Seedling survival and growth of three ectomycorrhizal caesalpiniaceous tree species in a Central African rain forest

Tree recruitment is determined in part by the survivorship and growth of seedlings. Two seedling cohorts of the three most abundant caesalpiniaceous species forming groves at Korup, Cameroon, were followed from 1995/1997 to 2002, to investigate why Microberlinia bisulcata, the most abundant species, currently has very few recruits compared with Tetraberlinia korupensis and T. bifoliolata. Numbers of seedlings dying, and the heights and leaf numbers of survivors, were recorded on 30 occasions. Survivorship after 2.5 y was 30% for M. bisulcata and 59% for the similar Tetraberlinia spp. together. After 7 y the corresponding values were 4 and 21%. Growth of all species was slow for the first 4 y; but survivors of T. korupensis became 63% taller, as the other species stagnated, by 7 y. The poor recruitment of M. bisulcata was the result of its very low seedling survival. Within species, the tallest seedlings of M. bisulcata and T. bifoliolata, but medium-height ones of T. korupensis, survived longest. This was likely due to higher root allocation in T. korupensis. Seedling dynamics of M. bisulcata and T. korupensis over 7 y accorded well with relative abundances of adult trees; T. bifoliolata is predicted to recruit later.

Clinical forensic radiology in strangulation victims: forensic expertise based on magnetic resonance imaging (MRI) findings

Based on only one objective and several subjective signs, the forensic classification of strangulation incidents concerning their life-threatening quality can be problematic. Reflecting that it is almost impossible to detect internal injuries of the neck with the standard forensic external examination, we examined 14 persons who have survived manual and ligature strangulation or forearm choke holds using MRI technique (1.5-T scanner). Two clinical radiologists evaluated the neck findings independently. The danger to life was evaluated based on the "classical" external findings alone and in addition to the radiological data. We observed hemorrhaging in the subcutaneous fatty tissue of the neck in ten cases. Other frequent findings were hemorrhages of the neck and larynx muscles, the lymph nodes, the pharynx, and larynx soft tissues. Based on the classical forensic strangulation findings with MRI, eight of the cases were declared as life-endangering incidents, four of them without the presence of petechial hemorrhage but with further signs of impaired brain function due to hypoxia. The accuracy of future forensic classification of the danger to life will probably be increased when it is based not only on one objective and several subjective signs but also on the evidence of inner neck injuries. However, further prospective studies including larger cohorts are necessary to clarify the value of the inner neck injuries in the forensic classification of surviving strangulation victims.

Sedation and weaning from mechanical ventilation: effects of process optimization outside a clinical trial

PURPOSE: We studied the effects of reorganization and changes in the care process, including use of protocols for sedation and weaning from mechanical ventilation, on the use of sedative and analgesic drugs and on length of respiratory support and stay in the intensive care unit (ICU). MATERIALS AND METHODS: Three cohorts of 100 mechanically ventilated ICU patients, admitted in 1999 (baseline), 2000 (implementation I, after a change in ICU organization and in diagnostic and therapeutic approaches), and 2001 (implementation II, after introduction of protocols for weaning from mechanical ventilation and sedation), were studied retrospectively. RESULTS: Simplified Acute Physiology Score II (SAPS II), diagnostic groups, and number of organ failures were similar in all groups. Data are reported as median (interquartile range).Time on mechanical ventilation decreased from 18 (7-41) (baseline) to 12 (7-27) hours (implementation II) (P = .046), an effect which was entirely attributable to noninvasive ventilation, and length of ICU stay decreased in survivors from 37 (21-71) to 25 (19-63) hours (P = .049). The amount of morphine (P = .001) and midazolam (P = .050) decreased, whereas the amount of propofol (P = .052) and fentanyl increased (P = .001). Total Therapeutic Intervention Scoring System-28 (TISS-28) per patient decreased from 137 (99-272) to 113 (87-256) points (P = .009). Intensive care unit mortality was 19% (baseline), 8% (implementation I), and 7% (implementation II) (P = .020). CONCLUSIONS: Changes in organizational and care processes were associated with an altered pattern of sedative and analgesic drug prescription, a decrease in length of (noninvasive) respiratory support and length of stay in survivors, and decreases in resource use as measured by TISS-28 and mortality.

