AIDS care and treatment in Sub-Saharan Africa: implementation ethics

With the advent of new AIDS treatment initiatives such as the World Health Organization's "3 by 5" program and the United States' "President's Emergency Plan for AIDS Relief," the ethical questions about AIDS care in the developing world have changed. No longer are they fundamentally about the conduct of research; now, we must turn our attention to developing treatment programs. In particular, we must think about how to spread limited treatment resources among the vast reservoir of people who need them.     

Muscle protein changes following eccentric exercise in humans

Summary This study characterized changes in the protein composition of human muscle tissue after eccentric exercise. Four subjects performed 70 maximum eccentric, isokinetic actions of the forearm flexors with one arm. The other arm served as control. A biopsy of the biceps muscle of each arm was taken 2 days after exercise when muscles were very sore (mean = 8.0; 1 = normal; 10 = very, very sore), and muscle damage was documented by a mean decrease of 0.2 radians in the relaxed elbow angle. Proteins from the biopsy tissue were solubilized in a high ionic strength buffer containing several proteolytic inhibitors. Protein concentrations of the extracts were determined and identical amounts loaded onto sodium dodecyl sulfate (SIDS) polyacrylamide gels (7.5, 12.5, and 17.5%). Densitometric analysis of the Coomassie brilliant blue stained gels revealed alterations in the amounts of three protein bands in the exercised tissue relative to the control. These changes were in the linear portion of the graph of absorbance versus protein amount. Wilcoxon's signed rank test showed the first two of the following bands to increase significantly in amount (P < 0.062). The average percentage changes [mean (SEM)] for these bands were 63 (21), 39 (5), and 82 (35). The corresponding molecular weights determined from known standards were 76 300 (860), 33 200 (310), and 12 000 (80) daltons, respectively. These changes imply that the increased synthesis, decreased degradation, or some combination thereof, of these three proteins may be necessary for the repair or regeneration response to exercise-induced muscle damage.     

A new double-cartilage block ossiculoplasty: long-term results.

OBJECTIVES: To determinate whether ossicular chain reconstruction performed with modified double-cartilage block (DCB) ossiculoplasty used by authors, leaving the intact perichondrium layer on the cartilage surface in contact with tympanic membrane, results in significant hearing results and prevents DCB displacement and DCB loss of stiffness when compared with the original DCB technique described by Luetje and Denninghoff. MATERIALS AND METHODS: Sixty-five ossicular reconstructions using DCB ossiculoplasty were performed from 1996 to 2001 in the whole study group. Eight patients had an inadequate follow-up and were excluded from the study. In the first 25 cases, the original DCB ossiculoplasty technique described by Luetje and Denninghoff was performed (Group 1). In the second group, 32 modified DCB ossiculoplasties were performed. The same author performed all cases. The main follow-up for the whole study group was 7 years. Audiometric data were calculated according to the 1995 American Academy of Otolaryngology-Head and Neck Surgery guidelines. MAIN OUTCOME MEASURES: Mean postoperative air-bone gap closure to less than 20 dB, incidence of DCB displacement from tympanic membrane, and incidence of loss of DCB stiffness. RESULTS: Comparison data of hearing results, incidence of DCB slippage, and incidence of DCB loss of stiffness in the group performed with original technique and in the group with modified technique showed statistical significance. Successful rehabilitation (pure-tone average air-bone gap <20 dB) of conductive hearing loss was obtained in 48% of cases in Group 1 (original DCB) and in 81.2% of cases in Group 2 (modified technique). In the group with original DCB ossiculoplasty, the displacement of implant and its loss of stiffness occurred more often than in the second group. CONCLUSION: The modified DCB represents an excellent partial ossicular replacement prosthesis. The perichondrium layer left attached on the cartilage surface in contact with tympanic membrane increases the stability of DCB and prevents the displacement and the loss of stiffness of the cartilage. The modified DCB ossiculoplasty is easy to perform. Hearing results are satisfactory and lasting. The cost is null, and the tolerance is excellent.     

Bone sialoprotein plays a functional role in bone formation and osteoclastogenesis

Bone sialoprotein (BSP) and osteopontin (OPN) are both highly expressed in bone, but their functional specificities are unknown. OPN knockout (-/-) mice do not lose bone in a model of hindlimb disuse (tail suspension), showing the importance of OPN in bone remodeling. We report that BSP(-/-) mice are viable and breed normally, but their weight and size are lower than wild-type (WT) mice. Bone is undermineralized in fetuses and young adults, but not in older (> or =12 mo) BSP(-/-) mice. At 4 mo, BSP(-/-) mice display thinner cortical bones than WT, but greater trabecular bone volume with very low bone formation rate, which indicates reduced resorption, as confirmed by lower osteoclast surfaces. Although the frequency of total colonies and committed osteoblast colonies is the same, fewer mineralized colonies expressing decreased levels of osteoblast markers form in BSP(-/-) versus WT bone marrow stromal cultures. BSP(-/-) hematopoietic progenitors form fewer osteoclasts, but their resorptive activity on dentin is normal. Tail-suspended BSP(-/-) mice lose bone in hindlimbs, as expected. In conclusion, BSP deficiency impairs bone growth and mineralization, concomitant with dramatically reduced bone formation. It does not, however, prevent the bone loss resulting from loss of mechanical stimulation, a phenotype that is clearly different from OPN(-/-) mice.     

