Neonatal Ureaplasma urealyticum colonization increases pulmonary and cerebral morbidity despite treatment with macrolide antibiotics.

OBJECTIVE: To evaluate the influence of Ureaplasma urealyticum (UU) colonization on neonatal pulmonary and cerebral morbidity. METHODS: Single-center case-control study including all preterm infants with positive UU tracheal colonization between 1990 and 2012. Cases were matched with controls by birth year, gestational age, birth weight, and sex. All cases had received macrolide antibiotics for UU infection starting at the time of first positive culture results from tracheal aspirates. Main outcome parameters included presence and severity of hyaline membrane disease (IRDS), duration of ventilation, bronchopulmonary dysplasia at 36 postmenstrual age and neurological morbidities (seizures, intra-/periventricular hemorrhages-I/PVH, periventricular leukomalacia-PVL). RESULTS: Of 74 cases identified 8 died and 4 had to be excluded; thus, 62 preterm infants were compared to 62 matched controls. UU was significantly associated with IRDS (79 vs. 61 %, p = 0.015), BPD (24 vs. 6 %, p = 0.003), seizures (23 vs. 5 %, p = 0.002) and I/PVH (45 vs. 24 %, p = 0.028). Cases had longer duration of mechanical ventilation and total duration of invasive and non-invasive ventilation (median 11 vs. 6 days p = 0.006 and 25 vs. 16.5 days p = 0.019, respectively). CONCLUSION: UU was found to be significantly associated with pulmonary short- and long-term morbidity and mild cerebral impairment despite treatment with macrolide antibiotics.

Late treatment failures in cerebrospinal fluid in patients on long-term maintenance ART with ritonavir-boosted protease PI monotherapy.

BACKGROUND: Antiretroviral treatment (ART) with ritonavir-boosted protease inhibitor monotherapy (rb-PMT) remains a potentially attractive strategy for treatment simplification in HIV-infected individuals. However, long-term follow-up in particular with respect to HIV-RNA suppression in cerebrospinal fluids (CSF) is still lacking. METHODS: Patients who participated in one of the three monotherapy trials [indinavir/r, ATARITMO (atazanavir/r), MOST (lopinavir/r)] at our HIV clinic and remained successfully suppressed during the entire trial (plasma < 50 copies/mL, CSF < 100 copies/mL) were offered to continue their monotherapy under close monitoring. While on rb-PMT, patients were asked to provide CSF samples in yearly or 2-yearly intervals. All patients fully suppressed in plasma and CSF for at least 12 months were included in the analysis. Patients demonstrating any failure in plasma or CSF resumed triple combined ART. RESULTS: A total of 27 patients (5 women and 22 men) fulfilled the entry criteria. The median follow-up time was 4.8 (1.1-10.9) years with an overall experience of 139 patient-years on monotherapy. Eleven of 27 (41 %) patients (2 women and 9 men) developed virologic failure (1 in plasma only, 4 in CSF only, 4 both in plasma and CSF and 2 in plasma with CSF not available). Plasma failure occurred in 7 patients after a median follow-up of 25 (13-32) months, and CSF failure in 8 patients after a median follow-up of 30 (14-64) months. Seven patients are still on rb-PMT with atazanavir/r. Failure was associated with shorter duration of fully suppressed plasma viral load prior to starting (p < 0.022). CONCLUSION: For selected patients, rb-PMT might be a valid long-term treatment strategy. Nevertheless, even after 12 months of full HIV-RNA suppression, more than 1/3 of patients may still develop failure in either plasma or CSF. Given the observation of isolated CSF failure, treatment monitoring with regular lumbar puncture should be recommended in rb-PMT. Only monotherapy with atazanavir/r was successful beyond 39 months. Monotherapy failure was significantly associated with a shorter duration of complete HIV-RNA suppression in plasma prior to rb-PMT start. Further investigation is needed to better identify predictors for patients that will qualify for successful long-term rb-PMT.

[Purulent lymphadenitis after peritonsillar abscess under immunosuppression. An often forgotten differential diagnosis]. / Eitrige Lymphadenitis nach Abszesstonsillektomie bei Immunsuppression. Eine oft vergessene Differenzialdiagnose.

In the present case study, a 75-year-old, immunosuppressed man presented with recurrent cervical abscesses after a peritonsillar abscess. In the cervical region, an ulcer developed with persistent wound healing deficit. Subsequently, the patient's general condition deteriorated, showing symptoms of a Landouzy sepsis. In the course of the examination, Mycobacteria tuberculosis was detected in the cervical ulcer. He suffered from latent tuberculosis, which was reactivated by a combination of his disease, immunosuppressive therapy and the preceding peritonsillar abscess. Upon treatment with tuberculostatics, the patient fully recovered.

Participation, characteristics and retention rates of HIV-positive immigrants in the Swiss HIV Cohort Study.

