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Within a clinical trial on scanning time-domain optical mammography reported on in a companion publication (part I), craniocaudal and mediolateral projection optical mammograms were recorded from 154 patients, suspected of having breast cancer. Here we report on in vivo optical properties of the subset of 87 histologically validated carcinomas which were visible in optical mammograms recorded at two or three near-infrared wavelengths. Tumour absorption and reduced scattering coefficients were derived from distributions of times of flight of photons recorded at the tumour site employing the model of diffraction of photon density waves by a spherical inhomogeneity, located in an otherwise homogeneous tissue slab. Effective tumour radii, taken from pathology, and tumour location along the compression direction, deduced from off-axis optical scans of the tumour region, were included in the analysis as prior knowledge, if available. On average, tumour absorption coefficients exceeded those of surrounding healthy breast tissue by a factor of about 2.5 (670 nm), whereas tumour reduced scattering coefficients were larger by about 20% (670 nm). From absorption coefficients at 670 nm and 785 nm total haemoglobin concentration and blood oxygen saturation were deduced for tumours and surrounding healthy breast tissue. Apart from a few outliers total haemoglobin concentration was observed to be systematically larger in tumours compared to healthy breast tissue. In contrast, blood oxygen saturation was found to be a poor discriminator for tumours and healthy breast tissue; both median values of blood oxygen saturation are the same within their statistical uncertainties. However, the ratio of total haemoglobin concentration over blood oxygen saturation further improves discrimination between tumours and healthy breast tissue. For 29 tumours detected in optical mammograms recorded at three wavelengths (670 nm, 785 nm, 843 nm or 884 nm), scatter power was derived from transport scattering coefficients. Scatter power of tumours tends to be larger than that of surrounding healthy breast tissue, yet the 95% confidence intervals of both medians overlap.

Objectives:Inter-individual variations in sea level performance after altitude training have been attributed, at least in part, to an inter-individual variability in hypoxia induced erythropoiesis. The aim of the present study was to examine whether the variability in the increase in total haemoglobin mass after training at moderate altitude could be predicted by the erythropoietin response after 4 h exposure to normobaric hypoxia at an ambient Po2corresponding to the training altitude.Methods:Erythropoietin levels were measured in 16 elite junior swimmers before and after 4 h exposure to normobaric hypoxia (Fio20.15, ∼2500 m) as well as repeatedly during 3 week altitude training (2100–2300 m). Before and after the altitude training, total haemoglobin mass (CO rebreathing) and performance in a stepwise increasing swimming test were determined.Results:The erythropoietin increase (10–185%) after 4 h exposure to normobaric hypoxia showed considerable inter-individual variation and was significantly (pConclusions:The results of the present prospective study confirmed the wide inter-individual variability in erythropoietic response to altitude training in elite athletes. However, their erythropoietin response to acute altitude exposure might not identify those athletes who respond to altitude training with an increase in total haemoglobin mass.

To investigate the vasoreactivity of cerebral hemisphere in patients with dizziness and syncope, we compared changes in total haemoglobin (THbl) and regional oxygen saturation (rSO2) of the right and left frontal lobes in response to head-down manoeuvre. Ninety-six right-handed subjects (aged 59 +/- 19 years) were asked to perform a head-down or a standing manoeuvre. Head-down manoeuvre produced a greater increase in right side THbl in subjects under 70 years of age (8.5 +/- 3.1) when compared with subjects older than 70 years (0.40 +/- 0.08). In contrast, the head-down manoeuvre had no effects on left side THbl, irrespective of patient age. Similarly, the head-down manoeuvre resulted in a greater decrease of right side rSO2 in subjects under 70 years of age (-5.2 +/- 2.1%) when compared with subjects older than 70 years (0.31 +/- 0.9%). In contrast, the head-down manoeuvre had no effects on left side rSO2, irrespective of patient age. The head-down manoeuvre produced a smaller increase in right side THbl in subjects with dizziness (0.38 +/- 0.19) than in those without dizziness (9.4 +/- 3.5). A standing manoeuvre produced a smaller increase in right side THbl in subjects with syncope (-0.057 +/- 0.047) than in those without syncope (0.063 +/- 0.028). The head-down manoeuvre produced a decrease in right side rSO2 in subjects without dizziness (-6.4 +/- 2.4%) and a slight increase in right side rSO2 in subjects with dizziness (1.1 +/- 0.4%). Subjects with dizziness (67 +/- 2.1 years) were significantly older than those without dizziness (53 +/- 2.7 years) or those with syncope (44 +/- 4.2 years). These data indicate that reduced vasoreactivity to right hemispheric pressure changes is associated with dizziness in older subjects. Further, decreases in right hemispheric THbl during a standing manoeuvre are associated with syncope in relatively younger subjects.

