Screening for pulmonary tuberculosis in a Tanzanian prison and computer-aided interpretation of chest X-rays

Setting: Tanzania is a high-burden country for tuberculosis (TB), and prisoners are a high-risk group that should be screened actively, as recommended by the World Health Organization. Screening algorithms, starting with chest X-rays (CXRs), can detect asymptomatic cases, but depend on experienced readers, who are scarce in the penitentiary setting. Recent studies with patients seeking health care for TB-related symptoms showed good diagnostic performance of the computer software CAD4TB.Objective: To assess the potential of computer-assisted screening using CAD4TB in a predominantly asymptomatic prison population.Design: Cross-sectional study.Results: CAD4TB and seven health care professionals reading CXRs in local tuberculosis wards evaluated a set of 511 CXRs from the Ukonga prison in Dar es Salaam. Performance was compared using a radiological reference. Two readers performed significantly better than CAD4TB, three were comparable, and two performed significantly worse (area under the curve 0.75 in receiver operating characteristics analysis). On a superset of 1321 CXRs, CAD4TB successfully interpreted >99%, with a predictably short time to detection, while 160 (12.2%) reports were delayed by over 24 h with conventional CXR reading.Conclusion: CAD4TB reliably evaluates CXRs from a mostly asymptomatic prison population, with a diagnostic performance inferior to that of expert readers but comparable to local readers.     

High resolution melting analysis for the identification of novel mutations in DKC1 and TERT genes in patients with dyskeratosis congenita

Dyskeratosis congenita (DC) is a rare inherited bone-marrow failure syndrome with high clinical heterogeneity. Cells derived from DC patients present short telomeres at early ages, as a result of mutations in genes encoding components of the telomerase complex (DKC1, TERC, TERT, NHP2 and NOP10), or the shelterin complex (TINF2). However, mutations have been identified only in around 50% of the cases, indicating that other genes could be involved in the development of this disease. Indeed, mutations in TCBA1 or chromosome segment C16orf57 have been described recently. We have used HRM technology to perform genetic analysis in the above mentioned genes, in Spanish patients showing both, some clinical features of DC and short telomeres. The mutations have been identified by PCR amplification of DC genes followed by high resolution melting (HRM) and direct DNA sequencing analysis. We have identified seven new families with DC, three with X-linked DC and four with autosomal dominant DC, in which we have found two novel mutations in DKC1 (p.His68Arg and p.Lys390del) and four novel mutations in TERT gene (p.Pro530Leu, p.Arg698Trp, p.Arg971His and p.Arg698Gln). The results show that the use of HRM analysis enables a rapid and inexpensive identification of mutations in dyskeratosis congenita associated genes.     

Ovarian 'tumor' of the adrenogenital syndrome: the first reported case.

We report the case of a 36-year-old woman with congenital adrenal hyperplasia from 21-hydroxylase deficiency who had been receiving replacement therapy with corticosteroids since birth. At the age of 35 years, she developed abrupt aggravation of her virilizing symptoms and underwent an adrenalectomy and partial left oophorectomy. Persistent virilization and high testosterone levels led to right oophorectomy and completion left oophorectomy 6 months later. Each adnexa contained ovarian or paraovarian soft brown masses that on microscopic examination were identical to the testicular tumor of the adrenogenital syndrome. This represents the first reported case of this pathology (well known in the testis) in the ovary.     

Effects of fentanyl on procedural pain and discomfort associated with central venous catheter insertion: A prospective,randomized, double-blind,placebo controlled trial

Context:

Central venous catheter (CVC) insertion induces pain and discomfort to a conscious patient despite application of a local anesthetic (LA) field block and this pain can be greatly lessened by using additional analgesics.

Aim:

The aim of this study is to evaluate the efficacy of fentanyl along with LA field infiltration in controlling pain and discomfort associated with CVC insertion.

Settings and Design:

A prospective, randomized, double-blind, placebo-controlled trial was conducted at tertiary referral center.

Materials and Methods:

Fifty-four patients scheduled for planned CVC were randomly assigned to receive either fentanyl (2 μg/kg) or 0.9% normal saline. Pain and discomfort using a verbal numeric rating pain scale at 5 times points during CVC insertion were assessed and analyzed.

Results:

The median interquartile range pain score is worst for placebo group after LAI (5 [3-6]) and in the immediate postprocedure period (5 [4-5]) which was significantly attenuated by addition of fentanyl (3.5 [2-5] and 3 [2-4]) (P = 0.009 and 0.001 respectively). Overall, fentanyl and placebo group were not statistically different with median discomfort score except at T10 (P = 0.047).

