Interactions Between Cytomegalovirus, Human Herpesvirus-6, and the Recurrence of Hepatitis C After Liver Transplantation

Recurrence of hepatitis C (HCV) following liver transplantation is common. Herpesvirus reactivation following transplant may have an immunomodulatory effect resulting in increased HCV replication. We studied whether cytomegalovirus (CMV) and human herpesvirus-6 (HHV-6) may be associated with HCV recurrence and viral load after transplant. We prospectively followed 66 HCV liver-transplant recipients with serial viral load testing for CMV and HHV-6. Infection and viral load were correlated with the development of biopsy-proven HCV recurrence and HCV viral loads. Histologic recurrence of HCV occurred in 41/66 (62.1%) patients. In the primary analysis, CMV infection and disease, and HHV-6 infection were not associated with HCV recurrence. Peak CMV and HHV-6 viral loads were not significantly different in patients with and without recurrence. No correlation was observed between HCV viral loads at 1 and 3 months post-transplant and peak HHV-6 or CMV viral loads. In a subgroup analysis, HHV-6 infection was associated with the development of more severe recurrence (hepatitis and/or fibrosis score > or = 2) (p = 0.01). Also, fibrosis scores at last follow up were higher in patients with CMV disease (1.67 vs. 0.56; p = 0.016) and in patients with HHV-6 infection (1.18 vs. 0.55; p = 0.031). In conclusion, HHV-6 and CMV infection and viral load were not associated with increased overall rates of HCV recurrence or HCV viral load after liver transplantation but may be associated with more severe forms of recurrence.     

Systematic and random errors in compression testing of trabecular bone

We sought to quantify the systematic and random errors associated with-artifacts in the platens compression test for trabecular bone. Our hypothesis was that while errors may depend on anatomic site, they do not depend on apparent density and therefore have substantial random components. Trabecular bone specimens were first tested nondestructively using newly developed accurate protocols and then were tested again using the platens compression test. Percentage differences in modulus between the techniques (bovine) proximal tibia [n = 18] and humerus [n = 17] and human lumbar spine, [n = 9] were in the range of 4-86%. These differences did not depend on anatomic site (p = 0.21) and were only weakly dependent on apparent density and specimen aspect ratio (r² < 0.10). The mean percentage difference in modulus was 32.6% representing the systematic component of the end-artifact error. Neglecting the minor variations explained by density and specimen size (approximately 10%), an upper bound on the random error from end-artifacts in this experiment was taken as the SD of the modulus difference (±18.2%). Based on a synthesis of data taken from this study and from the literature, we concluded that the systematic underestimation error in the platens compression test can be only approximated and is in the range of 20-40%; the substantial random error (±12.5%) confounds correction, particularly when the sample size is small. These errors should be considered when interpreting results from the platens test, and more accurate testing techniques should be used when such errors are not acceptable.     

Primary care referrals for lumbar spine radiography: diagnostic yield and clinical guidelines.

BACKGROUND: Primary care requests for radiographs of the lumbar spine have come under increasing scrutiny. Guidelines aiming to reduce unnecessary radiographs by limiting referrals to patients at high risk of serious disease have been widely distributed. Trial evidence suggests that guidelines can reduce radiography referrals. It is not clear whether this reduction has been achieved in routine practice. AIM: This study, using routine data, was conducted to measure trends in pnmary care referrals for lumbar spine radiography at two hospitals between 1994 and 1999. DESIGN OF STUDY: Analysis of primary care requests for lumbar spine radiography from computerised records. SETTING: Addenbrooke's Hospital, Cambridge (1 July 1994 to 30 June 1999), and Ipswich General Hospital (1 July 1995 to 30 June 1999), United Kingdom. METHOD: All primary care requests for lumbar radiography were identified electronically from computerised information systems. A random sample of 2100 radiography reports were classified according to clinical importance. These classifications were used to examine whether the proportion of radiographs demonstrating potentially more serious findings had increased between 1994 and 1999. RESULTS: There was no evidence that primary care referrals for radiography of the lumbar spine had decreased between 1994 and 1999 at either hospital. General practitioners did not progressively refer more high-risk patients for lumbar radiography. Only a small proportion of patients had important radiographic findings that might warrant specialist referral or specific therapy. CONCLUSION: The implementation of diagnostic guidelines offers much to the NHS. However in these two hospitals, the reduction in radiograph utilisation evident in trials was not achieved. Guideline development is a resource intensive process; distribution must be supported by more effective implementation strategies.     

