Emergence of a Streptococcus pneumoniae isolate resistant to streptogramins by mutation in ribosomal protein L22 during pristinamycin therapy of pneumococcal pneumonia

OBJECTIVES: The aim of this study was to characterize the mechanism of resistance to macrolides and streptogramins of a Streptococcus pneumoniae strain isolated from blood cultures in an 80-year-old patient suffering from severe pneumonia unsuccessfully treated with pristinamycin. METHODS: Resistance genes erm(B) and mef(A) were searched for by PCR. Portions of genes for domains V and II of the 23S rRNA (rrl) and genes for ribosomal proteins L4 (rplD) and L22 (rplV) were amplified by PCR from total genomic DNA and sequenced. RESULTS: Resistance genes erm(B) and mef(A) were not detected. Only mutation in the rplV gene encoding ribosomal protein L22 was detected. The strain contained a six amino acid insertion ((107)KRTAHI(108)) in the C-terminus of the ribosomal protein L22. CONCLUSIONS: This is the first report of emergence of a pneumococcus resistant to streptogramins by mutation in ribosomal protein L22 during treatment with pristinamycin.     

Comparison of a functional restoration program with active individual physical therapy for patients with chronic low back pain: a randomized controlled trial

OBJECTIVE: To compare the short-term outcomes of active individual therapy (AIT) with those of a functional restoration program (FRP). DESIGN: Prospective randomized controlled study. SETTING: Two rehabilitation centers and private ambulatory physiotherapy facilities. PARTICIPANTS: One hundred thirty-two adults with chronic low back pain. Fifty-one percent of patients on sick leave or out of work (mean duration, 180d in the 2y before treatment). INTERVENTIONS: For 5 weeks, FRP (at 25h/wk) or AIT (at 3h/wk). MAIN OUTCOME MEASURES: Trunk flexibility, back flexor, and extensor endurance (Ito and Sorensen tests), general endurance, pain intensity, Dallas Pain Questionnaire (DPQ) scores, daily activities, anxiety depression, social interest, and work and leisure activities, and self-reported improvement (work ability, resumption of sport and leisure activities). RESULTS: All outcome measures improved after treatment except endurance in AIT. There was no between-group difference for pain intensity or DPQ daily activities or work and leisure activities scores. Better results were observed in FRP for all other outcome measures. There was a significant effect of treatment and the initial value for the gain of the Sorensen score with a treatment or initial value interaction; a significant effect of treatment and initial value on the gains of Ito, endurance, and DPQ social interest and anxiety depression scores, with no treatment or initial value interaction; and a significant effect of initial value but not treatment for the gains of DPQ daily activities and work and leisure activities scores. CONCLUSIONS: Low-cost ambulatory AIT is effective. The main advantage of FRP is improved endurance. We speculate that this may be linked to better self-reported work ability and more frequent resumption of sports and leisure activities.     

Intracortical haematogenous osteomyelitis

We present an unusual case of haematogenous osteomyelitis in the diaphysis of the tibia of an adult leading to a subacute presentation with an extracortical abscess. Fluid from the abscess grew methicillin resistant Staphylococcus aureus (MRSA) on culture; MRSA with the same antibiogram had been grown from the patient’s blood seven years earlier following a bowel resection. Drainage of the abscess and curettage of the bone lesion together with appropriate antibiotic therapy led to resolution of the osteomyelitis.     

F 16915 prevents heart failure-induced atrial fibrillation: a promising new drug as upstream therapy

Atrial fibrillation (AF) is a common complication of heart failure. The aim of the present study was to investigate the effects of a new pure docosahexaenoic acid derivative called F 16915 in experimental models of heart failure-induced atria dysfunction. The atrial dysfunction-induced AF was investigated (1) in a dog model of tachypacing-induced congestive heart failure and (2) in a rat model of heart failure induced by occlusion of left descending coronary artery and 2 months reperfusion. F 16915 (5 g/day for 4 weeks) significantly reduced the mean duration of AF induced by burst pacing in the dog model (989?±?111 s in the vehicle group to 79?±?59 s with F 16915, P?<?0.01). This dose of F 16915 also significantly reduced the incidence of sustained AF (5/5 dogs in the vehicle group versus 1/5 with F 16915, P?<?0.05). In the rat model, the percentage of shortening fraction in the F 16915 group (100 mg/kg p.o. daily) was significantly restored after 2 months (32.6?±?7.4 %, n?=?9 vs 17.6?±?3.4 %, n?=?9 in the vehicle group, P?<?0.01). F 16915 also reduced the de-phosphorylation of connexin43 from atria tissue. The present results show that treatment with F 16915 reduced the heart dilation, resynchronized the gap junction activity, and reduced the AF duration in models of heart failure. Thus, F 16915 constitutes a promising new drug as upstream therapy for the treatment of AF in patients with heart failure.     