Recently, localized intramuscular haemodynamic disturbance has been recognized as one of the cardinal features of a chronically painful muscle. To test this hypothesis, we have carried out several studies that have assessed intramuscular haemodynamics to understand more about haemodynamic alteration under conditions of an experimentally induced vasoreactive challenges in healthy controls and in patients with chronic muscle pain using near infra?red (NIR) spectroscopy. In addition, we have validated the NIR based haemodynamic signals by comparing against a water signal intensity change taken from a transverse T2?weighted magnetic resonance image (MRI) of the muscles. As a result, we discovered that muscle pain patients have a diminished ability to vasodilate in painful muscle. We also provided powerful evidences that NIR data (total haemoglobin level), transcutaneously taken from the muscles in humans could be an analogue of intramuscular haemodynamics.

Near infrared spectroscopy was used to measure changes in cerebral haemoglobin and cytochrome concentration in obstructive sleep apnoea. During deep apnoeas, two different patterns in the changes in these signals can be seen.

SUMMARY This study investigated physiological and behavioural aspects of diving development in pups of the harbour seal Phoca vitulina. Behavioural data (4280 h, 6027 dives) from time/depth recorders (N=13) deployed on pups aged 0–19 days are presented concomitantly with physiological measurements (N=8, sampled both early and late in the nursing period) of blood oxygen stores and body composition. Pups grew from 12.6±1.8 kg (mean age 2 days, total body fat 16±4 %) to 22.2±2.5 kg (mean age 16 days, total body fat 35±5 %; means ± s.d.) over the duration of the experiment. Pups less than 5 days of age had an elevated haematocrit and reduced plasma volume compared with older pups. Although plasma volume and blood volume increased, mass-specific blood oxygen stores (total haemoglobin) fell during the study period. Simultaneously, the following behavioural indicators of diving ability increased: the proportion of time spent in the water, dive depth, dive duration, bottom time and maximum daily swimming velocity. In addition, the proportion of dives that were identified by cluster analyses as being U-shaped increased significantly with age. On the basis of the measured blood oxygen stores, less than 1 % of the recorded dives exceeded the calculated aerobic dive limit. Thus, development in blood oxygen stores or rates of oxygen consumption did not seem to restrain the rate of neonatal dive development in harbour seals. It appears that behavioural modifications (experience and learning) may be the primary rate-limiting factors for ontogeny of diving skills in neonates of this species.

Background and aims Near-infrared spectroscopy (NIRS) is a non-invasive method to measure changes in the concentration of oxygenated (ΔO2Hb) and deoxygenated haemoglobin (ΔHHb). Changes in total haemoglobin (ΔcHb = ΔO2Hb+ΔHHb) give information on changes in cerebral blood volume (CBV). Moreover cerebral tissue oxygenation index (cTOI = ΔO2Hb/ΔcHb*100%) is detected. The aim was to evaluate changes of CBV during postnatal transition in term newborns. Methods This observational study was conducted at the Medical University Graz. Included were term infants without need for respiratory support after caesarean section. NIRS measurements were carried out with ‘NIRO-200-NX’ (Hamamatsu; Japan) over 15 min. Results 109 term infants (55 female) with mean gestational age of 39+0 weeks (±7 days) and birth weight of 3245 g (±441) were included. CBV: Related to the baseline at 2 min of age (min), median (25th; 75th percentiles) ΔcHb was 0 micromoles (µM) (-5;4) at 3 min, -1 µM (-8;5) at 5 min, -7 µM (-17;0) at 10 min, and -13 µM (-26;1) at 15 min. ΔcHb, representing the behaviour of CBV, was slowly decreasing during transition period. cTOI: Median (25th;75th percentiles) cTOI was 56% (50;65) at 2 min, 57% (51;64) at 3 min, 64% (58;72) at 5 min, 74% (69;79) at 10 min, and 72% (67;78) at 15 min. cTOI was slowly increasing from 2 min to 7 min, reaching a steady state after 8 min. Conclusion In healthy newborns CBV was slowly decreasing over the whole study period. We hypothesise, that increasing left-to-right shunt via ductus arteriosus may account for decreasing CBV in this period. These findings add information for a better understanding of haemodynamic processes during transition.

