The canal system in the diaphysial compacta of the femur in some mammals

The Haversian canal system in the diaphysial compacta of the femur in 4 mammalian species (dog, pig, bovine, horse) was studied on the decalcified bone using a method developed by the authors. In the microscopic studies we found that in all species the network aspects vary with the depth of the compacta layer. In all layers, there is a background of longitudinal canals with more or less regular trajectories describing large curves. The anastomoses linking them are main elements that define the variety of the network aspects both from layer to layer and from species to species. The canal densities vary between broad limits in the dog and horse, but less in the pig and bovine. The mean density decreases in the following order of species: dog, pig, horse and bovine femur. The Haversian canal diameter varies within narrow limits in the dog and pig. The limits are broader in the horse and bovine. The mean diameter diminishes in the following order of species: bovine, dog, horse, pig. We can conclude that the canal network differs from one species to another from all points of view: the canal system is homogeneous in none of these parameters.     

In vitro evaluation of human muscle satellite cell migration prior to fusion into myotubes

We developed a short-time assay to evaluate muscle satellite cell migration, based on the fact that during myogenic differentiation, myoblasts migrate preferentially towards high cellular density areas where myotubes would form. This assay consists of a computer-assisted count of cells within a randomly chosen field, performed every hour for eight hours, and compared with the cell number at the start time of the experiment. Nine primary myoblast cultures were tested in triplicate. The method relies on several requisites. (1) Negligible cell proliferation: cell division was nearly absent in 8h experiments. (2) Directional cell movement: a major flow of cells, either entering or exiting the fields, was constantly observed.Counter-flows, detected by visual counting, involved minor percentages of cells. (3) Constant migration rate: a linear increase in cell count variations over 8h and a very high degree of intra- assay homogeneity were observed. Individual primary cell culture characteristics (depending on characteristics of the different donors) were the sole factor with a significant impact on migration rate. Automatic cell counting conveniently assessed the inhibitory effect of GRGDTP, an inhibitor of integrin-mediated cell adhesion. The method described here is rapid, does not require heavy equipment, and allows studies under serum-free conditions required to test molecules interfering with cell migration, in the course of the in vitro myogenic process.     

ICAM‐1 and β3 integrin immunoexpression in malignant melanoma cells: can they be used as additional predictors?

Malignant melanoma usually progresses from the intraepidermal microenvironment through a distinct radial growth phase, in which malignant potential cannot always be accurately evaluated, to invasion of the dermis (vertical growth phase) and metastasis. During these stages malignant cells interact with each other and with the extracellular matrix. This interaction is mediated by cell surface adhesion molecules such as the beta(3) integrin subunit and ICAM-1. Our aim was to investigate whether the expression of these two molecules is associated with the various histopathologic prognosticators commonly evaluated in malignant melanoma. Using a standard three-step immunoperoxidase technique we evaluated the above molecules' expression in a documented series of 66 cutaneous malignant melanomas. Forty-five were superficial spreading melanomas, including 18 in mixed growth phase. Positive immunoreaction was estimated by image analysis. ICAM-1 immunopositivity status was significantly more frequent among malignant melanomas of the nodular type (p=0.0001), and was associated with the vertical growth phase, Breslow thickness of >0.77 mm, and with evident lymphocytic infiltration. beta(3) integrin immunopositivity showed similar results in certain respects; it was more frequently detected in superficial spreading melanomas in which vertical growth had developed (p=0.002) and in cases with regression. There appears to be an association of these molecules with histopathologic features that predict increased tumorigenicity of malignant melanocytes.     

Left-handedness in asthmatic children

Left-handedness has been associated with asthma and allergic disorders. The Geschwind–Behan–Galaburda (GBG) hypothesis could explain this association. In view of previous findings, we investigated the distribution of laterality scores among asthmatic children and controls aged 4–8 years old. Seventy families with asthmatic children were administered the International Study of Asthma and Allergy in Childhood (ISAAC) questionnaire and the Edinburgh Left-handedness Inventory. A sample of 70 families with non-asthmatic, healthy children was used as controls. The majority of children had mild asthma. Ambidexterity was the main feature in the asthmatic children. A statistically significant difference in the laterality quotient (LQ) distribution was found in the group of asthmatic children with allergic rhinitis (LQ mean value in the asthmatic children with allergic rhinitis: 42.85 vs. 79.50 in the rest of the asthmatic children). These results suggest that there is a tendency towards left-handedness in asthmatic children and lend support to the GBG hypothesis.     