Transgenic system for conditional induction and rescue of chronic myocardial hibernation provides insights into genomic programs of hibernation

A key energy-saving adaptation to chronic hypoxia that enables cardiomyocytes to withstand severe ischemic insults is hibernation, i.e., a reversible arrest of contractile function. Whereas hibernating cardiomyocytes represent the critical reserve of dysfunctional cells that can be potentially rescued, a lack of a suitable animal model has hampered insights on this medically important condition. We developed a transgenic mouse system for conditional induction of long-term hibernation and a system to rescue hibernating cardiomyocytes at will. Via myocardium-specific induction (and, in turn, deinduction) of a VEGF-sequestering soluble receptor, we show that VEGF is indispensable for adjusting the coronary vasculature to match increased oxygen consumption and exploit this finding to generate a hypoperfused heart. Importantly, ensuing ischemia is tunable to a level at which large cohorts of cardiomyocytes are driven to enter a hibernation mode, without cardiac cell death. Relieving the VEGF blockade even months later resulted in rapid revascularization and full recovery of contractile function. Furthermore, we show that left ventricular remodeling associated with hibernation is also fully reversible. The unique opportunity to uncouple hibernation from other ischemic heart phenotypes (e.g., infarction) was used to determine the genetic program of hibernation; uncovering hypoxia-inducible factor target genes associated with metabolic adjustments and induced expression of several cardioprotective genes. Autophagy, specifically self-digestion of mitochondria, was identified as a key prosurvival mechanism in hibernating cardiomyocytes. This system may lend itself for examining the potential utility of treatments to rescue dysfunctional cardiomyocytes and reverse maladaptive remodeling.

Infliximab inhibits bone resorption by circulating osteoclast precursor cells in patients with Rheumatoid Arthritis and Ankylosing Spondylitis

OBJECTIVE: To examine the effects of infliximab on bone resorption by osteoclast precursor cells (OCPs) in patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS) and to compare the results with changes in disease activity. METHODS: Before and during 24 weeks of infliximab treatment peripheral blood mononuclear cells of 9 RA and 10 AS patients were seeded onto ivory wafers and adherent cells, including OCPs, were grown in medium promoting osteoclast differentiation. Bone resorption was evaluated morphometrically and correlated to disease activity. 19 healthy individuals were studied in parallel. In addition, biochemical bone markers were assessed in all patients at baseline and after 24 weeks. RESULTS: OCPs from RA patients showed a higher bone resorption at baseline when compared to AS patients. Blocking of TNFalpha with infliximab resulted in a strong reduction of bone resorption by OCPs in both cohorts and did occur faster in RA compared to AS patients. This inhibition coincided with reduction of clinical disease activity in both patient cohorts and with an increase of serum osteocalcin levels and a relative decrease of collagen crosslinks in RA compared to AS patients. CONCLUSION: These results provide an explanation on the cellular level for the anticatabolic effect of TNF neutralization on bone. The variation in the kinetics of bone resorption by the OCPs in patients with RA and AS suggests disease-specific differences in the type or in the preactivation of OCPs.

Autonomic cardiovascular regulation in obesity

Obese persons suffer from an increased mortality risk supposedly due to cardiovascular disorders related to either continuously lowered parasympathetic or altered sympathetic activation. Our cross-sectional correlation study establishes the relationship between obesity and autonomic regulation as well as salivary cortisol levels. Three patient cohorts were sampled, covering ranges of body mass index (BMI) of 27-32 (n=17), 33-39 (n=13) and above 40 kg/m(2)(n=12), and stratified for age, sex and menopausal status. Autonomic cardiovascular regulation was assessed by use of heart rate variability and continuous blood pressure recordings. Spectral analytical calculation (discrete Fourier transformation) yields indices of sympathetic and parasympathetic activation and baroreflex sensitivity. Morning salivary cortisol was concurrently collected. Contrary to expectation, BMI and waist/hip ratio (WHR) were inversely correlated with sympathetic activity. This was true for resting conditions (r=-0.48, P<0.001; r=-0.33, P<0.05 for BMI and WHR respectively) and for mental challenge (r=-0.42, P<0.01 for BMI). Resting baroreflex sensitivity was strongly related to the degree of obesity at rest (BMI: r=-0.35, P<0.05) and for mental challenge (r=-0.53, P<0.001). Salivary cortisol correlated significantly with waist circumference (r=-0.34, P=0.05). With increasing weight, no overstimulation was found but a depression in sympathetic and parasympathetic activity together with a significant reduction in baroreflex functioning and in salivary cortisol levels.

