Large granular lymphocytes from patients with expanded LGL populations acquire cytotoxic functions and release lymphokines upon in vitro activation

The phenotypic and functional features of purified large granular lymphocytes (LGL) from ten patients with LGL population expansions and cytopenias are described. The predominant LGL phenotypes were T3+, T8+, Leu-11+/-; however, in two patients, LGL expressed a T3-, Leu-11+ phenotype. Variable combinations of other LGL markers (OKM1, Leu-7), and HLA-DR were detected in individual cases. In nine of ten cases, freshly isolated LGL did not exert cytolytic activity for K562 target cells, but purified LGL cultured in the presence of recombinant interleukin 2 (rIL2) acquired potent cytotoxic activity in all cases tested. LGL did not proliferate in response to phytohemagglutinin (PHA). However, LGL released variable amounts of IL2 and gamma- interferon (gamma-IFN) after PHA stimulation. In some cases, stimulation of fresh LGL with recombinant IL2 induced production of gamma-IFN. No correlation was found between the functional capabilities and the original phenotype of the expanded LGL populations.     

Suprachiasmatic neuron numbers and rest–activity circadian rhythms in older humans

The suprachiasmatic nucleus (SCN) of the hypothalamus, the master mammalian circadian pacemaker, synchronizes endogenous rhythms with the external day–night cycle. Older humans, particularly those with Alzheimer disease (AD), often have difficulty maintaining normal circadian rhythms compared to younger adults, but the basis of this change is unknown. We report that the circadian rhythm amplitude of motor activity in both AD subjects and age‐matched controls is correlated with the number of vasoactive intestinal peptide–expressing SCN neurons. AD was additionally associated with delayed circadian phase compared to cognitively healthy subjects, suggesting distinct pathologies and strategies for treating aging‐ and AD‐related circadian disturbances. Ann Neurol 2015;78:317–322     

Experience with autologous pericardial patch closure of ventricular septal defect

Background Conventionally, Ventricular Septal Defects (VSDs) are repaired with synthetic patch—Dacron (polyethylene terephthalate) or Goretex (expanded polytetrafluoroethylene). Recently, we began using glutaraldehyde—treated autologous pericardial patch to repair VSDs. We review our experience. Material and Method Between July to November 2005, 60 children had their VSDs repaired with glutaraldehyde—treated autologous pericardium. There were 40 males and 20 females, aged between 5 months and 12 years with a median age of 1 year. The diagnosis was isolated VSD in 37 patients, multiple VSD in 3; Tetralogy of Fallot (TOF) in 15 and Double Outlet Right Ventricle (DORV) in 5 patients. The chest was opened by a median sternotomy incision. After establishing cardiopulmonary bypass, a strip of pericardium was harvested from the patient and fixed in 0.6% glutaraldehyde (Polyscientific, Bayshore, NY) for about 20 minutes. It was then washed out with 0.9% saline solution. The defect was repaired with 4/0 or 5/0 prolene suture using a continuous suture technique. Results There was no hospital mortality. Postoperative echocardiogram revealed trivial shunts in 10 patients. Follow up was for 3 to 6 months (mean 2 months). No patient required reoperation for residual VSD. Conclusion Glutaraldehyde—treated autologous pericardium is an excellent material for surgical patch clousre of VSD. It is easily available and does not require sterilization. Further follow-up is required to assess its long term efficacy.     

Intradermal vaccination against hepatitis B virus infection in an endemic area (Nigeria), two year results

Summary To determine the efficacy and safety of hepatitis B vaccine (Hevac B) given intradermally, 125 Nigerians (aged 1 year to 45 years), who were negative for hepatitis B virus markers, and randomised into two groups were vaccinated. Group 1 (64 volunteers) was given 3 monthly doses of 2 µg vaccine mixed with adjuvant subcutaneously (Institut Pasteur Production-Hevac B) while group 2 (61 volunteers) received 3 doses of 2 µg non-adjuvated vaccine intradermally given 1 month apart. A month after the third dose 83 per cent of group 1, 71 per cent of group 2 showed positive response by developing antibody to hepatitis B surface antigen. The levels of antibody were significantly higher in group 1 at each stage of the follow-up period, including a month after a booster vaccination was given. The positive response was maintained in almost all the initial responders for the 24 month duration of the study. No significant side effect was documented in any of the participants. The results suggest that population at risk in developing countries could be protected with small doses of vaccine administered intradermally.With 1 Figure     

Increasing the use of second-line therapy is a cost-effective approach to prevent the spread of drug-resistant HIV: a mathematical modelling study

Introduction

Earlier antiretroviral therapy (ART) initiation reduces HIV-1 incidence. This benefit may be offset by increased transmitted drug resistance (TDR), which could limit future HIV treatment options. We analyze the epidemiological impact and cost-effectiveness of strategies to reduce TDR.

Methods

We develop a deterministic mathematical model representing Kampala, Uganda, to predict the prevalence of TDR over a 10-year period. We then compare the impact on TDR and cost-effectiveness of: (1) introduction of pre-therapy genotyping; (2) doubling use of second-line treatment to 80% (50–90%) of patients with confirmed virological failure on first-line ART; and (3) increasing viral load monitoring from yearly to twice yearly. An intervention can be considered cost-effective if it costs less than three times the gross domestic product per capita per quality adjusted life year (QALY) gained, or less than $3420 in Uganda.

