Treatment partners and adherence to HAART in Central Mozambique.

Adherence to highly active antiretroviral treatment (HAART) has been associated with increased survival rates and decreased drug resistance in various settings. There is growing concern that loss to follow-up will increase and adherence rates will decrease as HAART programs are expanded in resource-limited settings. In Central Mozambique, an innovative program was implemented, using community-based (trained community activists) and self-selected (family members or friends) "treatment partners" to provide psycho-social support to patients on HAART. We calculated adherence rates based on pharmacy records for all patients who refilled their medication for at least six consecutive months between September 2004 and June 2006. Medical charts were reviewed for a subset of 375 patients having high (> or =90%) adherence and 59 patients having low (<90%) adherence. Multivariate logistic regression analysis assessed the association between the type of treatment partner used and adherence to HAART. A total of 305 patients (70%) had self-selected treatment partners, 121 (28%) had community-based treatment partners, and 8 (2%) had no treatment partner. In adjusted analysis, patients who had no treatment partner were more likely to have low adherence (OR 9.47; 95% confidence interval 2.37-37.86 compared to self-selected treatment partner). Patients with community-based treatment partners did not have significantly lower adherence than patients with self-selected treatment partners. While it cannot be determined from these data which aspects or types of peer support are most effective in maintaining adherence, it appears that peer support was beneficial to this study population. While the study results are not directly applicable to other populations, other HAART programs should consider the potential benefit of providing treatment support to patients.

One year after ART initiation: psychosocial factors associated with stigma among HIV-positive Mozambicans.

The pathways through which stigma is associated with psychological distress remains understudied in Africa. This study evaluates stigma among 277 Mozambicans who were on an antiretroviral therapy (ART) regimens for a full year. Using bivariate and multiple regression analyses, we examine psychosocial factors (disclosure decisions, perceived social support, and depression) associated with stigma, at ART initiation and 1 year later. We found 1 year after initiating ART, participants reported no change in stigma, a decrease in perceived social support, and an increase in depressive symptomology. Disclosing HIV status to friends (versus family or partner) was associated with lower levels of stigma. These findings suggest that HIV care in comparable settings should include counselling, support groups, and peer support, that includes stigma and disclosure concerns prior to and during the first year following diagnosis. Most importantly, assessment and treatment of depression should be incorporated into ongoing HIV care.

Condom use after voluntary counselling and testing in central Mozambique.

OBJECTIVE: To evaluate the efficacy of voluntary counselling and testing (VCT) for HIV/AIDS in changing risky sexual behaviour in central Mozambique. METHOD: Longitudinal cohort study of men and women aged at least 18 years from October 2002 to June 2003. We interviewed 622 participants in VCT groups and 598 in non-VCT groups. The interviews occurred before counselling and 4 and 6 months afterwards. RESULTS: Reported use of condoms while having sex with a friends/prostitute increased over each time period in the VCT group and between baseline and first visit in the non-VCT group. Both men and women in the VCT group increased their condom use over time, but the women in the non-VCT group did not. Reported always/sometimes use of condoms for both literate and illiterate subjects was higher and rose over time in the VCT group. CONCLUSION: People who undergo voluntary counselling and testing fro HIV/AIDS change their behaviour, presumably as a result of their counselling.

QT dispersion estimated from 80 body surface potential map leads and from standard 12-leads ECG in psychiatric patients treated with dosulepin.

The aim of the study was to detect changes of the QT dispersion (QTd) due to cardiotoxicity of tricyclic antidepressant dosulepin. Electrocardiographic and body surface potential mapping (BSPM) recordings were obtained using Cardiag 112.2 diagnostic system from 27 psychiatric outpatients treated with prophylactic doses of dosulepin and compared to those obtained from 37 healthy volunteers. From these recordings the QTd and the dispersion of heart rate-corrected QT interval QTc were evaluated. These parameters were estimated both from 80 BSPM leads and from 12 standard ECG leads. Acquired data were statistically correlated by Spearman rank order correlation coefficient with dosulepin plasma levels. The average QTd evaluated from BSPM leads (+/-SD) in the dosulepin group was significantly higher [70 (+/-21) ms] than that in the control group [34 (+/-12) ms] (P< 0.001). Moreover, the correlation between QTd and the dosulepin plasma level was statistically significant as well (P< 0.001) with the value of correlation coefficient 0.7871. The QTd evaluated from standard 12 ECG leads was increased in dosulepin group as well [46 (+/-18) ms vs. 28 (+/-10) ms - P< 0.05] but we have not found any significant correlation of the QTd with the dosulepin plasma level. According to the above-mentioned results we can conclude that the QTd estimated from BSPM leads (but not that estimated from 12-lead ECG) could be used as a marker of the dosulepin effect on the myocardium.