Chronic lymphocytic leukemia with 6q- shows distinct hematological features and intermediate prognosis.

Cytogenetic and fluorescence in situ hybridization studies were successfully performed in 217 chronic lymphocytic leukemia (CLL). In all, 13 patients with 6q21 deletion were identified and characterized in comparison with 92 patients with 'favourable' karyotype (normal or 13q-), 69 cases with 'intermediate risk' (1-2 anomalies) and 43 cases with 'unfavourable' karyotype (complex, 11q- or 17p-). Six out of 13 cases with 6q- showed an excess of atypical lymphocytes, a finding confirmed at the histologic level; >20% CD38+ cells were seen in 5/6 cases. IGVH mutational status revealed >98% homology to the germline sequence in 4/10 cases. When compared with the 'favourable' group, patients with 6q- showed a higher white blood cell (WBC) count, frequent splenomegaly, atypical morphology, CD38+ and short time from diagnosis to first treatment and short survival. A higher median WBC count was found in the 6q- group vs the intermediate-risk group; survival was shorter in the unfavourable group. To ascertain if the 6q- anomaly was an independent factor predicting for an inferior outcome among those patients with 'favourable' cytogenetics, we performed an analysis of prognostic factors in 105 patients (92 'favourable' plus 13 with 6q-), showing that the 6q- chromosome maintained its prognostic significance at multivariate analysis (P=0.02) along with stage (P=0.01). We conclude that CLL with 6q- is characterized by a high incidence of atypical morphology, classical immunophenotype with CD38 positivity and intermediate incidence of IGVH somatic hypermutation. Clinicobiological features and outcome show that this cytogenetic subset of CLL should be allocated in an intermediate-risk category.     

Mepivacaine Alters Vascular Responsiveness to Vasoconstrictors in Aortic Rings from Normal and Aortic‐Banded Rats

Abstract: The present study investigated the effects of mepivacaine on the response of rat aorta to vasoconstrictors in normal and aortic‐banded animals. Cardiac hypertrophy was induced in Wistar rats by aortic banding, while sham‐operated animals served as controls. Isolated aortic rings with or without endothelium were contracted with potassium chloride and phenylephrine in the presence of mepivacaine (10^?3 M). Maximal tension was measured at the highest concentration of potassium chloride and phenylephrine. Maximal response to potassium chloride was reduced in the presence of mepivacaine both in normal and aortic‐banded rings. As regards the vascular reactivity to phenylephrine, aortic rings with intact endothelium from aortic‐banded rats have shown increased response as compared to normal. After mepivacaine administration this difference between normal and aortic‐banded rats was abolished. In conclusion, in a model of cardiac hypertrophy such as that of aortic‐banding, increased response to α1‐adrenergic stimulation is observed, which is blunted by mepivacaine administration.     

Biomarkers in the clinical management of patients with atrial fibrillation and heart failure

Atrial fibrillation (AF) and heart failure (HF) are two cardiovascular diseases with an increasing prevalence worldwide. These conditions share common pathophysiologiesand frequently co-exit. In fact, the occurrence of either condition can ‘cause’ the development of the other, creating a new patient group that demands different management strategies to that if they occur in isolation. Regardless of the temproral association of the two conditions, their presence is linked with adverse cardiovascular outcomes, increased rate of hospitalizations, and increased economic burden on healthcare systems. The use of low-cost, easily accessible and applicable biomarkers may hasten the correct diagnosis and the effective treatment of AF and HF. Both AF and HF effect multiple physiological pathways and thus a great number of biomarkers can be measured that potentially give the clinician important diagnostic and prognostic information. These will then guide patient centred therapeutic management. The current biomarkers that offer potential for guiding therapy, focus on the physiological pathways of miRNA, myocardial stretch and injury, oxidative stress, inflammation, fibrosis, coagulation and renal impairment. Each of these has different utility in current clinincal practice.

