End-stage periventricular leukomalacia: MR evaluation

A prospective study was performed to assess the capabilities of magnetic resonance (MR) imaging in evaluation of end-stage periventricular leukomalacia (PVL) in six children, aged 31-54 months, in whom PVL had been documented by neurologic ultrasonography during the neonatal period. Eight children of similar age (four premature infants and four full-term infants) with normal neurologic development served as controls. A characteristic triad of PVL abnormalities was seen on MR images: (a) abnormally increased periventricular white-matter signal intensity on the first and second echo images of a T2-weighted sequence (repetition time = 2,000-2,400 msec, echo times = 20 or 30 and 80 msec), most commonly observed in the trigone regions of the lateral ventricles bilaterally; (b) marked loss of periventricular white matter in these regions of abnormal signal intensity, predominantly in the periatrial regions; and (c) compensatory focal ventricular enlargement adjacent to regions of abnormal signal intensity. In patients with the classic periatrial distribution of PVL lesions, general correlation between the degree of neurologic impairment and the severity of MR abnormalities was demonstrated. MR imaging was useful in detecting subtle forms of PVL in cases in which neurologic damage was subclinical.     

Procoagulant activity of reversibly acylated human factor Xa

The plasma clotting factors used to treat hemophiliacs who have developed inhibitory antibodies have a shared history of limited clinical safety and utility. To improve on existing bypass factors, we have developed a reversibly acylated form of human plasma factor Xa capable of providing a time-dependent release of procoagulant activity. Factor Xa was treated with p-amidinophenyl p'-anisate to generate anisoyl Xa. The chemical modification of the protein involves acylation of the active site serine residue of factor Xa. Anisoyl Xa deacylated in a time, pH, and temperature-dependent manner. Active factor Xa generated on deacylation of anisoyl Xa exhibited amidolytic and prothrombinase complex activities in in vitro assays, the level being comparable to those of untreated factor Xa. When Anisoyl Xa was infused into rabbits, active factor Xa was generated on deacylation of the acylated enzyme, which shortened the activated partial thromboplastin time (APTT) in a dose-dependent manner. The duration of effect on rabbit APTT could be directly correlated to the level of human plasma factor Xa. Because anisoyl Xa bypasses the "tenase" complex that is compromised in hemophilia A and B and is unaffected by inhibitory antibodies, it has the potential to be used as an effective bypass therapy.     

Shwachman syndrome: Exocrine pancreatic dysfunction and variable phenotypic expression

BACKGROUND & AIMS: Shwachman syndrome is an inherited condition with multisystemic abnormalities, including exocrine pancreatic dysfunction. The aim of this study was to evaluate the occurrence and progression of features in a large cohort of patients. METHODS: Clinical records of 25 patients with Shwachman syndrome were reviewed. RESULTS: Mean birth weight (2.92 +/- 0.51 kg) was at the 25th percentile. However, by 6 months of age, mean heights and weights were less than the 5th percentile. After 6 months of age, growth velocity was normal. Severe fat maldigestion due to pancreatic insufficiency was present in early life (fecal fat, 26% +/- 17% of fat intake; age, < 2 years). Serial assessment of exocrine pancreatic function showed persistent deficits of enzyme secretion, but 45% of patients showed moderate age-related improvements leading to pancreatic sufficiency. Neutropenia was the most common hematologic abnormality (88%), but leukopenia, thrombocytopenia, and anemia were also frequently encountered. Patients with hypoplasia of all three bone marrow cellular lines (n = 11) had the worst prognosis; 5 patients died, 2 of sepsis and 3 of acute myelogenous leukemia. Other findings included hepatomegaly and/or abnormal liver function test results and skeletal abnormalities. CONCLUSIONS: A wide and varied spectrum of phenotypic abnormalities among patients with Shwachman syndrome is described. Pancreatic acinar dysfunction is an invariable abnormality. Patients with severe bone marrow involvement may have a guarded prognosis. (Gastroenterology 1996 Dec;111(6):1593-602)     

Comparison of horse and rabbit antithymocyte globulin in immunosuppressive therapy for refractory cytopenia of childhood

Refractory cytopenia of childhood is the most common subtype of myelodysplastic syndrome in children. In this study, we compared the outcome of immunosuppressive therapy using horse antithymocyte globulin (n=46) with that using rabbit antithymocyte globulin (n=49) in 95 patients with refractory cytopenia of childhood and hypocellular bone marrow. The response rate at 6 months was 74% for horse antithymocyte globulin and 53% for rabbit antithymocyte globulin (P=0.04). The inferior response in the rabbit antithymocyte globulin group resulted in lower 4-year transplantation-free (69% versus 46%; P=0.003) and failure-free (58% versus 48%; P=0.04) survival rates in this group compared with those in the horse antithymocyte globulin group. However, because of successful second-line hematopoietic stem cell transplantation, overall survival was comparable between groups (91% versus 85%; P=ns). The cumulative incidence of relapse (15% versus 9%; P=ns) and clonal evolution (12% versus 4%; P=ns) at 4 years was comparable between groups. Our results suggest that the outcome of immunosuppressive therapy with rabbit antithymocyte globulin is inferior to that of horse antithymocyte globulin. Although immunosuppressive therapy is an effective therapy in selected patients with refractory cytopenia of childhood, the long-term risk of relapse or clonal evolution remains. (ClinicalTrial.gov identifiers: {"type":"clinical-trial","attrs":{"text":"NCT00662090","term_id":"NCT00662090"}}NCT00662090)     

A systematic review of risk of HIV transmission through biting or spitting: implications for policy

Objectives

The perceived threat of HIV transmission through spitting and biting is evidenced by the increasing use of “spit hoods” by Police Forces in the UK. In addition, a draft parliamentary bill has called for increased penalties for assaults on emergency workers, citing the risk of communicable disease transmission as one justification. We aimed to review literature relating to the risk of HIV transmission through biting or spitting.

Methods

A systematic literature search was conducted using Medline, Embase and Northern Lights databases and conference websites using search terms relating to HIV, AIDS, bite, spit and saliva. Inclusion and exclusion criteria were applied to identified citations. We classified plausibility of HIV transmission as low, medium, high or confirmed based on pre‐specified criteria.

Results

A total of 742 abstracts were reviewed, yielding 32 articles for full‐text review and 13 case reports/series after inclusion and exclusion criteria had been applied. There were no reported cases of HIV transmission related to spitting and nine cases identified following a bite, in which the majority occurred between family (six of nine), in fights involving serious wounds (three of nine), or to untrained first‐aiders placing fingers in the mouth of someone having a seizure (two of nine). Only four cases were classified as highly plausible or confirmed transmission. None related to emergency workers and none were in the UK.

Conclusions

There is no risk of transmitting HIV through spitting, and the risk through biting is negligible. Post‐exposure prophylaxis is not indicated after a bite in all but exceptional circumstances. Policies to protect emergency workers should be developed with this evidence in mind.