Alcohol screening and brief interventions in primary care - Evidence and a pragmatic practice-based approach.

BACKGROUND: Risky alcohol drinking is a common problem in adults presenting in Australian general practice. Preventive health guidelines recommend routine delivery of alcohol screening and brief intervention (ASBI) by general practitioners (GPs). However, ASBIs have rarely been implemented successfully in a sustainable manner. OBJECTIVE: In this article, we explain the current state of empirical evidence for the effectiveness of ASBI in primary care and describe a pragmatic interpretation of how this evidence applies to routine care. DISCUSSION: The empirical evidence surrounding ASBIs is complex. ASBIs are efficacious in research settings, but their effectiveness when compared with control interventions in real-world practice is less certain. Alcohol assessment within therapeutic doctor-patient relationships, rather than the specific formal tools, may be the 'active ingredient'. A pragmatic, practice-based approach to early detection of risky drinking is to focus on strategies that allow asking patients about their drinking more regularly, documenting it, and using quality improvement methodology to improve alcohol recording data completeness for the practice population.

Magnetic resonance imaging features of vascular leiomyoma of the ankle.

Vascular leiomyoma is a benign soft tissue tumour with a predilection for middle-aged women. It is most often seen in the extremities, particularly in the lower leg. The typical lesion is a small, slow-growing subcutaneous nodule. These tumours are often unexpected or preoperatively confused with other soft tissue tumours including low-grade sarcomas, leading to wide surgical excision. This may partly be due to the relatively few studies delineating the characteristic imaging features of this entity. Here, the imaging findings of a case of vascular leiomyoma in the ankle are presented. Literature review of the magnetic resonance imaging findings of published reports and series of vascular leiomyomas of the extremities is also performed.

Early Maladaptive Schemas, Depression Severity, and Risk Factors for Persistent Depressive Disorder: a Cross-sectional Study.

OBJECTIVE: To investigate associations of the five early maladaptive schemas (EMS) domains with depression severity by comparing patients with persistent depressive disorder (PDD), patients with major depressive disorder (MDD), and controls with no psychiatric disorders. METHODS: Patients with PDD (n = 30), patients with MDD (n = 24), and controls with no psychiatric disorders (n = 30) were recruited. Participants were assessed using the Mini-International Neuropsychiatric Interview 5.0 version (MINI), the Beck Depression Inventory-Second Edition (BDI-II), and the Young Schema Questionnaire-3rd Edition Short Form (YSQ-S3). RESULTS: The five EMS domains (YSQ-S3 score) significantly correlated with depression severity (BDI-II score), with correlation coefficients ranging from 0.583 to 0.788. After controlling for age, education, and sex, the two best predictors of depression severity were domains 'over-vigilance and inhibition' and 'disconnection and rejection'. For domains of disconnection and rejection, impaired autonomy and performance, and over-vigilance and inhibition, the total YSQ-S3 score was significantly higher in the PDD group than both the MDD and control groups. For the domain of impaired limits, the total YSQ-S3 score was significantly higher in both the PDD and MDD groups than the control group. CONCLUSION: All five EMS domains correlated significantly with depression severity. PDD and MDD differed in psychopathology. The EMS domains of disconnection and rejection, impaired autonomy and performance, and over-vigilance and inhibition may be specific risk factors for PDD.

Enhanced vascular responses to adrenomedullin in mice overexpressing receptor-activity-modifying protein 2.