Results

The prevalence of TDR is predicted to rise from 6.7% (interquartile range [IQR] 6.2–7.2%) in 2014, to 6.8% (IQR 6.1–7.6%), 10.0% (IQR 8.9–11.5%) and 11.1% (IQR 9.7–13.0%) in 2024 if treatment is initiated at a CD4 <350, <500, or immediately, respectively. The absolute number of TDR cases is predicted to decrease 4.4–8.1% when treating earlier compared to treating at CD4 <350 due to the preventative effects of earlier treatment. Most cases of TDR can be averted by increasing second-line treatment (additional 7.1–10.2% reduction), followed by increased viral load monitoring (<2.7%) and pre-therapy genotyping (<1.0%). Only increasing second-line treatment is cost-effective, ranging from $1612 to $2234 (IQR $450-dominated) per QALY gained.

Conclusions

While earlier treatment initiation will result in a predicted increase in the proportion of patients infected with drug-resistant HIV, the absolute numbers of patients infected with drug-resistant HIV is predicted to decrease. Increasing use of second-line treatment to all patients with confirmed failure on first-line therapy is a cost-effective approach to reduce TDR. Improving access to second-line ART is therefore a major priority.     

Complicated first-trimester pregnancies: evaluation with endovaginal US versus transabdominal technique

Endovaginal ultrasound (US) was performed in 38 pregnant women at 5-12 menstrual weeks, when the initial transabdominal sonograms had been considered inconclusive or equivocal. Clinical follow-up disclosed 32 intrauterine pregnancies (12 living, 18 spontaneous incomplete abortions, and two embryonic demises) and six ectopic pregnancies. In the 32 intrauterine pregnancies (normal and abnormal), the correct diagnosis was made in all cases with endovaginal US. The endovaginal images demonstrated the intrauterine embryo, its heart motion, and the yolk sac more clearly and more often when these structures were not apparent on the transabdominal scans. Abnormal gestational sacs were better resolved. In the six cases of ectopic pregnancy, while an extrauterine ectopic sac was visualized in only three, absence of an intrauterine gestational sac was confirmed in all cases with endovaginal scanning. No endovaginal study yielded less information than its transabdominal counterpart. Endovaginal sonography is likely to be diagnostic when transabdominal images fail to yield a definitive diagnosis in early pregnancies.     

The frequency of bifid mandibular condyle in a Turkish patient population

Objective

The objective of this study was to investigate the frequency and pattern of bifid mandibular condyles (BMCs).

Methods

A retrospective study was performed using panoramic radiographs from 10 200 patients undergoing dental treatment in the Department of Oral and Maxillofacial Radiology (Erzurum, Turkey) between 1996 and 2008.

Results

Of the 10 200 patients, 32 (0.3%) had BMCs, of whom 17 were female (53.1%) and 15 were male (46.9%). The age range of the patients with BMCs was 5 to 71 years (mean age 30.0±0.40). Of these 32 patients, 24 (75.0%) had unilateral and 8 (25.0%) had bilateral BMCs, none of the patients had a history of trauma. No symptoms associated with bifid condyles were observed in any of the patients with BMCs.

Conclusions

It is possible that BMC is a more frequent condition than is commonly perceived. However, because of the minimal symptoms associated with this condition, the authors believe that it will remain an incidental finding upon routine radiographic examination, rather than a clinical observation. Nevertheless, in symptomatic cases or in cases where surgical treatment is planned, panoramic radiographs should be supplemented with CT.     

The Four-Dimensional Symptom Questionnaire (4DSQ): a validation study of a multidimensional self-report questionnaire to assess distress, depression, anxiety and somatization

Background

The Four-Dimensional Symptom Questionnaire (4DSQ) is a self-report questionnaire that has been developed in primary care to distinguish non-specific general distress from depression, anxiety and somatization. The purpose of this paper is to evaluate its criterion and construct validity.

Methods

Data from 10 different primary care studies have been used. Criterion validity was assessed by comparing the 4DSQ scores with clinical diagnoses, the GPs' diagnosis of any psychosocial problem for Distress, standardised psychiatric diagnoses for Depression and Anxiety, and GPs' suspicion of somatization for Somatization. ROC analyses and logistic regression analyses were used to examine the associations. Construct validity was evaluated by investigating the inter-correlations between the scales, the factorial structure, the associations with other symptom questionnaires, and the associations with stress, personality and social functioning. The factorial structure of the 4DSQ was assessed through confirmatory factor analysis (CFA). The associations with other questionnaires were assessed with Pearson correlations and regression analyses.

Results

Regarding criterion validity, the Distress scale was associated with any psychosocial diagnosis (area under the ROC curve [AUC] 0.79), the Depression scale was associated with major depression (AUC = 0.83), the Anxiety scale was associated with anxiety disorder (AUC = 0.66), and the Somatization scale was associated with the GPs' suspicion of somatization (AUC = 0.65). Regarding the construct validity, the 4DSQ scales appeared to have considerable inter-correlations (r = 0.35-0.71). However, 30–40% of the variance of each scale was unique for that scale. CFA confirmed the 4-factor structure with a comparative fit index (CFI) of 0.92. The 4DSQ scales correlated with most other questionnaires measuring corresponding constructs. However, the 4DSQ Distress scale appeared to correlate with some other depression scales more than the 4DSQ Depression scale. Measures of stress (i.e. life events, psychosocial problems, and work stress) were mainly associated with Distress, while Distress, in turn, was mainly associated with psychosocial dysfunctioning, including sick leave.

Conclusion

The 4DSQ seems to be a valid self-report questionnaire to measure distress, depression, anxiety and somatization in primary care patients. The 4DSQ Distress scale appears to measure the most general, most common, expression of psychological problems.