Atrial fibrillation (AF) is the most common type of arrhythmia having an annual prevalence of 33 million patients worldwide, along with a three times higher prevalence in women than in men.^[1] There are a number associated risk factors including heart failure, diabetes, hypertension, hyperthyroidism, obesity, structural and ischemic heart disease. However, up to 20% of AF cases cannot be connected with those factors.^[2] The development of AF involves a complex interplay between genetic, molecular and environmental factors. Their better identificationcould alter the possible management and treatment of symptomatic and asymptomatic patients, incuding those that are yet diagnosed via the ECG.^[3-5] Atrial fibrosis is likely play a key role in the development and prognsosi of AF. The extent of the fibrotic process can predict the response to the use of ablation as a treatment.^[6-8] The fibrotic mechanism is not yet fully clarified, but according to some studies, the renin-angiotensin axis^[9] and transforming growth factor (TGF) β1, play a key role in the cardiac fibrosis.^[10]Atrial fibrillation is linked with cardiovascular diseases, mortality, central nervous system side effects.^[11] Most specifically, AF often precedes or follows the development of HF, both share pathophysiological paths that contribute to cardiac remodelling and the combined presence of the two conditions is connected with an adverse prognosis.^[12]Heart failure (HF) is a clinical syndrome presenting with typical symptoms (breathlessness on exertion, paroxysmal nocturnal dyspnea, orthopnea and fatigue) and signs (elevated jugular venous pressure, pulmonary oedema and peripheral oedema) as a result of a structural and/or functional cardiac abnormalities. These lead to a reduced cardiac output and/or elevated intracardiac pressures at rest or during stress, which result in many physiological changes, including multiple morphological, biochemical and molecular alterations referred to cardiac remodeling.^[13,14] The current definition includes stages based on the symptoms observed in the patients requiring medical assistance, however prior to any clinical symptoms patients can present with asymptomatic structural or functional cardiac abnormalities [systolic or diastolic left ventricular (LV) dysfunction]. The early recognition of these precursors can lead to better outcomes, in terms of both hospitalization and mortality in patients with HF. The prevalence of HF varies according to the definition used, but is approximately 1%–2% of the adult population in developed countries, rising to ≥ 10% among people > 70 years of age worldwide. ^[15-18] Among people > 65 years old presenting to primary care with breathlessness on exertion, one in six will have undiagnosed HF. ^[19,20] The lifetime possibility of developing HF at age 55 is 33% for men and 28% for women.^[17] The pathophysiology of HF is mediated by a variety of biological mechanisms, with complex interactions between endothelial cells, monocytes, macrophages, cardiomyocytes, fibrocytes and the neuro-endocrine system. On top is the interplay with systemic conditions such as diabetes, advanced age, hypertension, obesity, dyslipidemia and chronic kidney disease. Cardiac troponins and natriuretic peptides are the most widely used diagnostic biomarkers in the management of HF,^[21] although there are a number of novel ones are also available, but not widely used in clinical practice.     

Characteristics and re-offending outcomes of ‘limiting-term’ forensic patients found unfit to stand trial in New South Wales,Australia

There are little published data on the characteristics or outcomes of offenders found unfit to stand trial who receive a ‘qualified finding of guilt’ in a Special Hearing in New South Wales (NSW) and are detained for a ‘limiting term’ (LT) under the supervision of the NSW Mental Health Review Tribunal (MHRT). We examined NSW MHRT records linked to re-offending data, to report on the characteristics and outcomes of 69 LT patients in a cohort spanning two decades. The most common diagnoses were schizophrenia (54%) and intellectual disability (33%). Patients were detained on average for 4.2 years, which is slightly shorter than the average maximum term imposed. Of the 55 people for whom criminal record data were available, 9.1% were charged with an offence during the first year post-release and 60% overall were charged for at least one post-release offence during a follow-up period ranging from 4.7 to 11.1 years.     

Apolipoprotein E and presenilin-1 genotypes in Huntington’s disease

Huntington’s disease (HD) is an autosomal dominant degenerative disease of the central nervous system manifested by involuntary movements (chorea), psychiatric manifestations, and cognitive impairment with a variable age at onset. This variability is mainly attributed to genetic factors. The so-called aging genes [e.g., those for apolipoprotein E (APOE) and presenilin-1 (PS-1) have been implicated in determining the age at onset of Alzheimer’s disease, a disease sharing common clinical features with HD. In 60 unrelated patients suffering from HD (mean age at onset 40.1 years, range 20–65) we determined number of CAG repeats and the distribution of the APOE alleles (ɛ2, ɛ3, ɛ4) and PS-1 alleles. The results showed that: (a) The age at onset was higher in the group of patients with the ɛ4 allele (51.6 vs. 38.0 P < 0.002), (b) The correlation between the age at onset and the number of CAG repeats was strong in patients with the ɛ3/ɛ3 genotype while it was not detected in patients with ɛ3/ɛ4 genotype. (c) No correlation was found between age at onset and PS-1 alleles. In conclusion, APOE seems to be a significant factor influencing the age at onset of Huntington’s disease. Received: 13 May 1998 Received in revised form: 9 December 1998 Accepted: 31 December 1998