Enhanced chondrogenesis and Wnt signaling in PTH-treated fractures.

Studies have shown that systemic PTH treatment enhanced the rate of bone repair in rodent models. However, the mechanisms through which PTH affects bone repair have not been elucidated. In these studies we show that PTH primarily enhanced the earliest stages of endochondral bone repair by increasing chondrocyte recruitment and rate of differentiation. In coordination with these cellular events, we observed an increased level of canonical Wnt-signaling in PTH-treated bones at multiple time-points across the time-course of fracture repair, supporting the conclusion that PTH responses are at least in part mediated through Wnt signaling. INTRODUCTION: Since FDA approval of PTH [PTH(1-34); Forteo] as a treatment for osteoporosis, there has been interest in its use in other musculoskeletal conditions. Fracture repair is one area in which PTH may have a significant clinical impact. Multiple animal studies have shown that systemic PTH treatment of healing fractures increased both callus volume and return of mechanical competence in models of fracture healing. Whereas the potential for PTH has been established, the mechanism(s) by which PTH produces these effects remain elusive. MATERIALS AND METHODS: Closed femoral fractures were generated in 8-wk-old male C57Bl/6 mice followed by daily systemic injections of either saline (control) or 30 microg/kg PTH(1-34) for 14 days after fracture. Bones were harvested at days 2, 3, 5, 7, 10, 14, 21, and 28 after fracture and analyzed at the tissue level by radiography and histomorphometry and at the molecular and biochemical levels level by RNase protection assay (RPA), real-time PCR, and Western blot analysis. RESULTS: Quantitative muCT analysis showed that PTH treatment induced a larger callus cross-sectional area, length, and total volume compared with controls. Molecular analysis of the expression of extracellular matrix genes associated with chondrogenesis and osteogenesis showed that PTH treated fractures displayed a 3-fold greater increase in chondrogenesis relative to osteogenesis over the course of the repair process. In addition, chondrocyte hypertrophy occurred earlier in the PTH-treated callus tissues. Analysis of the expression of potential mediators of PTH actions showed that PTH treatment significantly induced the expression of Wnts 4, 5a, 5b, and 10b and increased levels of unphosphorylated, nuclear localized beta-catenin protein, a central feature of canonical Wnt signaling. CONCLUSIONS: These results showed that the PTH-mediated enhancement of fracture repair is primarily associated with an amplification of chondrocyte recruitment and maturation in the early fracture callus. Associated with these cellular effects, we observed an increase in canonical Wnt signaling supporting the conclusion that PTH effects on bone repair are mediated at least in part through the activation of Wnt-signaling pathways.     

Pretransplant survival is shorter in HIV-positive than HIV-negative subjects with end-stage liver disease.

Despite improved survival after liver transplantation (OLTX) in HIV-positive individuals treated with highly active antiretroviral therapy (HAART), some transplant candidates do not survive to OLTX. To determine if pretransplant outcome is related to severity of liver disease and/or HIV infection, we prospectively evaluated 58 consecutive HIV-positive candidates seen at a single center from 1997-2002. Of the 58, 15 (25.9%) were transplanted, whereas 21 (36.2%) died before OLTX, a median one month of evaluation, with more than half of those (12 of 21, 57.1%) dying from infection. By contrast, of 1,359 HIV-negative candidates, 860 (63.3%) were transplanted, whereas 211 (15.5%) died before OLTX (P < 0.001). The cumulative survival following initial evaluation was significantly shorter among HIV-positive than HIV-negative candidates (880 vs. 1,427 days, P = 0.035, Breslow) but was not related to the initial pretransplant MELD score (16 vs. 15), INR (1.5 vs. 1.5), creatinine (1.3 vs. 1.3 mg/dL), or total bilirubin (6.6 vs. 5.7 mg/dL), respectively, all P > 0.05. Among untransplanted HIV-positive candidates, the 21 who died did not differ from the 22 surviving in initial MELD (15 vs. 13), CD4 (230 vs. 327/microL), HIV load (both < 400 copies/mL), HAART intolerance (10/21, 47.6% vs. 10/22, 45.4%), or HCV infection (16/21, 76.2% vs. 16/22, 72.3%), all P > 0.05. Further, the 21 did not differ from the 15 transplanted in pre-OLTX CD4, HIV load, or MELD score, all P > 0.05. In conclusion, pretransplant survival appears shorter in HIV-positive OLTX candidates and is unrelated to severity of liver or HIV disease. Further study is warranted to determine risk factors for poorer pretransplant outcomes.     

