A vaccine against coccidioidomycosis is justified and attainable.

Coccidioides is a fungal pathogen of humans which can cause a life-threatening respiratory disease in immunocompetent individuals. Recurrent epidemics of coccidioidal infections in Southwestern United States has raised the specter of awareness of this soil-borne microbe, particularly among residents of Arizona and Southern California, and has galvanized research efforts to develop a human vaccine against coccidioidomycosis. In this review, we discuss the rationale for such a vaccine, examine the features of host innate and acquired immune response to Coccidioides infection, describe strategies used to identify and evaluate vaccine candidates, and provide an update on progress toward development of a vaccine against this endemic pathogen.     

A de novo mutation affecting human TrkB associated with severe obesity and developmental delay

An 8-year-old male with a complex developmental syndrome and severe obesity was heterozygous for a de novo missense mutation resulting in a Y722C substitution in the neurotrophin receptor TrkB. This mutation markedly impaired receptor autophosphorylation and signaling to MAP kinase. Mutation of NTRK2, which encodes TrkB, seems to result in a unique human syndrome of hyperphagic obesity. The associated impairment in memory, learning and nociception seen in the proband reflects the crucial role of TrkB in the human nervous system.     

Saliva as a diagnostic specimen for testing respiratory virus by a point-of-care molecular assay: a diagnostic validity study

Objectives

Automated point-of-care molecular assays have greatly shortened the turnaround time of respiratory virus testing. One of the major bottlenecks now lies at the specimen collection step, especially in a busy clinical setting. Saliva is a convenient specimen type that can be provided easily by adult patients. This study assessed the diagnostic validity, specimen collection time and cost associated with the use of saliva.

Endometrial and subendometrial blood flow measured during early luteal phase by three-dimensional power Doppler ultrasound in excessive ovarian responders

BACKGROUND: Impaired implantation in assisted reproduction cycles with high serum estradiol (E(2)) concentrations may be related to suboptimal endometrial perfusion. Endometrial and subendometrial blood flow were compared between excessive responders (serum E(2) on the day of HCG >20 000 pmol/l) and moderate responders (E(2) < or =20 000 pmol/l). METHODS: Three-dimensional (3D) ultrasound examination with power Doppler was performed 2, 4 and 7 days after HCG in 32 patients who did not have embryo transfer in order to measure endometrial thickness, pulsatility index (PI)/resistance index (RI) of uterine vessels, and endometrial volume, vascularization index (VI)/flow index (FI)/vascularization flow index (VFI) of endometrial and subendometrial regions. RESULTS: Excessive responders tended to have lower endometrial and subendometrial VI/VFI on HCG +2 and more absent endometrial/subendometrial blood flow. They had significantly higher endometrial FI and subendometrial VFI than moderate responders on HCG +7. Only in the excessive responder group, uterine PI/RI declined significantly from HCG +2 to HCG +7 and endometrial VI/VFI increased significantly from HCG +4 to HCG +7. CONCLUSION: Changes in uterine Doppler flow indices, and endometrial and subendometrial 3D power Doppler flow indices during the early luteal phase were significantly different between moderate and excessive responders.     

Neonatal sepsis in the neonatal intensive care unit: characteristics of early versus late onset.

Neonatal sepsis is a major cause of death in newborns despite sophisticated neonatal intensive care. This retrospective study reviewed the clinical characteristics of cases of culture-proven sepsis in a neonatal intensive care unit from January 1992 to December 2001. Patients were divided into those with onset of sepsis in the first 7 days of life (early-onset group) and those with onset after the seventh day of life (late-onset group). A total of 270 cases with 325 episodes of sepsis and 353 isolated pathogens were identified and included in the study. The male-to-female ratio was 1.4. The majority of cases of sepsis occurred in low birth weight (75.9%) and premature babies (76.7%). Late onset occurred in 71.9% of cases. Patients with late onset had a lower mortality rate than those with early onset (11.3% vs 28.9%). Coagulase-negative staphylococci (20.1%) was the most common organism isolated, but infection with Pseudomonas aeruginosa was associated with the highest morality rate (55.0%). Late-onset sepsis was significantly more common in very low birth weight and premature infants. The most frequently encountered pathogens in the early-onset group were group B streptococci (GBS) and Escherichia coli, while in the late-onset group, the organisms were coagulase-negative staphylococci and Enterobacteriaceae, including E. coli, Klebsiella pneumoniae, and Acinetobacter baumannii. GBS infection resulted in the highest mortality when the onset of sepsis was within the first 24 hours of life.     

Evaluation and Validation of an Enzyme-Linked Immunosorbent Assay and an Immunochromatographic Test for Serological Diagnosis of Severe Acute Respiratory Syndrome

A newly developed severe acute respiratory syndrome (SARS)-specific enzyme-linked immunosorbent assay (ELISA) was further validated to confirm cutoff values and evaluate its diagnostic performance with clinical samples. In parallel, an immunochromatographic test was also evaluated. A total of 227 clinical serum specimens collected from SARS patients were used in the study, together with 385 samples from healthy donors. By use of an immunofluorescent (IF) test as the “gold standard, ” both the ELISA and the immunochromatographic test were able to detect immunoglobulin G antibodies to SARS not only from late-convalescent-stage samples (>21 days from the onset of clinical symptoms), as previously established, but also from early-acute-phase samples (1 to 10 days from onset). The ELISA, using an optical density (OD) of 0.25 as its cutoff value, produced the best sensitivity while maintaining high specificity. It detected SARS-specific antibodies in 58, 70, 75, and 95%, respectively, of the four groups of samples collected from patients 1 to 10 days, 11 to 20 days, 21 to 30 days, and more than 30 days after the onset of clinical symptoms. Similarly, the immunochromatographic test detected SARS-specific antibodies in 55, 68, 81, and 79% of the four groups, respectively. The overall specificities for the ELISA and the rapid test were 99.5 and 97.7%, respectively. Although the positive correlation observed between the ELISA OD values and the IF titers was moderate (r = 0.6915; P < 0.001), the detection rates of both the ELISA and the rapid test were found well in agreement with the IF titers.     

