study, adoption of the species-specific systems as proposed here may improve the prognostic value of histologic grading for feline mammary carcinoma.

Chromosome-specific microsatellite sets for fluorescence-based, semi-automated genome mapping.

To facilitate large-scale genetic mapping of the human genome, we have developed chromosome-specific sets of microsatellite marker loci suitable for use with a fluorescence-based automated DNA fragment analyser. We present 254 dinucleotide repeat marker loci (80% from the Généthon genetic linkage map) arranged into 39 sets, covering all 22 autosomes and the X chromosome. The average distance between adjacent markers is 13 centiMorgans, and less than 4% of the genome lies more than 20 cM from the nearest marker. Each set of microsatellites consists of up to nine marker loci, with allele size ranges that do not overlap. We selected marker loci on the basis of their reliability in the polymerase chain reaction, polymorphism content, map position and the accuracy with which alleles can be scored automatically by the Genotyper program.

A standardised template for reporting lower limb kinematic waveform movement compensations from a sensor-based portable clinical movement analysis toolkit.

Objectives: To develop a standardised template to support physiotherapist reporting of lower limb kinematic waveform data. Design: Within and between user agreement identification of movement compensation strategies. Setting: University Health Board Physiotherapy Department. Participants: Fourteen individuals with anterior cruciate ligament reconstruction performed overground gait, double-leg squat, and stair ascent wearing body-worn sensors. Six users viewed 252 kinematic waveforms of hip, knee and ankle joint angles in the sagittal and frontal planes. Main outcome measures: Between and within-user observed agreement and themes from movement analysis reports. Results: Between-user observed agreement for presence of a movement compensation was 0.6-0.9 for the sagittal plane and 0.75-1.0 for the frontal place. Within-user observed agreement was 0.57-1.00 for the sagittal plane and 0.71-1.00 for the frontal plane. Three themes and seven categories were identified from the waveform interpretations: Amount (qualitative and quantitative description), timing (phase, discrete time point, cycle), and nature (peak, range of motion, timing) of the compensation. Conclusion: There was good agreement between users at identifying the presence of movement compensation from the kinematic waveforms, but there was variation in how movement compensations were described. An interactive report, a standardised template for interpretation of kinematic waveforms, and training to support the clinical application of a movement analysis toolkit are proposed.

Sudden death associated with myocardial contraction band necrosis in Boer goat kids.

Parenteral selenium (Se) and vitamin E (Vit E) were administered to all newborn kids at a Boer goat farm where there was previous high neonatal mortality assumed to be due to nutritional myopathy. All treated kids were affected by severe respiratory distress and died within 8 hours of Se/Vit E administration. Gross lesions included severe pulmonary edema, hydrothorax, and hydropericardium. The primary histopathologic finding was severe, acute, and monophasic myocardial contraction band necrosis. The diagnosis was accidental acute selenosis based on trace mineral analysis of the liver. This case highlights an important differential diagnosis in cases of acute myocardial contraction band necrosis and sudden death in goats and emphasizes the need for caution when administering parenteral Se/Vit E preparations.

Malignant Neuroendocrine Tumour (Carcinoid) of the Spleen in an African Pygmy Hedgehog (Atelerix albiventris).

A malignant neuroendocrine tumour (carcinoid) of the spleen was diagnosed on post-mortem examination of a 3-year-old, male African pygmy hedgehog (Atelerix albiventris). The animal presented with a history of inappetence, weight loss, lethargy, a wide-based gait and a palpable abdominal mass. The gross pathological, histopathological, histochemical and immunohistochemical findings are described. Primary splenic carcinoids are reported rarely in the human medical literature and this is believed to be the first report in a non-human animal.

Risk factors for severity of diabetic polyneuropathy: intensive longitudinal assessment of the Rochester Diabetic Neuropathy Study cohort.