Retrospective review of the preoperative biliary and gastrointestinal evaluation for gastric bypass surgery

BACKGROUND: The purpose of this study was to analyze the frequency and results of preoperative biliary and gastrointestinal (GI) evaluation of patients undergoing Roux-en-Y gastric bypass (RYGB). METHODS: Retrospective review of the preoperative evaluation of 144 consecutive RYGB patients. RESULTS: Cholecystectomy had already been performed in 43 (30%) patients; 22% of those patients with an intact gallbladder had cholelithiasis. Ten patients (7%) had an upper GI x-ray (UGI), and 94 patients (65%) had an esophagogastroduodenoscopy (EGD). Abnormalities were found in 40% of the UGIs and 84% of the EGDs. A total of 96 patients (67%) were tested for Helicobacter pylori; 11% were positive. Twenty-one patients (15%) underwent preoperative colonoscopy; 48% were abnormal, but most of the abnormalities were not clinically significant. Three patients had barium enema x-ray, which was normal in all cases. CONCLUSIONS: The preoperative biliary and GI evaluation of bariatric surgery patients should include a routine ultrasound of the gallbladder. Routine preoperative EGD will detect a significant number of abnormalities that should be treated, but should rarely alter the bariatric surgical procedure or result in denial of bariatric surgery. Many abnormalities will be asymptomatic. Patients should be routinely screened for H. pylori and, if positive, treated before bariatric surgery. Lower GI evaluation should be performed selectively based on the patient's symptoms, physical findings, and guidelines for colorectal cancer and polyp screening.     

Mutational specificity of the syn 1,2-dihydrodiol 3,4-epoxide of 5-methylchrysene

The mutational specificity of the syn dihydrodiol epoxide of 5-methylchrysene in the supF gene of the pSP189 vector was examined. Transversion mutations at GC pairs predominated with G → T and G → C changes accounting for 42 and 21% of total base change mutations. The types of mutations found reflect the previously determined chemical preference of this reactive species for reaction with deoxyguanosine residues in DNA.     

Characterization of adenosine receptors involved in adenosine-induced bronchoconstriction in allergic rabbits.

1. Recent work has suggested that adenosine may be involved in asthma via the activation of A1 receptors. However, the role of the recently cloned A3 receptor in airways is largely unknown. In the present study, we have investigated the role of the A3 receptor in adenosine-induced bronchoconstriction in allergic rabbits. 2. Aerosol challenge of antigen (Ag) immunized rabbits with the adenosine precursor, adenosine 5'-monophosphate (AMP), resulted in a dose-dependent fall in dynamic compliance (Cdyn). The maximum fall in Cdyn in these rabbits was significantly greater than that in litter matched, sham immunized animals (P < 0.05). However, there was no significant difference in the maximum increase in airways resistance (Rt) between Ag and sham immunized rabbits (P > 0.05). 3. Aerosol challenge of Ag immunized rabbits with cyclopentyl-adenosine (CPA) (A1-receptor agonist) elicited a dose-dependent fall in Cdyn in Ag immunized rabbits and the maximum fall in Cdyn in these rabbits was significantly greater than that observed in sham immunized rabbits (P < 0.05). Similarly, CPA induced dose-dependent increases in R1 in Ag immunized rabbits whereas sham immunized rabbits failed to respond to CPA within the same dose range. The maximum increase in RL in Ag immunized rabbits was significantly greater than that of sham immunized rabbits (P < 0.05). 4. Aerosol challenge of either Ag or sham immunized rabbits with the A3 agonist aminophenylethyladenosine (APNEA) did not elicit dose-dependent changes in either RL or Cdyn. Moreover, there was no significant difference in the maximum response, measured by either parameter, between the two animal groups (P > 0.05). 5. These data provide further evidence for a role of the A1 receptor in the airways, but do not support a role for the A3 receptor in adenosine-induced bronchoconstriction in the allergic rabbit.     

Hepatitis B immunisation rates among infants in ethnic groups with high prevalences of hepatitis B surface antigen carriers

Abstract: To determine hepatitis B immunisation rates in infants from ethnic groups with hepatitis B surface antigen chronic carrier prevalence over 5 per cent, a questionnaire was sent to all Maternal and Child Health Centres in Victoria, requesting information on the hepatitis B and diphtheria–tetanus–pertussis (DTP) or combined diphtheria–tetanus (CDT) immunisation status for all infants born between 1 July 1992 and 30 June 1993 and at risk of hepatitis B infection because of maternal ethnicity. We received data on 3611 of 5744 infants (62.9 per cent) in targeted ethnic groups. Of these, 12.8 per cent had not received hepatitis B vaccine, and 81.6 per cent, 76.8 per cent and 64.0 per cent had received at least one, two and three doses respectively, while 84 per cent had received at least three doses of DTP vaccine and/or CDT vaccine. Coverage with DTP or CDT was higher than for hepatitis B vaccine ( P < 0.001), and coverage was better in areas with a higher percentage of infants in high–prevalence ethnic groups ( P < 0.001). Changes in the program in Victoria in terms of timing of the first dose of vaccine plus greater attention to follow–up may lead to improved hepatitis B immunisation rates among infants in targeted ethnic groups. Adoption of universal infant hepatitis B immunisation, by increasing familiarity with hepatitis B vaccine, is likely to be the best way to increase immunisation coverage for these infants.     

Intravenous Phenylephrine Preconditioning of Cardiac Grafts From Non–Heart-Beating Donors

Background. Hypoxia and warm ischemia produce severe injury to cardiac grafts harvested from non-heart-beating donors. To potentially improve recovery of such grafts, we studied the effects of intravenous phenylephrine preconditioning.

