Scleroderma lung disease, variation in screening, diagnosis and treatment practices between rheumatologists and respiratory physicians.

BACKGROUND: Interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH) represent the leading causes of death in systemic sclerosis (SSc). Screening for these complications has assumed greater importance, but is not universal. The aim of this study is to determine the self-reported screening, diagnosis and treatment practices of rheumatologists and respiratory physicians for SSc-related lung disease. METHODS: Email survey of 270 rheumatologists and 600 respiratory physicians. RESULTS: Responses were received from 42 (16%) rheumatologists and 68 (11%) respiratory physicians. Of SSc patients seen by rheumatologists, 17% had ILD and 7.5% had a diagnosis of PAH compared with 31% and 21% for respiratory physicians. Forty per cent of all physicians screened asymptomatic SSc patients without a known diagnosis of ILD or PAH less than annually or not at all. The most commonly used screening investigations were pulmonary function tests (PFT) (95%) and transthoracic echocardiogram (TTE) (78%). In suspected ILD, both groups used high-resolution computed tomography scans and PFT in >90% of patients. In suspected PAH, both used TTE and PFT (>90%); right heart catheterisation was used by only 50% of physicians. In treatment of ILD, rheumatologists used intravenous (IV) cyclophosphamide more often (CYC) (59% vs 28%, P= 0.003) and more respiratory physicians used oral CYC (44% vs 28%, P= 0.012). In PAH, more respiratory physicians used warfarin (68% vs 40%, P= 0.006). Only approximately 65% of physicians had used specific PAH therapy, which may reflect lack of access to a designated PAH treatment centre. CONCLUSION: The heterogeneity of responses revealed in this study raises the importance of screening, diagnosis and treatment algorithms in the management of this potentially life-threatening disease.

Hospital-based directly observed therapy for HIV-infected children and adolescents to assess adherence to antiretroviral medications.

BACKGROUND: The introduction of highly active antiretroviral therapy for HIV led to significant declines in HIV-associated morbidity and mortality in children. Nonadherence to antiretroviral therapy is the leading cause of treatment failure in HIV-infected patients. The ability to recognize nonadherence is suboptimal, and differentiating it from other causes of inadequate viral suppression may be difficult. OBJECTIVES: The purpose of this work was to examine the efficacy of hospital-based directly observed therapy in assessing adherence to antiretroviral medications in HIV-infected children and adolescents suspected of nonadherence and failing other interventions. METHODS: The medical charts of all HIV-infected patients admitted to the University of Chicago Comer Children's Hospital for directly observed therapy from July 2004 to June 2006 were reviewed. Patients were hospitalized for 7 days. Data collected included demographics, clinical and immune class category, previous and current antiretroviral medications, viral resistance tests, HIV-1 RNA viral load, and CD4+ T-cell number and percentage before and after directly observed therapy. RESULTS: There were 9 perinatally infected patients with a total of 13 admissions. The median age was 13 years, and 8 had been treated with multiple antiretroviral regimens. Three common patterns of changes in the viral load over time were observed. In the first, the viral load dropped at the end of the directly observed therapy period and stayed low thereafter. In the second, the drop in the viral load seen at the end of the period was not sustained. In the third, there was no change in the viral load during or after the directly observed therapy period. Compared with the viral load at admission, the viral load at the end of directly observed therapy was lower in 8 patients with a mean +/- SD decrease of 0.8 +/- 0.55 log10 copies per mL. CONCLUSIONS: Short, hospital-based directly observed therapy was helpful in confirming nonadherence to antiretroviral medications, therefore impacting future therapeutic decisions in HIV-infected children and adolescents. Short, hospital-based directly observed therapy should be considered in patients with poor virological control for whom outpatient interventions have failed.

Hypoxia inducible factor 1 alpha regulates T cell receptor signal transduction.

