WHO Group 5 Drugs and Difficult Multidrug-Resistant Tuberculosis: a Systematic Review with Cohort Analysis and Meta-Analysis

It is often necessary to include WHO group 5 drugs in the treatment of extensively drug-resistant tuberculosis (XDR-TB) and fluoroquinolone-resistant multidrug-resistant tuberculosis (MDR-TB). As clinical evidence about the use of group 5 drugs is scarce, we conducted a systematic review using published individual patient data. We searched PubMed and OvidSP through 7 April 2013 for publications in English to assemble a cohort with fluoroquinolone-resistant MDR-TB treated with group 5 drugs. Favorable outcome was defined as sputum culture conversion, cure, or treatment completion in the absence of death, default, treatment failure, or relapse. A cohort of 194 patients was assembled from 20 articles involving 12 geographical regions. In descending order of frequency, linezolid was used in treatment of 162 (84%) patients, macrolides in 84 (43%), clofazimine in 65 (34%), amoxicillin with clavulanate in 56 (29%), thioridazine in 18 (9%), carbapenem in 16 (8%), and high-dose isoniazid in 16 (8%). Cohort analysis with robust Poisson regression models and random-effects meta-analysis similarly suggested that linezolid use significantly increased the probability (95% confidence interval) of favorable outcome by 57% (10% to 124%) and 55% (10% to 121%), respectively. Defining significant associations by risk ratios ≥ 1.2 or ≤ 0.9, neither cohort analysis nor meta-analysis demonstrated any significant add-on benefit from the use of other group 5 drugs with respect to outcome for patients treated with linezolid, although selection bias might have led to underestimation of their effects. Our findings substantiated the use of linezolid in the treatment of XDR-TB or fluoroquinolone-resistant MDR-TB and call for further studies to evaluate the roles of other group 5 drugs.     

Can Intermittent Dosing Optimize Prolonged Linezolid Treatment of Difficult Multidrug-Resistant Tuberculosis?

We evaluated treatment with linezolid, dosed at 800 mg once daily for 1 to 4 months as guided by sputum culture status and tolerance and then at 1,200 mg thrice weekly until ≥1 year after culture conversion, in addition to individually optimized regimens among 10 consecutive patients with extensively drug-resistant tuberculosis or fluoroquinolone-resistant multidrug-resistant tuberculosis. All achieved stable cure, with anemia corrected and neuropathy stabilized, ameliorated, or avoided after switching to intermittent dosing. Serum linezolid profiles appeared better optimized.     

Dignity Amidst Liminality: Healing Within Suffering Among Chinese Terminal Cancer Patients

This study critically examines the concepts of dignity and liminality at the end-of-life, in an effort to better understand the processes of healing within suffering among Chinese terminal cancer patients receiving palliative care services in Hong Kong. Meaning-oriented interviews were conducted with 18 Chinese terminal patients, aged 44 to 98, to elicit the narratives and stories of their illness experience. All interviews were analyzed using grounded theory and supplemented by ethnographic observations and field notes. Two major themes and eight subprocesses of healing adopted by patients to achieve and maintain dignity were identified: (a) personal autonomy, which encompasses the need to (i) regain control over living environments, (ii) maintain self-sufficiency despite institutional care, (ii) make informed care decisions to reduce sense of burden, and (iv) engage in future planning to create a lasting legacy; and (b) family connectedness, which encompasses the need to (i) maintain close ties with family members to express appreciation, (ii) achieve reconciliation, (iii) fulfill family obligations, and (iv) establish a continuing bond that transcends generations. Implications of these themes for advanced care planning and life review interventions were discussed with the goal of enhancing patient autonomy and family connectedness, and thereby providing structure and meaning for Chinese terminal patients and their families at the end of life.     

Computed tomography in the diagnosis of early ankylosing spondylitis

Computed tomography (CT) was compared with plain radiography and quantitative sacroiliac (SI) scintigraphy in 28 patients with early ankylosing spondylitis (AS) of less than or equal to 10 years duration. Compared with conventional radiography, CT improved delineation of the SI joints and revealed more abnormalities and higher grades of sacroiliitis; this was significant in patients with early AS of less than or equal to 3 years duration. Quantitative sacroiliac scintigraphy showed higher SI joint: sacrum ratios of radioisotope uptake in patients with AS compared with controls. However, its diagnostic usefulness was limited by the frequency of inconsistent results and the lack of specificity. CT examination of the SI joints may be a useful adjunct in the diagnosis of early AS.     