OBJECTIVE: Data from observational cohorts may be influenced by population structure and loss to follow-up (LTFU). Quality of care may be associated with participation in cohort networks. We aimed to study the participation, characteristics and retention rates of immigrants in the Swiss HIV Cohort Study (SHCS). METHODS: We compared enrolment over time (1996-1999, 2000-2003 and 2004-2008) and LTFU between individuals from different geographical regions. In 2008, we performed a cross-sectional survey to investigate the proportion of individuals not participating in the SHCS but who were in care at SHCS institutions. Predictors for LTFU were analysed using Cox proportional hazard models, and those for nonparticipation using logistic regression. RESULTS: A total of 7840 individuals entered the SHCS during the observation period. The proportion of immigrants increased over time, especially the proportion of women from sub-Saharan Africa, which increased from 21 to 48% during the observation period. Overall LTFU was 3.76 [95% confidence interval (CI) 3.58-3.95]/100, with the highest hazard ratio in men from sub-Saharan Africa (2.82/100 patient-years; 95% CI 2.30-3.46/100), compared with men from northwestern countries. Other predictors for LTFU were age <30 years, lower education, injecting drug use, and higher baseline CD4 cell counts. Participants taking antiretroviral therapy had reduced LTFU. The survey showed that 84% of HIV-infected patients in care at SHCS institutions were enrolled in the cohort. Nonparticipation was more likely among men from non-European regions (odds ratio 2.73; 95% CI 2.29-3.24), women from sub-Saharan Africa (odds ratio 3.01; 95% CI 2.40-3.77) and women from Latin America/Caribbean (odds ratio 2.10; 95% CI 1.30-3.39). CONCLUSIONS: Numbers of HIV-infected immigrants are increasing but they are underrepresented in the SHCS, and immigrants are more likely to be lost to follow-up.

A randomized blinded trial of combination therapy with cyclophosphamide in patients-with active multiple sclerosis on interferon beta.

OBJECTIVE: To evaluate the efficacy and safety of combination therapy with pulse cyclophosphamide given with methylprednisolone (MP) and interferon beta (IFNbeta)-Ia in multiple sclerosis (MS) patients with active disease during IFNbeta monotherapy. METHODS: This was a randomized, single-blind, parallel-group, multicenter trial in MS patients with a history of active disease during IFNbeta treatment. Patients were randomized to either cyclophosphamide 800 mg/m2 plus methylprednisolone 1 g IV (CY/MP) or methylprednisolone once a month for six months and then followed for an additional 18 months. All patients received three days of methylprednisolone 1 g IV at screening and 30 mcg IFNbeta-Ia IM weekly for the entire 24 months. The primary endpoint was change from baseline in the mean number of gadolinium-enhancing (Gd+) lesions. Secondary clinical endpoints included time to treatment failure. RESULTS: Fifty-nine patients were randomized to treatment: 30 to CY/MP and 29 to MP Change from baseline in the number of Gd+ lesions was significantly different between treatment groups at three (P =0.01), six (P =0.04) and 12 months (P =0.02), with fewer lesions in the CY/MP group. The cumulative rate of treatment failure was significantly lower in the CY/MP group compared with the MP group (rate ratio =0.30; 95% confidence interval, 0.12-0.75; P =0.011). CY/MP treatment was well tolerated. CONCLUSION: Combination therapy with CY/MP and IFNbeta-Ia decreased the number of Gd+ lesions and slowed clinical activity in patients with previously active disease on IFNbeta alone.

Binding of inositol phosphates to arrestin.

Arrestin binds to phosphorylated rhodopsin in its light-activated form (metarhodopsin II), blocking thereby its interaction with the G-protein, transducin. In this study, we show that highly phosphorylated forms of inositol compete against the arrestin-rhodopsin interaction. Competition curves and direct binding assays with free arrestin consistently yield affinities in the micromolar range; for example, inositol 1,3,4,5-tetrakisphosphate (InP4) and inositol hexakisphosphate (InP6 bind to arrestin with dissociation constants of 12 microM and 5 microM, respectively. Only a small control amount of inositol phosphates is bound, when arrestin interacts with phosphorylated rhodopsin. This argues for a release of bound inositol phosphates by interaction with rhodopsin. Transducin, rhodopsin kinase, or cyclic GMP phosphodiesterase are not affected by inositol phosphates. These observations open a new way to purify arrestin and to inhibit its interaction with rhodopsin. Their physiological significance deserves further investigation.

Regulation of rhodopsin kinase by autophosphorylation.

Rhodopsin kinase (RK) catalyzes the phosphorylation of rhodopsin (Rho) as one of the steps in quenching photoactivated Rho. In this work, we investigated the autophosphorylation of RK and how it affects the interaction between RK and Rho. RK undergoes intramolecular phosphorylation, resulting in the incorporation of three or four phosphates per RK molecule. Phosphorylated RK subsequently is a substrate for protein phosphatases 2A and 2B. We isolated three forms of RK based on their differential interactions with heparin-Sepharose. Fully phosphorylated RK (alpha-RK) binds tightly to Rho but has significantly lower affinity to phosphorylated Rho, whereas unphosphorylated RK (gamma-RK) binds avidly to both forms of Rho. The heterogenous intermediately phosphorylated RK (beta-RK) was not studied. Our data support the hypothesis that RK dissociates from Rho when both Rho and RK become phosphorylated, thereby allowing the binding of arrestin to phosphorylated Rho. These results suggest that autophosphorylation plays an important role in regulating the binding of RK to Rho and that the binding sites of RK and arrestin overlap at least partially.

Environmental forces expand management slots for physicians.

Changes in the health care industry and health man-power have had a profound effect on the roles of physicians in hospital and health care management. Modified matrix and team approaches are methods by which physicians can be more effective in a variety of expanded opportunities.

The management of surgical facilities in hospitals.

Hospitals are often faced with the problem of apparent inefficiency or ineffectiveness of operating room management. There can be many contributing factors, and a systematic approach is needed to solve this problem. The article delineates eight management components and suggests that implementation and continuous evaluation of these components will promote the efficient operation of surgical facilities.