Serological evidence for the association of Bartonella henselae infection with arrhythmogenic right ventricular cardiomyopathy

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an important cause of sudden death in young adults. On the basis of histopathological findings its pathogenesis may involve both a genetic origin and an inflammatory process. Bartonella henselae may cause endomyocarditis and was detected in myocardium from a young male who succumbed to sudden cardiac death. HYPOTHESIS: We hypothesized that chronic infection with Bartonella henselae could contribute to the pathogenesis of ARVC. METHODS: We investigated sera from 49 patients with ARVC for IgG antibodies to Bartonella henselae. In this study, 58 Swiss blood donors tested by the same method served as controls. RESULTS: Six patients with ARVC (12%) had positive (>1:256) IgG titres in the immunofluorescence test with Bartonella henselae. In contrast, only 1 elevated titre was found in 58 controls (p < or = 0.05). Interestingly, all patients with increased titres had no familial occurrence of ARVC. CONCLUSIONS: Further studies in larger patient cohorts seem justified to investigate a possible causal link between chronic Bartonella henselae and ARVC, in particular its sporadic (nonfamilial) form.

Gender and the use of antiretroviral treatment in resource-constrained settings: findings from a multicenter collaboration

AIMS: To compare the gender distribution of HIV-infected adults receiving highly active antiretroviral treatment (HAART) in resource-constrained settings with estimates of the gender distribution of HIV infection; to describe the clinical characteristics of women and men receiving HAART. METHODS: The Antiretroviral Therapy in Lower-Income Countries, ART-LINC Collaboration is a network of clinics providing HAART in Africa, Latin America, and Asia. We compared UNAIDS data on the gender distribution of HIV infection with the proportions of women and men receiving HAART in the ART-LINC Collaboration. RESULTS: Twenty-nine centers in 13 countries participated. Among 33,164 individuals, 19,989 (60.3%) were women. Proportions of women receiving HAART in ART-LINC centers were similar to, or higher than, UNAIDS estimates of the proportions of HIV-infected women in all but two centers. There were fewer women receiving HAART than expected from UNAIDS data in one center in Uganda and one center in India. Taking into account heterogeneity across cohorts, women were younger than men, less likely to have advanced HIV infection, and more likely to be anemic at HAART initiation. CONCLUSIONS: Women in resource-constrained settings are not necessarily disadvantaged in their access to HAART. More attention needs to be paid to ensuring that HIV-infected men are seeking care and starting HAART.

Long-term immunologic response to antiretroviral therapy in low-income countries: a collaborative analysis of prospective studies

BACKGROUND: Few data are available on the long-term immunologic response to antiretroviral therapy (ART) in resource-limited settings, where ART is being rapidly scaled up using a public health approach, with a limited repertoire of drugs. OBJECTIVES: To describe immunologic response to ART among ART patients in a network of cohorts from sub-Saharan Africa, Latin America, and Asia. STUDY POPULATION/METHODS: Treatment-naive patients aged 15 and older from 27 treatment programs were eligible. Multilevel, linear mixed models were used to assess associations between predictor variables and CD4 cell count trajectories following ART initiation. RESULTS: Of 29 175 patients initiating ART, 8933 (31%) were excluded due to insufficient follow-up time and early lost to follow-up or death. The remaining 19 967 patients contributed 39 200 person-years on ART and 71 067 CD4 cell count measurements. The median baseline CD4 cell count was 114 cells/microl, with 35% having less than 100 cells/microl. Substantial intersite variation in baseline CD4 cell count was observed (range 61-181 cells/microl). Women had higher median baseline CD4 cell counts than men (121 vs. 104 cells/microl). The median CD4 cell count increased from 114 cells/microl at ART initiation to 230 [interquartile range (IQR) 144-338] at 6 months, 263 (IQR 175-376) at 1 year, 336 (IQR 224-472) at 2 years, 372 (IQR 242-537) at 3 years, 377 (IQR 221-561) at 4 years, and 395 (IQR 240-592) at 5 years. In multivariable models, baseline CD4 cell count was the most important determinant of subsequent CD4 cell count trajectories. CONCLUSION: These data demonstrate robust and sustained CD4 response to ART among patients remaining on therapy. Public health and programmatic interventions leading to earlier HIV diagnosis and initiation of ART could substantially improve patient outcomes in resource-limited settings.

