Alterations in cerebral diazepam binding inhibitor expression in drug dependence: a possible biochemical alteration common to drug dependence

Mechanisms for formation of drug dependence and expression of withdrawal syndrome have not fully clarified despite of huge accumulation of experimental and clinical data at present. Several clinical features of withdrawal syndrome are considered to be common among patients with drug dependence induced by different drugs of abuse. One of them is anxiety. Recent investigations have revealed that diazepam binding inhibitor (DBI), a peptide consisting of 87 amino acids with molecular weight of about 10 kDa, serves as an inverse agonist for benzodiazepine (BZD) receptors with endogenously anxiogenic potential. These lines of data suggest that cerebral DBI expression in brain may participates in formation of drug dependence and/or emergence of withdrawal syndrome. Based on this working hypothesis, we have examined DBI expression in the brain derived from mice depended on alcohol (ethanol), nicotine, and morphine to investigate functional relationship between cerebral DBI expression and drug dependence. Cerebral DBI expression significantly increases in animals with drug dependence induced by these drugs, and in the cases of nicotine- and morphine-dependent mice concomitant administration of antagonists for nicotinic acetylcholine and opioid receptors, respectively, abolished the increase. Abrupt cessation of administration of drugs facilitated further increase in DBI expression. Therefore, these alterations in DBI expression have close relationship with formation of drug dependence and/or emergence of withdrawal syndrome, and are considered to be a common biochemical process in drug dependence induced by different drugs of abuse. Finding and elucidation of mechanisms for common biochemical alterations among drug dependence may provide a clue to clarify mechanisms for formation of drug dependence and/or emergence of withdrawal syndrome.     

The Prevalence of Mental Disorders among the Homeless in Western Countries: Systematic Review and Meta-Regression Analysis

Background

There are well over a million homeless people in Western Europe and North America, but reliable estimates of the prevalence of major mental disorders among this population are lacking. We undertook a systematic review of surveys of such disorders in homeless people.

Methods and Findings

We searched for surveys of the prevalence of psychotic illness, major depression, alcohol and drug dependence, and personality disorder that were based on interviews of samples of unselected homeless people. We searched bibliographic indexes, scanned reference lists, and corresponded with authors. We explored potential sources of any observed heterogeneity in the estimates by meta-regression analysis, including geographical region, sample size, and diagnostic method. Twenty-nine eligible surveys provided estimates obtained from 5,684 homeless individuals from seven countries. Substantial heterogeneity was observed in prevalence estimates for mental disorders among the studies (all Cochran''s χ² significant at p < 0.001 and all I ² > 85%). The most common mental disorders were alcohol dependence, which ranged from 8.1% to 58.5%, and drug dependence, which ranged from 4.5% to 54.2%. For psychotic illness, the prevalence ranged from 2.8% to 42.3%, with similar findings for major depression. The prevalence of alcohol dependence was found to have increased over recent decades.

Conclusions

Homeless people in Western countries are substantially more likely to have alcohol and drug dependence than the age-matched general population in those countries, and the prevalences of psychotic illnesses and personality disorders are higher. Models of psychiatric and social care that can best meet these mental health needs requires further investigation.     

Drug use among youths

The levels of drug use among youths under 14 have remained extremely low for the past few years, as well as in most European countries. Yet, patterns of early drug use are often related to high-risk behaviours that require specific public policy strategies. Over the last years, the Government has set the target of reducing levels of drug use among specific groups such as young people: an awareness-raising media campaign has been launched and a specific outpatients clinics setting has been implemented for cannabis users in particular. This paper examines the relationship between health service providers and criminal justice authorities underlying the effectiveness of the current system. It underlines the need for an early screening and early interventions so as to avoid the shift from simple use to misuse or dependence.     

Utilisation by homeless people of acute hospital services in London.

OBJECTIVES--To estimate the numbers and distribution of homeless people in London; to quantify the utilisation of acute inpatient services by homeless people in two health authorities; and to predict the total numbers of admissions in homeless people in district health authorities across London. DESIGN--Data were collected from various sources on the distribution of homeless people across London boroughs. All unplanned acute inpatient admissions during November 1990 to relevant hospitals were identified. SETTING--Bloomsbury and Paddington and North Kensington, two former inner London district health authorities. SUBJECTS--Homeless people in London residing in bed and breakfast and private sector leased accommodation, residing in hostels, and of no fixed abode. MAIN OUTCOME MEASURES--Number and cost of acute unplanned admissions in homeless people in two health authorities in November 1990; predicted number of such admissions each year in district health authorities in London. RESULTS--There were at least 60,000 homeless people in London in March 1990. The majority were housed in temporary accommodation (55,412). There were at least 3295 hostel dwellers and 651 people sleeping rough. Homeless people accounted for 105 (8%) of the 1256 acute unbooked admissions in residents of Bloomsbury and Paddington and North Kensington health authorities in November 1990. Considerable variations in the pattern of acute unplanned admissions in homeless people were observed in the two districts with respect to housing status and specialty of admission. The total number of acute unplanned admissions in homeless people across London each year was estimated at 7598, ranging from 38 in Bexley to 1515 in Parkside. CONCLUSIONS--The results have fundamental implications for resource allocation across London. Allocation must take better account of the heterogeneity, uneven distribution, and extra health needs of homeless people.     

