Abnormal esophageal transit in patients with typical reflux symptoms but normal endoscopic and pH profiles

There is a small, well-known cohort of patients who, despite classic reflux symptoms, have a normal esophageal pH profile and endoscopic picture. The treatment of these patients has proved problematic. In an attempt at determining the pathophysiology of this subgroup, we investigated the esophageal transit, using the radiolabeled solid bolus esophageal egg transit technique, in 58 such patients: 25 males, 33 females, mean age 39.5 years (range: 13 to 65 years). The egg transit was normal in 31 (53.4%) patients. In the remaining 27 (46.6%) patients, the condensed image analysis showed the following specific abnormal transit patterns: "step" delay pattern, demonstrating segmental hold-up in mid- or distal esophagus in 16 (59.3%); nonspecific delay in 6 (22.2%); oscillatory pattern in 3 (11.1%); and total nonclearance during the study period (4 minutes) in 2 (7.4%) patients. The patients with abnormal transit patterns had demographic parameters and symptom scores similar to those found in patients with normal transit. This study shows that almost 50% of patients with reflux symptoms and negative pH and endoscopy have abnormal esophageal transit, and almost two thirds of these patients display segmental transit delay in the lower half of the esophagus. The effect on symptomatology by prokinetic agents in the patient subgroup needs evaluation.     

Does early intervention with a light mobilization program reduce long-term sick leave for low back pain?

STUDY DESIGN: A controlled randomized clinical trial was performed. OBJECTIVE: To investigate the effect of a light mobilization program on the duration of sick leave for patients with subacute low back pain. SUMMARY OF BACKGROUND DATA: Early intervention with information, diagnostics, and light mobilization may be a cost-effective method for returning patients quickly to normal activity. In this experiment, patients were referred to a low back pain clinic and given this simple and systematic program as an outpatient treatment. METHODS: In this study, 457 patients sick-listed 8 to 12 weeks for low back pain, as recorded by the National Insurance Offices, were randomized into two groups: an intervention group (n = 237) and a control group (n = 220). The intervention group was examined at a spine clinic and given information and advice to stay active. The control group was not examined at the clinic, but was treated with conventional primary health care. RESULTS: At 12-month follow-up assessment, 68.4% in the intervention group had returned to full-duty work, as compared with 56.4% in the control group. CONCLUSIONS: Early intervention with examination, information, and recommendations to stay active showed significant effects in reducing sick leave for patients with low back pain.     

P-glycoprotein expression in Ehrlich ascites tumour cells after in vitro and in vivo selection with daunorubicin.

Fluctuation analysis experiments were performed to assess whether selection or induction determines expression of P-glycoprotein and resistance in the murine Ehrlich ascites tumour cell line (EHR2) after exposure to daunorubicin. Thirteen expanded populations of EHR2 cells were exposed to daunorubicin 7.5 x 10(-9) M or 10(-8) M for 2 weeks. Surviving clones were scored and propagated. Only clones exposed to daunorubicin 7.5 x 10(-9) M could be expanded for investigation. Drug resistance was assessed by the tetrazolium dye (MTT) cytotoxicity assay. Western blot was used for determination of P-glycoprotein. Compared with EHR2, the variant cells were 2.5- to 5.2-fold resistant to daunorubicin (mean 3.6-fold). P-glycoprotein was significantly increased in 11 of 25 clones (44%). Analysis of variance supported the hypothesis that spontaneous mutations conferred drug resistance in EHR2 cells exposed to daunorubicin 7.5 x 10(-9) M. At this level (5 log cell killing) of drug exposure, the mutation rate was estimated at 4.1 x 10(-6) per cell generation. In contrast, induction seemed to determine resistance in EHR2 cells in vitro exposed to daunorubicin 10(-8) M. The revertant EHR2/0.8/R was treated in vivo with daunorubicin for 24 h. After treatment, P-glycoprotein increased in EHR2/0.8/R (sevenfold) and the cell line developed resistance to daunorubicin (12-fold), suggesting that in EHR2/0.8/R the mdr1 gene was activated by induction. In conclusion, our study demonstrates that P-glycoprotein expression and daunorubicin resistance are primarily acquired by selection of spontaneously arising mutants. However, under certain conditions the mdr1 gene may be activated by induction.     

