Mitochondrial myopathy with predominant respiratory dysfunction in a patient with A3243G mutation in the mitochondrial tRNA(Leu(UUR))gene

Two treatment regimens for disseminated Lyme borreliosis (mainly neurologic and musculoskeletal manifestations) were compared in a randomized trial. A group of 30 patients received oral cefixime 200 mg combined with probenecid 500 mg three times daily for 100 days. Another group of 30 patients received intravenous ceftriaxone 2 g daily for 14 days followed by oral amoxicillin 500 mg combined with probenecid 500 mg three times daily for 100 days. There was no statistically significant difference in the outcome of infection between the two groups. However, the total number of patients with relapses or no response at all and the number of positive polymerase chain reaction findings after therapy were greater in the cefixime group. The general outcomes of infection in patients with disseminated Lyme borreliosis after 3-4 months of therapy indicate that prolonged courses of antibiotics may be beneficial in this setting, since 90% of the patients showed excellent or good treatment responses.     

Abnormal hippocampal spatial representations in alphaCaMKIIT286A and CREBalphaDelta- mice

Hippocampal "place cells" fire selectively when an animal is in a specific location. The fine-tuning and stability of place cell firing was compared in two types of mutant mice with different long-term potentiation (LTP) and place learning impairments. Place cells from both mutants showed decreased spatial selectivity. Place cell stability was also deficient in both mutants and, consistent with the severities in their LTP and spatial learning deficits, was more affected in mice with a point mutation [threonine (T) at position 286 mutated to alanine (A)] in the alpha calmodulin kinase II (alphaCaMKIIT286A) than in mice deficient for the alpha and Delta isoforms of adenosine 3'5'-monophosphate-responsive element binding proteins (CREBalphaDelta-). Thus, LTP appears to be important for the fine tuning and stabilization of place cells, and these place cell properties may be necessary for spatial learning.     

Direct interaction of hepatitis C virus core protein with the cellular lymphotoxin-beta receptor modulates the signal pathway of the lymphotoxin-beta receptor

Previous studies suggest that the core protein of hepatitis C virus (HCV) has a pleiotropic function in the replication cycle of the virus. To understand the role of this protein in HCV pathogenesis, we used a yeast two-hybrid protein interaction cloning system to search for cellular proteins physically interacting with the HCV core protein. One such cellular gene was isolated and characterized as the gene encoding the lymphotoxin-beta receptor (LT-betaR). In vitro binding analysis demonstrated that the HCV core protein binds to the C-terminal 98 amino acids within the intracellular domain of the LT-betaR that is involved in signal transduction, although the binding affinity of the full-length HCV core protein was weaker than that of its C-terminally truncated form. Our results also indicated that the N-terminal 40-amino-acid segment of the HCV core protein was sufficient for interaction with LT-betaR and that the core protein could form complexes with the oligomeric form of the intracellular domain of LT-betaR, which is a prerequisite for downstream signaling of this receptor. Similar to other members of the tumor necrosis factor (TNF) receptor superfamily, LT-betaR is involved in the cytotoxic effect of the signaling pathway, and thus we have elucidated the biological consequence of interaction between the HCV core protein and LT-betaR. Our results indicated that in the presence of the synergizing agent gamma interferon, the HCV core protein enhances the cytotoxic effects of recombinant forms of LT-betaR ligand in HeLa cells but not in hepatoma cells. Furthermore, this enhancement of the cytolytic activity was cytokine specific, since in the presence of cycloheximide, the expression of the HCV core protein did not elicit an increase in the cytolytic activity of TNF in both HeLa and hepatoma cells. In summary, the HCV core protein can associate with LT-betaR, and this protein-protein interaction has a modulatory effect on the signaling pathway of LT-betaR in certain cell types. Given the known roles of LT-betaR/LT-alpha1,beta2 receptor-ligand interactions in the normal development of peripheral lymphoid organs and in triggering cytolytic activity and NF-kappaB activation in certain cell types, our finding implies that the HCV core protein may aggravate these biological functions of LT-betaR, resulting in pathogenesis in HCV-infected cells.     

A national survey to medical and dental schools to assess the level of undergraduate teaching and research about HIV/AIDS in the UK

Rats given an antagonist against N-methyl-D-aspartate, (+)-10, 11-dihydro-5-methyl-5H-debenzo (a, d) cycloheptene-5, 10-imine (MK-801), were compared with control rats for their activity and exploratory behavior (habituation, exploration time to the spatial change of one of 4 objects and to the new object) in a circular open field. Rats given 0.07 mg/kg dose of MK-801 displayed no significant differences with the controls. Rats given 0.1 mg/kg dose of MK-801 failed to respond to the spatial change, whereas they displayed habituation and exploration to the new object at the same degree as the control rats. Rats given 0.3 mg/kg dose of MK-801 displayed hyperactivity and did not display habituation and exploration. The result suggests that the 0.1 mg/kg dose of MK-801, which dose not affect on activity, habituation and exploration to the new object in rats, selectively affects on acquisition of spatial information and reduces their spatial exploration.     