OBJECTIVE: Chronic hyperglycemia relates to the occurrence of diabetic polyneuropathy (DPN), but has not yet been shown to relate to its overall severity In addition, the degree and duration of hyperglycemia, which measure of chronic hyperglycemia is most predictive of defined levels of severity of DPN, and which other putative risk factors are involved remain unknown. RESEARCH DESIGN AND METHODS: In a longitudinal study of 264 diabetic individuals in Rochester, MN, risk factors and other diabetic complications assessed at regular intervals during an average of approximately 7 years were tested for their association with a composite score of severity of DPN at the last examination. RESULTS: In multivariate analysis, diabetic retinopathy severity level (at last examination), mean ln(24-h proteinuria x duration of diabetes), and mean GHb were the main covariates for severity of DPN (R2 = 0.33). Excluding markers of microvessel and macrovessel disease, the independent risk factors were mean In(GHb x duration of diabetes), GHb, and type of diabetes (R2 = 0.23). CONCLUSIONS: We found that diabetic microvessel disease, chronic hyperglycemia exposure, and type of diabetes are associated with severity of DPN, and we believe these factors are implicated in its cause. Each of the five markers of microvessel disease was a strong covariate for severity of DPN. Mean GHb predicts severity of DPN better than duration of diabetes, and the latter predicts severity of DPN better than mean fasting plasma glucose. Knowing the severity of microvessel disease, the degree of chronic hyperglycemia exposure, and the type of diabetes provides useful information to evaluate whether a coexisting polyneuropathy and its severity is probably due to diabetes.

Does prediabetes cause small fiber sensory polyneuropathy? Does it matter?

BACKGROUND AND OBJECTIVES: The association between prediabetes and distal polyneuropathy (DPN) remains controversial. Here we test whether the prevalence of small fiber sensory distal polyneuropathy is increased in prediabetes. METHODS: Prospectively recruited cohorts of healthy subjects and those with prediabetes from Olmsted County, Minnesota, were assessed for positive neuropathic sensory symptoms, or pain symptoms characteristic of small fiber sensory DPN. Hyperalgesia and hypoalgesia were assessed by "smart" quantitative sensation testing (QST). The prevalence of symptoms and QST abnormalities were compared among the groups. RESULTS: There was no significant increase in the prevalence of positive neuropathic sensory or pain symptoms, nor of hyper- or hypoalgesia in the prediabetes group. There was an increased prevalence of hypoalgesia of the foot only in newly diagnosed diabetes. CONCLUSIONS: Based on positive sensory and pain symptoms and QSTs, we did not find an increase in small fiber sensory DPN in prediabetes. Recognizing that obesity and diabetes mellitus are implicated in macro- and microvessel complications, physicians should encourage healthy living and weight loss in patients with prediabetes. In medical practice, alternate causes should be excluded before concluding that small fiber sensory distal neuropathy is secondary to prediabetes.

No evidence for axonal atrophy in human diabetic polyneuropathy.

In rats with streptozin-induced diabetes mellitus, the caliber of distal myelinated fiber (MF) axons in relation to the number of myelin lamellae is smaller than in controls. This finding usually has been attributed to axonal atrophy, but shrinkage or maldevelopment has also been considered. For human diabetic polyneuropathy (DP), axonal atrophy has been assumed by some investigators, but convincing evidence has not been demonstrated. We morphometrically evaluated transverse sections of 33 sural nerves from carefully evaluated diabetic patients > or = 30 years old without (8 patients) or with (25 patients) DP and compared them with 24 nerves from healthy subjects > or = 30 years old. Nerves from diabetic patients and controls were obtained under identical conditions and processed and evaluated in the same way, using an observer blind to the disease condition. Using computer digitization of electron micrographs, we evaluated the axonal area, perimeter, index of circularity, number of myelin lamellae, and frequency of adaxonal sequestration of 50.4 (mean) +/- 5.8 (SD) MF per sural nerve for healthy subjects and diabetic patients > or = 30 years old. The regression lines of the natural log (In) of axonal area on number of myelin lamellae of diabetic patients (with or without DP) were not significantly different from the regression lines of nerves of healthy subjects for large MFs-the most reliable group in which to recognize atrophy. Likewise, the regression lines of index of circularity (IC) (an index that is decreased with atrophy or shrinkage) on number of myelin lamellae for large fibers was not significantly different between the disease and control groups. The rate of adaxonal sequestration was not significantly higher in DP than in healthy subjects. These results do not support the hypothesis that axonal atrophy occurs in human DP. For small MF, or all MF, some significant differences in regression lines of In axonal area or IC on number of lamellae were found, but these changes are probably explained by events of remyelination and axonal regeneration, which can affect these relationships and are known to occur in DP.

Longitudinal assessment of diabetic polyneuropathy using a composite score in the Rochester Diabetic Neuropathy Study cohort.

