A revised rule of thumb for predicting haematocrit rise in premature infants following packed red blood cell transfusion

The purpose of this study is to compare a revised rule of thumb with the Harriet Lane and Behrman's formulas for predicting haematocrit rise following packed red blood cell (PRBC) transfusion in premature neonates. Pre- and post-transfusion, equilibrated central haematocrits were obtained within 24 h of transfusion in 12 premature neonates undergoing 18 transfusions. Iatrogenic blood loss between pre- and post-transfusion haematocrit determinations was measured for each transfusion event, and infants with detectable, non-iatrogenic blood loss were excluded. Expected haematocrit rise was calculated three different ways using the Behrman, Harriet Lane, and proposed formulas (see text). The Harriet Lane formula predicted haematocrit rise with a correlation, r = 0.66 and slope m = 0.43. The Behrman's formula predicted haematocrit rise with a correlation r = 0.81 and slope m = 0.60. The proposed formula predicted haematocrit rise with a correlation r = 0.79 and slope m = 0.56. On the basis of these findings, we propose the following formula: Quantity PRBC transfused (ml) = 4/3 X desired haematocrit rise X weight (Kg) This formula takes into account the higher blood volume per kilogram body weight seen in premature infants while estimating PRBC unit haematocrit as 0.75 to obviate the need of measurement before each transfusion and, therefore, is an accurate, practical, and simple replacement for the Harriet Lane and Behrman's formulas.     

Haemophilia A: molecular insights.

Haemophilia A is the most common inherited bleeding disorder caused by defects in the F8C gene that encodes coagulation factor VIII. This X-linked recessive disorder occurs in approximately 1:5000 males. Haemophilia A is diagnosed based on normal prothrombin time, altered activated partial thromboplastin time and reduced factor VIII activity in plasma. Carrier females are usually asymptomatic and can be identified only by molecular analysis. The most frequent mutations in F8C are intron 22 and 1 inversions, which occur in approximately 50% and 5% of patients, respectively, with a severe phenotype. Large gene deletions are observed in approximately 5% of alleles from patients with severe haemophilia A. The remaining severe cases and all moderate and mild cases result from numerous point mutations and small insertions/deletions, which are de novo mutations in one-third of cases. Thus, molecular diagnosis of carrier status and prenatal diagnosis in families without intron 22 or 1 inversions is based on scanning techniques or gene sequencing. When the disease-causing mutation cannot be identified, molecular diagnosis is performed by linkage analysis of several DNA polymorphic markers linked to F8C. Given the clinical heterogeneity among haemophilic patients, many groups, including our own, have examined the relationships between prothrombotic gene variants and haemophilic phenotype to investigate whether prothrombotic gene variants modify clinical expression of the disease.     

Expression of CDX2 and MUC2 in Barrett's mucosa

Barrett's mucosa is a risk factor for esophageal adenocarcinoma and should be detected at an early stage. It is defined by the presence of columnar epithelium with goblet cells in the lower esophagus, but histologic diagnosis can be uncertain in the absence of distinct goblet cells. We investigated 55 biopsies from 48 patients with endoscopically plain Barrett's esophagus and performed immunohistochemistry for CDX2 and MUC2. In addition, alcian blue (pH 2,5)/PAS staining was done. In histologically unequivocal Barrett's mucosa, nuclear expression of CDX2 in goblet cells and many columnar cells, as well as cytoplasmic positivity for MUC2 in goblet cells, could be observed. Alcian blue (pH 2,5)/PAS stained acidic mucins in goblet cells and in some non-goblet columnar cells. In six cases, no definite Barrett's mucosa was present, and no expression of MUC2 could be observed. In these biopsies, there was granular cytoplasmic and/or focal nuclear staining for CDX2 in non-goblet columnar epithelial cells, indicating their intestinal differentiation. We suggest that this peculiar mucosa is the precursor of unequivocal Barrett's mucosa and would designate it early Barrett's mucosa. Alcian blue for acidic mucins is inconsistent in this epithelium and does not reliably indicate early intestinal differentiation.     

Degeneration of oxidative muscle fibers in HTLV-1 tax transgenic mice.

The HTLV-1 tax gene under control of the HTLV-1 long terminal repeat (LTR) was introduced into transgenic mice. Previously tax protein expression in the muscle and peripheral nerves of three independent mouse lines was reported. Here the localization of this transgenic protein at a cellular and subcellular level is described. Tax protein was expressed in oxidative muscle fibers that developed severe progressive atrophy. It localized to the cytoplasma where it was associated with structures resembling degenerating Z bands. This pattern of muscle fiber involvement is similar to that observed in human retroviral associated myopathy. This transgenic mouse model suggests that preferential expression of the HTLV-1 viral promoter in oxidative muscle fibers may explain the productive infection of these fibers in HTLV-1 myopathy.     

February 2003: a 53-year-old male with new onset seizures

The February COM. A 53-year-old obese man presented with new onset seizures and an MRI scan revealed a large cystic and necrotic heterogeneously enhancing left frontal mass. Craniotomy revealed a firm subdural tumor on the cortical surface that was delivered en-bloc preserving the pial planes and stripping it from the falx cerebri. The tumor consisted of multiple irregular fragments of white-tan rubbery tissue admixed with globules of bosselated, white-tan rubbery tissue and a fragment of bone. Sections of the tumor revealed mature hyaline cartilage with no atypia of the chondrocytes. There was focal mineralization and endochondral ossification. A diagnosis of intracranial mesenchymal osteochondroma was made. Osteochondroma, a benign cartilaginous neoplasm comprised of mature hyaline cartilage with focal ossification, is the most common benign bone tumor. Extraskeletal (mesenchymal) osteochondromas are known to originate from non-skeletal or non-cartilaginous tissue. Intracranial osteochondromas are uncommon, typically arising from the base of the skull. Only about 15% of intracranial osteochondromas arise supratentorially, from the dura, usually in a parafalcine frontoparietal location and some have been a component of Maffucci's syndrome and Ollier disease. Intracranial osteochondromas can occur at any age with a predilection for younger individuals. Intracranial mesenchymal osteochondromas exhibit a benign clinical course. Typically, the histomorphology resembles mature hyaline cartilage without anaplastic proliferation of chondrocytes or nuclear atypia, with a lobular arrangement of clusters of lacunae containing single chondrocytes. Transition to osteochondrosarcoma has rarely been documented.     