Low oxygen pressures exist in many solid tissues, including primary and secondary lymphoid organs. One key element in cellular adaptation to hypoxia is induced expression of hypoxia inducible factor (Hif) 1alpha. Here, we have examined the effect of Hif-1alpha, isolated from the myriad other effects of hypoxia, on T cell receptor (TCR) signaling in thymocytes. Because pVHL (von Hippel-Lindau protein) directs the proteolysis of Hif-1alpha under "normoxic" conditions, we achieved constitutive stabilization of Hif-1alpha through thymic deletion of Vhlh and reversed Hif-1alpha stabilization with double deletion of Vhlh and Hif-1alpha. We found that constitutive activity of Hif-1alpha resulted in diminished Ca(2+) response upon TCR crosslinking despite equivalent activation of phospholipase C(gamma1), normal intracellular Ca(2+) stores, and normal entry of Ca(2+) across the plasma membrane. Altered Ca(2+) response was instead due to accelerated removal of Ca(2+) from the cytoplasm into intracellular compartments, which occurred in association with Hif-1alpha-dependent overexpression of the calcium pump SERCA2 (sarcoplasmic/endoplasmic reticulum calcium ATPase 2). These data suggest a unique mechanism for control of TCR signaling through Hif-1alpha, which may be operative at the physiologic oxygen tensions seen in solid lymphoid organs.

Nutrient induced thermogenesis during major colorectal excision--a pilot study.

OBJECTIVE: Hypothermia may occur during general anaesthesia and is associated with postoperative coagulopathy, ischaemic cardiac events, wound infections and increased metabolic expenditure due to shivering. The purpose of the present pilot study was to determine whether the administration of certain amino acids (Vamin 18) during general anaesthesia could prevent postoperative hypothermia. PATIENTS AND METHODS: Two groups of patients were studied. The study group comprised 10 patients who underwent complex major colorectal operations. In this group an infusion of 500 mls of Vamin 18 (Fresenius Kabi Ltd) was commenced immediately after induction of anaesthesia but prior to the skin incision. In a control group (n=10) who underwent similar surgical procedures Vamin 18 was not administered. In both groups core body temperature, using an oesophageal probe was recorded during the procedure and recovery period. Ambient theatre and recovery room temperature and other body warming techniques were standardized for all patients. Statistical analysis was performed using t-test for comparison of linear temperature changes at different times during the procedure for both groups of patients. RESULTS: The body temperature was statistically significantly reduced in both groups at skin incision when compared with temperature prior to induction of anaesthesia. ( STUDY GROUP: mean 0.74 degrees C, SD=0.38, P =<0.001; CONTROL GROUP: mean 0.54 degrees C, SD=0.43, P=0.003]. The increase in body temperature between the time of skin incision and recovery period was statistically significant (P=0.012) in the study group but not so in the control group (P=0.730). CONCLUSION: The results of the present pilot study demonstrate that complex colorectal operations are associated with a decrease in body temperature which is most marked immediately after the induction of anaesthesia. The perioperative administration of Vamin 18 appears to increase the rate of recovery of body temperature. The impact of this thermogenic effect on perioperative morbidity and mortality should be studied in a prospective randomised clinical trial.

Clindamycin treatment of methicillin-resistant Staphylococcus aureus infections in children.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) with a narrower antibiotic resistance pattern have emerged. There is a risk for the appearance of resistance during clindamycin therapy of erythromycin-resistant MRSA infections because of the linked resistance mechanisms. METHODS: We analyzed clindamycin-susceptible MRSA organisms from children (1987 to 2000) along with clinical data. Antibiotic susceptibilities of organisms were tested, pulsed field gel electrophoresis (PFGE) was done and the linked resistance mechanism was detected by the D test. RESULTS: An average of 11 clindamycin-susceptible MRSA per year were obtained from children since 1993. Of 88 isolates 33 (38%) were erythromycin-resistant. The latter were less often community-acquired (45% vs. 69%), more often from infants <1 month of age (24% vs. 4%) and less likely to be in the community acquisition-associated PFGE Group 1 (62% vs. 87%) than those that were susceptible. The D test was positive in 31 of 33 erythromycin-resistant isolates. A 9-month-old boy with pneumonia/empyema caused by a clindamycin-susceptible, erythromycin-resistant, D test-positive MRSA developed a PFGE-identical clindamycin-resistant isolate and clinical relapse during clindamycin treatment. In contrast a 12-year-old girl with abscesses caused by a similar MRSA developed another abscess after clindamycin therapy, but the organism was unchanged in susceptibility. CONCLUSIONS: Erythromycin resistance was present in 38% of clindamycin-susceptible MRSA in children, and clindamycin resistance was detected during treatment in one child. Clindamycin remains a treatment option if the clinician is notified of the risk by the microbiology laboratory and the clinical situation is suitable.