Adrenomedullin (AM) levels are elevated in cardiovascular disease, but little is known of the role of specific receptor components. AM acts via the calcitonin receptor-like receptor (CLR) interacting with a receptor-activity-modifying protein (RAMP). The AM1 receptor is composed of CLR and RAMP2, and the calcitonin gene-related peptide (CGRP) receptor of CLR and RAMP1, as determined by molecular and cell-based analysis. This study examines the relevance of RAMP2 in vivo. Transgenic (TG) mice that overexpress RAMP2 in smooth muscle were generated. The role of RAMP2 in the regulation of blood pressure and in vascular function was investigated. Basal blood pressure, acute angiotensin II-raised blood pressure, and cardiovascular properties were similar in wild-type (WT) and TG mice. However, the hypotensive effect of IV AM, unlike CGRP, was enhanced in TG mice (P<0.05), whereas a negative inotropic action was excluded by left-ventricular pressure-volume analysis. In aorta relaxation studies, TG vessels responded in a more sensitive manner to AM (EC50, 8.0+/-1.5 nmol/L) than WT (EC50, 17.9+/-3.6 nmol/L). These responses were attenuated by the AM receptor antagonist, AM(22-52), such that residual responses were identical in all mice. Remaining relaxations were further inhibited by CGRP receptor antagonists, although neither affected AM responses when given alone. Mesenteric and cutaneous resistance vessels were also more sensitive to AM in TG than WT mice. Thus RAMP2 plays a key role in the sensitivity and potency of AM-induced hypotensive responses via the AM1 receptor, providing evidence that this receptor is a selective target for novel therapeutic approaches.

Inhibition of prostate cancer cell growth by human secreted PDZ domain-containing protein 2, a potential autocrine prostate tumor suppressor.

A possible role of the PDZ domain-containing protein 2 (PDZD2) in prostate tumorigenesis has been suggested. Besides, PDZD2 is posttranslationally cleaved by a caspase-dependent mechanism to form a secreted PDZ domain-containing protein 2 (sPDZD2) with unknown functions in humans. In this study, we demonstrate the endogenous expression of PDZD2 and secretion of sPDZD2 in cancerous DU145, PC-3, 22Rv1, LNCaP, and immortalized RWPE-1 prostate epithelial cells. Inhibition of endogenous sPDZD2 production and secretion by DU145, PC-3, 22Rv1, and RWPE-1 cells via the caspase-3 inhibitor Z-DEVD-FMK resulted in increased cell proliferation, which was abrogated by treatment with exogenous recombinant sPDZD2. Whereas sPDZD2-induced antiproliferation in DU145, PC-3, and 22Rv1 cells, it induced apoptosis in LNCaP cells. The data suggest that endogenous sPDZD2, produced by caspase-3-mediated cleavage from PDZD2, may function as a novel autocrine growth suppressor for human prostate cancer cells. The antiproliferative effect of sPDZD2 was apparently mediated through slowing the entry of DU145, PC-3, and 22Rv1 cells into the S phase of the cell cycle. In DU145 cells, this can be attributed to stimulated p53 and p21(CIP1/WAF1) expression by sPDZD2. On the other hand, the apoptotic effect of sPDZD2 on LNCaP cells was apparently mediated via p53-independent Bad stimulation. Together our results indicate the presence of p53-dependent and p53-independent PDZD2/sPDZD2 autocrine growth suppressive signaling pathways in human prostate cancer cells and suggest a novel therapeutic approach of harnessing the latent tumor-suppressive potential of an endogenous autocrine signaling protein like sPDZD2 to inhibit prostate cancer growth.

The calcitonin gene-related peptide (CGRP) receptor antagonist BIBN4096BS blocks CGRP and adrenomedullin vasoactive responses in the microvasculature.

Calcitonin gene-related peptide (CGRP) is a potent microvascular dilator neuropeptide that is considered to play an essential role in neurogenic vasodilatation and in maintaining functional integrity in peripheral tissues. We have examined the effect of the nonpeptide CGRP antagonist BIBN4096BS on responses to CGRP and the structurally related peptide adrenomedullin, AM, in murine isolated aorta and mesentery preparations, and in the cutaneous microvasculature in vivo. We show for the first time that BIBN4096BS is an effective antagonist of CGRP and AM responses in the murine mesenteric and cutaneous microvasculature, and of CGRP in the murine aorta. After local administration, BIBN4096BS selectively inhibits the potentiation of microvascular permeability in the cutaneous microvasculature by CGRP and AM, with no effect on responses induced by other microvascular vasodilators. BIBN4096BS reversed both newly developed and established vasoactive responses induced by CGRP. The ability of CGRP to potentiate plasma extravasation was lost when coinjected with compound 48/80 (where mast cells would be activated to release proteases), but regained when soybean trypsin inhibitor was coinjected with compound 48/80. These results demonstrate that BIBN4096BS is a selective antagonist of responses induced by CGRP and AM in the mouse microvasculature, and CGRP in the mouse aorta. The ability of BIBN4096BS to block an established CGRP microvascular vasodilatation indicates that the sustained vasodilator activity of CGRP is due to the retention of the active intact peptide and the continued involvement of the CGRP receptor.

