Maculopapular eruption with enlarged macrophages in eight patients receiving G-CSF or GM-CSF

In the last years, granulocyte and granulocyte-macrophage colony-stimulating factors (G-CSF and GM-CSF) are being increasingly used and several cutaneous eruptions have been reported in relation to these treatments. In 1991 Horn et al. described three patients with maculopapular eruption that paralleled the time of infusion of GM-CSF. Two of the cases showed an increase in the number and size of macrophages in the biopsy specimen. Since then, several cases have been reported showing this histopathological alteration that has been considered characteristic of reaction to G-CSF or GM-CSF. Although maculopapular eruption with enlarged macrophages can appear after chemotherapy treatment, we have found that the presentation of this eruption after the beginning of cytokine treatment is suggestive of the involvement of G-CSF and GM-CSF in the eruption. We described eight cases of patients treated with G-CSF or GM-CSF that developed maculopapular eruptions with enlarged macrophages.     

'Acute on chronic' effect of depot leuprolide in patients with stage D2 cancer of prostate

During a phase III open study of depot leuprolide for stage D2 cancer of the prostate, we studied the effect of depot leuprolide on chronic leuprolide users. To determine whether there was a transient elevation of testosterone or luteinizing hormone (LH) 4-24 h and 3-5 days following the monthly injections, we monitored the changes of testosterone and LH before injection and 24 h post-injection in 10 patients who have been under depot leuprolide Rx for 24-36 weeks, and in 35 patients before injection and 3-5 days post-injection who have received depot leuprolide for 8-24 weeks prior to monitoring. Comparison of the data between pre-injection within 24 h and 3-5 days post-injection showed no significant changes of testosterone and LH values between these levels for either testosterone (P = 0.31) or LH (P = 0.45). We therefore conclude that there was no 'acute on chronic' effect of depot formulation in chronic users of depot leuprolide.     

Oocyte morphology predicts outcome of intracytoplasmic sperm injection

To examine the influence of cytoplasmic morphology on the success rate of intracytoplasmic sperm injection (ICSI), the morphology of 837 metaphase II oocytes was assessed after cumulus stripping. The main abnormalities detected were excessive granularity, cytoplasmic inclusions such as vacuoles, smooth endoplasmic reticulum clustering and refractile bodies. Microinjection was performed in 538 oocytes with normal cytoplasm, 142 out of 161 with excessive granularity and 112 out of 138 with cytoplasmic inclusions. Very poor oocytes were not injected. No difference was found in fertilization rate. The embryos achieved cleaved normally and a similar number of good quality embryos among the three groups was noted. The outcome of transfer of embryos derived solely from normal oocytes (group A: 72 patients, 183 embryos) was compared with those from oocytes with cytoplasmic abnormalities (group B: 34 patients, 85 embryos). In group A, 17 clinical pregnancies (24% per patient, implantation rate 10%) were established. In group B, only one clinical pregnancy (3% per patient, implantation rate 1%) was established, from the transfer of embryos derived from oocytes with homogeneous granularity of the cytoplasm. No pregnancy resulted following the transfer of embryos from eggs with cytoplasmic inclusions. The difference was statistically significant. The outcome of ICSI is dependent on the quality of the oocytes retrieved. Normal fertilization and early embryo development were achieved in oocytes with abnormal cytoplasm morphology, but the resulting embryos failed to demonstrate the same implantation potential as those derived from oocytes with normal cytoplasm.      

Comparison of the structure of human intervertebral discs in the cervical,thoracic and lumbar regions of the spine

Posterior and anterior heights, cross-sectional area and shape were measured for all the intervertebral discs in four spines from elderly human cadavers. Disc height was a minimum at the T4-5 level; thoracic discs were less wedge-shaped than those in the cervical and lumbar regions. Cross-sectional area increased from the cranial to caudal extremity; at the L5-S1 level the nucleus pulposus occupied a high proportion of this area. Cervical discs tended to have an elliptical cross-sectional shape, thoracic discs were more circular and lumbar discs tended to have an elliptical cross-section which was flattened or re-entrant posteriorly. This shape distribution was quantified by defining a shape index which had a maximum value of 1 for a circular cross-section. Orientations of the reinforcing fibres in the outer lamellae of the anterior annulus fibrosus were measured from 27 discs by X-ray diffraction. For these measurements, C3-4, T7-8 and L2-3 were chosen as representative of cervical, thoracic and lumbar discs. The fibre tilt, with respect to the axis of the spine, was significantly less in the cervical discs (at 65 degrees) than in the thoracic and lumbar discs (about 70 degrees). These findings are interpreted in relation to differing functional requirements and possible mechanisms of failure in the cervical, thoracic and lumbar regions of the spine in the light of current knowledge on the biomechanics of the intervertebral disc.     

