The intraventricular conduction time of fetal heart in pregnancies with suspected fetal growth retardation

Summary. Electrocardiographs from 68 fetuses with ultrasound evidence of growth retardation were recorded from the maternal abdomen; QRS duration was measured and compared to normal standards previously obtained in our Institute. Of these fetuses, 54 were small-for-gestational-age at birth and 44 exhibited QRS duration values below -2SD for their gestational age. All but one of the 14 normal fetuses showed normal QRS values (positive predictive value = 98%; negative predictive value = 57%). Of 11 fetuses with QRS duration values below -4SD, nine were particularly small, below the 2nd centile of weight for gestation. QRS duration measurements may represent a sensitive method for identifying fetal growth-retardation. The QRS duration also seems to provide a reliable prognosis of perinatal outcome. Normal values are a reassuring factor: abnormal cardiotocographic records were observed in only 2 out of 23 cases and no low Apgar scores or perinatal deaths occurred. QRS values below -4 SD proved to be associated with abnormal cardiotocographic records (7/13), low Apgar scores (5/15) and perinatal deaths (3/15).     

Effect of mesalazine on mucosal immune biomarkers in irritable bowel syndrome: a randomized controlled proof-of-concept study

Background  Intestinal immune infiltration contributes to symptoms in patients with irritable bowel syndrome (IBS).
Aim  To assesses the effect of mesalazine (mesalamine) on mucosal immune cells in patients with IBS, through a pilot study.
Methods  A randomized, double-blind, placebo-controlled trial in 20 patients with IBS in tertiary care setting. Patients were randomized to receive placebo or 800 mg mesalazine three times daily for 8 weeks. The primary endpoint was a significant reduction in total colonic immune cells on biopsies obtained at the end of treatment compared to baseline. Secondary endpoints included effects on subsets of immune cells, inflammatory mediators and symptom severity. Intention-to-treat analysis was performed.
Results  Mesalazine markedly reduced immune cells as compared with placebo ( P  = 0.0082); this effect was ascribed to a marked inhibition of mast cells ( P  = 0.0014). Mesalazine significantly increased general well-being ( P  = 0.038), but had no significant effects on abdominal pain ( P  = 0.084), bloating ( P  = 0.177) or bowel habits. No serious drug-related adverse events were reported during the study.
Conclusions  Mesalazine is an effective and safe approach to reduce mast cell infiltration and may improve general well-being in patients with IBS. These results support the hypothesis that immune mechanisms represent potential therapeutic targets in IBS.     

Epidemiology of low bone mineral density and fractures in children with severe cerebral palsy: a systematic review

Aim  Children with severe cerebral palsy (CP) are at risk for developing low bone mineral density (BMD) and low-impact fractures. The aim of this study was to provide a systematic literature review of the epidemiology of fractures and low BMD in children with severe CP, with an emphasis on risk factors. Gross Motor Function Classification System (GMFCS) levels IV and V were criteria for severe cerebral palsy.
Method  The literature (PubMed) was searched and eligible studies were given a level of evidence score using the Scottish Intercollegiate Guidelines Network criteria.
Results  Seven studies were found concerning epidemiology of fractures, 11 studies described epidemiology of low BMD, and 14 studies concerned risk factors. The methodological quality of most of these studies was poor. Five studies were considered well-conducted with low risk of confounding and bias. In these studies, the incidence of fractures in children with moderate to severe CP approached 4% per year, whereas the prevalence of low BMD in the femur was 77%. Limited ambulation, feeding difficulties, previous fractures, anticonvulsant use, and lower body fat mass were associated with low BMD z-scores.
Interpretation  There is only a limited amount of high-quality evidence on low BMD and fractures in children with severe CP.     

Unrelated donor bone marrow transplantation for children and adolescents with aplastic anaemia or myelodysplasia

Allogeneic transplantation from an HLA-matched family member has been shown to be effective in reconstituting normal haemopoiesis in young people with severe cytopenias, classified as myelodysplastic syndrome (MDS) or severe aplastic anaemia (SAA). Unrelated donor transplant is a therapeutic choice for patients without a suitable family member donor. We report the outcome of seven patients < 20 years old with SAA and 10 with MDS treated with BMT from an HLA A,B DRB1 matched ( n  =8) or A or B locus mismatched ( n  =9) unrelated donor at the University of Minnesota between March 1988 and August 1995. Primary graft failure occurred in two patients and secondary graft failure in one, who was subsequently successfully engrafted with a second donor marrow infusion. Grades II–IV GVHD occurred in 10/16 (63%), and grades III–IV in 6/16 (37%) evaluable patients. Nine of the 17 patients (six with MDS and three with SAA) survive with full donor chimaerism, a median of 1.2 years post-BMT (range 3 months to 7 years). We recommend early referral for consideration of unrelated donor BMT for young patients with MDS, and patients with SAA without response to immunosuppression.     

Induction of macrophage activation and opsonizing antibodies by Trypanosoma cruzi subpopulations

Macrophage activation and production of opsonizing antibodies were studied in mice either infected with a lethal and reticulotropic Trypanosoma cruzi strain, RA, or with a non lethal and myotropic strain, CA-I, as well as with a clone, K98 (derived from CA-I), similar to the parental strain. Measurement of macrophage respiratory burst by chemiluminescence disclosed that T. cruzi infection induced an enhancement of the respiratory burst, no matter the parasite subpopulation employed. But, while in mice surviving RA infection the respiratory burst was higher than during the acute period and parasitaemia was efficiently controlled, in mice infected with K98 enhanced respiratory burst coexisted with measurable levels of parasitaemia either at acute or chronic infection periods. Macrophage activation was also proved by enhanced trypanocidal activity in macrophages derived from mice infected with any of the parasite subpopulations. Sera from RA mice opsonized and lysed T. cruzi bloodstream forms efficiently, whereas sera from CA-I or K98 mice neither lysed nor opsonized this parasite stage. All three subpopulations assayed here showed IgG bound to their membranes in vivo and similar capping kinetics, but only antibodies bound to RA parasites invariably triggered lysis. Therefore, the role played by macrophage activation in resistance and control of Pm levels is related to some features of each T. cruzi subpopulation, such as its capacity to invade macrophages and to elicit opsonizing antibodies.     