Because there are little satisfactory data on change in severity of diabetic polyneuropathy (DP) over time from study of population-based cohorts of diabetic patients in epidemiologic surveys of DP, it is difficult to predict outcome or morbidity or to identify risk factors; it is also difficult to estimate statistical power for use in controlled clinical trials. In this longitudinal study of almost 200 patients from the Rochester Diabetic Neuropathy Study (RDNS) cohort, we assess which symptoms, clinical examinations, tests, or combinations of examinations and tests (composite scores) are best used as minimal criteria for the diagnosis of DP and as a quantitative measure of severity of DP. An abnormality (> or = 97.5th percentile) of a composite score that included the Neuropathy Impairment Score of the lower limbs plus seven tests (NIS(LL)+7 tests), was a better minimal criteria for DP than clinical judgment alone or previously published minimal criteria. First, it provided a more comprehensive assessment of neuropathic impairment. Second, it avoided the overestimated frequency of DP when the minimal criteria for DP was any one or two abnormalities from multiple measurements. Minimal criteria using nerve conduction and reduced heart beat response to deep breathing identified approximately twice as many patients with DP than did clinical examination and vibration detection threshold using CASE IV. This difference could be used to subclassify state 1 DP. Although various individual measures of DP, for example, vibration detection threshold (as evaluated by CASE IV and the 4, 2, and 1 stepping algorithm [see text]), were good measures of worsening, the composite score NIS(LL)+7 tests (assessing neuropathic impairment) was much better at showing monotone worsening. Using this composite score, the average diabetic patient in the RDNS worsened by 0.34 points per year, whereas patients with diabetic polyneuropathy worsened by 0.85 points per year. On the assumption that a therapeutic agent may prevent worsening of DP but not cause improvement, controlled clinical trials of patients with DP would need to be conducted for a period of 3 years to achieve a meaningful change of 2 NIS points (the level of abnormality considered by a Peripheral Nerve Society consensus group to be clinically meaningful).

An improved test for Haemophilus influenzae precipitins in the serum of patients with chronic respiratory disease.

The detection of antibacterial precipitins in the serum of patients with chronic lower respiratory infections has been shown to be of great value in the assessment of pathogenicity of the corresponding bacterial species in the sputum. The test used hitherto, however, is time-consuming and cumbersome owing to the need to distinguish, by immunoelectrophoresis, between antibodies specific to the organism in question and those which react with antigens common to various Gram-negative species. A method has now been devised for the preparation of an extract of Haemophilus influenzae containing species-specific antigens only. Use of this extract obviates the need for immuno-electrophoresis and improves the sensitivity of the test.

Increase of plasma IL-6 concentration with age in healthy subjects.

The present study demonstrated that plasma IL-6 concentration was higher in older subjects than in younger ones and significantly in the male group (P = 0.02); Spearman rank correlation showed that plasma IL-6 concentration was positively correlated with age (r = 0.28, N = 55, P < 0.05); there was a highly significant correlation between the concentrations in plasma IL-6 and IL-1 alpha (r = 0.51, N = 52, P < 0.001). These findings suggest the possibility that age-related changes of plasma IL-6 and IL-1 alpha may provide a pathological basis for the susceptibility to such illness as commonly occurs in elderly people, especially Alzheimer's disease as the two interleukins can induce the production of alpha 1-antichymotrypsin and beta-amyloid protein precursor.

Transcendental meditation, mindfulness, and longevity: an experimental study with the elderly.

Can direct change in state of consciousness through specific mental techniques extend human life and reverse age-related declines? To address this question, 73 residents of 8 homes for the elderly (mean age = 81 years) were randomly assigned among no treatment and 3 treatments highly similar in external structure and expectations: the Transcendental Meditation (TM) program, mindfulness training (MF) in active distinction making, or a relaxation (low mindfulness) program. A planned comparison indicated that the "restful alert" TM group improved most, followed by MF, in contrast to relaxation and no-treatment groups, on paired associate learning; 2 measures of cognitive flexibility; mental health; systolic blood pressure; and ratings of behavioral flexibility, aging, and treatment efficacy. The MF group improved most, followed by TM, on perceived control and word fluency. After 3 years, survival rate was 100% for TM and 87.5% for MF in contrast to lower rates for other groups.

A review of the risk factors for endometrial carcinoma.

To summarize the review, the medical literature indicates that certain constitutional factors as well as the use of exogenous estrogen are associated with an increased risk of endometrial cancer. In addition, the absolute increase in the risk of this neoplasm with use of estrogen does not appear to be constant but depends upon the specific constitutional factors present. Therefore, particular caution should be exercised in prescribing replacement estrogens for women who already have an increased risk of endometrial cancer, such as those who are overweight or those who give a history of late onset of menopause. It should be noted, however, that the greatest absolute increase in risk with estrogen use appears to occur in women with no other known risk factors for the disease.

Differences in the perceptions of HIV risk amongst dental care providers in Western Australian clinics.

