Assay of cytomegalovirus susceptibility to ganciclovir in renal and heart transplant recipients

Ganciclovir (GCV) prophylaxis or pre-emptive therapy significantly reduce the rate of cytomegalovirus (CMV) disease and viremia, but increase the potential for emergence of ganciclovir-resistant CMV strains. The inhibitor concentration at 50% (IC(50)) of GCV from 156 CMV isolates from 59 renal or heart transplant recipients was calculated by means of a rapid phenotypic susceptibility assay. Twenty-seven strains were from 14 patients undergoing GCV therapy. The IC(50) was higher in patients under the prophylaxis regimen. One CMV strain, from a heart transplant recipient, became GCV-resistant after 1 month of therapy (IC(50)=13.7 micromol/l). These data, together with clinical and virological markers, suggested that a switch to foscarnet was necessary, and good evolution was observed. Thus, assay of CMV susceptibility to GCV could be helpful in clinical management.     

Failure to thrive and intestinal diseases in congenital disorders of glycosylation]

Congenital disorders of glycosylation type I (GDG-I) is a class of genetic multisystem disorders characterised by defective glycosylation of glycoproteins. The characteristics and mechanisms of failure to thrive and intestinal diseases present in CDG-I are anectodal. PATIENTS AND METHODS: The aim of this study was to analyse 7 CDG-I (4 CDG-Ia, 2 CDG-Ib and 1 CDG-Ix) with important digestive symptoms and failure to thrive in order to characterise the mechanisms implied. RESULTS: Four children had no skin abnormality or dysmorphia (1 CDG-Ia, 2 CDG-Ib, 1 CDG-Ix). An encephalopathy with cerebellar hypoplasia was present only in the 4 CDG-Ia. Failure to thrive and diarrhea were present during the first month of life in 6 and appeared at 5 years in one CDG-Ia associated to mild or severe hepatopathy in all patients. One CDG-Ia, 1 CDG-Ib, 1 CDG-Ix had an exsudative enteropathy. A positive steatorrhea was present in 3 patients. Five patients had an abnormal small bowel biopsy. Abnormalities were variable: moderate inflammation of the chorion without villous atrophy in 2, intra-enterocyte fat accumulation without villous atrophy in 2, and partial villous atrophy with lymphangectasia in 1. In 2 CDG-Ia the intestinal biopsy was normal. Enteral nutrition in 4 and parenteral nutrition in 2 were effective in 4 patients and 1 patient with an exsudative enteropathy respond to a free fat diet (CDG-Ix). CONCLUSION: The digestive symptoms with failure to thrive is a common feature of CDG-I and could be the first symptoms. The diagnostic should be suspected if no other cause is found. Mechanisms of the intestinal symptoms appear to be multiple such as inflammation, abnormal enterocyte lipid transport or intestinal permeability related to the abnormal glycosylation of intestinal mucosa glycoproteins.     

Fine-needle aspiration biopsies of breast masses. An additional experience with 1153 cases (1985 to 1988) and a meta-analysis.

A series of 1153 fine-needle aspiration biopsies (FNAB) of breast masses obtained during the period 1985 to 1988 in one institution was examined. The following diagnostic accuracy values were found: sensitivity, 93.0%; specificity, 92.4%; predictive positive value, 93.7%; and efficiency, 92.8%. These results were compared with a previously published series for the period 1976 to 1984. The diagnostic accuracy values did not differ significantly between the two series.     