Open-field behavior, habituation and passive avoidance learning: Effect of ACTH and hydrocortisone on Normal and adrenalectomized rats

Exploratory behavior (GMA) and habituation rate (IH) were studied in an open-field situation in normal and adrenalectomized rats. Following this procedure the rats were subjected to passive avoidance learning (PA). Wide-spreading individual differences were observed in the exploratory behavior and the tendency of habituation of normal rats. As compared to the normal values, either the adrenalectomy which was performed 24 hr, 7 days and 28 days prior to the experiments or the ACTH and hydrocortisone treatment failed to modify the GMA and the IH significantly. An improvement of PA was found in the normal rats following ACTH and hydrocortisone treatment. In the adrenalectomized animals the hydrocortisone proved to be effective, whereas ACTH did not influence PA. No correlation was found between GMA, IH versus PA values and the influence of ACTH and hydrocortisone administration on these parameters. It is concluded that the direction of PA is unpredictable on the basis of the open-field test performed on R-Amsterdam strain of rats, and the effect of ACTH on passive avoidance learning is mediated through the adrenal glands.     

Inflammatory cytokine response to Vibrio vulnificus elicited by peripheral blood mononuclear cells from chronic alcohol users is associated with biomarkers of cellular oxidative stress

Vibrio vulnificus is the leading cause of death in the United States associated with the consumption of raw seafood, particularly oysters. In epidemiological studies, primary septicemia and inflammation-mediated septic shock caused by V. vulnificus is strongly associated with liver disease, often in the context of chronic alcohol abuse. The present study was undertaken to determine whether clinical biomarkers of liver function or cellular oxidative stress are associated with peripheral blood mononuclear cell inflammatory cytokine responses to V. vulnificus. Levels of interleukin-1 beta (IL-1 beta), IL-6, IL-8, and tumor necrosis factor alpha elicited in response to V. vulnificus and measured in cell supernatants were not associated with the liver biomarkers aspartate aminotransferase (AST) or alanine aminotransferase (ALT) or the AST/ALT ratio. In contrast, reduced glutathione (GSH) levels were associated with the release of all four cytokines (IL-1 beta [R(2) = 0.382; P = 0.006], IL-6 [R(2) = 0.393; P = 0.005], IL-8 [R(2) = 0.487; P = 0.001], and TNF-alpha [R(2) = 0.292; P = 0.021]). Those individuals with below-normal GSH levels produced significantly less proinflammatory cytokines in response to V. vulnificus. We hypothesize that persons with markers for cellular oxidative stress have increased susceptibility to V. vulnificus septicemia.     

Role of Biological Mimicry in the Pathogenesis of Rat Arthritis Induced by Mycoplasma arthritidis

Complement fixation (CF), immunofluorescence, and agar gel double-diffusion tests were used to demonstrate an antigenic relationship between rat tissues and Mycoplasma arthritidis. Rabbit antisera against six strains of M. arthritidis exhibited positive reactions in the CF test with an ethyl alcohol-saline extract of rat muscle, whereas only 6 of 18 antisera against other Mycoplasma species were positive. With the use of gel diffusion techniques, absorption of various M. arthritidis antigens with antiserum against rat muscle removed at least one precipitin band when the absorbed mycoplasma antigens were reacted against homologous antisera. Rabbit antiserum against M. arthritidis was conjugated with fluorescein isothiocyanate and reacted against frozen sections of muscle tissues of various animals. As controls, unlabeled normal rabbit serum and rabbit anti-M. arthritidis serum were included to determine the specificity of the reaction. Rat, hamster, and mouse skeletal muscle exhibited specific fluorescence, whereas chicken, beef, frog, and turtle muscles exhibited no specific fluorescence. Mice injected at birth with rat lymphocytes were found to be more susceptible to subsequent infection by M. arthritidis than were normal mice or mice injected at birth with mouse lymphocytes. These results indicate the occurrence of a heterogenetic antigen(s) common to M. arthritidis and rat tissues. Preliminary evidence suggests that this heterogenetic antigen(s) may enable the mycoplasmas to become established in their host.     

45X/46X,r(X) with syndactyly and severe mental retardation

Two white females, age 2 1/2 and 33 years, respectively, were investigated because of severe mental retardation associated with neurologic abnormalities, coarse face, and soft tissue syndactyly involving upper and lower limbs. Each had cytogenetic findings of a mosaic variant of Ullrich-Turner syndrome with X ring chromosome in peripheral lymphocyte and skin fibroblasts. Early X replication occurred in one-third of the X ring chromosomes; there was no evidence for X-autosome translocation involving either X and an autosomal duplication; results of studies for fragility of the X chromosomes were unremarkable. In situ hybridization with an X centromere probe was positive for the ring. To our knowledge, the unusual constellation of cytogenetic, physical, and mental findings seen in these 2 individuals has not been reported previously.