Clinical remission of late-onset depression in elderly Chinese: a short-term outcome study.

OBJECTIVE: Better understanding of the relationship between executive and memory functions and treatment response in late-onset depression may improve our ability to identify those individuals who are less likely to benefit from traditional pharmacological interventions. This study aimed to investigate the remission rate in elderly Chinese people with late-onset depression, and to examine the predictors of outcomes. METHODS: Patients aged 60 years or older with late-onset depression without dementia were recruited into the study. Mood symptoms were assessed by the 24-item Hamilton Rating Scale for Depression and Neuropsychiatric Inventory at 12 and 24 weeks. Cognitive domains assessed included global cognitive function, episodic memory, executive functions, and processing speed. The clinical characteristics and cognitive scores were compared among the early remitters, late remitters, and non-remitters. RESULTS: Of the 105 subjects, 42 (40%) had remission at 12 weeks and were categorised as early remitters, 41 (39%) who did not remit at 12 weeks achieved remission at 24 weeks (late remitters), and 22 (21%) had not achieved remission at 24 weeks (non-remitters). Executive function, processing speed, episodic memory, apathy and depression severity were related to remission outcomes. Regression analyses found that severity of baseline apathy and depression were predictors of remission at 12 and 24 weeks, respectively. CONCLUSIONS: This study identified 2 subgroups of patients according to outcomes. One group with clinical characteristics similar to vascular depression achieved a late response to treatment. The other group were non-remitters who had features of depression-executive dysfunction syndrome, which might have underlying degenerative process and presented with the co-occurrence of depression and mild cognitive impairment.

Association between late-onset depression and incident dementia in Chinese older persons.

OBJECTIVE. Previous studies have shown that depression is a precursor / prodrome or susceptible state for the development of dementia. This study aimed to examine the relationship between late-onset depression and subsequent cognitive and functional decline in a cohort of non-demented older Chinese persons at their 2-year follow-up and investigate for possible predictors of cognitive decline. METHODS. A total of 81 depressed subjects and 468 non-depressed community controls were recruited. RESULTS. Subjects with late-onset depression showed significantly more incident Clinical Dementia Rating (CDR) scale decline (odds ratio = 3.87, 95% confidence interval = 2.23-6.70) and dementia (odds ratio = 3.44, 95% confidence interval = 1.75-6.77) than those without depression. A higher proportion of depressed CDR 0 subjects had CDR and functional decline than their non-depressed counterparts. Depressed CDR 0.5 subjects had significantly higher rates of functional decline and lower rates of improvement in CDR than their non-depressed counterparts. CONCLUSION. Diagnosis of depression was a robust predictor of incident very mild dementia (i.e. CDR of 0.5) and depression severity was a predictor of progression to dementia from CDR of 0.5. The association between depression and the risk of CDR decline and dementia was observed in non-demented Chinese subjects. Depression was also associated with persistent mild cognitive deficits in CDR 0.5 subjects.

Cognitive function, functional performance and severity of depression in Chinese older persons with late-onset depression.