The distribution of erythrocyte phospholipids in hereditary spherocytosis demonstrates a minimal role for erythrocyte spectrin on phospholipid diffusion and asymmetry

In the human erythrocyte membrane phosphatidylcholine and sphingomyelin reside mainly in the outer leaflet, whereas the aminophospholipids, phosphatidylethanolamine and phosphatidylserine, are mainly found in the inner leaflet. Maintenance of phospholipid asymmetry has been assumed to involve interactions between the aminophospholipids and the membrane skeleton, in particular spectrin. To investigate whether spectrin contributes to maintaining the phospholipid transbilayer distribution and kinetics of redistribution, we studied erythrocytes from hereditary spherocytosis patients whose spectrin levels ranged from 34% to 82% of normal. The phospholipid composition and the accessibility of membrane phospholipids to hydrolysis by phospholipases were in the normal range. Spin-labeled phosphatidylserine and phosphatidylethanolamine analogues that had been introduced into the outer leaflet were rapidly transported at 37 degrees C to the inner leaflet, whereas the redistribution of spin-labeled phosphatidylcholine was slower. The kinetics of transbilayer movement of these spin-labeled phospholipid in all samples was in the normal range and was not affected by the level of spectrin. Although these erythrocyte membranes contained as little as 34% of the normal level of spectrin and were characterized by several physical abnormalities, the composition, distribution, and transbilayer kinetics of the phospholipids were found to be normal. We therefore conclude that spectrin plays, at best, only a minor role in maintaining the distribution of erythrocyte membrane phospholipid.     

Infection-related ventilator-associated complications in ICU patients colonised with extended-spectrum β-lactamase-producing Enterobacteriaceae

Purpose

To investigate the clinical significance of infection-related ventilator-associated complications (IVAC) and their impact on carbapenem consumption in mechanically ventilated (MV) patients colonised with extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBLE).

Methods

Inception cohort study from the French prospective multicenter OUTCOMEREA database (17 ICUs, 1997–2015) including all ESBLE carriers (systematic rectal swabbing at admission then weekly and/or urinary or superficial surgical site colonisation) with MV duration?>?48 h and?≥?1 episode of IVAC after carriage documentation. All ICU-acquired infections were microbiologically documented.

Results

The 318 enrolled ESBLE carriers (median age 68 years; males 67%; medical admission 68%; imported carriage 53%) experienced a total of 576 IVAC comprising 361 episodes (63%) without documented infection, 124 (21%) related to infections other than ventilator-associated pneumonia (VAP), 73 (13%) related to non-ESBLE VAP and 18 (3%) related to ESBLE VAP. Overall, ESBLE infections accounted for only 43 episodes (7%). Carbapenem exposure within the preceding 3 days was the sole independent predictor of ESBLE infection as the causative event of IVAC, with a protective effect (adjusted odds ratio 0.2, 95% confidence interval 0.05–0.6; P?<?0.01). Carbapenems were initiated in 9% of IVAC without infection, 15% of IVAC related to non-VAP infections, 42% of IVAC related to non-ESBLE VAP, and 56% of IVAC related to ESBLE VAP (ESBLE VAP versus non-ESBLE VAP: P?=?0.43).

Conclusions

IVAC in ESBLE carriers mostly reflect noninfectious events but act as a strong driver of empirical carbapenem consumption. ESBLE infections are scarce yet hard to predict, strengthening the need for novel diagnostic approaches and carbapenem-sparing alternatives.

     

Efficacy and safety of ciprofloxacin oral suspension versus trimethoprim-sulfamethoxazole oral suspension for treatment of older women with acute urinary tract infection

OBJECTIVES: To compare the efficacy and safety of ciprofloxacin (CIP) oral suspension to trimethoprim/sulfamethoxazole (TMP/SMX) oral suspension among older women with acute urinary tract infections (UTIs). DESIGN: Prospective, randomized, open-label, multicenter study of older women (age 65 and older). SETTING: Community and nursing home. PARTICIPANTS: A total of 261 older women were evaluable for safety. Of these, 172 (86 community, 86 nursing home) were evaluable for clinical and bacteriological efficacy. INTERVENTION: Patients were randomized to a 10-day regimen of either CIP (250 mg/5 mL twice daily) or TMP/SMX (160/800 mg/20 mL twice daily). MEASUREMENTS: Clinical response 4 to 10 days posttherapy. RESULTS: For the efficacy-valid population, posttherapy clinical resolution was statistically superior following CIP (97%) versus TMP/SMX (85%) (95% CI=2.0-21.3; P= .009). Eradication of pretreatment bacterial isolates posttherapy was also higher following CIP (95%) versus TMP/SMX (84%) (95% CI=2.7-21.3; P= .019). For the intent-to-treat population, posttherapy clinical resolution was significantly higher in the CIP group (96%) than in the TMP/SMX group (87%) (95% CI=0.2-16.7; P= .025). Safety was assessed in the intent-to-treat population and the incidence of drug-related adverse events were significantly lower following CIP (17%) than following TMP/SMX (27%) (P= .047). Premature discontinuation due to these events was also less prevalent with CIP than with TMP/SMX (2% vs 11%, respectively) (P= .004). CONCLUSION: CIP suspension showed higher clinical success and bacteriological eradication rates than did TMP/SMX for both community-based and nursing home-residing older women with acute UTIs. Furthermore, CIP suspension was associated with significantly lower rates of adverse events and premature discontinuations compared with TMP/SMX suspension.