The Construction of the First Validated (Evidence Based) Guideline for Dual Diagnosis of ADHD and SUD; Data from Focus Groups

This study aims to obtain more information about the expectations and experiences of patients with attention deficit hyperactivity disorder (ADHD) and substance use disorder (SUD) and about the opinions of addiction care professionals. This information has been used to develop the first multidisciplinary guideline for identification and treatment of ADHD in addicted patients. Focus group interviews were performed with two groups of professionals and a group of patients of one of them. The interviews were transcribed and analyzed using QSR NVivo 9 software. The analysis revealed a great difference between addicted inpatients and outpatients as to the possibilities of diagnosing and treating ADHD. It is difficult to make a proper diagnosis in patients who are not fully abstinent, as there are no validated diagnostic instruments for this target group. Observation is seen as more important than questionnaires but there have been no studies on the utility of observation. Patients often ask for non-pharmacological treatment. Underdiagnosing of ADHD in addicted patients is a persistent problem. Additional research is required into diagnostic tools for making a proper diagnosis in patients not fully abstinent as well as into pharmacological interactions. Observation, degree of distress and cognitive examination should form part of the diagnostic process. The positive experiences in the residential addiction services with non-pharmacological well-grounded, structured treatment methods for addiction offer a perspective to develop specific methodologies adapted to patients with comorbid ADHD.     

Gastric polyps

Summary When roentgen examination shows a sharply defined polyp less than 2 cm. in diameter, the polyp is of a benign adenomatous type, and conservative treatment is recommended. If the polyp is smooth and larger than 2 cm. in diameter it is usually benign. However, since there may be such findings with a polypoid carcinoma, surgery is indicated. Of 138 cases studied the polyps resembled a villous adenoma on roentgen and pathologic examination in 8. These lesions have a high malignant potential and should be removed. Irregular contour defects should be considered as carcinomas no matter what the size.Thirty-one patients with the roentgen diagnosis of a benign polyp, observed for 9 months to 12 years, revealed no essential change in appearance during the period of observation. Some of the differences in the statistics relative to the malignant potential of gastric polyps may be due to the inclusion of villous adenomas or papillomas, polypoid carcinomas, and small flat ulcerating carcinomas.     

The infant feeding choices and experiences of women living with HIV in Kinshasa, Democratic Republic of Congo

HIV transmission through breastfeeding is a significant public health challenge. While breastfeeding provides important nutrition, and results in reduced morbidity and mortality, there is a risk of HIV transmission through breastfeeding. International prevention of mother-to-child transmission (PMTCT) guidelines recommend exclusive breastfeeding for six months among HIV-infected women on antiretroviral therapy. Promoting exclusive feeding has proved difficult in settings where mixed feeding is a cultural norm. Understanding the factors that influence HIV infected women's infant feeding choices and practices is critical to promoting adherence to PMTCT guidelines. We conducted in-depth interviews with 40 HIV+ pregnant and post-partum women in Kinshasa, Democratic Republic of Congo to understand their infant feeding experiences. Interviews were conducted in Lingala, and transcribed and translated into French for analysis. Deductive and inductive codes were applied, and matrices were created to facilitate cross-case analysis. Women had limited understanding of the specific mechanisms through which their infant feeding practices influenced HIV transmission risk. Clinical staff was the primary source of women's knowledge of HIV mother-to-child-transmission. Among the 24 post-partum women in the sample, seven women adhered to exclusive breastfeeding and two women to exclusive formula feeding for at least six months. Women's beliefs and awareness about HIV transmission through breastfeeding, as well as the information and support from clinical staff and other members of their support networks positively influenced their exclusive feeding. Common barriers to exclusive feeding included financial constraints, breast health problems, misinformation about HIV transmission, local norms, and prior feeding experiences. Health care workers play a key role in providing correct information on PMTCT and supporting women's infant feeding choices to adhere to guidelines of exclusive infant feeding. Optimizing provider-patient communication and creating a supportive environment surrounding infant feeding is critical.     

