The presurgical management with erythrocytapheresis of a patient with a high-oxygen-affinity, unstable Hb variant (Hb Bryn Mawr)

BACKGROUND: Hemoglobin (Hb) Bryn Mawr is an unstable Hb variant resulting in congenital hemolytic anemia. This variant Hb also has an increased affinity for oxygen. The perioperative transfusion management of this disorder is described, and the first genomic analysis of this Hb variant is given. CASE REPORT: An 11-year-old boy, heterozygous for Hb Bryn Mawr, was referred for cholecystectomy. Sequence analysis of genomic DNA confirmed that the patients was heterozygous for a T–>C transition in the codon for amino acid 85, causing a substitution of serine for phenylalanine in the beta-globin chain. On the basis of whole-blood O2 dissociation studies, projected tissue O2 delivery would have been suboptimal during general anesthesia; therefore, a partial red cell exchange transfusion was performed to lower variant Hb and prevent tissue hypoxia during surgery. The red cell mass to be exchanged (50%) was determined from the calculated increase in O2 delivery capacity required to maintain an O2 extraction of 4 to 5 mL of O2 per dL of whole blood. The p50 of whole blood from the patients immediately after the exchange transfusion was 16.0 torr. At the time of surgery, the p50 was normal (25.9 torr). The patient's whole blood 2,3 DPG levels were 4.70 mmol per mL of red cells (before transfusion) (normal range=4.8 +/? 0.3 mmol/mL red cells), 4.07 mmol per mL of red cells (immediately after transfusion), and 4.55 mmol per mL of red cells (48 hours after transfusion). CONCLUSION: This patient with Hb Bryn Mawr was prepared for surgery with a partial exchange transfusion to prevent tissue hypoxia during anesthesia. Decreased 2,3 DPG levels immediately after transfusion resulted in increased O2 affinity of whole blood; however, 48 hours after exchange transfusion, a normal p50 (due to both removal of variant Hb and regeneration of 2,3, DPG) was observed. Partial exchange transfusion is useful in the preoperative management of patients with Hb variants characterized by increased O2 affinity.     

An assessment of whole blood impedance aggregometry using blood from normal subjects and haemodialysis patients

Impedance aggregometry allows the measurement of platelet responses in whole blood as well as in PRP. The variability of haematocrit values encountered when applying this technique to haemodialysis patients prompted an investigation of the effects of red cells on platelet aggregation in whole blood. Collagen induced aggregation was measured in both PRP and whole blood from haemodialysis patients and healthy controls, Platelets from haemodialysis patients were less aggregable than those from the controls when tested in PRP, but more aggregable when tested in whole blood. Blood samples with a range of haematocrit values were prepared by mixing PRP and autologous red cells, and used to study the effect of haematocrit on platelet aggregation. In blood from control subjects aggregation rate was reduced by rising haematocrit but no reduction of maximum aggregation occurred until haematocrit exceeded 40%. In contrast uraemic platelets showed increased responses in the presence of red cells. In a limited cross-over study no significant difference was found in the effect on platelet aggregation of washed erythrocytes from uraemic and non-uraemic donors. It is concluded that red cell presence influences platelet aggregation by complex mechanisms during impedance aggregometry and that this effect must be considered when interpreting results.     

Pancreatic abscess: predictive value of early abdominal CT

The value of a recently reported grading system of early abdominal computed tomography (CT) for predicting development of pancreatic abscess in patients with acute pancreatitis was reassessed. When the previously described CT grading system was used in another patient population, it did not demonstrate the same degree of prognostic value of baseline CT. In this series pancreatic abscess occurred in only eight of 29 patients (28%) with grade E CT scans (with grade E representing the most severe involvement), compared with 60% in the previous series. Of 44 patients with either grade D or E baseline CT scans, abscesses developed in only 30%, with a minimum clinical follow-up of 3 months. A second grading system, which used a semiquantitative analysis of the degree of peripancreatic inflammation (a "CT severity score"), also did not strongly correlate with the future risk of abscess, The authors conclude that early abdominal CT should be performed selectively in patients with acute pancreatitis and reserved for patients who are either diagnostic dilemmas or who fail to respond to supportive treatment and have clinically suspected surgical complications such as pancreatic abscess.     

Maternal comprehension of two growth monitoring charts in Sri Lanka

OBJECTIVE: To investigate the maternal comprehension of two different growth charts and to identify the group of mothers with poor comprehension. DESIGN: An experimental prospective study. SETTING: A child welfare clinic at the De Soysa Hospital for Women, Colombo, Sri Lanka. SUBJECTS: 932 mothers were studied regarding their interpretation of the type of growth chart their infants had been allocated. A total of 413 mothers interpreted the 'road-to-health' chart and 519 mothers interpreted the revised chart. A validated scoring system was used to assess comprehension. The two groups of mothers were comparable. RESULTS: 62.4% (324) mothers who interpreted the revised chart had good comprehension. Only 20.6% (85) mothers had similar comprehension with the road-to-health chart. Education up to or beyond grade 8 in school significantly improved comprehension. CONCLUSION: The design of the growth chart has a powerful effect on maternal comprehension of growth patterns. Length of schooling rather than literacy alone is a marker of a comprehending mother. The policy implications of these findings are that governments and agencies may need to redesign parent held growth charts to achieve better comprehension by mothers.     