Cutaneous anergy in pregnant and nonpregnant women with human immunodeficiency virus.

OBJECTIVE: To determine the prevalence of cutaneous anergy in pregnant and nonpregnant women who are seropositive for human immunodeficiency virus. METHODS AND MATERIALS: The medical records of 159 women seropositive for human immunodeficiency virus were reviewed. Demographic characteristics and tuberculin skin test results were abstracted from the chart. Tuberculin skin testing was performed by the Mantoux method (5 tuberculin units of purified protein derivative injected intradermally). Anergy testing was performed using any two of the three following antigens; tetanus toxoid, mumps, or Candida skin test antigen. A positive tuberculin test was defined as induration of 5 mm or more, and a positive test for the other antigens was defined as any amount of induration over the skin test area. Anergy was defined as any amount of induration to the other antigens. A CD4+T lymphocyte count was obtained at the time of skin testing. Continuous variables were analyzed using the Mann Whitney-U test. Categorical data were analyzed with the chi-square or Fisher's exact test as appropriate. A two-tailed P value < 0.05 was considered significant. RESULTS: There were 102 nonpregnant and 57 pregnant women who returned to have their skin test results read. There was no significant difference in the prevalence of positive, negative or anergic skin test results between groups. The CD4+T lymphocyte count (mean +/- standard deviation) in patients with anergic results was similar between pregnant (375 +/- 256/mm3) and nonpregnant (358 +/- 305/mm3) women (P = 0.64). CONCLUSION: The prevalence of cutaneous anergy is similar among pregnant and nonpregnant women seropositive for human immunodeficiency virus.     

Diagnostic imaging of ankle syndesmosis injuries: A general review

Literature on the various techniques for imaging injuries to the ankle syndesmosis to determine the most appropriate imaging modality for diagnosing syndesmosis ligament disruption and instability was reviewed using the following data sources: Pubmed, Google scholar, SportsDiscus, E‐journals and PLOSone. Search terms used were: syndesmosis paired with injury, imaging, radiology, X‐ray, stress X‐ray, arthrography, ultrasound, nuclear medicine scan, CT scan, MRI and arthroscopy. Articles were selected by reading abstracts and the full article if indicated. Further articles were derived from the references of the primary articles. Plain x‐rays of the ankle will detect approximately half on AP view to two‐thirds on mortise view of syndesmosis injuries. Syndesmosis injuries frequently occur in association with tibial or fibular fractures. Intra‐operative stress radiography failed to detect approximately half of instabilities confirmed at arthroscopy. The current benchmark imaging techniques to diagnose syndesmosis injury and diastasis are arthroscopy and high‐power (3T) MRI. Ultrasound is a promising, developing, cost‐effective imaging technique which is yet to reach its full diagnostic potential. CT and nuclear medicine scans have limited roles. MRI (3T) scanning in the plane of the syndesmotic ligaments is the investigation of choice to detect ankle syndesmosis injuries. In the presence of associated injuries requiring surgery, arthroscopic viewing with stress examination is the diagnostic benchmark when available.     

Treatment of osteopenia

The majority of osteoporotic fractures happen in individuals with BMD t-scores in the osteopenic range (?2, 5< t-score <?1). However, widespread use of anti-osteoporotic medication in this group based on t-score alone is not advisable because: 1) the number needed to treat is much higher (NNT?>?100) than in patients with fractured and t-score below ?2,5 (NNT 10?C20); 2)while specific osteoporosis treatments have demonstrated significant reductions of the fracture risk in patients with t-score <?2, 5, the efficacy in patients in the osteopenic range is less well established. Therefore, an osteopenic t-score does not in itself constitute a treatment imperative. Generally, osteopenia has to be associated with either low energy fracture(s) or very high risk for future fracture as assessed with risk calculators like FRAX to warrant specific osteoporosis therapy. Vertebral fractures are now conveniently assessed using lateral x-rays from DXA machines. In the vast majority of cases antiresorptive treatments (mainly hormone replacement therapy and SERMS in younger and bisphosphonates or Denosumab in older women) are the treatments of choice in this group of patients,??only rarely is anabolic therapy indicated.