Implementation of MET/CBT 5 for adolescents

Implementation of effective substance abuse treatment programs in community settings is a high priority. The selection of a proven cost-effective model is a first step; however, difficulty arises when the model is imported into a community setting. The Center on Substance Abuse Treatment selected a brief substance abuse treatment program for adolescents, the MET/CBT-5 program, determined to be the most cost-effective protocol in the Cannabis Youth Treatment trial, for implementation in two cohorts of Effective Adolescent Treatment grantees. A qualitative investigation of the protocol implementation with nine sites in the second cohort chronicled adaptations made by grantees and prospects for sustainability. The study found that agencies introduced adaptations without seeming to be aware of potential effects on validity. In most sites, sessions were lengthened or added to accommodate individual client needs, address barriers to client participation, and provide consistency with current norms of treatment. Implications for fidelity of future implementation projects are addressed.

Thoracic endovascular aortic repair: impact of urgency on outcome and quality of life

OBJECTIVES: Endovascular repair of the descending thoracic aorta is a very promising technique in elective and, particularly, emergency situations. This study assessed the impact of urgency of the procedure on outcome and mid-term quality of life in surviving patients. METHODS: Post hoc analysis of prospectively collected data of 58 consecutive patients (January 2001-December 2005) with surgical pathologies of the descending thoracic aorta treated by endovascular means. Six patients were excluded due to recent operations on the ascending aorta before thoracic endovascular repair. The remaining patients (n=52) were 69+/-10 years old, and 43 were men (83%). Twenty-seven had been treated electively, and 25 for emergency indications. Reasons for emergency were acute type B aortic dissections with or without malperfusion syndrome in 14, and aortic ruptures in 11 cases. Follow-up was 29+/-16 months. Endpoints were perioperative and late morbidity and mortality rates and long-term quality of life as assessed by the short form health survey (SF-36) and Hospital Anxiety and Depression Scale questionnaires. RESULTS: Cohorts were comparable regarding age, sex, cardiovascular risk factors, and comorbidities. Perioperative mortality was somewhat higher in emergency cases (12% vs 4%, p=0.34). Paraplegia occurred in one patient in each cohort (4%). Overall quality of life after two and a half years was similar in both treatment cohorts: 72 (58-124) after emergency, and 85 (61-105) after elective endovascular aortic repair (p=0.98). Normal scores range from 85 to 115. Anxiety and depression scores were in the normal range and comparable. CONCLUSIONS: Thoracic endovascular aortic repair is an excellent and safe treatment option for the diseased descending aorta, particularly in emergency situations. Early morbidity and mortality rates can be kept very low. Mid-term quality of life was not affected by the urgency of the procedure. Similarly, mid-term anxiety and depression scores were not increased after emergency situations.

Outcome and quality of life after surgical and endovascular treatment of descending aortic lesions

BACKGROUND: Thoracic endovascular aortic repair (TEVAR) represents an attractive alternative to open aortic repair (OAR). The aim of this study was to assess outcome and quality of life in patients treated either by TEVAR or OAR for diseased descending thoracic aorta. METHODS: A post hoc analysis of a prospectively collected consecutive series of 136 patients presenting with surgical diseases of the descending aorta between January 2001 and December 2005 was conducted. Fourteen patients were excluded because of involvement of the ascending aorta. Assessed treatment cohorts were TEVAR (n = 52) and OAR (n = 70). Mean follow-up was 34 +/- 18 months. End points were perioperative and late mortality rates and long-term quality of life as assessed by the Short Form Health Survey (SF-36) and Hospital Anxiety and Depression Score questionnaires. RESULTS: Mean age was significantly higher in TEVAR patients (69 +/- 10 years versus 62 +/- 15 years; p = 0.002). Perioperative mortality rates were 9% (OAR) and 8% (TEVAR), respectively (p = 0.254). Accordingly, cumulative long-term mortality rates were similar in both cohorts. Overall quality-of-life scores were 93 (63-110, OAR) and 83 (60-112, TEVAR), respectively. Normal quality-of-life scores range from 85 to 115. Anxiety and depression scores were not increased after open surgery. CONCLUSIONS: Thoracic endovascular aortic repair and OAR both provide excellent long-term results in treatment of thoracic aortic disease. Long-term quality of life, however, is reduced after thoracic aortic repair. Interestingly, TEVAR patients did not score higher in overall quality of life despite all advantages of minimized access trauma. Similarly, anxiety and depression scores are not reduced by TEVAR, possibly reflecting a certain caution against the new technology.