Socioeconomic gradient in morbidity and mortality in people with diabetes: cohort study findings from the Whitehall Study and the WHO Multinational Study of Vascular Disease in Diabetes.

OBJECTIVE: To assess whether the inverse socioeconomic mortality gradient observed in the general population persists in diabetic people. DESIGN: The Whitehall cohort study and the London cohort of the WHO multinational study of vascular disease in diabetes. SETTING: London. SUBJECTS: 17,264 male civil servants (17,046 without diabetes, 218 with diabetes) aged 40-64 examined in 1967-9, and 300 people with diabetes aged 35-55 from London clinics examined in 1975-7. Both cohorts were followed up until January 1995. MAIN OUTCOME MEASURES: Mortality from all causes, cardiovascular disease, and ischaemic heart disease. RESULTS: In both cohorts people in the lower social groups were older, had higher blood pressure, and were more likely to smoke. In the Whitehall study, the prevalence of heart disease was higher in the lowest social group compared with the highest group, by 6% among non-diabetic people (P = 0.0001) and by 14% among diabetic subjects (P = 0.02). In the WHO study proteinuria was more common in the lowest social group compared with the highest (27% v 15%, P = 0.01), as was retinopathy (54% v 48%, P = 0.5). There was a clear socioeconomic gradient in all cause mortality in both cohorts, with death rates being about twice as high in the lowest compared with the highest social groups. In the Whitehall study this gradient was similar in both diabetic and non-diabetic subjects, and it persisted for mortality from cardiovascular disease and from ischaemic heart disease. About half of the increased risk of death in the lowest social group was accounted for by blood pressure and smoking. CONCLUSIONS: We confirm the existence of an inverse socioeconomic mortality gradient in diabetic people and suggest that this is largely due to conventional cardiovascular risk factors.     

Casualty departments and the monitoring of drug dependence.

In a month-long prospective survey of patients attending London casualty departments with drug-related problems, 395 drug-dependent patients were identified. A check against the official Home Office index of notified addicts showed that 226 (57%) were not known to the Home Office. Of 92 patients who used narcotics only 53% were known with certainty to the Home Office, and when the source of notification was checked it became clear that in at least 77% of incidents involving narcotic addicts in casualty departments the addict was not reported. Repeated research in casualty departments could play a valuable role in monitoring drug dependence and might provide information supplementary to that obtained from the specialised drug treatment clinics and other sources of notification.     

Visual problems in the elderly population and implications for services.

OBJECTIVE--To determine the prevalence of visual disability and common eye disease among elderly people in inner London. DESIGN--Cross sectional random sample survey. SETTING--Inner London health centre. SUBJECTS--Random sample of people aged 65 and over taken from practice''s computerised age-sex register. MAIN OUTCOME MEASURES--Presenting binocular Snellen 6 m distance acuity and best monocular 3 m Sonksen-Silver acuity to classify prevalence of blindness by World Health Organisation criteria (less than 3/60 in better eye) and American criteria for legal blindness (better eye equal to 6/60 or less) and of low vision by WHO criteria (best acuity 6/18) and visual impairment by American criteria (less than 6/12 or 20/40 but greater than 6/60 or 20/200 in better eye). Principal cause of visual loss by diagnosis, referral indication by cause to hospital eye service, and proportion of cases known to primary care. RESULTS--207 of 288 (72%) eligible people were examined. 17 (8%) housebound subjects were examined at home. The prevalence of blindness was 1% by WHO criteria and 3.9% by American criteria. The prevalence of low vision (WHO criteria) was 7.7%. The prevalence of visual impairment (American criteria) was 10.6%. Cataract accounted for 75% of cases of low vision. Only eight out of 16 patients with low vision were known by their general practitioner to have an eye problem. 56 subjects (27%) would probably have benefited from refraction. Comparisons with studies in the United States and Finland suggested higher rates in this sample, mainly due to the prevalence of disabling cataract. CONCLUSION--There seems to be a considerable amount of undetected ocular disease in elderly people in the community.     