Conclusions:

Preprocedural bolus fentanyl infusion provides adequate analgesia and can be safely used for alleviating pain during CVC insertion in conscious patients.     

p53 pathway activation by telomere attrition in X-DC primary fibroblasts occurs in the absence of ribosome biogenesis failure and as a consequence of DNA damage

Background

Dyskeratosis congenita (DC) is a rare inherited bone marrow failure syndrome with high clinical heterogeneity. Various mutations have been reported in DC patients, affecting genes that code for components of H/ACA ribonucleoproteins, proteins of the telomerase complex and components of the shelterin complex.

Objectives

We aim to clarify the role of ribosome biogenesis failure in senescence induction in X-DC since some studies in animal models have reported a decrease in ribosome biogenesis as a major role in the disease.

Methods

Dyskerin was depleted in normal human fibroblasts by expressing two DKC1 shRNAs. Common changes in gene expression profile between these dyskerin-depleted cells and X-DC fibroblasts were analyzed.

Results

Dyskerin depletion induced early activation of the p53 pathway probably secondary to ribosome biogenesis failure. However, the p53 pathway in the fibroblasts from X-DC patients was activated only after an equivalent number of passes to AD-DC fibroblasts, in which telomere attrition in each division rendered shorter telomeres than control fibroblasts. Indeed, no induction of DNA damage was observed in dyskerin-depleted fibroblasts in contrast to X-DC or AD-DC fibroblasts suggesting that DNA damage induced by telomere attrition is responsible for p53 activation in X-DC and AD-DC fibroblasts. Moreover, p53 depletion in senescent DC fibroblasts rescued their proliferative capacity and reverted the morphological changes produced after prolonged culture.

Conclusions

Our data indicate that ribosome biogenesis do not seem to play an important role in dyskeratosis congenita, conversely increasing DNA damage and activation of p53 pathway triggered by telomere shortening is the main activator of cell senescence.     

Kiwira Virus,a Newfound Hantavirus Discovered in Free-tailed Bats (Molossidae) in East and Central Africa

A novel hantavirus, named Kiwira virus, was molecularly detected in six Angolan free-tailed bats (Mops condylurus, family Molossidae) captured in Tanzania and in one free-tailed bat in the Democratic Republic of Congo. Hantavirus RNA was found in different organs, with the highest loads in the spleen. Nucleotide sequences of large parts of the genomic S and L segments were determined by in-solution hybridisation capture and high throughput sequencing. Phylogenetic analyses placed Kiwira virus into the genus Mobatvirus of the family Hantaviridae, with the bat-infecting Quezon virus and Robina virus as closest relatives. The detection of several infected individuals in two African countries, including animals with systemic hantavirus infection, provides evidence of active replication and a stable circulation of Kiwira virus in M. condylurus bats and points to this species as a natural host. Since the M. condylurus home range covers large regions of Sub-Saharan Africa and the species is known to roost inside and around human dwellings, a potential spillover of the Kiwira virus to humans must be considered.     

Laboratory tests in hepatic failure

Laboratory tests of liver function are widely used and often poorly understood. As in any field of medicine, they should be used as part of a diagnostic process involving history-taking and clinical examination. Interpretation of tests will depend on the situation in which they are used: to obtain a diagnosis, to assess prognosis in acute or chronic liver failure or to monitor disease progression and response to treatment.     

Coronary artery bypass in patients with severe left ventricular dysfunction

We retrospectively reviewed the case records of 82 patients with severe left ventricular dysfunction (ejection fraction < 30%) who underwent coronary artery bypass grafting between March 1993 and February 2000. They were aged 28 to 76 years (mean, 60 years), and 66 of them were male. Significant comorbid factors included hypertension (93%), diabetes mellitus (85%), and hypercholesterolemia (49%). The number of grafts used ranged from 1 to 3. The majority of the patients (91%) belonged to the Canadian Cardiovascular Society angina class III. Coronary angiography revealed single-vessel (in 16% of the patients), double-vessel (52%), and triple-vessel disease (32%), and left main stem disease (18%). Seven patients (9%) died within 48 hours after surgery. The mean duration of hospital stay was 7 +/- 2 days. The 75 patients who survived were followed up for 3 months to 7 years. At the 1-year follow-up, 61 of the 68 patients (90%) who were alive moved up from angina class III to class I. Our observations suggest that coronary bypass carries an acceptable mortality risk and may offer a better quality of life in patients with poor ventricular function.