Germline E-cadherin mutations in hereditary diffuse gastric cancer: assessment of 42 new families and review of genetic screening criteria.

BACKGROUND: Mutations in the E-cadherin (CDH1) gene are a well documented cause of hereditary diffuse gastric cancer (HDGC). Development of evidence based guidelines for CDH1 screening for HDGC have been complicated by its rarity, variable penetrance, and lack of founder mutations. METHODS: Forty three new gastric cancer (GC) families were ascertained from multiple sources. In 42 of these families at least one gastric cancer was pathologically confirmed to be a diffuse gastric cancer (DGC); the other family had intestinal type gastric cancers. Screening of the entire coding region of the CDH1 gene and all intron/exon boundaries was performed by bi-directional sequencing. RESULTS: Novel mutations were found in 13 of the 42 DGC families (31% overall). Twelve of these mutations occur among the 25 families with multiple cases of gastric cancer and with pathologic confirmation of diffuse gastric cancer phenotype in at least one individual under the age of 50 years. The mutations found include small insertions and deletions, splice site mutations, and three non-conservative amino acid substitutions (A298T, W409R, and R732Q). All three missense mutations conferred loss of E-cadherin function in in vitro assays. Multiple cases of breast cancers including pathologically confirmed lobular breast cancers were observed both in mutation positive and negative families. CONCLUSION: Germline truncating CDH1 mutations are found in 48% of families with multiple cases of gastric cancer and at least one documented case of DGC in an individual under 50 years of age. We recommend that these criteria be used for selecting families for CDH1 mutational analysis.

Procalcitonin (PCT) in cardiac surgery: diagnostic value in systemic inflammatory response syndrome (SIRS), sepsis and after heart transplantation (HTX).

PURPOSE: Since it is of great importance to distinguish between a systemic inflammatory response syndrome (SIRS) and an infection caused by microbes especially after heart transplantation (HTX), we examined patients following heart surgery by determining procalcitonin (PCT), because PCT is said to be secreted only in patients with microbial infections. METHODS: Sixty patients undergoing coronary artery bypass grafting (CABG) and 14 patients after heart transplantation were included in this prospective study. In the CABG group we had 30 patients without any postoperative complications (group A). Furthermore we took samples of 30 patients who suffered postoperatively from a sepsis (group B, n=15) or a systemic inflammatory response syndrome (C, n=15). In addition we measured the PCT-levels in 65 blood samples of 14 patients after heart transplantation (Group I: rejection > IIa, II: viral infection (CMV), III: bacterial/fungal infection, IV: controls). RESULTS: In all patients of group A the pre- and intraoperative PCT-values and the measurement at arrival on intensive care unit (ICU) were less than 0.2 ng/ml. On the second postoperative day the PCT-value was 0.33+/-0.15 ng/ml in the control group. At the same time it was 19.6+/-6.2 ng/ml in sepsis and 0.7+/-0.4 ng/ml in systemic inflammatory response syndrome patients (P<0.05). In transplanted patients we could find the following PCT-values: Gr.I: 0.18+/-0.06 II: 0.30+/-0.09 III: 1.63+/-1.16 IV: 0.21+/-0.09 ng/ml (P<0.05 comparing group III with I, II and IV). CONCLUSIONS: These results show that extracorporeal circulation (ECC) and systemic inflammatory response syndrome do not initiate a PCT-secretion. Septic conditions cause a significant increase of PCT. In addition, PCT is a reliable indicator concerning the essential differentiation of bacterial or fungal--not viral--infection and rejection after heart transplantation.

Evidence of a founder BRCA1 mutation in Scotland.