Substance use in remand prisoners: a consecutive case study.

OBJECTIVES: To determine the prevalence of drug and alcohol use among newly remanded prisoners, assess the effectiveness of prison reception screening, and examine the clinical management of substance misusers among remand prisoners. DESIGN: A consecutive case study of remand prisoners screened at reception for substance misuse and treatment needs and comparison of findings with those of prison reception screening and treatment provision. SETTING: A large adult male remand prison (Durham). SUBJECTS: 548 men aged 21 and over awaiting trial. MAIN OUTCOME MEASURES: Prevalence of substance misuse; treatment needs of substance misusers; effectiveness of prison reception screening for substance misuse; provision of detoxification programmes. RESULTS: Before remand 312 (57%) men were using illicit drugs and 181 (33%) met DSM-IV drug misuse or dependence criteria; 177 (32%) men met misuse or dependence criteria for alcohol. 391 (71%) men were judged to require help directed at their drug or alcohol use and 197 (36%) were judged to require a detoxification programme. The prison reception screen identified recent illicit drug use in 131 (24%) of 536 men and problem drinking in 103 (19%). Drug use was more likely to be identified by prison screening if an inmate was using multiple substances, using opiates, or had a diagnosis of abuse or dependence. 47 (9%) of 536 inmates were prescribed treatment to ease the symptoms of substance withdrawal. CONCLUSIONS: The prevalence of substance misuse in newly remanded prisoners is high. Prison reception health screening consistently underestimated drug and alcohol use. In many cases in which substance use is identified the quantities and numbers of different substances being used are underestimated. Initial management of inmates identified by prison screening as having problems with dependence producing substances is poor. Few receive a detoxification programme, so that many are left with the option of continuing to use drugs in prison or facing untreated withdrawal.     

Prognosis of angina with and without a diagnosis: 11 year follow up in the Whitehall II prospective cohort study

Objective To investigate the prognosis of angina among people with and without diagnosis by a doctor and an abnormal cardiovascular test result.Design Prospective cohort study with a median follow up of 11 years.Setting 20 civil service departments originally located in London.Participants 10 308 civil servants aged 35-55 years at baseline.Main outcome measures Recurrent reports of angina; quality of life (SF-36 physical functioning); non-fatal myocardial infarction; death from any cause (n = 344).Results 1158 (11.4%) participants developed angina, and 813 (70%) had no evidence of diagnosis by a doctor at the time of the initial report. Participants without a diagnosis had an increased risk of impaired physical functioning (age and sex adjusted odds ratio of 2.36 (95% confidence interval 1.91 to 2.90)) compared with those who had neither angina nor myocardial infarction throughout follow up. Among reported cases of angina without a diagnosis, the 15.5% with an abnormality on a study electrocardiogram had an increased risk of death (hazard ratio 2.37 (1.16 to 4.87)). These effects were similar in magnitude to those in participants with a diagnosis of angina.Conclusion Undiagnosed angina was common and had an adverse impact on prognosis comparable to that of diagnosed angina, particularly among people with electrocardiographic abnormalities. Efforts to improve prognosis among people with angina should take account of this submerged clinical iceberg.     

The aftermath of Angie's overdose: is soap (opera) damaging to your health?

In a study designed to evaluate the behavioural impact of a fictional parasuicide--namely, Angie''s overdose on the popular television soap opera EastEnders--information about cases of deliberate overdose treated in accident and emergency departments in 63 hospitals throughout Britain was obtained for the week after the televised overdose (experimental period) and the week before the overdose (control period). After adjusting for trends in the equivalent weeks in a control year (1985) the increase in the cases of parasuicide treated by hospitals during the experimental week was not found to be significant. A significant increase (31%) was found among people aged greater than or less than 45, but this is not thought to be reliable. The increase among women alone (21%) was significant with a one tailed test. Contrary to expectations there was a positive association between trends in overdose and distance from London--that is, the further the distance of the region from London the greater the increase in cases of overdose during the experimental period--and a negative association between trends in overdose and viewing figures--that is, the higher the viewing figure the less the impact on the incidence of overdoses. These findings do not lend support to the claim that there was a strong imitation effect after this televised parasuicide.     

Risk behaviours for HIV infection among injecting drug users attending a drug dependency clinic.

