A 17-year-old with rash, fever, myalgias, and nephritis

Patients on hemodialysis are at increased risk for developing active tuberculosis (TB) after primary infection. Although this increased risk is well documented, the prevalence of TB infection, as indicated by a positive tuberculin skin test (TST), is not well described. End-stage renal disease is also known to be a risk factor for skin test anergy, but the rate of anergy in hemodialysis patients is unclear. We sought to identify rates of anergy and TST positivity in patients at four hemodialysis units in St Louis, Missouri, from June 1996 through August 1996. Data obtained from patients and medical records included age, years on hemodialysis, medical history, and basic laboratory data. Patients without a history of TB or a positive TST had a TST with Tubersol, as well as candida and tetanus controls, placed by the Mantoux method. Tests were read 48 hours later. Of the patients enrolled at these units, 307 of 331 (93%) were evaluated. Patients had a mean age of 58 years (range, 19 to 91 years) and had been on hemodialysis for a mean of 3.7 years (range, 1 week to 18.7 years). Blacks made up 81% of the population. A history of a positive TST was obtained from 24 patients (8%), and an additional seven (2%) had a history of active TB. Of the 276 patients tested, 93 did not respond to either control antigen, but five of these patients had a positive TST, leaving 88 (32%) anergic. Anergy was related to age, immunosuppressive drug use, and the reagents used, but not to urea reduction ratio. Positive TSTs were found in 17 of 188 of nonanergic patients (9%) (6% of all tested patients). Overall, 48 of 307 patients (16%) had a positive TST or history of TB. TB or a positive TST was associated with liver disease and peptic ulcer disease, but not socioeconomic status. All 17 newly identified TST-positive patients received chest radiographs. No new cases of active TB were found. Only two of 17 of these patients (12%) were started on isoniazid (INH) prophylaxis. We identified high rates of TST positivity and anergy in the hemodialysis patients tested. Hemodialysis patients should receive regular TST screening, and INH prophylaxis needs to be more strongly encouraged. Studies are ongoing to define the rate of TST conversion over time.     

The Ohio mental health consumer outcomes system: reflections on a major policy initiative in the US

This article describes the key elements of Ohio's development and implementation of a statewide system of consumer outcomes measurement for adults and youth, 1996–2003. A complete history would include the view from each component of this decentralized mental health system and from its major participants: consumers and families, providers, and local boards. Copyright © 2003 John Wiley & Sons, Ltd.     

Differential effects of LHRH and somatostatin analogs on human breast cancer.

We have been interested in the possible direct effects of luteinizing hormone releasing hormone (LHRH) and somatostatin (SS) analogs on the growth of human mammary tumor cells. Four recently synthesized peptide hormones including the LHRH agonists D-Trp6-LHRH and zoladex, LHRH antagonists SB30 and SB75, and the somatostatin analog RC 160 were analyzed for their effects on DNA synthesis of MCF-7 breast cancer cells in culture. At 48 hr, D-Trp6-LHRH and SB30 did not show significant effects (dose range, 10(-12)-10(-6) M). However, the combination of these two peptides at 10(-10) M produced significant inhibition of 3[H]thymidine incorporation (50% control). At 72 hr in the absence of estradiol-stimulated growth, D-Trp6-LHRH showed inhibition at 10(-12) and 10(-10) M (P less than 0.005 and 0.001). At higher concentrations, no significant inhibition was noted. In contrast to D-Trp6, SB30 (antagonist) showed no inhibition but significant stimulation of DNA synthesis at 10(-6) and 10(-4) M. In the presence of added estradiol (10(-9) M), complete reversal of D-Trp6-LHRH analog inhibition is noted. In contrast, there is persistent stimulation by SB30 (P less than 0.001). At 96 hr, D-Trp6-LHRH continued to show maximal inhibition of 70% in the absence of estradiol. SB30 stimulated DNA synthesis 100% at 10(-6) M. At 72 hr, the SS analog RC 160 demonstrated significant inhibition (53%) that was similar to D-Trp6 and SB75 peptides.(ABSTRACT TRUNCATED AT 250 WORDS)     

The safety and efficacy of OP-1 (rhBMP-7) as a replacement for iliac crest autograft for posterolateral lumbar arthrodesis: minimum 4-year follow-up of a pilot study.