BRCA1 mutations have been identified in breast and ovarian cancer families from diverse ethnic backgrounds. We studied 17 different families with the BRCA1 2800delAA mutation; seven were ascertained in Scotland (Dundee, Edinburgh, Glasgow, St Andrews), five in Canada (Toronto, Victoria) and five in the United States (Chicago, Philadelphia, Seattle). Overall there was a clear preponderance of Scottish ancestry. Genotype analysis performed on key members from 17 families was consistent with a common haplotype, strongly suggesting a single ancestral origin. A possible link was established between two families by tracing their genealogies through the records of the Registrar General for Scotland. This is the first example of a BRCA1 mutation likely to be derived from a common founder in Scotland. Further studies will be necessary to estimate more accurately the population frequency of the BRCA1 2800delAA mutation among unselected cases of breast and ovarian cancer in Scotland and the UK.

Markers of activated hemostasis and fibrinolysis in patients with pulmonary malignancies: comparison of plasma levels in central venous and pulmonary venous blood.

Malignancy frequently is accompanied by activated coagulation and fibrinolysis indicating a hypercoagulable state. The purpose of our study was to estimate the contribution of local tumor-induced mechanisms to the activation of hemostasis and fibrinolysis. In a prospective study, we compared the plasma levels of thrombin-antithrombin complexes, prothrombin fragment 1+2, and D-dimers in blood samples that simultaneously were drawn from the superior vena cava and the pulmonary vein of a tumor-bearing pulmonary lobe. Samples from the superior vena cava were drawn before operation and served as controls. After thoracotomy, a second group of samples was simultaneously taken from the pulmonary veins of the tumor-bearing lobe and the superior vena cava. Forty-five patients with pulmonary malignancies were included (25 adenocarcinomas and 20 squamous cell carcinomas). There were no significant differences of thrombin-antithrombin complexes, prothrombin fragment 1+2, and D-dimers levels in patients suffering from adenocarcinoma and from squamous cell carcinoma. Intraoperatively, prothrombin fragment 1+2 and D-dimers levels were markedly increased when compared with the preoperative values (p<0.0001). There was no increase of thrombin-antithrombin complexes levels due to the operative traumatization. Prothrombin fragment 1+2, thrombin-antithrombin complexes, and D-dimers plasma levels were significantly higher in the pulmonary venous blood than in the blood simultaneously drawn from the superior vena cava (p<0.0001). Our findings indicate that malignant lung tumors directly contribute to the activation of hemostasis and fibrinolysis in these clinical settings.

Post-perfusion syndrome and disturbed microcirculation after cardiac surgery: the role of angiotensin-converting-enzyme inhibitors.

BACKGROUND: The sympathoadrenal and the renin-angiotensin system (RAS) are involved in blood pressure regulation. They are known to be activated during cardiac surgery. We investigated the influence of preoperative RAS-blockade using angiotensin-converting-enzyme inhibitors (ACEI) on hemodynamic variables and on the perioperative need for exogenous catecholamines. METHODS: 240 patients undergoing coronary artery bypass grafting (CABG) or valve surgery were divided into three matched groups (group A: pre- and postoperative ACEI; group B: ACEI only pre-, not postoperatively; group C: no ACEI). In these three groups we analyzed hemodynamic variables, the need for catecholamines and the incidence of a "post-perfusion syndrome" or systemic inflammatory response syndrome (SIRS) with impaired microcirculation. RESULTS: There were significant differences in the intra- and postoperative need for catecholamines in groups A and B compared to C (intraop. A: 35%, B: 35%, C: 15%; postop. A: 21.2%, B: 16.2%, C: 10%) (p < 0.05). In the ACEI groups (A and B) there were 9 patients with a postoperative SIRS, only 2 cases in group C. Furthermore 4 patients of group B suffered from disturbances of the intestinal microcirculation postoperatively. CONCLUSIONS: Long-term ACEI treatment before cardiac surgery raises the perioperative need for catecholamines. Patients with preoperative long-term use of ACEI who do not receive ACEI postoperatively face an increased risk of impaired microcirculation. The inhibition of angiotensin-II (AT II) generation causes the vasodilatatory effects of ACEI, and could be one reason for a post-perfusion syndrome or a SIRS.