To study a range of possible risk factors for HIV among injecting drug user patients attending a clinic in London were interviewed from November 1986 to November 1987. Serum samples were tested for viral markers. Of 116 patients, 101 had shared injecting equipment, 75 on the first occasion of injecting and 76 during the past year. Seventy said that sharing was because equipment was not available. In the past year 102 had been sexually active, a third having two to 20 partners; a quarter of the women had exchanged sexual intercourse for money. The four patients who were positive for antibody to HIV antigen had shared equipment or had intercourse with drug users from areas with a high prevalence of HIV. Eleven patients had injected drugs while in prison. Despite a low prevalence of HIV infection this infection remains a threat to drug users in London; strenuous efforts are still needed to prevent its further transmission.     

A General Method for Evaluating Deep Brain Stimulation Effects on Intravenous Methamphetamine Self-Administration

Substance use disorders, particularly to methamphetamine, are devastating, relapsing diseases that disproportionally affect young people. There is a need for novel, effective and practical treatment strategies that are validated in animal models. Neuromodulation, including deep brain stimulation (DBS) therapy, refers to the use of electricity to influence pathological neuronal activity and has shown promise for psychiatric disorders, including drug dependence. DBS in clinical practice involves the continuous delivery of stimulation into brain structures using an implantable pacemaker-like system that is programmed externally by a physician to alleviate symptoms. This treatment will be limited in methamphetamine users due to challenging psychosocial situations. Electrical treatments that can be delivered intermittently, non-invasively and remotely from the drug-use setting will be more realistic. This article describes the delivery of intracranial electrical stimulation that is temporally and spatially separate from the drug-use environment for the treatment of IV methamphetamine dependence. Methamphetamine dependence is rapidly developed in rodents using an operant paradigm of intravenous (IV) self-administration that incorporates a period of extended access to drug and demonstrates both escalation of use and high motivation to obtain drug.     

City of Details: Interpreting the Personality of London

This article investigates the ways in which a group of enthusiasts for London constitute their city. The 'personality' attributed to London is described, as well as the interpretive acts that reveal it. These people, who also lead walking tours across the city, privilege 'detail' as their term of analysis. The article examines the identified qualities of that category, in particular its perceived capacity to animate the plural time-spaces of the city. This sensitivity to detail is presented as part of a sensing of place, which allows people to regard themselves as uniquely able to see the city. The article is intended as a contribution to the ethnography of London.     

Psychological and social problems in HIV infection: interviews with general practitioners in London.

OBJECTIVE--To assess current practice and opinions of general practitioners in London about managing psychological and social problems relating to HIV infection. DESIGN--A stratified random sample of general practitioners, including those with a range of experience of people with HIV infection, were interviewed by medically trained interviewers. SETTING--Doctor''s surgeries. PARTICIPANTS--270 General practitioners working within the area covered by London postcodes. RESULTS--Two thirds of doctors had treated at least one patient with HIV infection and described their work with these patients. General practitioners were counselling and educating many of their patients about AIDS and associated risk behaviours and were aware of the need for careful attention to confidentiality. Doctors with no experience of patients with HIV infection were often older, in singlehanded practice, less inclined to deal with drug abusers or to counsel their patients on risk behaviours, and more in favour of insurance companies'' policies towards people with HIV infection. CONCLUSIONS--General practitioners in London are quickly becoming involved in the care of patients with HIV infection and their relatives and friends. Many are counselling patients and testing for antibodies themselves and regard this as an integral part of their work. A considerable workload in primary care comprised patients who obsessively fear contracting HIV infection.     

Prevention and control of HIV infection in the Osh region of the Kyrgyz Republic

A total of 178 cases of HIV infection were diagnosed in the Osh region of the Kyrgyz Republic for January 1, 2003, the intensity of the prevalence of HIV infection being 14.5 per 100,000 of the population with this figure for the whole republic being equal to 5.9. In the dynamics of the HIV infection epidemic two periods were detected. During the first 3 years (1998-2000) a few individual imported cases of HIV infection were registered in the region. During the last 2 years (2001-2002) 98.8% of all cases of HIV infection registered in the region, as well as the presence of an epidemic outbreak among injection drug users (IDU), were detected. The risk factors of getting HIV infection were the intravenous use of drugs and a low level of information among young people concerning the routes of transmission of this infection and means of protection from HIV/AIDS: the promotion of healthy life style among young people, the introduction of the programs of "harm reduction" among IDU and the rules of safe sex.     

