Dexamethasone concentration in vitreous and serum after oral administration

OBJECTIVE: To assess the outcomes of changes in mental health policy introduced in Italy in 1978. METHODS: Data on psychiatric services, before and after the policy change, are presented. Effects of change are evaluated through indicators related to four issues: transfer of care, criminalisation of the mentally ill, suicides, and homelessness. RESULTS: Admissions of new patients to mental hospitals have been stopped and the size of the mental hospital population is now very low (26 per 100,000 population). Psychiatric care has been shifted to community services including general hospital psychiatric units. There has been an overall reduction of psychiatric hospitalisation. However, the provision of residential facilities is inadequate and community services are unevenly distributed across the country. Few negative effects of changing patterns of care have been reported, although the low quality of data limits the validity of such a conclusion. Outcome of care in areas where the full range of community services is available has been rated as satisfactory. CONCLUSIONS: Although care of the mentally ill has been shifted to community services, we lack hard data on the social and clinical outcome of community care at the nation-wide level. Long-term monitoring and evaluation of community services is a high priority in Italy.     

Measurement of myocardial blood flow with oxygen-15 labelled water: comparison of different administration protocols

Positron emission tomography (PET) in conjunction with C15O2 or H215O can be used to measure myocardial blood flow (MBF) and tissue fraction (TF), i.e. the fraction of the tissue mass in the volume of the region of interest. However, with C15O2 inhalation, the tissue fraction in the septum is overestimated. Bolus injection of H215O together with arterial cannulation gives very precise results but is invasive. The purpose of this study was to develop a method which circumvents these problems. A four-parameter model with parameters for MBF, TF and spill-over fractions from both left and right ventricular cavities was developed. This method was compared with a three-parameter model (no right ventricular cavity spill-over) in both septal and non-septal regions of interest for three different administration protocols: bolus injection of H215O, infusion of H215O and inhalation of C15O2. It was found that MBF can be measured with intravenous administration of H215O without the requirement for arterial cannulation. The four-parameter protocol with bolus injection was stable in clinical studies. The four-parameter model proved essential for the septum, where it gave highly significantly better fits than did the three-parameter model (P<0.00003 in each of 15 subjects). Administration of H215O together with this four-parameter model also circumvented the problem of overestimation of TF in the septum seen with C15O2 inhalation. In addition, the radiation dose of H215O protocols is lower than that of C15O2 inhalation. Using a left atrial input curve instead of a left ventricular cavity input curve gave the same mean MBF and TF.     

Substance abuse issues in cancer patients. Part 2: Evaluation and treatment

The relationship between the therapeutic use of potentially abusable drugs for symptom control and the multifaceted nature of abuse and addiction is extremely complex. Research is only beginning to elucidate the nature of this relationship and its clinical implications. At present, practical management is based primarily on clinical experience and anecdotal observations. In part I of this two-part series (published last month), the authors explored the epidemiology of substance abuse in the cancer population, provided definitions of addiction and abuse appropriate for the oncology setting, and offered guidelines for the assessment of aberrant drug-taking behavior. In this second part, the authors provide recommendations for the evaluation and treatment of patients with cancer who have a history of substance abuse. Suggested therapeutic goals are outlined, and plans for inpatient and outpatient management and detailed.     

Differential responses of granulosa cells from small and large follicles to follicle stimulating hormone (FSH) during the menstrual cycle and acyclicity: effects of tumour necrosis factor-alpha