Gastric mucosal blood flow in rats after administration of 16,16-dimethyl prostaglandin E2 at a cytoprotective dose

The purpose of the present study was to determine whether the gastric cytoprotective effect of a prostaglandin such as 16,16-dimethyl prostaglandin (dmPGE2) is mediated by an increase in mucosal blood flow. Gastric mucosal blood flow was measured in urethane-anesthetized rats by the hydrogen gas clearance technique. In control rats given no ethanol, intragastric administration of dmPGE2 (10 micrograms/kg body wt) produced a significant reduction (15.3%) in gastric mucosal blood flow 30 min after treatment. This dose of dmPGE2 significantly reduced the formation of the gross gastric lesions produced by absolute ethanol in anesthetized rats. In vehicle-pretreated animals, blood flow was invariably absent in the ethanol-induced mucosal lesion areas. In the nonlesion areas, gastric mucosal blood flow was the same in prostaglandin-pretreated and vehicle-pretreated animals as in control (no ethanol) rats. Thus, although dmPGE2 pretreatment protected against ethanol-induced gastric mucosal injury and prevented the accompanying blood flow stasis, it did not do this by an increase in gastric mucosal blood flow. The protection also is not due to a decrease in flow because, in separate groups of anesthetized rats, a 15% reduction in gastric mucosal blood flow induced by either hemorrhage or intravenous vasopressin did not protect the gastric mucosa against absolute ethanol-induced injury. Whether the maintenance of gastric mucosal blood flow is a primary or secondary effect of prostaglandin cytoprotection remains to be determined.     

Luteinizing hormone-releasing hormone stimulates arachidonic acid release in rat granulosa cells

The effect of LHRH on arachidonic acid release was studied in rat granulosa cells in primary culture. In cells prelabeled with [3H]arachidonic acid, LHRH caused an increase in the level of [3H]arachidonic acid released in the culture medium, to 125-150% of control levels at the end of a 60-min incubation period. In subsequent time-course and dose-response experiments, a significant effect on [3H]arachidonic acid release could be observed as early as 15 min after LHRH addition, and the lowest effective dose was 10(-8) M LHRH. Addition of LH, FSH, prostaglandin F2 alpha, or (Bu)2cAMP was without effect. Likewise, an agonistic LHRH analog (LHRHa, 10(-8) M) also markedly stimulated [3H]arachidonic acid from cultured granulosa cells, and the effects of both LHRH and LHRHa were blocked by concomitant presence of a potent LHRH antagonist. In addition to [3H]arachidonic acid release in the culture medium, the effect of LHRH on the level of radiolabel present in cellular phospholipids was also examined. In granulosa cells prelabeled with [3H] arachidonic acid, LHRH significantly depleted the level of radioactivity previously incorporated into cellular phosphatidylinositol, as early as 5 min after its addition, to 85% of control levels. The level of radiolabel found in other major phospholipids such as phosphatidylserine/phosphatidylcholine and phosphatidylethanolamine, as well as the intracellular level of unesterified [3H]arachidonic acid, were not significantly affected by LHRH. The effect of LHRH on [3H]arachidonic acid release from prelabeled phospholipids as well as the LHRH-induced loss of radioactivity previously incorporated into phosphatidylinositol could be reversed by verapamil, suggesting a possible calcium dependency. Taken together, these data support the notion that arachidonic acid liberation from phospholipids may be associated with the mechanism of action of LHRH on ovarian cells.     

Hypoglossal nerve palsy in nasopharyngeal carcinoma.

BACKGROUND: The aim of the study was to use magnetic resonance (MR) imaging to determine the cause of hypoglossal nerve palsy and the sites of injury in patients with nasopharyngeal carcinoma before radiation therapy and during postradiation therapy follow-up. METHODS: The clinical records and MR studies of 21 patients with hypoglossal nerve palsy were retrospectively studied. These 21 patients belonged to a cohort of 387 patients with nasopharyngeal carcinoma (153 with newly diagnosed disease and 234 on postradiation follow-up) who underwent MR imaging in a 2.5-year period. RESULTS: Four patients had hypoglossal nerve palsy at initial diagnosis and all of them had extensive skull base invasion from tumor extending postero-inferiorly to the level of the foramen magnum. The nerve was invaded in the carotid sheath (3), hypoglossal nerve canal (3), and premedullary cistern (1). In 17 patients developing hypoglossal nerve palsy after radiotherapy, only two (12%) had evidence of tumor recurrence. Radiation-induced neuropathy was the probable cause in 14 patients and 1 case was judged indeterminate. MR evidence of fibrosis was demonstrable along the course the nerve in four patients (29%), involving the carotid sheath (4), hypoglossal nerve canal (2), and premedullary cistern (1). No patient had MR evidence of radiation change in the brain stem. Seven patients had a history of a boost dose of radiation to the parapharyngeal region on one or both sides, and nerve palsy occurred on the boosted side in six of them. CONCLUSION: Hypoglossal nerve palsy on presentation was caused by locally advanced nasopharyngeal tumor whereas a palsy arising after radiation therapy was more frequently caused by postradiation damage rather than cancer.     