The determinants of the spread of HIV among injection drug addicts in Ukraine

The main tendencies in the development of drug addiction in the Ukraine, the dynamics of the spread of HIV among drug addicts introducing drugs intravenously, epidemiological data on HIV, AIDS and drug addiction, as well as prognoses on the development of HIV infection are presented. Since 1995 the number of HIV-infected persons grew 34-fold, the number of cases of HIV infection resulting from the intravenous use drugs rose to 70% simultaneously with the rise (about 34-fold) of the number of persons infected with HIV through sexual contacts (about 13 fold). In 1996-1997 such tendency increased. On the whole, the proportion of drug addicts introducing drugs by intravenous injection was 83% in the Ukraine. By April 1, 1998, official registration covered 18,800 HIV-infected persons, including 270 foreign nationals, as well as 499 AIDS patients, including 487 Ukrainian citizens, among them 28 children. Out of 18,800 HIV-infected persons, 78.3% were drug addicts, most of them young people aged 15-30 years; about 18% were young people under 20 years of age, 80% being males. According to the model the rapid spread of HIV from the group of drug addicts to the heterosexual population, the total number of HIV-infected persons reaching 1,500,000 is expected in the country by 2014.     

Increasing antituberculosis drug resistance in the United Kingdom: analysis of national surveillance data

Objective To identify recent trends in, and factors associated with, resistance to antituberculosis drugs in England, Wales, and Northern Ireland.Design Cohort of tuberculosis cases reported to the enhanced tuberculosis surveillance system matched to data on drug susceptibility and national strain typing data.Setting England, Wales, and Northern Ireland 1998-2005.Main outcome measures Unadjusted and adjusted odds ratios for drug resistance and associated factors. Proportion of multidrug resistant tuberculosis cases clustered.Results 28 620 culture confirmed cases were available for analysis. The proportion of cases resistant to isoniazid increased from 5% to 7%. Rifampicin resistance increased from 1.0% to 1.2% and multidrug resistance from 0.8% to 0.9%. Ethambutol and pyrazinamide resistance remained stable at around 0.4% and 0.6%, respectively. Regression analyses showed a significant increase in isoniazid resistance outside London (odds ratio 1.04, 95% confidence interval 1.01 to 1.07, a year, associated with changes in age (0.98, 0.98 to 0.99, a year), place of birth (1.49, 1.16 to 1.92), and ethnicity (P<0.05). In London, the rise (1.05, 1.02 to 1.08, a year) was related mainly to an ongoing outbreak. Increases in rifampicin resistance (1.06, 1.01 to 1.11, a year) and multidrug resistance (1.06, 1.00 to 1.12, a year) were small. A fifth of patients with multidrug resistant tuberculosis in 2004-5 had indistinguishable strain types, and one case was identified as extensively drug resistant.Conclusions The rise in isoniazid resistance reflects increasing numbers of patients from sub-Saharan Africa and the Indian subcontinent, who might have acquired resistance abroad, and inadequate control of transmission in London. The observed increases highlight the need for early case detection, rapid testing of susceptibility to drugs, and improved treatment completion.     

Antituberculous drug resistance in Manitoba from 1980 to 1989.

OBJECTIVES: To estimate the magnitude of antituberculous drug resistance and identify the risk factors for its development in tuberculosis patients in Manitoba over a 10-year period. As well, to examine the clinical course of the patients whose initial or subsequent isolates of Mycobacterium tuberculosis were resistant to one or more drugs. DESIGN: Comparison of drug-resistant and non-drug-resistant cases of tuberculosis. SETTING: Manitoba. PATIENTS: All people with tuberculosis reported to the Central Tuberculosis Registry of Manitoba between Jan. 1, 1980, and Dec. 31, 1989. MAIN OUTCOME MEASURES: Of 1478 cases of active tuberculosis 1086 were culture positive, and drug susceptibility testing was performed in these cases. The clinical course, including outcome of treatment, of all drug-resistant cases was described. RESULTS: Of 1086 culture-positive cases of tuberculosis 77 (7.1%) were drug resistant. Odds ratios suggested that the risk of drug resistance was significantly higher among the immigrants than among the other Canadians. Compared with the other Canadians the risk of drug resistance was 9.9 times greater among the immigrants in whom tuberculosis developed within the first year after arrival in Canada and 5.4 times greater among the immigrants in whom it developed 2 to 5 years after arrival in Canada. Of the 71 patients with drug-resistant disease whose type of resistance was known 62% had never taken antituberculous drugs before and 38% had. Most (91%) of the 77 cases of drug-resistant disease were resistant to first-line drugs, especially isoniazid and streptomycin. Thirty-two (42%) of the 77 cases were resistant to two or more first-line drugs. Of patients with drug-resistant disease a subgroup of 10 had disease that became resistant to several drugs over the 10-year period. The outcome of treatment in these individuals was poor, and they presented a particular public health problem. CONCLUSION: Resistance to one or more first-line antituberculous drugs continues to complicate the treatment of tuberculosis and may facilitate the spread of the disease.