Uneventful propofol anaesthesia in a patient with acute intermittent porphyria.

A patient with acute intermittent porphyria was anaesthetized with propofol as part of general anaesthesia for cholecystectomy. Post-operatively, no clinical sequelae resulted and urinary porphyrins did not exceed pre-operative values.     

Cerebral haemodynamics during the Mueller manoeuvre in humans

Voluntary negative intra‐thoracic pressure (Mueller manoeuvre) is known to reduce arterial blood pressure (ABP). To investigate changes in cerebral blood flow velocity (CBFV) during 15 s Mueller manoeuvres at –30 mmHg intra‐thoracic pressure, 27 young (aged 21–31 years, group A) and 11 older (52–64 years, group B) healthy adults were studied using transcranial Doppler and non‐invasive ABP measurement (Finapres). After closely following the initial ABP drop, CBFV showed an overshoot during temporary recovery of ABP. Then ABP and CBFV decreased significantly to below baseline. While ABP declined further until the end of the manoeuvre, CBFV increased in group A 4·7 s (2·4–8·5) (median and range) and in group B 5·7 s (4·1–7·2) after the onset of the CBFV decrease. Critical closing pressure (CCP), calculated for each cardiac cycle from the dynamic pressure–flow relationship (DPFR), indicated a reduction of intra‐cranial pressure during the first half of the strain. DPFR‐related estimation of cerebrovascular resistance provided a more physiological response than the conventional cerebrovascular resistance quotient ABP/CBFV, and decreased about 1·5 s before the observed CBFV increase. A modification of the previously described dynamic auto‐regulation index ROR correlated significantly with CO₂ reactivity values (r=0·61, P=0·001). In conclusion, changes in CBFV during Mueller manoeuvres are likely to reflect dynamic cerebral auto‐regulation and may provide an estimate of dynamic cerebral auto‐regulation capacity. In older adults, the maximal dynamic auto‐regulatory response seems to be unchanged, but the onset of reaction is slightly delayed.     

Health conditions and role limitation in three European Regions: a public-health perspective

Objective

To describe the distribution of role limitation in the European population aged 18-64 years and to examine the contribution of health conditions to role limitation using a public-health approach.

Subtyping social anxiety disorder in developed and developing countries

Background: Although social anxiety disorder (SAD) is classified in the fourth edition of The Diagnostic and Statistical Manual (DSM‐IV) into generalized and non‐generalized subtypes, community surveys in Western countries find no evidence of disjunctions in the dose–response relationship between number of social fears and outcomes to support this distinction. We aimed to determine whether this holds across a broader set of developed and developing countries, and whether subtyping according to number of performance versus interactional fears would be more useful. Methods: The World Health Organization's World Mental Health Survey Initiative undertook population epidemiological surveys in 11 developing and 9 developed countries, using the Composite International Diagnostic Interview to assess DSM‐IV disorders. Fourteen performance and interactional fears were assessed. Associations between number of social fears in SAD and numerous outcomes (age‐of‐onset, persistence, severity, comorbidity, treatment) were examined. Additional analyses examined associations with number of performance fears versus number of interactional fears. Results: Lifetime social fears are quite common in both developed (15.9%) and developing (14.3%) countries, but lifetime SAD is much more common in the former (6.1%) than latter (2.1%) countries. Among those with SAD, persistence, severity, comorbidity, and treatment have dose–response relationships with number of social fears, with no clear nonlinearity in relationships that would support a distinction between generalized and non‐generalized SAD. The distinction between performance fears and interactional fears is generally not important in predicting these same outcomes. Conclusion: No evidence is found to support subtyping SAD on the basis of either number of social fears or number of performance fears versus number of interactional fears. Depression and Anxiety, 2010. © 2009 Wiley‐Liss, Inc.     

Synthesis and biological activity of potent HIV-1 protease inhibitors based on Phe-Pro dihydroxyethylene isosteres

Peptidomimetic inhibitors of HIV-1 PR are still a key resource in the fight against AIDS. Here we describe the synthesis and biological activity of HIV-1 PR inhibitors based on four novel dihydroxyethylene isosteres of the Phe-Pro and Pro-Pro dipeptides. The isosteres, containing four stereogenic centers, were synthesized in high yield and excellent stereoselectivity via the cyclization of epoxy amines derived from α-amino acids. The inhibitors were assembled by coupling the isosteres with suitable flanking groups and were screened against recombinant HIV PR showing activities in the subnanomolar to micromolar range. Two Phe-Pro-based inhibitors active at the nanomolar level were further investigated: both inhibitors combine the ability to suppress HIV-1 replication in infected MT-2 cells with low cytotoxicity against the same cells, thereby displaying a high therapeutic index. These results demonstrate the potential of the new Phe-Pro dihydroxyethylene isostere as a core unit of powerful HIV-1 PR inhibitors.     