Diagnostic value of procalcitonin: the influence of cardiopulmonary bypass, aprotinin, SIRS, and sepsis.

BACKGROUND: The reasons for a systemic inflammatory response syndrome (SIRS) following ECC are not yet fully understood. Procalcitonin (PCT) blood levels may distinguish between bacterial infections and a non-bacterial systemic inflammation. We investigated the influence of ECC, ECC modified by application of aprotinin, systemic inflammation, and bacterial infection on the PCT values. METHODS: 20 CABG patients were randomized and divided in two groups. Group A served as the control group, while group B perioperatively received a high dose of aprotinin. Blood samples for measurement of PCT were taken 6 times perioperatively. Furthermore, blood samples were taken from 20 preoperatively comparable patients who suffered from bacterial infection (n = 10) (group C) or a SIRS (n = 10) (group D) after ECC; in these groups PCT was determined daily after the onset of inflammation. RESULTS: There was no significant elevation of PCT in group A or B at any time. In sepsis patients a significant elevation of PCT was seen, with the peak level of 18.6+/-6.3 ng/ml on the second day after diagnosis; the PCT level of SIRS patients remained constantly low (<0.9 ng/ml). CONCLUSIONS: In this study it was demonstrated that ECC and the use of aprotinin did not have any influence on the secretion of PCT. A systemic bacterial infection caused a significant increase of PCT, whereas PCT values remained normal in case of a SIRS. So it seems to be possible to distinguish between a primary SIRS and a bacterial sepsis by means of PCT.

Modified surgical concept for fulminant pulmonary embolism.

Surgical intervention in fulminant pulmonary embolism (PE) is still associated with an overall 30% fatal outcome which increases to about 60% when cardiopulmonary resuscitation (CPR) is necessary. Despite unfavorable conditions like hemodynamic instability, failed lysis or CPR, the surgical strategy might have a certain impact on the patient's outcome since 30-40% of the surgical mortality is related to persistent right heart failure and early thromboembolic recurrence. From 1/88 to 8/94 a total of 25 patients (15 females, 10 men, mean age 57 [25-78]) years underwent emergency pulmonary embolectomy with the use of the heart-lung machine. Seventeen patients were operated upon between 1988 and 1992. A standard approach by central pulmonary artery incision with extraction of adjacent pulmonary emboli using forceps, suction of Fogarty catheters was used. Six of these patients (35%) died, with four out of six operated upon under CPR. Since 1993 we have used a modified surgical strategy in eight patients. Five patients (63%) were operated on after or under CPR. In these cases, left and right pulmonary arteries were incised peripherally and all segmental arteries were desobliterated selectively using small suction devices. Thereafter the right atrium was opened and inspected. After removal of the inferior caval vein cannula all inferior body blood was taken with cardiotomy suction while both legs and the abdomen were massaged centripetally to mobilize additional fresh thrombotic material. In three cases up to 50 cm long thrombi could be delivered. All patients have survived to date with two patients receiving a LGM caval filter placed percutaneously after bilateral postoperative phlebography had revealed ongoing thrombotic disease. We conclude that selective desobliteration of every segmental pulmonary artery in combination with simultaneous clearance of major body veins from additional thrombotic material will probably lower surgical mortality in these critically ill patients.

The dose dependent effect of cyclic AMP on ribonucleotide reductase in mitogen stimulated mononuclear cells.

Cyclic adenosine monophosphate arrests proliferating T lymphocytes in the G1 phase of the cell cycle. Here we demonstrate that exogenous and endogenous elevations in cyclic AMP concentration result in diminished mitogen stimulation, cell cycle arrest, and decreased ribonucleotide reductase messenger RNA concentrations in peripheral blood mononuclear cells. At lower concentrations (less than 1mM) of dibutyryl cyclic AMP that do not generate cell cycle arrest there is inhibition of ribonucleotide reductase activity without decreased messenger RNA concentration for the M2 subunit of ribonucleotide reductase. However, at higher concentrations of dibutyryl cyclic AMP there is G1 cell cycle arrest and reduced M2 specific messenger RNA concentration. Thus, cyclic AMP inhibition of lymphocyte activation may occur by different mechanisms that are dose dependent.