Survey of Vitamin and Mineral Supplementation after Gastric Bypass and Biliopancreatic Diversion for Morbid Obesity

Background: The authors investigated whether practice patterns of bariatric surgeons correlate with published data regarding metabolic deficiencies after Roux-en-Y gastric bypass (RYGB) and biliopancreatic diversion (BPD). Methods: 109 surgeons completed a questionnaire to determine use of supplements and frequency of lab tests. Results: Regarding supplements routinely prescribed after RYGB, 96% of surgeons gave multivitamins, 63% gave iron, and 49% gave vitamin B₁₂. After BPD, 96% of surgeons gave multivitamins, 67% gave iron, 42% gave vitamin B₁₂, 97% gave calcium, 63% gave fat-soluble vitamins, and 21% gave protein supplements. Regarding laboratory tests obtained routinely after RYGB, 95% of surgeons do complete blood counts, 56% do iron determinations, 66% do vitamin B₁₂ determinations, 58% do folate determinations, 76% do electrolyte determinations, and 8% test for proteins. After BPD, 96% of surgeons do complete blood counts, 80% do iron determinations, 67% do vitamin B₁₂ determinations, 71% do folate determinations, 88% do electrolyte determinations, 84% do protein determinations, and 46% test for fat-soluble vitamins. Regarding frequency of blood tests, after RYGB, 22% of surgeons obtain them after 3 months, 33% after 6 months, and 41% after 12 months; 4% do not routinely obtain postoperative laboratory tests. After BPD, 46% of surgeons obtain them after 3 months, 33% after 6 months, and 16% after 12 months; one does not obtain laboratory tests. Surgeons estimated these deficiencies after RYGB: 16% iron, 12% vitamin B₁₂, 14% anemia, 5% protein, and 3% calcium. They estimated these deficiencies after BPD: 26% iron, 11% vitamin B₁₂, 21% anemia, 18% protein, 16% calcium, and 6% fat-soluble vitamins. The estimated incidence of deficiencies after RYGB was considerably lower than the published incidence. Unnecessary tests were commonly performed (electrolytes after RYGB). Conclusion: Despite wide variations in the performance of laboratory tests and the use of supplements, the practice patterns of most surgeons protect patients from developing severe metabolic deficiencies after RYGB and BPD.     

Effects of dobutamine on hemodynamics and left ventricular performance after cardiopulmonary bypass in cardiac surgical patients.

BACKGROUND: Dobutamine is commonly used to improve ventricular performance after cardiopulmonary bypass. The authors determined the effect of dobutamine on hemodynamics and left ventricular performance immediately after cardiopulmonary bypass in patients undergoing coronary artery bypass graft surgery. METHODS: One hundred patients received sequential 3-min infusions of dobutamine at 0-40 microg x kg(-1) x min(-1) immediately after cardiopulmonary bypass. Ten additional patients who received no dobutamine served as controls. Hemodynamics and left ventricular performance (fractional area change by transesophageal echocardiography, stroke volume index, and thermodilution cardiac index) were measured. Mixed-effects modeling accounted for repeated-measures data and interindividual differences and allowed for potential effects of covariates. RESULTS: Heart rate increased in a dose-dependent manner. The slope of HR versus dobutamine dose was steeper in individuals in whom peak dobutamine dose was not reached compared with that in the remaining individuals; slope decreased 2.71 +/- 0.68% per year of age. Dobutamine affected blood pressure minimally, but slightly decreased pulmonary capillary wedge pressure and central venous pressure. Systemic vascular resistance initially increased with dobutamine 10 microg x kg(-1) x min(-1) and remained constant with larger doses. Dobutamine produced a dose-dependent increase in left ventricular performance, primarily by increasing heart rate, because stroke volume index decreased with dobutamine dose. CONCLUSION: Our results suggest that the response to graded dobutamine infusion in the post-cardiopulmonary bypass period differs from that previously reported. After cardiopulmonary bypass, the dominant mechanism by which dobutamine improves left ventricular performance is by increasing heart rate. Dobutamine affects blood pressure minimally.