The effect of discontinuation of postmilking teat disinfection in low somatic cell count herds. I. Incidence of clinical mastitis

Results are described of a split-udder trial on the effect of discontinuation of postmilking teat disinfection on the incidence of clinical mastitis in seven dairy herds with a low bulk milk somatic cell count and a high incidence of clinical mastitis. Overall incidence of clinical mastitis was non-significantly lower (18%), whereas the incidence of the most prevalent pathogen associated with clinical mastitis, Escherichia coli, was significantly lower in quarters for which postmilking teat disinfection was discontinued. We concluded that discontinuation of postmilking teat disinfection may decrease the incidence of clinical Escherichia coli mastitis in herds for which standard mastitis prevention measures are executed adequately, bulk milk somatic cell count is low, and incidence of clinical mastitis is high. However, because an increase in intramammary infections with contagious pathogens may occur, care is recommended when advising discontinuation of postmilking teat disinfection.     

Routine antenatal screening for syphilis in Lothian: a study of the results 1988 to 1994

A retrospective study was carried out of the cases of positive syphilis serology detected by routine antenatal screening within Edinburgh (and surrounding district) over the six years 1988 to 1994. The study demonstrated a low incidence of syphilis with only 15 pregnancies in 58,445 screened. In eight cases serology and history were suggestive of late latent syphilis and in the remainder of previous infection which had been treated. All women were delivered of liveborn infants at term without stigmata of congenital syphilis. Lack of identifiable risk factors in women with positive serology suggests that routine rather than selective screening should continue.     

Limb reduction defects in fetuses with homozygous alpha-thalassaemia-1

Limb reduction defect is a rare event. Its exact pathogenesis is unknown. We retrospectively reviewed the outcome of 130 fetuses affected by homozygous alpha-thalassaemia-1 and found that 11 of them (8 per cent; 95 per cent confidence interval: 4-13 per cent) had terminal transverse limb reduction defects. Chromosome study was available in ten fetuses with limb defects and the results were normal. We postulate that the strong association between homozygous alpha-thalassaemia-1 and limb reduction is related to the hypoxic insult in early gestation. This may be the final common pathway in the pathogenesis of other forms of limb reduction defects.     

Application of distance-dependent resolution compensation and post-reconstruction filtering for myocardial SPECT

Compensation for distance-dependent resolution can be directly incorporated in maximum likelihood reconstruction. Our objective was to examine the effectiveness of this compensation using either the standard expectation maximization (EM) algorithm or an accelerated algorithm based on use of ordered subsets (OSEM). We also investigated the application of post-reconstruction filtering in combination with resolution compensation. Using the MCAT phantom, projections were simulated for 360 degrees data, including attenuation and distance-dependent resolution. Projection data were reconstructed using conventional EM and OSEM with subset size 2 and 4, with/without 3D compensation for detector response (CDR). Also post-reconstruction filtering (PRF) was performed using a 3D Butterworth filter of order 5 with various cutoff frequencies (0.2-1.2 cycles cm(-1)). Image quality and reconstruction accuracy were improved when CDR was included. Image noise was lower with CDR for a given iteration number. PRF with cutoff frequency greater than 0.6 cycles cm(-1) improved noise with no reduction in recovery coefficient for myocardium but the effect was less when CDR was incorporated in the reconstruction. CDR alone provided better results than use of PRF without CDR. Results suggest that using CDR without PRF, and stopping at a small number of iterations, may provide sufficiently good results for myocardial SPECT. Similar behaviour was demonstrated for OSEM.     

Management of anorectal foreign bodies: a cause of obscure anal pain

BACKGROUND: Few patients with anorectal foreign bodies will freely admit to transanal introduction. The results of long-term follow-up in these patients have been sparse. METHODS: Data from April 1989 to April 1997 were extracted from a prospective computerized database. The clinical features and the results of a departmental management protocol for anorectal foreign bodies were analysed. In addition, long-term outcomes were obtained by telephone interview. RESULTS: Thirty patients (25 men, 5 women) with a mean age of 46 (range 16-72) years) were treated for this condition. While 10 patients (33.3%) admitted to transanal insertion, the remaining 20 (66.7%) complained of anal pain. Among the latter, the foreign body was subsequently found on routine digital rectal examination in nine patients (45%), on X-ray in nine (45%) and it was passed out unexpectedly after fleet enema in two (10%). Factors which raised suspicion for X-rays included atypical gender behaviour, lax anal sphincters and bloody or mucoid rectal discharge. Transanal recovery was successful with sedation in 12 (40%), general anaesthesia in 13 (43.3%), and laparotomy was needed in three (10%; which included one perforated bowel at presentation). There were two complications (6.7%; one minor rectal abrasion and one bronchopneumonia). There was no long-term faecal incontinence or re-impaction of foreign bodies at 63 (range 8-96) months of follow-up. CONCLUSIONS: Foreign bodies should be suspected in patients with obscure anal pain. Judicious transanal extraction under sedation or general anaesthesia was usually successful with minimal short- and long-term complications.     

Melatonin protects 6-OHDA-induced neuronal death of nigrostriatal dopaminergic system

In vivo neuroprotective effects of melatonin on the nigrostriatal dopaminergic system in rats unilateral 6-hydroxydopamine (6-OHDA) lesions were tested. Two weeks after lesioning the dopamine receptor agonist, apomorphine produced rotational asymmetry. In contrast, melatonin treatment significantly reduced the motor deficit following apomorphine challenge. Analysis by tyrosine hydroxylase (TH) immunocytochemistry revealed the loss of cell bodies in the substantia nigra (SN) and absence of terminals in the dorsolateral striatum ipsilaterally. Melatonin treatment also resulted in the survival of dopaminergic neurons in SN and TH-immuoreactive terminals in the dorsolateral striatum. These behavioral and histochemical results may indicate a neuroprotective action of melatonin and suggest a potential pharmacological role in the treatment of Parkinson's disease.