Reduction of scar formation in full-thickness wounds with topical celecoxib treatment

Adult wound repair occurs with an initial inflammatory response, reepithelialization, and the formation of a permanent scar. Although the inflammatory phase is often considered a necessity for successful adult wound healing, fetal healing studies have shown the ability to regenerate skin and to heal wounds in a scarless manner in the absence of inflammation. The cyclooxygenase-2 (COX-2) enzyme, a known mediator of inflammation, has been shown to contribute to a variety of inflammatory conditions and to the development of cancer in many organs. To examine the role of COX-2 in the wound healing process, incisional wounds were treated topically with the anti-inflammatory COX-2 inhibitor celecoxib. Acutely, celecoxib inhibited several parameters of inflammation in the wound site. This decrease in the early inflammatory phase of wound healing had a significant effect on later events in the wound healing process, namely a reduction in scar tissue formation, without disrupting reepithelialization or decreasing tensile strength. Our data suggest that in the absence of infection, adult wound healing is able to commence with decreased inflammation and that anti-inflammatory drugs may be used to improve the outcome of the repair process in the skin by limiting scar formation.     

Functional Symptoms and Somatoform Disorders in Children and Adolescents: The Role of Standardised Measures in Assessment

Functional or unexplained medical symptoms (physical symptoms that are not adequately explained by organic factors and where a major role for psychological factors is assumed) are common amongst children in the general population but can also be an expression of somatisation and somatoform disorders. Co-morbid psychopathology is common. We describe measures mostly used in research into problems related to somatisation in children and adolescents that may be helpful to clinical researchers. Some address the nature and severity of physical symptoms, others document illness attitudes, beliefs and functional impairment, and a third group assesses emotional symptoms. Questionnaires can be helpful for clinicians in quantifying (i) the nature and severity of somatic symptoms and associated functional impairment, (ii) contributory health attitudes and illness beliefs and (iii) co-morbid or primary anxiety and depressive disorders. Together with pain and activity diaries and careful documentation of school attendance, these measures may also be helpful in monitoring treatment response.     

Effect of olanzapine treatment on platelet glutamine synthetase-like protein and glutamate dehydrogenase immunoreactivity in schizophrenia.

According to contemporary views, the glutamatergic system is implicated in the pathogenesis of schizophrenia, and atypical neuroleptics exert their effects (at least partially) through the glutamatergic system. Immunoreactive glutamate-metabolising enzymes, such as glutamine synthetase-like protein (GSLP) and two glutamate dehydrogenase isoenzymes (GDH), have been discovered in human platelets. The amount of GSLP in the platelets of 40 chronic patients with schizophrenia was found to be significantly higher than in 33 controls (consistent with our previous finding of increased amounts of GSLP in the prefrontal cortex of chronic schizophrenia patients). Moreover, survival analysis of the group of patients treated with olanzapine for 28 weeks showed that the larger amount of GSLP measured in platelets before treatment, the shorter the treatment time needed to achieve a positive clinical response (defined a priori as > or = 20% reduction in PANSS total score from the initial level before the treatment). Hence, GSLP level may serve as a predictor of the treatment duration to achieve a positive outcome with olanzapine. Both GSLP and GDH were found significantly changed in the course of treatment; hence, treatment with olanzapine influences the amounts of glutamate-metabolising enzymes in the platelets of chronic schizophrenia patients.     

Twelve years'' experience of computer-aided diagnosis in a district general hospital.

This paper describes experience in a modern district general hospital with a small desktop system for computer-aided diagnosis of acute abdominal pain, over a 12-year period involving 5512 cases. When compared with a baseline year (1973) in which unaided performance was monitored, during an initial study period (1974-76) the diagnostic accuracy of junior staff rose by between 10 and 15%. This higher performance level was then maintained for a decade (1976-86) despite changes in staff. The perforation rate among appendicitis cases fell from 27% to 12.5%, accompanied by a smaller fall in negative laparotomy rates. The saving in surgical bednights devoted to acute abdominal pain was approximately 15%, and the notional cost of resources saved during the first 6 years of operation was 120,000 pounds. Other hospitals have shown--in the short term--benefits similar to those obtained at Airedale District General Hospital. The long-term benefits of the system at Airedale reinforce the conclusions of the earlier short-term trials that a comparable system should probably be offered to all DGHs in the UK, not as an exercise in 'artificial intelligence' but as an effective continuing stimulus to good clinical practice.