This paper examines the perceived risk of occupationally contracting HIV among dental care providers. This examination is based upon responses to a mailed questionnaire from all registered dentists (76 per cent response rate, n = 550) and dental therapists (63 per cent response rate, n = 208) in Western Australia during 1992. Results indicate that: 1) dental care providers who perceive a high risk of occupationally contracting HIV report a more conservative, cautious approach to HIV infection than do providers who perceive less risk of contracting the virus; 2) dental therapists are more likely than dentists to report a higher degree of perceived risk of occupationally contracting HIV; and 3) dentists are more likely than dental therapists to perceive compliance with universal precaution guidelines in dental practices in which they work. Reasons are presented for a suspicion that both sets of perceptions may be exaggerated. The need to educate dental therapists on the realistic risks of occupationally contracting HIV and to educate dentists on the value of compliance (and of appearing to comply) with universal precaution guidelines in order to help reduce undue stress and hindrances in the provision of safe and effective dental care in this era of AIDS concludes this paper.

Retrospective review of endoscopic plantar fasciotomy--1992 through 1994.

Endoscopic plantar fasciotomy is a rewarding procedure for both patient and surgeon. A vast majority of the patients have complete or near-complete resolution of heel pain at 6 months postoperatively. The procedure, however, is not without side effects and complications. This retrospective statistical study describes the postoperative side effects and complications of endoscopic plantar fasciotomy from 1992 to 1994. The procedure has been modified in an attempt to reduce several of the more commonly reported side effects.

Mixed cavernous and capillary intraosseous hemangioma of the foot.

Hemangiomas of bone are rare lesions accounting for approximately 1% of all primary bone tumors. Intraosseous hemangiomas of the foot are especially rare, with only sparse reports in the literature. Presented here is a case study of an erosive bony lesion of the midfoot that was microscopically and histopathologically proven to be a mixed cavernous and capillary hemangioma. Eradication of the lesion during diagnostic biopsy obviated further treatment.

Rhinitis and meningitis in two shelter cats caused by Streptococcus equi subspecies zooepidemicus.

In the past 6 years there have been increasing reports describing outbreaks of a severe fatal respiratory disease associated with Streptococcus equi subspecies zooepidemicus (SEZ) in dogs maintained in shelters, research facilities and kennels. Although SEZ appears to be an emerging pathogen of dogs kept in intensively housed environments, this bacterium has not been reported as a cause of death in intensively housed cats. This report describes fatal SEZ infection in two adult cats housed in separate animal shelter facilities. Both cats had acute onset of illness, which progressed to death in less than 24h. Post-mortem examination revealed rhinitis and meningitis and SEZ was demonstrated in the nasal cavity and brain. Polymerase chain reaction and sequence analysis of a 500 base pair region of the 16S rRNA gene confirmed the identity of the bacterium.

Ultra scale-down approach to correct dispersive and retentive effects in small-scale columns when predicting larger scale elution profiles.

Ultra scale-down approaches represent valuable methods for chromatography development work in the biopharmaceutical sector, but for them to be of value, scale-down mimics must predict large-scale process performance accurately. For example, one application of a scale-down model involves using it to predict large-scale elution profiles correctly with respect to the size of a product peak and its position in a chromatogram relative to contaminants. Predicting large-scale profiles from data generated by small laboratory columns is complicated, however, by differences in dispersion and retention volumes between the two scales of operation. Correcting for these effects would improve the accuracy of the scale-down models when predicting outputs such as eluate volumes at larger scale and thus enable the efficient design and operation of subsequent steps. This paper describes a novel ultra scale-down approach which uses empirical correlations derived from conductivity changes during operation of laboratory and pilot columns to correct chromatographic profiles for the differences in dispersion and retention. The methodology was tested by using 1 mL column data to predict elution profiles of a chimeric monoclonal antibody obtained from Protein A chromatography columns at 3 mL laboratory- and 18.3 L pilot-scale. The predictions were then verified experimentally. Results showed that the empirical corrections enabled accurate estimations of the characteristics of larger-scale elution profiles. These data then provide the justification to adjust small-scale conditions to achieve an eluate volume and product concentration which is consistent with that obtained at large-scale and which can then be used for subsequent ultra scale-down operations.

Behaviour disorder in an adolescent with terminal deletion of chromosome 3.

Individuals with terminal deletion of the long arm of chromosome 3 are rare and survival into adulthood has not been previously reported. A 15-year-old with this condition was studied and the difficulties in management of the manifest behaviours are described. This chromosomal abnormality may be associated with mental and functional deterioration as well as severe self-injurious behaviour, commencing in early childhood.