The presence of immune stimulatory cells in fresh and cryopreserved donor aortic and pulmonary valve allografts

BACKGROUND AND AIM OF THE STUDY: Heart valve allografts (HVA) used for valve replacement or ventricular outflow tract reconstruction may suffer from structural deterioration due to donor-specific immune responses. The presence of immune stimulatory cells, including dendritic cells and activated endothelial cells, has not been studied thoroughly in aortic or pulmonary HVA. The presence and distribution of these cells in both aortic and pulmonary HVA, before and after cryopreservation, was analyzed immunohistochemically. METHODS: Aortic (n = 16) and pulmonary (n = 13) HVA, discarded for implantation due to morphological or technical reasons, were obtained from 12 heart-beating and nine non-heart-beating tissue donors. Aortic and pulmonary HVA were dissected longitudinally into two symmetric sections by splicing of the non-coronary aortic and non-facing pulmonary cusps. Each symmetric half contained one-and-a-half valve cusps attached to the vascular wall. Fresh halves were directly fixed in formaldehyde, and analyzed immunohistochemically. The corresponding halves of the valves were decontaminated, cryopreserved, stored for at least three weeks and thereafter thawed according to the Heart Valve Bank protocol before analysis. RESULTS: Activated endothelial cells, expressing PECAM-1 (CD31), VCAM-1 and HLA class II molecules covered at least 50% of fresh valvular surfaces. A comprehensive vascular network was found in the myocardial rim and adventitial layer, which was covered entirely by activated endothelial cells. HLA class II-positive macrophages (CD68) and T lymphocytes (CD3) were found scattered in the stroma and subendothelial layer of the valve leaflets. Mononuclear cell clusters were found predominantly in relation to native degenerative foci, and more often in aortic valves. No difference in cellular distribution was observed between the two donor types. Dendritic cells positive for both S100 and CD45 were not found in immuno-double-stained sections. Cryopreservation resulted in minor structural alterations in the vascular wall, and an increase of cells with pycnotic nuclei and reduction of adhesion molecule expression on endothelial cells. All fresh and cryopreserved aortic and pulmonary HVA contained abundant HLA class II-positive endothelial cells and sparse distribution of mononuclear cells in the luminal and adventitial layers. CONCLUSION: Cryopreservation minimally affected the extracellular matrix of HVA and diminished the cellularity of the valve graft, while the HLA class II expression of cells was not abrogated. Aortic valve allografts harbor more mononuclear cells than their pulmonary counterparts. The absence of dendritic cells (professional antigen-presenting cells) is compensated by the preservation of other cells expressing HLA class II molecules predominantly in the endothelium; this may be responsible for the initiation of a specific immune response against HVA.     

Computed CD4 percentage as a low-cost method for determining pediatric antiretroviral treatment eligibility

Background  

The performance of the WHO recommendations for pediatric antiretroviral treatment (ART) in resource poor settings is insufficiently documented in routine care.     

First Mouse Model for Combined Osteogenesis Imperfecta and Ehlers‐Danlos Syndrome

By using a genome‐wide N‐ethyl‐N‐nitrosourea (ENU)‐induced dominant mutagenesis screen in mice, a founder with low bone mineral density (BMD) was identified. Mapping and sequencing revealed a T to C transition in a splice donor of the collagen alpha1 type I (Col1a1) gene, resulting in the skipping of exon 9 and a predicted 18‐amino acid deletion within the N‐terminal region of the triple helical domain of Col1a1. Col1a1^Jrt/+ mice were smaller in size, had lower BMD associated with decreased bone volume/tissue volume (BV/TV) and reduced trabecular number, and furthermore exhibited mechanically weak, brittle, fracture‐prone bones, a hallmark of osteogenesis imperfecta (OI). Several markers of osteoblast differentiation were upregulated in mutant bone, and histomorphometry showed that the proportion of trabecular bone surfaces covered by activated osteoblasts (Ob.S/BS and N.Ob/BS) was elevated, but bone surfaces undergoing resorption (Oc.S/BS and N.Oc/BS) were not. The number of bone marrow stromal osteoprogenitors (CFU‐ALP) was unaffected, but mineralization was decreased in cultures from young Col1a1^Jrt/+ versus +/+ mice. Total collagen and type I collagen content of matrices deposited by Col1a1^Jrt/+ dermal fibroblasts in culture was ～40% and 30%, respectively, that of +/+ cells, suggesting that mutant collagen chains exerted a dominant negative effect on type I collagen biosynthesis. Mutant collagen fibrils were also markedly smaller in diameter than +/+ fibrils in bone, tendon, and extracellular matrices deposited by dermal fibroblasts in vitro. Col1a1^Jrt/+ mice also exhibited traits associated with Ehlers‐Danlos syndrome (EDS): Their skin had reduced tensile properties, tail tendon appeared more frayed, and a third of the young adult mice had noticeable curvature of the spine. Col1a1^Jrt/+ is the first reported model of combined OI/EDS and will be useful for exploring aspects of OI and EDS pathophysiology and treatment. © 2014 American Society for Bone and Mineral Research.