Left ventricular hypertrophy and geometry in a population sample of elderly males

BACKGROUND: Recent studies have shown that left ventricular geometric adaptationto hypertension is complex. The spectrum of geometric adaptationsin a general population and its relationship to systolic anddiastolic function has, however, not been investigated. OBJECTIVES AND METHODS: This echocardiographic and Doppler study investigated the relationshipsbetween left ventricular geometric shape (normal, concentricremodelling, concentric hypertrophy and eccentric hypertrophy)and left ventricular systolic and diastolic function in a populationsample of 584 males aged 70 in Uppsala, Sweden. The influencesof hypertension, coronary heart disease and diabetes mellituswere also evaluated. RESULTS: Sixteen percent of the healthy population (n=167) demonstratedthe presence of left ventricular hypertrophy (mainly eccentric).Subjects with hypertension (n=115) showed an increased leftventricular mass (eccentric left ventricular hypertrophy 31%,concentric left ventricular hypertrophy 15%), when comparedwith healthy subjects (P<0.001). Subjects with coronary heartdisease (n=32) without hypertension also showed an increasedleft ventricular mass (most often eccentric) (P<0.05). UsingDoppler determinations of cardiac index, no differences werefound in cardiac index between the geometric groups. Raisedtotal peripheral resistance, increased blood pressure and enlargedleft atrium were found in both concentric and eccentric leftventricular hypertrophy (P<0.01–0.05). Disturbed diastolicfunction was seen with a prolongation of the isovolumic relaxationtime in eccentric (P<0.01) and increased atrial-dependentleft ventricular filling in concentric left ventricular hypertrophy(P<0.05). CONCLUSIONS: Alterations in left ventricular geometry were common in thispopulation-based study of elderly males, both in healthy subjectsand in subjects with hypertension or coronary heart disease.Raised total peripheral resistance and left ventricular diastolicdysfunction were common findings in both concentric and eccentricleft ventricular hypertrophy.     

Developmental surveillance in general practice

During a two-year study of a developmental surveillance programme covering all children under 5 in a large general practice in the south of England, 2157 children were examined, including 382 newborn babies seen at home. Suspected disorders--excluding those found during non-routine consultations--were discovered in 232 children (15% of boys and 11% of girls), of whom 171 (104 boys and 67 girls) were referred to specialist agencies. The number and nature of the disorders show that routine surveillance on the lines proposed by the Court Committee is worth while. Nevertheless, such programmes could not be started on a national scale without increased resources for the specialist services to which more children would need to be referred.     

Dependence and perceived difficulty in activities of daily living in adults with cerebral palsy and spina bifida

Purpose : The purpose of this study was to identify differences between two groups of subjects: one with cerebral palsy, the other with spina bifida in their dependence and their perceived difficulty in performing daily activities according to the Functional Independence Measure (FIM) and the Instrumental Activity Measure (IAM), and to compare these findings with the reported use of assistance. Method : Community-living persons, 53 with cerebral palsy and 20 with spina bifida, aged 20 to 39 years, participated in semistructured interviews in their homes, where rating was performed using items from FIM and IAM. Results : Differences were found for the reported use of assistance and the dependence rated according to FIM and IAM. Significant differences for dependence were found between the CP and SB subjects concerning Eating, Bladder and Bowel items and for perceived difficulty concerning toileting, bladder and bowel. There was close overall agreement between dependence and perceived difficulty, except for the item walk/wheelchair. Conclusions : Subjects in both groups needed help in basic and instrumental ADL. The ability of spina bifida subjects was more influenced in toileting, bladder, bowel than the cerebral palsy subjects and tended also to be so in mobility instrumental tasks. FIM and IAM do not cover all aspects of significance in community-living adults. Further items have to be developed, covering personal care and occupational as well as leisure domains.     

Changes on 5-HT2 receptor mRNAs in striatum and subthalamic nucleus in Parkinson's disease model

Abnormal interactions between the serotonin and dopamine systems may underlie the high prevalence of non-motor complications in Parkinson's disease (PD). Here, we demonstrate that the genes encoding serotonin 5-HT2A and 5-HT2C receptors are differently regulated by dopamine in the 6-hydroxydopamine (6-OHDA) rat model of PD. Nigrostriatal cell loss causes an up-regulation of 5-HT2AR mRNA, but a down-regulation of 5-HT2CR mRNA, in striatum. Repeated injections with L-DOPA/benserazide reverse the effect of 6-OHDA lesioning on 5-HT2AR, but not on 5-HT2CR, gene expression. Neither 6-OHDA-lesioning nor L-DOPA/benserazide treatment had any effect on 5-HT2AR mRNA in cortex or on 5-HT2CR mRNA in nucleus subthalamicus. These data suggest that the regulation of 5-HT2AR in striatum, in the 6-OHDA rat model of PD, is mainly dependent upon alterations in dopamine levels. 5-HT2CR, on the other hand, are regulated by nigrostriatal cell loss and by the accompanied reduction of factor(s), other than dopamine, that are normally co-expressed with dopamine. The apparent imbalance between 5-HT2AR and 5-HT2CR levels in this PD model indicates a potential role for these receptors in the pathophysiology of neuropsychiatric symptoms, such as depression and L-DOPA-induced hallucinations, which are co-morbid with PD. The fact that 5-HT2CR are differentially regulated as compared to 5-HT2AR to alterations in the dopamine tone predicts that pharmacological manipulations at 5-HT2CR, but not at 5-HT2AR, will result in similar effects in PD patients whether they are treated or not with dopamine replacement.     

