Assessment of fetal-maternal haemorrhage in mothers with hereditary persistence of fetal haemoglobin.

Kleihauer examination of peripheral blood cannot be used reliably to detect transplacental fetal-maternal haemorrhage in mothers with hereditary persistence of fetal haemoglobin (HPFH). In Rh(D) negative pregnancies diagnostic confusion with a large fetal-maternal haemorrhage could result in the administration of inappropriately excessive amounts of anti-D immunoglobulin, and the inability to diagnose and quantify transplacental haemorrhage in maternal HPFH by current methods could result in insufficient anti-D administration and subsequent Rh(D) sensitisation. Accordingly, a method to detect and quantify fetal-Rh(D) positive maternal haemorrhage using erythrocyte fluorescent immunocytometry was developed. An indirect immunofluorescence method with IgG anti-D immunoglobulin as the primary antibody was used, combined with quantitative analysis on a fluorescence activated cell sorter. The method was accurate, specific, and sensitive and could detect a contaminating population of 0.1% Rh(D) positive cells in Rh(D) negative blood--a level of fetal-maternal haemorrhage well covered by a single dose of 500 IU of anti-D immunoglobulin.     

Restrictive dermopathy: a report of three cases.

We report three infants with a rare syndrome of restrictive dermopathy, in which rigidity of the skin at birth is associated with characteristic facial anomalies, generalised arthrogryposis, bony abnormalities, and lung hypoplasia. The skin has a distinctive pathology with compaction of the dermal collagen and fibrosis of the subcutaneous tissue. The inheritance is likely to be autosomal recessive and the condition appears to be fatal in the early neonatal period.     

Tel Hashomer camptodactyly syndrome: report of a case with myopathic features.

A child with the Tel Hashomer camptodactyly syndrome is reported. Although muscle weakness and hypoplasia are reported features of this syndrome, further investigation of muscle function has not previously been carried out. We report a raised creatine kinase and an abnormal electromyogram and muscle biopsy in this syndrome. The histology of the muscle biopsy shows a wide range fibre diameter in type 1 and type 2 fibres with a relative deficiency of type 2b fibres. It is suggested that this condition may be primarily a myopathy.     

Comparative structural analysis of calmodulins from Trypanosoma brucei, T. congolense, T. vivax, Tetrahymena thermophila and bovine brain

Calmodulin is an intracellular calcium receptor protein utilized extensively by eukaryotic cells to mediate responsiveness to calcium signals. The present study evaluates the effects on protein structure of amino acid substitutions in trypanosome calmodulin. Calmodulin conformation, hydrophobicity and antigenic determinants are compared among Trypanosoma brucei, Trypanosoma congolense, Trypanosoma vivax, Tetrahymena thermophila and bovine brain. Trypanosome calmodulin differs from brain and Tetrahymena calmodulins based upon isoelectric point, retention time on a C-2/C-18 reverse phase column and interaction with polyclonal antibodies against trypanosome calmodulin by radioimmunoassay or Western procedures. These same analyses do not distinguish trypanosome calmodulins from each other. Polyclonal antibodies against Tetrahymena calmodulin are equally specific and do not recognize the trypanosome or brain calmodulins. Calcium-induced exposure of hydrophobic binding sites are quantitated using the fluorescent probe, N-phenyl-1-naphthylamine. All calmodulins, regardless of source, enhance the fluorescence of N-phenyl-1-naphthylamine 3-4 fold in the presence of calcium. These data demonstrate the extent to which functional calmodulins vary in their structures. We conclude that African trypanosomes share a common calmodulin that is structurally distinct from calmodulin of vertebrates or Tetrahymena.     

Life events and early onset depression: cause or consequence?

BACKGROUND: Adverse life events prior to episodes of depression are assumed to play a causal role. Earlier studies have, however, not adequately controlled for the potential confounding effects of previous depression. METHOD: A two-phase study was nested within a six-wave population based cohort study of 1947 adolescents. Interviews at two assessment phases with the CIS-R and CIDI were used to generate ICD-10 diagnoses of depressive disorder. Life events with longer-term contextual threat were reported for the 6 months before first diagnosis and categorized on the basis of participant appraisal as negative and neutral/positive in effects. Previous depressive and anxiety symptoms were measured 6 months earlier. RESULTS: Pre-existing depressive and anxiety symptoms predicted later events, increasing three-fold the risks for both neutral/positive and negative events in females and increased seven-fold the risk of negative events in males. Life events in turn predicted the onset of depressive disorder independently of previous symptoms. Single negative events held an over five-fold elevated risk and multiple events an almost eight-fold higher risk. Personal threat and loss were associated with disorder in females but not males. CONCLUSIONS: The findings are consistent with a causal role for life events in early episodes of depression. The association also reflects a reciprocal relationship in which earlier symptoms predict later events, perhaps as a result of an individual's attempts to change unfavourable social circumstances.     