Longitudinal neuropsychological evaluation of HIV-infected intravenous drug users

The present study aimed to describe the cognitive status of a group of HIV-positive asymptomatic intravenous drug users (IVDU) and changes which occurred over a 12-month follow-up period. Forty-two HIV positive IVDU were selected and matched for age, sex, educational level and pattern of drug abuse with 39 seronegative IVDU controls. Baseline and follow-up evaluation included neuropsychological tests exploring attention, language, memory, logic and visuomotor abilities, biological markers and clinical parameters. About one-third of both seropositive and seronegative subjects showed at baseline slight cognitive deficits, ‘which did not change during the follow-up period.     

Modified β-Cyclodextrin (SBE7-β-CyD) with Viscous Vehicle Improves the Ocular Delivery and Tolerability of Pilocarpine Prodrug in Rabbits

The complexation of pilocarpine prodrug, O,O'-dipropionyl-(1,4-xylylene) bispilocarpate, with various β-cyclodextrin (β-CyD) derivatives was studied by the phase solubility method. The effects of coadministered sulphobutyl ether β-CyD (SBE7-β-CyD) with and without poly(vinyl alcohol) (PVA) on the miotic response and eye irritation of the prodrug were investigated in pigmented rabbits. The pilocarpine prodrug formed 1:1 inclusion complexes with variably substituted sulphobutyl ether derivatives of β-CyD (SBE4-β-CyD and SBE7-β-CyD), and 1:1 and 1:2 complexes with hydroxypropyl-β-CyD (HP-β-CyD) at pH 7:4. Coadministered SBE7-β-CyD eliminated the eye irritation due to the pilocarpine prodrug, but also decreased the miotic response. Ocular absorption of the prodrug was improved by increasing the viscosity of prodrug/SBE7-β-CyD solution with PVA without inducing any eye irritation. Eye irritation due to viscous prodrug/SBE7-β-CyD solutions was comparable with isotonic NaCl solution. We conclude that administration of pilocarpine prodrug in viscous SBE7-β-CyD solution decreases substantially eye irritation while ocular absorption is not affected.     

The long-term efficacy of interferon alfa in chronic hepatitis C patients: A critical review

With current therapeutic regimens, sustained responses occur in no more than 25% of patients with chronic hepatitis C who are treated with interferon. Relapses occur usually within 6 months from therapy suspension, but clinical and virologic recurrencies can be observed as late as after 3 years of follow up. The rate of long-term responses seems to depend on the dosage and the period of administration of interferon, but the best therapeutic protocol remains unknown. As a direct marker of permanent recovery is not available, indirect signs of disease resolution are: (i) continuously normal alanine aminotransferase levels; (ii) clearance of HCV-RNA; (iii) disappearance of anti-C100/NS4; and (iv) significant histological improvements assessed at least 2 years after therapy withdrawal. Known baseline predictive features of long-term response are the absence of cirrhosis, low viraemic levels and infection with HCV of type III or IV genotype (Okamoto's classification). According to recent reports, the lower the heterogeneity of the hypervariable region of the envelope 2 gene of HCV, the higher the chance of a sustained remission. There is not yet any consensus on the efficacy of a second therapeutic course of interferon in inducing a permanent response, and controlled trials are needed to clarify this issue.     

Duplex-Doppler assessment of cirrhosis in patients with chronic compensated liver disease

Portal venous flow velocity (PFV) was measured with duplex-Doppler equipment in 50 normal subjects and in 117 patients with suspected chronic liver disease who showed no evidence of decompensation such as ascites, hepatic encephalopathy, jaundice or oesophageal bleeding. All the patients underwent percutaneous liver biopsy which demonstrated non-cirrhotic liver disease in 58 cases (CH-patients: steatosis 8, persistent chronic hepatitis 8, active chronic hepatitis 42) and liver cirrhosis in the other 59 cases (LC-patients). The normal subjects and the CH-patients had similar values of max-PFV and mean-PFV (max-PFV 26.7±3.2 and 25.7±3.4 cm/s respectively; mean-PFV 22.9±2.8 and 22.4±3.8 cm/s respectively). The LC-patients’ values (max-PFV 19.3±3.5; mean-PFV 16.9±2.9) were significantly lower than those of the normal subjects (P<0.001) and of the CH-patients (P<0.001). Considering the normal max-PFV to be in the range 20–33.1 cm/s (mean±2 s.d. of the normal subjects, 95% confidence limits), max-PFV was reduced in 0/50 normal subjects, 1/58 CH-patients and 39/59 LC-patients (66.1% sensitivity; 98.2% specificity). In conclusion, the duplex-Doppler measurement of PFV is of great interest in the diagnostic study of patients with suspected chronic compensated liver disease and in the early diagnosis of cirrhosis. A low max-PFV is a reliable pointer to liver cirrhosis, whereas a normal max-PFV indicates a non-cirrhotic liver disease but is less probative. Each centre should standardize normal PFV values in order to establish their own threshold value for diagnosing liver cirrhosis.