An autopsy-proved case of AIDS in Taiwan

The first case of AIDS positively identified in a non-foreigner in Taiwan was a 25-year-old unmarried male who had practiced homosexuality for ten years. The patient began to have abdominal pain accompanied with loose stools and weight loss in June 1985, followed by fever, cough, headache, dizziness, and loss of memory. Facial hyperpigmentation and extensive oroesophageal candidiasis were noted. Laboratory studies showed severe lymphopenia with a reversed T-helper to T-suppressor ratio, cutaneous anergy and polyclonal gammopathy. Human immunodeficiency virus (HIV) antibodies were positive by ELISA and Western blot, and the virus was isolated from the blood. At autopsy, disseminated cytomegalovirus infection, extensive CNS toxoplasmosis and early lesions of Kaposi's sarcoma were demonstrated. The detection of HIV in the adrenal medulla supports the consensus that the virus is neurotropic.     

Community-acquired anaerobic bacteremia in adults: one-year experience in a medical center.

A prospective observational study was conducted to evaluate the clinical characteristics and outcome of community-acquired anaerobic bacteremia. From June 1 2001 through May 31 2002, 52 patients with community-acquired anaerobic bacteremia were enrolled at the emergency department in a teaching hospital. There were 19 patients (34%) with polymicrobial bacteremia and Escherichia coli was the most common copathogen (n = 6). Of 62 anaerobic isolates, species of the Bacteroides fragilis group were the most common isolates (n = 28, 45%), followed by Clostridium spp. (n = 11, 18%). Among the 52 patients enrolled, up to 27% had underlying malignancy and the gastrointestinal tract accounted for 48% of the sources of infection. Clinical manifestations suggesting anaerobic infections were common and three-quarters (n = 39) of 52 patients received adequate empirical antimicrobial treatment. Documentation of anaerobic bacteremia seldom influenced antimicrobial treatment. The 30-day mortality was 25%. Although univariate analysis revealed that underlying malignancy (p=0.003), leukopenia (p=0.044) and absence of fever (p=0.047) were associated with mortality, only malignancy (p=0.007) was an independent risk factor in the multivariate analysis.     

Rapid and complete donor chimerism after unrelated mismatched cord blood transplantation in 5 children with beta-thalassemia major.

Hematopoietic stem cell transplantation is currently the only curative therapy for beta-thalassemia major. However, <30% of patients have unaffected HLA-identical siblings to serve as donors. We investigated the feasibility of using umbilical cord blood transplants from unrelated HLA mismatched donors and a myeloablative preparative regimen that did not involve total body irradiation. Between October 2003 and November 2004, 5 children with beta-thalassemia major received busulfan, cyclophosphamide, and antithymocyte globulin before cord blood transplantation (median dose, 8.8 x 10(7) cells per kilogram of body weight) from unrelated donors (1 or 2 of 6 HLA antigens were mismatched) and were then evaluated for engraftment, adverse effects, and treatment outcome. The median times to neutrophil engraftment, red blood cell transfusion independence, and platelet engraftment were 12, 34, and 46 days after transplantation, respectively. All patients showed grade II or III acute graft-versus-host disease; none developed extensive chronic graft-versus-host disease until the date of last contact. All patients were alive at a median follow-up of 303 days after transplantation, with complete donor chimerism and transfusion independence. These results are encouraging and clearly show the feasibility of unrelated mismatched umbilical cord blood transplantation in the treatment of children with beta-thalassemia major.     

A randomized study comparing the use of sublingual to vaginal misoprostol for pre-operative cervical priming prior to surgical termination of pregnancy in the first trimester

BACKGROUND: Misoprostol is an effective agent for pre-operative cervical priming before surgical termination of pregnancy in the first trimester. Previous studies have shown that both oral and vaginal routes are equally effective for such a purpose. This study aimed to compare a new route of sublingual administration to the vaginal route of administration for pre-operative cervical priming in first trimester surgical abortion. METHODS: Eighty women with gestational age <12 weeks were randomized by a computer-generated model to receive 400 micro g of misoprostol either sublingually or vaginally 3 h prior to vacuum aspiration. The primary outcome measure was the degree of cervical dilatation, and secondary outcomes included the force required to dilate the cervix from 3 to 8 mm, intra-operative blood loss and incidence of pre-operative side-effects. RESULTS: There was no significant difference in the baseline cervical dilatation (sublingual: 7.6 +/- 1.3 mm; vaginal: 7.7 +/- 0.73 mm), cumulative force required to dilate the cervix from 3 to 8 mm (sublingual: 9.0 +/- 9.8 N; vaginal: 6.6 +/- 5.4 N) and total blood loss (sublingual: 52.1 +/- 20.2 ml; vaginal: 48.3 +/- 12.3 ml). Pre-operative side-effects were also similar. CONCLUSIONS: Both sublingual and vaginal misoprostol are effective in cervical priming before surgical termination of pregnancy in the first trimester. Sublingual misoprostol has the advantage of being more convenient to administer and may be more suitable for day surgery.