Isoelectric focusing of human hemoglobin: its application to screening, to the characterization of 70 variants, and to the study of modified fractions of normal hemoglobins

Isoelectric focusing on slabs of acrylamide gel was adapted for the screening of abnormal hemoglobins, the characterization of 70 human variants, and the study of minor fractions of normal hemoglobin. The screening method was as fast and inexpensive as conventional techniques, allowed the simultaneous analysis of some 50 samples of whole blood, and yielded resolution superior to that obtained by other methods with hemolysates. Among the 70 variants, 31 mutants could not be separated from HbS by cellulose acetate electrophoresis. The characterization technique of electrofocusing allowed us to distinguish between most variants. Only one mutant, Hb Galveston, could be confused with HbS. Hb Koln, the most frequent unstable mutant, exhibited a special pattern. HbA1C was separated from HbA. Preliminary results indicate that quantitation of HbA1C by gel scanning is feasible.     

Stem cell factor retards differentiation of normal human erythroid progenitor cells while stimulating proliferation

Stem cell factor (SCF), the ligand for the c-kit tyrosine kinase receptor, markedly stimulates the accumulation of erythroid progenitor cells in vitro. We now report that SCF delays erythroid differentiation among the progeny of individual erythroid progenitors while greatly increasing the proliferation of these progeny. These effects appear to be independent of an effect on maintenance of cell viability. Highly purified day-6 erythroid colony-forming cells (ECFC), consisting mainly of colony-forming units-erythroid (CFU-E), were generated from human peripheral blood burst-forming units-erythroid (BFU-E). Addition of SCF to the ECFC in serum-free liquid culture, together with erythropoietin (EP) and insulin-like growth factor 1 (IGF-1), resulted in a marked increase in DNA synthesis, associated with a delayed peak in cellular benzidine positivity and a delayed incorporation of 59Fe into hemoglobin compared with cultures without SCF. In the presence of SCF, the number of ECFC was greatly expanded during this culture period, and total production of benzidine-positive cells plus hemoglobin synthesis were ultimately increased. To determine the effect of SCF on individual ECFC, single-cell cultures were performed in both semisolid and liquid media. These cultures demonstrated that SCF, in the presence of EP and IGF-1, acted on single cells and their descendants to delay erythroid differentiation while substantially stimulating cellular proliferation, without an enhancement of viability of the initial cells. This was also evident when the effect of SCF was determined using clones of ECFC derived from single BFU-E. Our experiments demonstrate that SCF acts on individual day-6 ECFC to retard erythroid differentiation while simultaneously providing enhanced proliferation by a process apparently independent of an effect on cell viability or programmed cell death.     

Familial adenomatous polyposis (Gardner's syndrome) and thyroid carcinoma

Summary The case history of a 24-year-old woman with Gardner's syndrome [familial adenomatous polyposis (FAP)] and papillary thyroid carcinoma is presented, representing the 37th report of this association. Although FAP is transmitted as an autosomal dominant trait with similar penetrance in both sexes, thyroid carcinoma has been found almost exclusively in women (94.3%). The majority have been papillary carcinomas (88.5%), which have become apparent during the third decade (average 23.6, range 16–40 years). Most (55.5%) thyroid carcinomas have been discovered 1–17 years after FAP was identified, although some have been found before (29.6%), or at the same time (14.8%) FAP was diagnosed. Multicentric papillary carcinomas have been reported in 64% (14 of 22) of FAP patients, a frequency at least twofold greater than usual. Although papillary carcinoma found before age 30 (as it was in most patients with FAP) typically has an excellent prognosis, one patient with FAP developed distant metastases from thyroid carcinoma and a 28-year-old woman's death was attributed to papillary carcinoma. The high frequency of multicentric papillary thyroid carcinoma in young patients with FAP and the potential for metastases and death due to thyroid carcinoma warrant aggressive diagnostic screening at regular intervals with neck palpation, ultrasonography, and if necessary, fineneedle aspiration biopsy. When thyroid carcinoma is found, total or near-total thyroidectomy should be considered because of the tumor's high likelihood of being multifocal. Since almost 30% of the thyroid carcinomas associated with FAP have been diagnosed 4–12 years before polyposis was identified, young patients presenting with thyroid carcinoma should be questioned regarding bowel function and a family history of gastrointestinal disease, and consideration should be given to periodic testing for fecal occult blood.The views expressed herein are those of the authors and do not necessarily reflect those of the Army or the Department of Defense.