OBJECTIVES. The relationship between cognitive status and depressive symptoms and their liability to cause functional decline are of clinical and public health importance as it appears to be common, frequently coexists, and may be treatable. This study examined the relationship of depression severity and cognitive performance and the impact of such an interaction on functional ability in Chinese elderly subjects with late-onset depression. METHODS. A total of 105 non-demented elderly patients with late-onset depression were recruited. Impairment in instrumental activities of daily living and severity of depression were respectively assessed with the Disability Assessment for Dementia scale and the 24-item Hamilton Depression Rating Scale. Various cognitive domains were assessed including global cognitive function, delayed episodic memory, and executive functions. The relationship between specific cognitive impairment and mood symptom severity was assessed. The clinical correlates of functional performance were also examined. RESULTS. Increasingly severe depression was associated with lower scores in the Mini-Mental State Examination, delayed recall, and poorer performance in the Trail Making Test-Part A (after adjusting for the effect of age and education). The severity of apathy correlated negatively with the Mini-Mental State Examination scores only. Among the depressed subjects, greater levels of depression and apathy, poorer performance in Trail Making Test-Part B, and mild parkinsonian signs were associated with lower functional scores. CONCLUSIONS. Lack of interest and motivation, depressive mood, compounded by behavioural abnormalities resulting from executive dysfunction, accounted for functional disability in elderly subjects with late-onset depression. These relationships may provide the background for developing interventions targeting functional deficits associated with specific cognitive dysfunctions and depression.

Cognitive and functional impairment in Chinese elderly with late-onset depression.

OBJECTIVES. To investigate cognitive and functional impairment in Chinese elderly subjects with late-onset depression. METHODS. Subjects with late-onset depression and who were clinically non-demented were recruited. Their cognitive and functional scores were compared with those of cognitively normal elderly controls and elderly persons with mild cognitive impairment. Functional ability was assessed by the Disability Assessment for Dementia score. Various cognitive domains were assessed including global cognitive function, delayed episodic memory, working memory, and categorical verbal fluency test. RESULTS. A total of 105 depressed subjects and 324 non-depressed controls (149 normal elderly controls and 175 with mild cognitive impairment) were recruited. The depression group had significantly poorer performance in all cognitive assessments compared to the normal elderly control group. The depression group had a similar cognitive profile to those with mild cognitive impairment, except that its subjects had slightly better performance in the Categorical Verbal Fluency Test, delayed recall testing, and the Chinese version of the Alzheimer's Disease Assessment Scale-Cognitive subscale test. Depressed subjects had significantly lower functional scores in instrumental activities of daily living than the non-depressed, normal elderly controls, and those with mild cognitive impairment. CONCLUSIONS. Our results demonstrate that Chinese elderly with late-onset depression had cognitive impairments in multiple domains similar to those encountered in the age- and sex-matched non-depressed controls with mild cognitive impairment. However, their functional performance was significantly poorer than that in these controls. This study provided extensive characterisation of the range and depth of cognitive and functional impairments in elderly patients with late-onset depression.

2-year study of chemical composition of bulk deposition in a south China coastal city: comparison with east Asian cities.

Using the emission strengths of the precursor gases, the nature of soil in China, the ventilation power and half value rainout region length, the nss-SO42-, NO3-, Ca2+, and NH4+ concentrations, and pH of rainwater at Hong Kong and other cities of China and Japan are compared and rationalized. The chemical composition of Hong Kong bulk deposition from 1998 to 2000 is taken from our collection and analysis of 156 daily samples. The volume-weighted average (VWA) pH is 4.2 over the whole study period. Nonsea salt- (nss-) sulfate is the most abundant species in the samples, and the pH mostly depended upon the concentrations of the major species nss-SO42, NO3-, Ca2+, and NH4+. All species concentrations show higher levels in the cold season (especially NO3- and Ca2+), which indicates the dominant dilution effects in the warm season due to heavy rainfall and the influence of the continental outflow of pollutants during the cold season. For Hong Kong bulk deposition, the VWA pH is slightly lower in the cold season, and there is a slight decrease in VWA pH over the period from 1994 to 2000. The impact of acid rain in Hong Kong is briefly discussed.

Temporal lobe atrophy on MRI in Parkinson disease with dementia: a comparison with Alzheimer disease and dementia with Lewy bodies.