Evidence for a role of the 5-HT1B receptor and its adaptor protein, p11, in L-DOPA treatment of an animal model of Parkinsonism

Parkinson's disease (PD) is characterized by a progressive degeneration of substantia nigra dopaminergic neurons projecting to the striatum. Restoration of dopamine transmission by L-DOPA relieves symptoms of PD but causes prominent side effects. There is a strong serotonin innervation of the striatum by serotonergic neurons that remains relatively preserved in PD. The study of this innervation has been largely neglected. Here, we demonstrate that chronic L-DOPA administration to 6-OHDA-lesioned rodents increases, via D1 receptors, the levels of the 5-HT1B receptor and its adaptor protein, p11, in dopamine-denervated striatonigral neurons. Using unilaterally 6-OHDA-lesioned p11 WT and KO mice, it was found that administration of a selective 5-HT1B receptor agonist, CP94253, inhibited L-DOPA-induced rotational behavior and abnormal involuntary movements in a p11-dependent manner. These data reveal an L-DOPA-induced negative-feedback mechanism, whereby the serotonin system may influence the symptomatology of Parkinsonism.     

Distribution, level, pharmacology, regulation, and signaling of 5-HT6 receptors in rats and marmosets with special reference to an experimental model of parkinsonism

Serotonin 5-HT(6) receptors have been implicated in the regulation of cognition, locomotion, and mood, but the elucidation of their functions is complicated by conflicting data using various animal models. Here, a systematic evaluation showed that autoradiographic binding with the selective 5-HT(6) receptor antagonist [(125) I]SB-258585 was similar in marmosets and rats. In both species, [(125) I]SB-258585 binding was enriched in the caudate-putamen. Various recently developed agonists and antagonists toward 5-HT(6) receptors exhibited similarities in their abilities to displace [(125) I]SB-258585 binding in marmosets and rats. The rank order of pEC50 values were as follows: (+)EMDT-CR = EMD386088>MS-245 = 5-HT>EMDT>(-)EMDT-CR; and (+)EMDT-CR = EMD386088>5-HT = MS-245 = EMDT>(-)EMDT-CR, in marmosets and rats, respectively. Unilateral 6-hydroxydopamine lesioning of dopaminergic axons caused a significant decrease of [(125) I]SB-258585 binding in the caudate-putamen of both marmosets and rats. Nonetheless, acute administration of the 5-HT(6) receptor agonist EMDT to unilaterally 6-hydroxydopamine-lesioned rats, caused an induction of egr-1, homer, and enkephalin mRNAs in the dopamine-depleted hemisphere, indicating a supersensitization of 5-HT(6) receptors following dopamine depletion. In conclusion, this study provides evidence for significant similarities in the distribution, level, pharmacology, and regulation of 5-HT(6) receptors between rats and marmosets.     

Cervical cytology screening convenient for the workforce.

The study describes the demographic details and smear results of women attending a Well Woman Clinic in an Occupational Health setting over a two year period. The clinic is located close to the place of work, run during working hours, and operated by a doctor and nurse. Charging fees acceptable to women attending or their employers, the service has made a modest profit and offers scope for increasing the income against fixed costs. The age range attending is older than commonly found at screening clinics. The abnormal smear detection rate, 115 per 1000 is high while the proportion of inadequate results at 50 per 1000 compares favourably with other clinics. In an area with 13 per cent Asian population, only 5 per cent of attenders were Asian but of these one fifth had abnormal smears. A cervical cytology screening facility timed and located for the convenience of the working woman is found to attract a group of women in the older age range who have a high abnormal smear rate, and those who fail to attend elsewhere.     

Cortical and nigral deafferentation and striatal cholinergic markers in the rat dorsal striatum: different effects on the expression of mRNAs encoding choline acetyltransferase and muscarinic m1 and m4 receptors

The regulation of the striatal m1 and m4 muscarinic receptor mRNA as well as the choline acetyltransferase (ChAT) mRNA expression by nigral dopaminergic and cortical glutamatergic afferent fibres was investigated using quantitative in situ hybridization histochemistry. The effects induced by a unilateral lesion of the medial forebrain bundle and a bilateral lesion of the sensorimotor (SM) cortex were analysed in the dorsal striatum 3 weeks after the lesions. Dopaminergic denervation of the striatum resulted in a marked decrease in the levels of m4 mRNA throughout the striatum, while the levels of muscarinic m1 mRNA and ChAT mRNA in cholinergic neurons were unaffected by the lesion. In contrast, following bilateral cortical ablation, the levels of the muscarinic m1 mRNA were significantly increased in the striatal projection area of the SM cortex, whereas the expression of m4 mRNA remained unchanged. Single cholinergic cell analysis by computer-assisted grain counting revealed a decreased labelling for ChAT mRNA per neuron following cortical ablation. However, in contrast to the topographical m1 mRNA changes, the decreased ChAT mRNA expression was evenly distributed within the striatum, suggesting an indirect cortical control upon striatal cholinergic interneurons. Altogether, these data suggest that dopaminergic nigral and glutamatergic cortical afferents modulate differentially cholinergic markers, at the pre- and post-synaptic levels. Beside the fact that nigral and cortical inputs exert an opposite control on cholinergic neurotransmission, our study further shows that this control involved different muscarinic receptor subtypes: the m4 and m1 receptors, respectively.     

Influence of age at first pregnancy on breast parenchymal pattern: a preliminary report

Two groups of women, aged 50 and 60, were randomly selected from a mammographic screening project. The parenchymal pattern was classified according to Wolfe. A correlation was found between a known risk factor, age at first pregnancy, and parenchymal pattern. The results support the hypothesis of a relationship between breast parenchymal pattern and risk of cancer development.