Methods. Thirty-seven blood-perfused rabbit hearts were studied. Three groups of non-heart-beating donors underwent intravenous treatment with phenylephrine at 12.5 (n = 8), 25 (n = 7), or 50 μg/kg (n = 7) before initiation of apnea. Non-heart-beating controls (n = 8) received saline vehicle. Hypoxic cardiac arrest occurred after 6 to 12 minutes of apnea, followed by 20 minutes of warm in vivo ischemia. A 45-minute period of ex vivo reperfusion ensued. Nonischemic controls (n = 7) were perfused without antecedent hypoxia or ischemia.

Results. Phenylephrine 25 μg/kg significantly delayed the onset of hypoxic cardiac arrest compared with saline controls (9.6 ± 0.5 versus 7.7 ± 0.4 minutes; p = 0.00001), yet improved recovery of left ventricular developed pressure compared with saline controls (57.1 ± 5.3 versus 41.0 ± 3.4 mm Hg; p = 0.04). Phenylephrine 25 μg/kg also yielded a trend toward less myocardial edema than saline vehicle (p = 0.09).

Conclusions. Functional recovery of nonbeating cardiac grafts is improved by preconditioning. We provide evidence that the myocardium can be preconditioned with phenylephrine against hypoxic cardiac arrest.     

Peripheral Blood Lymphocyte Surface Antigen Expression and Prognosis in Myeloma: Australian Leukaemia Study Group Study

The Australian Leukaemia Study Group myeloma study (MM1) aimed to determine the prognostic significance of clinical and immunophenotypic markers in patients with multiple myeloma. All patients were treated with standard dose melphalan and prednisone. Seventy-four patients were entered and the median survival was 27 months. Serum beta 2-microglobulin (βM) and albumin levels were the only significant clinical factors influencing survival (p = 0.007 and p = 0.008, respectively). Patients with raised levels of CD38+ lymphocytes at presentation had a significantly shorter survival than patients with normal levels (p = 0.01, logrank test, median 19 months vs 33 months). CD38 antigen expression was independent of β2M but patients with raised levels of CD38 had significantly lower levels of albumin than patients with normal levels (p = 0.001) which may explain their poorer survival. Salmon and Durie stage was not associated with antigen expression. No other B-cell antigens (CD10, CD19, CD20, CD21, CD22, CD23, FMC1 or FMC7) or plasma cell antigens tested (PCA-1) were found to be associated with prognosis. Patients who achieved plateau phase had a better prognosis than those who did not (p = 0.04 in a landmark analysis). Patients who achieved plateau phase following an objective response appeared to have a better prognosis than those who were in plateau phase at presentation (p = 0.09 in a landmark analysis). Light chain isotype suppression (LCIS) was not associated with a significant survival advantage and did not correlate with any known prognostic indicator. We conclude that phenotypic analysis of peripheral blood lymphocytes for CD38 antigen at diagnosis may be useful as a prognostic indicator in patients with myeloma.     

Depression symptoms in movement disorders: comparing Parkinson's disease, dystonia, and essential tremor.

Depression is common in Parkinson's disease (PD) and affects 30 to 50% of all patients. In contrast to the wealth of research on depression in PD, little is known about the occurrence of depression in other movement disorders. The primary objective of the current study was to determine whether the high prevalence of depression symptoms seen in PD is also found in other movement disorders, by directly comparing rates of specific depression symptoms and depression severity across PD, dystonia, and essential tremor (ET). Three hundred and fifty-four patients with PD, 83 patients with dystonia, and 53 patients with ET completed the Beck Depression Inventory (BDI). We found no significant between-groups differences for depression severity, frequency, or endorsement of specific depression symptoms. Forty-eight percent of PD patients, 37.3% of dystonia patients, and 34% of ET patients were found to be at least mildly depressed (BDI score of 10 or higher). The most commonly endorsed symptoms were fatigability, difficulty with work, anhedonia, and sleep disturbance. Clinicians should be aware that depression is a frequent problem in dystonia and ET, in addition to PD, and inquire about depression symptoms in these patients so that they can be appropriately treated.     

Tetralogy of Fallot

This article has discussed TOF, its occurrence, physiology, medical interventions and nursing implications. In its classic form, TOF consists of four anatomical aberrations: a large VSD, pulmonic stenosis, dextroposition of the aorta, and right ventricular hypertrophy. Surgical palliation versus primary intracardiac repair is a continuing discussion in medical literature. Children who have undergone intracardiac repair for TOF have an excellent prognosis for late survival, near 90% 10 years after repair. Nursing responsibilities in the care of the newborn diagnosed as having TOF encompass the well-being of the newborn as well as the family. Palliation increases pulmonary arterial flow, thus decreasing cyanosis and promoting measurable clinical improvement in the infant. Preparation of the family and child for surgery involves completing a baseline assessment of family dynamics, diagnosing stressors, composing objectives, carrying out interventions focused on developmental ability, and evaluating the effectiveness of the nursing process. Maintaining the physical and emotional integrity of a child just out of the operating room is a challenge. Parental support is important to the young child's feelings of security while hospitalized.