BACKGROUND CONTEXT: Although autogenous bone is still considered to be the gold standard graft material for promoting spinal fusion, other bone graft substitutes have been developed in an attempt to improve arthrodesis rates and avoid the complications associated with the procurement of autograft. The bone morphogenetic proteins (BMPs) represent a family of osteoinductive growth factors that are known to stimulate the osteoblastic differentiation of stem cells. Osteogenic protein-1 (OP-1) Putty is a commercially available BMP preparation that is already approved for use in humans. Previous clinical studies involving patients with degenerative spondylolisthesis have reported that the efficacy and safety of OP-1 Putty is comparable to that of autograft at both 1- and 2-year follow-up. PURPOSE: The purpose of this study was to evaluate the intermediate-term efficacy and safety of OP-1 Putty as an alternative to autogenous bone by comparing the 4-year radiographic, clinical, and safety data of these same patients who underwent decompression and uninstrumented fusion with either OP-1 Putty or iliac crest autograft. STUDY DESIGN/SETTING: A prospective, randomized, controlled, multicenter clinical pilot study. PATIENT SAMPLE: Thirty-six patients undergoing decompressive laminectomy and single-level uninstrumented fusion for degenerative spondylolisthesis and symptomatic spinal stenosis were randomized in a 2:1 fashion to receive either OP-1 Putty (24 patients) or autogenous iliac crest bone graft (12 patients). OUTCOME MEASURES: Patient-reported outcome measures consisting of Oswestry Disability Index and Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) scores were used to evaluate clinical efficacy. Perioperative data including operative time, estimated blood loss, and duration of hospital stay were also recorded for each surgery. Postoperatively, a neurological examination and an assessment of donor-site pain (if applicable) were performed at every follow-up visit. Radiographic fusion success was defined as the presence of continuous bridging bone formation between the transverse processes at the level of the spondylolisthesis with minimal motion evident on dynamic lateral x-ray films. The primary efficacy endpoint was the overall success rate, a composite measure derived from both radiographic and clinical parameters. The safety of OP-1 Putty was confirmed by comparing the nature and frequency of all adverse events and complications that were prospectively observed in either of the groups. METHODS: Thirty-six patients with degenerative spondylolisthesis and symptoms of neurogenic claudication underwent decompressive laminectomy and single-level uninstrumented fusion with either OP-1 Putty or autograft. All patients were evaluated at 6 weeks and 3, 6, 9, 12, and 24 months, after which time they were instructed to return on a yearly basis. Multiple neuroradiologists blinded to the assigned treatment reviewed static and dynamic X-ray films with digital calipers to assess fusion status according to the presence of continuous bridging bone across the transverse processes as well as the amount of residual motion evident at the level of interest. Oswestry Disability Index surveys and SF-36 questionnaires were used to assess clinical outcomes. RESULTS: At the 48-month time point, complete radiographic and clinical data were available for 22 of 36 patients (16 OP-1 Putty and 6 autograft) and 25 of 36 patients (18 OP-1 Putty and 7 autograft), respectively. Radiographic evidence of a solid arthrodesis was present in 11 of 16 OP-1 Putty patients (68.8%) and 3 of 6 autograft patients (50%). Clinically successful outcomes defined as at least a 20% improvement in preoperative Oswestry scores were experienced by 14 of 19 OP-1 Putty patients (73.7%) and 4 of 7 autograft patients (57.1%); these clinical findings were corroborated by similar increases in SF-36 scores. The respective overall success rates of the OP-1 Putty and autograft group were 62.5% and 33.3%. In this study, there were no incidents of local or systemic toxicity, ectopic bone production, or other adverse events directly related to the use of OP-1 Putty. CONCLUSION: Despite the challenges associated with obtaining a solid uninstrumented fusion in patients with degenerative spondylolisthesis, the rates of radiographic fusion, clinical improvement, and overall success associated with the use of OP-1 Putty were at least comparable to that of the autograft controls for at least 48 months after surgery. These results appear to validate the short-term results previously reported for OP-1 Putty and suggest that this material may potentially represent a viable bone graft substitute for certain fusion applications.     

Redox imbalance and ventilator-induced lung injury

Mechanical ventilation (MV) is an indispensable therapy in the care of critically ill patients with acute lung injury and the acute respiratory distress syndrome; however, it is also known to further lung injury in certain conditions of mechanical stress, leading to ventilator-induced lung injury (VILI). The mechanisms by which conventional MV exacerbates lung injury and inflammation are of considerable clinical significance. Redox imbalance has been postulated, among other mechanisms, to enhance/perpetuate susceptibility to VILI. A better understanding of these pathologic mechanisms will help not only in alleviating the side effects of mechanical forces but also in the development of new therapeutic strategies. Here, we review the relevance of oxidative stress in VILI from human studies as well as cellular and mouse models of mechanical stress. Potential therapeutic avenues for the treatment of VILI with exogenous administration of antioxidants also are discussed.     

Incidence and risk factors for sustained hepatic function toxicity 6 months after radioembolization: analysis of the radiation-emitting sir-spheres in non-resectable liver tumor (RESIN) registry

BackgroundTo quantify rates and risk factors for toxicity after hepatic radioembolization using resin yttrium-90 microspheres.MethodsRadiation-Emitting SIR-Spheres in Non-resectable liver tumor (RESIN) registry enrollees were reviewed with 614 patients included. Mean patient age was 63.1±12.5 years. The majority of patients were male (n=375, 61%) and white (n=490, 80%). Common tumor types were hepatocellular (n=197, 32%), colorectal (n=187, 30%) and neuroendocrine (n=56, 9%). Hepatotoxicity was measured using the Common Terminology Criteria for Adverse Events (CTCAE v 5). Potential risk factors for hepatotoxicity were tested using the Kruskal-Wallis or Pearson Chi-squared tests, and multivariate linear regressions.ResultsAt 6 months, 115 patients (18.7%) died (n=91, 14.8%), entered hospice (n=20, 3.3%) or sought treatment elsewhere (n=4, 4%). Seven (1.1%) deaths were from liver decompensation. Grade 3 toxicity rates were: bilirubin (n=85, 13.8%), albumin (n=28, 4.6%), ALT (n=26, 4.2%) and AST (n=37, 6.0%). For each of these liver function test components, baseline abnormal labs predicted Grade 3 toxicity at follow-up by Kruskal-Wallis test (P<0.001) and linear regression (all P<0.03). Other significant factors predicting toxicity at regression included elevated Body-Mass Index (albumin P=0.0056), whole liver treatment (bilirubin P=0.046), and lower tumor volume (ALT and INR, P<0.035 for both).ConclusionsBaseline liver function abnormalities prior to radioembolization is the strongest predictor of post-treatment Grade 3 toxicity with rates as high as 13.8%. Toxicity rates for specific lab values are affected by large volume treatments especially with low tumor volumes.