This study determined effects of follicle stimulating hormone (FSH) alone and in combination with tumour necrosis factor (TNF), on granulosa cells from small (5-10 mm diameter) and large (>10-25 mm) follicles during follicular and luteal phases of the cycle and during periods of acyclicity. Granulosa cells were collected from ovaries of premenopausal women undergoing oophorectomy. The cells were cultured with human FSH (2 ng/ml) and testosterone (1 microM) in the presence or absence of human TNF-alpha (20 ng/ml). Media were removed at 48 and 96 h after culture and progesterone, oestradiol and cAMP in media were measured by radioimmunoassays. FSH stimulated the accumulation of oestradiol from granulosa cells of small follicles during the follicular and luteal phases but not during acyclicity; and TNF reduced oestradiol accumulation in the presence of FSH. Interestingly, in granulosa cells from small follicles, progesterone and cAMP secretion increased in response to FSH and neither was affected by TNF. Thus, TNF specifically inhibited the conversion of testosterone to oestradiol in granulosa cells from small follicles. FSH stimulated oestradiol production by granulosa cells of large follicles obtained only during the follicular phase of the cycle and TNF inhibited the FSH-induced oestradiol secretion. Granulosa cells obtained from large follicles during the luteal phase and during acyclicity did not accumulate oestradiol in response to FSH. However, FSH increased progesterone and cAMP secretion by granulosa cells obtained from large follicles during the follicular and luteal phases. During the luteal phase alone, TNF in combination with FSH increased progesterone accumulation above that of FSH alone. FSH did not increase progesterone, oestradiol or cAMP secretion by granulosa cells obtained from large follicles during acyclicity. Thus, FSH increases progesterone, oestradiol and cAMP secretion by granulosa cells of small follicles during the follicular and luteal phases and TNF appears to inhibit FSH-induced oestradiol secretion specifically in those cells. In large follicles, FSH-stimulated granulosa cell secretion of oestradiol is limited to the follicular phase and this effect can be inhibited by TNF. In addition, when granulosa cells of large follicles do not increase oestradiol secretion in response to FSH, TNF stimulates progesterone secretion.     

Relationship between patient reports of urinary incontinence symptoms and quality of life measures

The aim of the present study was to assess the effect of normal growth and development on the Peer Assessment Rating index between 12 and 22 years of age. The sample consisted of 49 nonorthodontic subjects (24 male and 25 females) from the Nijmegen Growth Study. The mean age at the first observation was 12.2 +/- 0.7 years and at the second observation 22.1 +/- 0.6 years. The dental casts at these ages were scored with the Peer Assessment Rating index. The influence of the Angle classification and the treatment need on changes over time in the Peer Assessment Rating score were evaluated. The mean changes in the PAR scores over time between cases that have more than 30% improvement to those that have less than 30% improvement were calculated. The results indicate that there were no significant differences between the mean Peer Assessment Rating score at 12 years of age (12.20 +/- 0.91) and at 22 years of age (12.45 +/- 1.28), but there were relevant differences in individual cases. The changes were irrespective of the Angle classification or the treatment need. Changes over time in the weighted Peer Assessment Rating score were mainly correlated to changes in the anterior crossbite and the overjet. This correlation may be influenced, however, by the applied weighting factor for those occlusal traits.     

Substance abuse issues in cancer patients. Part 1: Prevalence and diagnosis

Although rare, drug abuse problems present a complex set of physical and psychosocial issues that complicate cancer treatment and pain/ symptom management. Most oncologists are not be well versed in either the conceptual or practical issues related to addiction. As a result, they often struggle in their attempts to effectively treat patients who are or have been substance abusers, and they find it difficult to understand issues of addiction in patients with pain who have no history of substance abuse. In the first installment of a two-part series, the authors explore the epidemiology of substance abuse. An examination of the distinctions between abuse and dependence leads to definitions of these terms appropriate for the oncology setting. Guidelines for assessing aberrant drug-taking behavior are also offered. Part 2, which will appear in the next issue of ONCOLOGY, will discuss the clinical management of cancer patients with a history of substance abuse.     