Comprehension of pretense in children with autism

In an attempt to tap underlying competencies, the ability of children with autism to comprehend pretend acts carried out by an experimenter was compared with that shown by controls. These acts consisted of the pouring of a pretend substance from an appropriate container onto a target figure. There was no significant difference in the groups' ability to identify the pretend substance involved, to predict the pretend outcome of the actions, or to reflect on the pretend nature of the episodes. However, the performance of controls on these latter two tasks was surprisingly poor, limiting the implications that might be drawn from the observed absence of group differences in comprehension abilities.We are very grateful to the teachers and headteachers of the following schools for their cooperation and assistance throughout the period of this research: John Worrall School, Sheffield; Doucecroft School, Kelvedon; East Hill First and Middle School, Sheffield; East Hill Second School, Sheffield; Mossbrook School, Sheffield; Priory School, Doncaster; The Rowan School, Dore; St. Mary's School, Sheffield. We also thank James Russell for his helpful comments of earlier drafts of this paper.     

Bipolar affective disorder. II. EEG, neuropsychological, and clinical correlates of CT abnormality

Since the clinical significance of CT abnormalities found in bipolar patients remains obscure, we studied 26 DSM-III bipolar patients who had specific CT abnormalities (third ventricle enlargement, and hyperdensity of the caudate, thalamus, anterior frontal white matter, and right temporal lobe) on numerous parameters such as EEG, the Halstead-Reitan Neuropsychological Battery, premorbid personality adjustment, family history of affective disorder, positive and negative symptoms, employment history, and response to lithium carbonate treatment. None of these measures could differentiate between the CT abnormal and CT normal subgroups. The implications of these findings are discussed.     

Effect of clonidine and atropine on rest tremor in the MPTP monkey model of parkinsonism

The purported alpha 2-adrenergic agonist clonidine was found to inhibit rest tremor at doses of 0.023-0.1 mg/kg in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine monkey model of parkinsonism. The effect was dose dependent, but sedation and reduced mobility were observed. Atropine at doses of 0.1-1 mg/kg also reduced tremor in a dose-dependent fashion, but side-effects in the form of agitation, dilated pupils, and dry mouth were seen. When the two drugs were combined, however, we saw a significant potentiation of the antitremor effect. We could even abolish tremor with doses of atropine and clonidine that by themselves were without effect. The side-effects were almost eliminated by the combination.     

Aspergillus osteomyelitis of the thumb in a 5-year-old child

Aspergillus osteomyelitis is a rare condition and is a recognized infection of the immunosuppressed. The pediatric cases that were documented suggest that in children, chronic granulomatous disease is the major underlying disease [Tack et al.1982 73(2):295–300, Baez-Escudero et al. 2000 Case report—primary sternal Aspergillus osteomyelitis. Infect Med 17(7):505–516]. We report an interesting case of Aspergillus osteomyelitis of the thumb in a 5-year-old boy with aplastic anemia. The infection progressed despite a combination of antifungal therapy with Voriconazole and surgical debridement. The thumb was amputated and the child recovered. This case highlights the difficulty in diagnosing Aspergillus osteomyelitis and also the failure of conventional management in this child, which resulted in the amputation of the thumb as a life-saving measure. We believe this to be the first case report of Aspergillus osteomyelitis in the thumb.