Outcome and quality of life in patients treated for abdominal aortic aneurysms: a single center experience

BACKGROUND: Durability of protection and long-term quality of life (QoL) are critical outcome parameters of abdominal aortic aneurysm (AAA) repair. The aim of the present study was to compare results of endovascular and open aneurysm repair (EVAR and OR) with adjusted standard populations, including stratification for urgency of presentation. METHODS: Retrospective analysis of prospectively collected data of 401 consecutive patients presenting with AAA between January 1998 and December 2002. Cross-sectional follow up was 58 +/- 29 months. Patients were grouped into three cohorts: elective EVAR (n = 68), elective OR (n = 244), and emergency OR (including symptomatic and ruptured AAA, n = 89). Endpoints were perioperative (i.e., 30 days or in-hospital) and late mortality rates, as well as long-term QoL as assessed by the Short Form health survey questionnaire (SF-36). RESULTS: Mean age was lower in the elective OR cohort (66 +/- 10 years) than in the EVAR cohort (72 +/- 7 years; p < .05). Perioperative mortality rates were 4.4%, 0.4%, and 10.1%, for the EVAR, elective OR, and emergency OR cohorts, respectively (p < .05). Corresponding cumulative survival rates after 4 years were 67%, 89%, and 69%, respectively. Long-term QoL SF-36 scores were in all cohorts similar to age- and gender-adjusted standard populations, which score between 85 and 115: 99.6 +/- 35.8 (EVAR), 101.3 +/- 32.4 (elective OR), and 100.4 +/- 36.5 (emergency OR). CONCLUSIONS: Long-term QoL is not permanently impaired after AAA repair, but returns in long-term survivors to what would be expected in a standard population. In this respect, differences were found neither between EVAR and OR, nor between elective and emergency repair. Perioperative mortality rates were highest in patients undergoing emergency OR. The outlook for such patients after the perioperative period, however, was similar to that for patients undergoing elective repair.

No role of matrixmetalloproteinase-3 genetic promoter polymorphism 1171 as a risk factor for cirrhosis in alcoholic liver disease

BACKGROUND: As only a minority of alcoholics develop cirrhosis, polymorphic genes, whose products are involved in fibrosis development were suggested to confer individual susceptibility. We tested whether a functional promoter polymorphism in the gene encoding matrix metalloproteinase-3 (MMP-3; 1171 5A/6A) was associated liver cirrhosis in alcoholics. METHODS: Independent cohorts from the UK and Germany were studied. (i) UK cohort: 320 alcoholic cirrhotics and 183 heavy drinkers without liver damage and (ii) German cohort: 149 alcoholic cirrhotics, 220 alcoholic cirrhotics who underwent liver transplantation and 151 alcoholics without liver disease. Patients were genotyped for MMP-3 variants by restriction fragment length polymorphism, single strand confirmation polymorphism, and direct sequencing. In addition, MMP-3 transcript levels were correlated with MMP-3 genotype in normal liver tissues. RESULTS: Matrix metalloproteinase-3 genotype and allele distribution in all 1023 alcoholic patients were in Hardy-Weinberg equilibrium. No significant differences in MMP-3 genotype and allele frequencies were observed either between alcoholics with or without cirrhosis. There were no differences in hepatic mRNA transcription levels according to MMP-3 genotype. CONCLUSIONS: Matrix metalloproteinase-3 1171 promoter polymorphism plays no role in the genetic predisposition for liver cirrhosis in alcoholics. Stringently designed candidate gene association studies are required to exclude chance observations.

Mumps

Mumps is a common childhood infection caused by the mumps virus. The hallmark of infection is swelling of the parotid gland. Aseptic meningitis and encephalitis are common complications of mumps together with orchitis and oophoritis, which can arise in adult men and women, respectively; other complications include deafness and pancreatitis. Clinical diagnosis can be based on the classic parotid swelling; however, this feature is not present in all cases of mumps and can also occur in various other disorders. Laboratory diagnosis is based on isolation of virus, detection of viral nucleic acid, or serological confirmation (generally presence of IgM mumps antibodies). Mumps is vaccine-preventable, and one dose of mumps vaccine is about 80% effective against the disease. Routine vaccination has proven highly effective in reducing the incidence of mumps, and is presently used by most developed countries; however, there have been outbreaks of disease in vaccinated populations. In 2005, a large epidemic peaked in the UK, and in 2006 the American midwest had several outbreaks. In both countries, the largest proportion of cases was in young adults. In the UK, susceptible cohorts too old to have been vaccinated and too young to have been exposed to natural infections were the primary cause of the mumps epidemic. In the USA, effectiveness and uptake in combination appear not to have been sufficient to obtain herd immunity for mumps in populations such as college students.