Community-acquired and clindamycin-susceptible methicillin-resistant Staphylococcus aureus in children.

BACKGROUND: Recognition of children with community-acquired (CA) infections caused by clindamycin-susceptible, methicillin-resistant Staphylococcus aureus (MRSA) prompted a retrospective study in two Chicago hospitals conducted from 1987 through 1997. METHODS: Laboratory records of MRSA isolates, antibiotic susceptibilities and information from patient medical records were reviewed. RESULTS: One hundred eleven MRSA isolates from 103 children were studied with 51 isolates CA and 77 susceptible to clindamycin. The CA infections were less frequently associated with prior surgery (P = 0.0039) or a foreign body (P = 0.0001), and clindamycin-susceptible MRSA infections were less frequently associated with a foreign body (P = 0.001) compared with nosocomially acquired or clindamycin-resistant MRSA infections. Clindamycin-susceptible MRSA sources were mostly skin, wound or abscess (69%). Soft tissue diagnoses predominated (70%), but 16% were serious invasive infections. Ninety percent of clindamycin-susceptible MRSA were susceptible to erythromycin and/or trimethoprim-sulfamethoxazole. Antibiotic undertreatment (45%) or overtreatment (17%) of children with the clindamycin-susceptible MRSA occurred, but clindamycin appeared to be effective when used. CONCLUSION: The impact of these organisms could be substantial if they become more frequent or widespread. S. aureus is a potential pathogen in large numbers of pediatric patients; microbiologic evaluation and both presumptive and definitive treatment of all these children may need to be changed.

Magnesium deficiency in critically ill patients.

A study was performed to assess the value of estimation of intracellular magnesium in peripheral blood cells (red and mononuclear blood cells) in critically ill patients as an index of tissue magnesium content. A magnesium loading test was used to diagnose magnesium depletion in 16 critically ill patients. Patients were divided into magnesium depleted and non-depleted groups according to their response to the loading test. Pre-infusion plasma and intracellular (blood cell) magnesium levels were measured. There were no significant difference between the magnesium depleted (mean plasma magnesium 0.81 mmol.l-1, red blood cell magnesium 2.34 mmol.l-1, mononuclear blood cell magnesium 25.16 mmol.kg-1 dry weight) and non-depleted groups (mean plasma magnesium 0.90 mmol.l-1, red blood cell magnesium 2.18 mmol.l-1, mononuclear blood cell magnesium 18.1 mmol.kg-1 dry weight). We conclude that the diagnosis of magnesium depletion cannot be excluded in the face of normal plasma, red blood cell or mononuclear blood cell concentrations of magnesium.

A comparison between mivacurium and suxamethonium in children.

The neuromuscular effects of mivacurium were compared with those of suxamethonium in 69 children (aged 2-12 years), during nitrous oxide, oxygen and halothane anaesthesia in a randomised open study. Neuromuscular block was monitored by measuring the acceleration of the thumb caused by contraction of the adductor pollicis muscle after supramaximal stimulation of the ulnar nerve at the wrist using an Accelograph. End-tidal carbon dioxide was maintained at about 4 kPa in both groups. The mean times (95% confidence intervals) for T1:T0 ratio to decrease to 75%, 50%, 25% and 5% of control values were 50 (42-59), 62 (52-74), 83 (68-100) and 93 (46-108) s respectively for mivacurium and 18 (15-22), 26 (22-30), 32 (28-37) and 43 (38-49) s respectively for suxamethonium. The times for T1:T0 ratio to recover to 25%, 50% and 70% of control values were 615 (542-698), 769 (687-859) and 901 (820-993) s respectively for mivacurium and 196 (179-214), 216 (201-234) and 242 (216-259) s respectively for suxamethonium. The range of maximum block was similar for both drugs. The average time to reach maximum block was 143 s for mivacurium and 56 s for suxamethonium. Intubating conditions were similar in the two groups.