Pitfalls in the economic evaluation of thrombolysis in myocardial infarction. The impact of national differences in the cost of thrombolytics and of differences in the efficacy across patient subgroups

BACKGROUND: The economic evaluation of the results of the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Artery (GUSTO) trial found that recombinant tissue plasminogen activator is more cost-effective than streptokinase for the treatment of acute myocardial infarction. AIM: We evaluated the impact on a cost effectiveness analysis, of the differences in the cost of thrombolytics among countries and of differences in efficacy across patient subgroups. METHODS: We considered the crude costs of streptokinase and recombinant tissue plasminogen activator in Germany, Italy, the United Kingdom, and the United States of America, and the 30-day mortality found in the GUSTO trial. We calculated the incremental costs for each life saved when streptokinase is substituted by recombinant tissue plasminogen activator. We also calculated the incremental costs for each life saved for two protocols implying a selective use of streptokinase and recombinant tissue plasminogen activator (age-selective protocol: recombinant tissue plasminogen activator in patients < or = 75 years, streptokinase in older patients; site-selective protocol: recombinant tissue plasminogen activator in anterior acute myocardial infarction, streptokinase in non-anterior acute myocardial infarction). RESULTS: The incremental costs for each life saved when streptokinase is substituted by recombinant tissue plasminogen activator in all GUSTO patients vary greatly among countries: the incremental costs for each life saved are 31%, 45%, and 97% higher in Germany, Italy, and the United States of America compared to the United Kingdom. The use of a site-selective protocol implies a halved cost-effectiveness ratio compared to the use of recombinant tissue plasminogen activator in all cases of acute myocardial infarction. CONCLUSIONS: (1) The cost-efficacy of recombinant tissue plasminogen activator vs streptokinase in acute myocardial infarction varies greatly among countries due to differences in the cost of drugs. (2) A selective use of thrombolytics for some sites of infarction is more cost-effective than the exclusive use of recombinant tissue plasminogen activator.     

ARDS. History, definitions, and physiology

Acute respiratory distress syndrome (ARDS) was formally described in 1971; however, physicians have been describing this syndrome and associating pulmonary edema with sepsis or toxic origins for over 100 years. Recently, an international conference accepted definitional criteria for ARDS that have become the accepted standard. ARDS is triggered by a large number of insults that often do not directly affect the lung. ARDS progresses pathologically through exudative, proliferative, and fibrotic phases.     

Effects of 18-methoxycoronaridine on acute signs of morphine withdrawal in rats

Ibogaine, an alkaloid found in the root bark of the African shrub Tabernanthe iboga, has been claimed to interrupt opioid dependence in humans; in animals, it has been shown to inhibit morphine self-administration and to attenuate signs of morphine withdrawal. However, ibogaine has some neurotoxicity, and because of this, efficacious and safer congeners of ibogaine have been sought, 18-Methoxycoronaridine (18-MC), a novel iboga alkaloid congener, has been shown, in animals, to mimic the effects of ibogaine on morphine self-administration without producing any ibogaine-like neurotoxiticity. In the present study, 18-MC was shown to attenuate five of seven signs of morphine withdrawal in rats. The data suggest that 18-MC will ameliorate symptoms of opioid dependence in humans.     

Treatment of articular cartilage defects of the knee with autologous chondrocyte implantation

alpha 1-Adrenergic receptor-mediated responses are overwhelming in adult rat hepatocytes. Inversely, beta-responses are predominant over alpha 1-responses in the hepatocytes that have been cultured at a low cell density (10(4) cells/cm2) for 24 h. The insulin-EGF-induced DNA synthesis in the beta-response-dominant hepatocytes was doubled by beta-agonists or cAMP-generating agents added far behind (16-20 h) the addition of insulin/EGF; i.e., immediately before the entry into the S-phase of the cell cycle. Agonists of alpha 1-adrenergic or other Ca2+, mobilising receptors added to the alpha 1-response-dominant hepatocytes increased DNA synthesis only if they were added within 1-2 h after the addition of insulin/EGF, at the early stage of G1-phase. Agonists of "non-dominant" receptors were rather antagonistic to agonists of "dominant" receptors. Thus, agonists of alpha 1-adrenergic (and other Ca2+ mobilising) receptors and agonists of beta-adrenergic (and other cAMP-generating) receptors acted as comitogens in their own particular manners in the presence of growth factors in hepatocytes in which the respective receptor functions were dominant.