Days out of role due to common physical and mental conditions: results from the WHO World Mental Health surveys

Days out of role because of health problems are a major source of lost human capital. We examined the relative importance of commonly occurring physical and mental disorders in accounting for days out of role in 24 countries that participated in the World Health Organization (WHO) World Mental Health (WMH) surveys. Face-to-face interviews were carried out with 62?971 respondents (72.0% pooled response rate). Presence of ten chronic physical disorders and nine mental disorders was assessed for each respondent along with information about the number of days in the past month each respondent reported being totally unable to work or carry out their other normal daily activities because of problems with either physical or mental health. Multiple regression analysis was used to estimate associations of specific conditions and comorbidities with days out of role, controlling by basic socio-demographics (age, gender, employment status and country). Overall, 12.8% of respondents had some day totally out of role, with a median of 51.1 a year. The strongest individual-level effects (days out of role per year) were associated with neurological disorders (17.4), bipolar disorder (17.3) and post-traumatic stress disorder (15.2). The strongest population-level effect was associated with pain conditions, which accounted for 21.5% of all days out of role (population attributable risk proportion). The 19 conditions accounted for 62.2% of all days out of role. Common health conditions, including mental disorders, make up a large proportion of the number of days out of role across a wide range of countries and should be addressed to substantially increase overall productivity.     

A multinational study of mental disorders, marriage, and divorce

Breslau J, Miller E, Jin R, Sampson NA, Alonso J, Andrade LH, Bromet EJ, de Girolamo G, Demyttenaere K, Fayyad J, Fukao A, Gălăon M, Gureje O, He Y, Hinkov HR, Hu C, Kovess‐Masfety V, Matschinger H, Medina‐Mora ME, Ormel J, Posada‐Villa J, Sagar R, Scott KM, Kessler RC. A multinational study of mental disorders, marriage, and divorce. Objective: Estimate predictive associations of mental disorders with marriage and divorce in a cross‐national sample. Method: Population surveys of mental disorders included assessment of age at first marriage in 19 countries (n = 46 128) and age at first divorce in a subset of 12 countries (n = 30 729). Associations between mental disorders and subsequent marriage and divorce were estimated in discrete time survival models. Results: Fourteen of 18 premarital mental disorders are associated with lower likelihood of ever marrying (odds ratios ranging from 0.6 to 0.9), but these associations vary across ages of marriage. Associations between premarital mental disorders and marriage are generally null for early marriage (age 17 or younger), but negative associations come to predominate at later ages. All 18 mental disorders are positively associated with divorce (odds ratios ranging from 1.2 to 1.8). Three disorders, specific phobia, major depression, and alcohol abuse, are associated with the largest population attributable risk proportions for both marriage and divorce. Conclusion: This evidence adds to research demonstrating adverse effects of mental disorders on life course altering events across a diverse range of socioeconomic and cultural settings. These effects should be included in considerations of public health investments in preventing and treating mental disorders.     

Cerebral haemodynamics during the Mueller manoeuvre in humans.

Voluntary negative intra-thoracic pressure (Mueller manoeuvre) is known to reduce arterial blood pressure (ABP). To investigate changes in cerebral blood flow velocity (CBFV) during 15 s Mueller manoeuvres at -30 mmHg intra-thoracic pressure, 27 young (aged 21-31 years, group A) and 11 older (52-64 years, group B) healthy adults were studied using transcranial Doppler and non-invasive ABP measurement (Finapres). After closely following the initial ABP drop, CBFV showed an overshoot during temporary recovery of ABP. Then ABP and CBFV decreased significantly to below baseline. While ABP declined further until the end of the manoeuvre, CBFV increased in group A 4.7 s (2.4-8.5) (median and range) and in group B 5.7 s (4. 1-7.2) after the onset of the CBFV decrease. Critical closing pressure (CCP), calculated for each cardiac cycle from the dynamic pressure-flow relationship (DPFR), indicated a reduction of intra-cranial pressure during the first half of the strain. DPFR-related estimation of cerebrovascular resistance provided a more physiological response than the conventional cerebrovascular resistance quotient ABP/CBFV, and decreased about 1.5 s before the observed CBFV increase. A modification of the previously described dynamic auto-regulation index ROR correlated significantly with CO2 reactivity values (r=0.61, P=0.001). In conclusion, changes in CBFV during Mueller manoeuvres are likely to reflect dynamic cerebral auto-regulation and may provide an estimate of dynamic cerebral auto-regulation capacity. In older adults, the maximal dynamic auto-regulatory response seems to be unchanged, but the onset of reaction is slightly delayed.