Tacrolimus and mycophenolate mofetil after nonmyeloablative matched-sibling donor allogeneic stem-cell transplantations conditioned with fludarabine and low-dose total body irradiation.

We evaluated tacrolimus/mycophenolate mofetil (MMF) for graft-versus-host disease (GVHD) prophylaxis after a nonmyeloablative stem cell transplantation (NST) from a matched sibling donor (MSD). Thirty-two patients (median age, 57 years) with advanced hematologic malignancies, who were poor candidates for a conventional myeloablative transplantation, received fludarabine (30 mg/m(2), day -4 to day -2), total-body irradiation (TBI) (200 cGy, day 0), infusion of donor peripheral blood progenitor cells (day 0), oral tacrolimus 0.06 mg/kg twice daily (from day 3), and oral MMF at 15 mg/kg twice daily (days 0-+27). Tacrolimus was tapered from day +100 to day +180 in those patients with indolent malignancies (n = 25), and from day +35 to day +56 in those with aggressive tumors (n = 7). Regimen toxicities and myelosuppression were mild, allowing 75% of patients to have entirely outpatient transplantations. One patient (3%) experienced a nonfatal graft rejection. Rates of grades II-IV and III-IV acute GVHD were 15.6% and 3%, respectively. Acute GVHD was diagnosed at median day +78 (range, days +31-+84). Extensive chronic GVHD was observed in 10 of 24 evaluable patients (41.6%) at a median onset of day +198 (range, days +128-+277), either spontaneously (n = 5) or elicited after tumor progression (n = 5). Five patients experienced transplantation-related mortality (TRM) (15.6%) from either acute GVHD-related multiorgan failure (MOF) (n = 3) or infectious complications (n = 2). At median follow-up of 19 months (range, 2-41 months), the overall survival, progression-free survival, and disease-free survival rates are 62.5%, 50%, and 40%, respectively. In conclusion, the use of tacrolimus/MMF after MSD NST is associated with encouraging rates of GVHD control.     

Hypoplasia of the cerebellar vermis and corpus callosum in thrombocytopenia with absent radius syndrome on MRI studies

Thrombocytopenia with absent radius (TAR) syndrome is infrequently (7%) associated with mental retardation. In those cases, the mental deficiency is presumed to be a consequence of intracranial hemorrhage due to the thrombo-cytopenia. We report on 2 infants with TAR syndrome. One had developmental delay with evidence of cerebral dysgenesis by magnetic resonance imaging (MRI). Such findings have not been noted in the literature, but may not have been investigated in most cases. The other infant with TAR syndrome, who has had normal psychomotor development, has a normal brain on MRI scan. Detailed neuroimaging studies, preferably MRI, should be considered in the evaluation of patients with TAR syndrome, especially when there are documented signs of developmental delay, with or without a history of intracranial hemorrhage. © 1994 Wiley-Liss, Inc.     

Central Role for Interleukin-4 in Regulating Nitric Oxide-Mediated Inhibition of T-Cell Proliferation and Gamma Interferon Production in Schistosomiasis

Schistosoma mansoni-infected wild-type (WT) mice develop a Th2 response and chronic disease. In contrast, infected interleukin-4 double-deficient (IL-4(-/-)) mice develop a Th1-like response and an acute, lethal syndrome. Disease severity in these animals correlates with excessive and prolonged production of nitric oxide (NO) associated with enhanced antigen-driven gamma interferon (IFN-gamma) production in the absence of IL-4. Strikingly, splenic lymphocytes from infected IL-4(-/-) mice failed to proliferate as well as those from infected WT mice following stimulation in vitro with antigen or anti-CD3 antibody. Contrary to antigen-driven IFN-gamma responses, anti-CD3 antibody stimulation of splenocytes resulted in significantly less IFN-gamma being produced by CD8 cells from infected IL-4(-/-) mice than by those from infected WT mice or normal mice. NO is largely responsible for the impaired T-cell functions in infected IL-4(-/-) mice, as inhibition of iNOS significantly enhanced proliferation and IFN-gamma production.