Lung oxidative stress as related to exercise and altitude. Lipid peroxidation evidence in exhaled breath condensate: a possible predictor of acute mountain sickness

Lung oxidative stress (OS) was explored in resting and in exercising subjects exposed to moderate and high altitude. Exhaled breath condensate (EBC) was collected under field conditions in male high-competition mountain bikers performing a maximal cycloergometric exercise at 670 m and at 2,160 m, as well as, in male soldiers climbing up to 6,125 m in Northern Chile. Malondialdehyde concentration [MDA] was measured by high-performance liquid chromatography in EBC and in serum samples. Hydrogen peroxide concentration [H₂O₂] was analysed in EBC according to the spectrophotometric FOX₂ assay. [MDA] in EBC of bikers did not change while exercising at 670 m, but increased from 30.0±8.0 to 50.0±11.0 nmol l⁻¹ (P<0.05) at 2,160 m. Concomitantly, [MDA] in serum and [H₂O₂] in EBC remained constant. On the other hand, in mountaineering soldiers, [H₂O₂] in EBC under resting conditions increased from 0.30±0.12 μmol l⁻¹ at 670 m to 1.14±0.29 μmol l⁻¹ immediately on return from the mountain. Three days later, [H₂O₂] in EBC (0.93 ±0.23 μmol l⁻¹) continued to be elevated (P<0.05). [MDA] in EBC increased from 71±16 nmol l⁻¹ at 670 m to 128±26 nmol l⁻¹ at 3,000 m (P<0.05). Changes of [H₂O₂] in EBC while ascending from 670 m up to 3,000 m inversely correlated with concomitant variations in HbO2 saturation (r=−0.48, P<0.05). AMS score evaluated at 5,000 m directly correlated with changes of [MDA] in EBC occurring while the subjects moved from 670 to 3,000 m (r=0.51, P<0.05). Lung OS may constitute a pathogenic factor in AMS.     

Environmental enrichment increases paired-pulse depression in rat auditory cortex

Temporal features are important for the identification of natural sounds. Earlier studies have shown that cortical processing of temporal information can be altered by long-term experience with modulated sounds. In a previous study, we observed that environmental enrichment dramatically increased the response of cortical neurons to single tone and noise burst stimuli in both awake and anesthetized rats. Here, we evaluate how enrichment influences temporal information processing in the auditory cortex. We recorded responses to repeated tones and noise bursts in awake rats using epidural evoked potentials and in anesthetized rats using microelectrodes. Enrichment increased the response of cortical neurons to stimuli presented at slow rates and decreased the response to stimuli presented at fast rates relative to controls. Our observation that enrichment substantially increased response strength and forward masking is consistent with earlier reports that long-term potentiation of cortical synapses is associated with increased paired-pulse depression. Enrichment also increased response synchronization at slow rates and decreased synchronization at fast rates. Paired-pulse depression increased within days of environmental enrichment and was restored to normal levels after return to standard housing conditions. These results are relevant to several clinical disorders characterized by abnormal gating of sensory information, including autism, schizophrenia, and dyslexia.     

A novel human homologue of yeast nucleosome assembly protein, 65 kb centromeric to the p57KIP2 gene, is biallelically expressed in fetal and adult tissues

Three genes on 11p15.5 are known to undergo genomic imprinting. The gene for insulin-like growth factor II (IGF2) is normally expressed from the paternal allele, while H19 and p57KIP2, a cyclin-dependent kinase inhibitor, are expressed from the maternal allele. Five germline balanced chromosomal rearrangement breakpoints from patients with Beckwith-Wiedemann syndrome (BWS) have been mapped to 11p15.5 between p57KIP2 and IGF2, and all are derived from the maternal chromosome. By positional cloning from BWS breakpoints, we have isolated a gene 100 kb and 65 kb centromeric to the proximal end of this BWS breakpoint cluster and p57KIP2, respectively. This gene is homologous to yeast nucleosome assembly protein (NAP1) and to a human homologue of NAP1, and we designate it hNAP2 (human nucleosome assembly protein 2). hNAP2 diverges in its expression pattern from IGF2, H19, and p57KIP2, and it shows biallelic expression in all tissues tested. Thus, hNAP2 is functionally insulated from the imprinting domain of 11p15.