OBJECTIVE: To investigate the extent of medial temporal lobe atrophy (MTA) on MRI in Parkinson disease (PD) with and without dementia compared with Alzheimer disease (AD) and dementia with Lewy bodies (DLB) and to determine whether MTA correlates with cognitive impairment in PD and PD dementia (PDD). METHODS: Coronal T1-weighted MRI scans were acquired from control subjects (n = 39) and patients with PD (n = 33), PDD (n = 31), DLB (n = 25), and AD (n = 31), diagnosed according to standardized clinical diagnostic criteria. Cognitive function was assessed using the Cambridge Cognitive Examination (CAMCOG), and MTA was rated visually using a standardized (Scheltens) scale. RESULTS: More severe MTA was seen in PDD (p = 0.007), DLB (p < 0.001), and AD (p < 0.001) vs control subjects. PD subjects had greater hippocampal atrophy than control subjects (p = 0.015) but less than subjects with DLB and AD, though not with PDD. MTA correlated with CAMCOG score and memory scores in the DLB group and with age in control, PDD, and AD groups. There were no correlations between MTA and cognitive impairment in PD, PDD, and AD. PDD and DLB had a similar profile of cognitive impairment and MTA. CONCLUSIONS: Medial temporal lobe atrophy (MTA) was seen in cognitively intact older subjects with Parkinson disease (PD) and was not more pronounced in Parkinson disease dementia (PDD). Alzheimer disease (AD) and, to a lesser extent, dementia with Lewy bodies (DLB) showed more pronounced MTA. Results suggest early hippocampal involvement in PD and that when dementia develops in PD, anatomic structures apart from the hippocampus are predominantly implicated. Greater hippocampal involvement in AD vs PDD and DLB is consistent with clinical, cognitive, and pathologic differences between the disorders.

New formulation of saquinavir (Fortovase) is more effective.

AIDS: The Food and Drug Administration (FDA) recently approved a new soft gel capsule formulation of saquinavir (Fortovase). Fortovase, manufactured by Hoffmann-LaRoche, has the same active ingredient as Invirase (saquinavir mesylate); however, the drugs cannot be used interchangeably. The approval was based on studies showing significant viral load reductions when used with two nucleoside analogues, and the drug is more readily absorbed than the non-gel version. Factors for considering converting patients to this drug are listed, along with known adverse effects and potential drug interactions.^ieng

Form and function of negation in early developmental Cantonese.

This study investigated the interface of form and function in the acquisition of negation in Cantonese-speaking children. The data, from the Hong Kong Cantonese Child Language Corpus, were longitudinal spontaneous samples of eight children aged 1;5 to 3;8. The main issues of the study were the sequence of emergence of negative markers mou5, m4 and mei6 and the acquisition trend of 11 semantic categories of negation in children's expressive language. The acquisition trend of the semantic categories matched Bloom's (1970, 1991a) finding that Non-existence preceded Rejection and Denial.

The effect of regular alcohol use on the management of non-insulin diabetes mellitus.

This is a retrospective study, in which we investigated the impact of regular alcohol use on the clinical management of non-insulin dependent diabetes mellitus (NIDDM) patients from the outpatient clinic of the VA Medical Center in New Orleans, Louisiana. The study population included randomly selected NIDDM patients of which 40% used alcohol regularly. The fasting blood sugar (FBS) in non-users of alcohol stayed in the "normal" (< or = 140 mg/dl) and "acceptable " (< or = 175 mg/dl) range and that of regular users of alcohol remained at the "fair" (< or = 235 mg/dl) and "poor" (> 235 mg/dl) range. NIDDM patients who were regular users of alcohol had a higher frequency of dose adjustments than that of non-users of alcohol (96% vs 4%, respectively). The treatment failure was significantly higher among patients who regularly used alcohol than among those who abstained (90 vs 10%, respectively). On the basis of our findings, it was recommended that attending physician should routinely identify the regular alcohol users and monitor blood alcohol levels of ambulatory NIDDM patients during their follow-up visits. Also, complete cessation of alcohol consumption should be established prior to making dosage adjustment in situations where the oral hypoglycemic agent fails.