Clinical and haematological features of 50 patients with sickle cell/beta-thalassemia (SB0 or SB+) are investigated. Total haemoglobin value was not significantly different (P greater than 0.05) in both types. Haemoglobin F and S were significantly higher (P less than 0.05) in SB0 than SB+ while haemoglobin A2 level was lower in SB0 than SB+. One SB0 case with exceptionally high HbF (32 per cent) with severe clinical course was found. In this case, the high HbF did not ameliorate the clinical severity. Heterogeneity in each type of sickle cell/beta-thalassemia is discussed. The differentiation of SB0 and sickle cell disease is best made on the basis of family study.

Ten type 1 diabetic patients recorded their daily home blood glucose values, pre- and post-prandially, for 12 weeks. Blood was collected weekly for HbA1c and total haemoglobin measurement. A rolling 28-day mean of all blood glucose values and a glycation index (the ratio of the HbA1c to the rolling mean blood glucose) were calculated. In the pooled patients' data, there was a large scatter of results about the HbA1c versus mean blood glucose regression line. There was less variation in the results of individual patients. The glycation indices showed marked inter-individual variation, and in 60% of patients there was an inverse relationship between glycation index and mean blood glucose, suggesting a non-linear relationship between mean blood glucose and HbA1c. Patients should be monitored on the basis of their own previous results, and in some patients blood HbA1c may be a less sensitive index of mean blood glucose concentration at higher glucose levels.

We evaluated a homogenous immunoturbidimetric assay for haemoglobin A 1c (Tina-quant® Haemoglobin A 1c , Boehringer Mannheim, GmbH, Mannheim, Germany) adapted to a Cobas® Mira S analyser (F. Hoffmann-La Roche & Co., Basel, Switzerland) and not requiring sample pretreatment. Between-day CV's determined over a 6 week period were 5.9% and 5.3% for mean haemoglobin A 1c values of 5.4% and 17.0% of total haemoglobin respectively. The imprecision was higher than with an in-house ion-exchange high performance liquid chromatographic method. Bilirubin, triacylglycerols and the labile fraction of haemoglobin A 1c did not interfere with the assay of haemoglobin A 1c . Fetal haemoglobin is not recognized by the antibodies used. Results correlated well with those obtained by high performance liquid chromatography. In conclusion, the Tina-quant® assay is not prone to common interferences and allows the rapid and automated determination of haemoglobin A 1c on open photometric analysers.

Total haemoglobin mass (tHb-mass) is one of the most important factors contributing to aerobic performance. Its level strongly depends on body size, so it is usually expressed in relation to kg body mass (BM), but some studies in male endurance athletes have shown that lean body mass (LBM) is a more appropriate reference for expression of tHb-mass. The aim of this study was to determine relationships between tHb-mass and selected anthropometric reference parameters in a discipline with diverse body mass. 43 highly trained judokas (28 males and 15 females) underwent tHb-mass determination (optimised CO rebreathing method) and anthropometric evaluation (skinfold, body mass and height measurement) with estimation of lean body mass (LBM), and body surface area (BSA). Linear regression analysis between tHb-mass and anthropometric indices was performed, and Pearson9s coefficients of correlation were calculated. Influence of gender on the tHb-mass/BM, /LBM and /BSA relationships was tested by analysis of covariance (ANCOVA). Gender differences in tHb-mass expressed in relation to this parameters were tested by Student9s t-test (significance level p 2 ; p

Background: The characteristics of cerebral autoregulation and the ideal range of systemic blood pressure in preterm infants remain unclear. Transcranial Ccerebral Doppler (TCD)1 and near infra-red spectroscopy (NIRS)2 are established techniques for the assessment of cerebral blood flow velocity (Fv) and cerebral oxygenation respectively. Aim: To study the correlation between a dynamic index of cerebral autoregulation, assessed using TCD, with indices obtained using NIRS in preterm infants and using these parameters, study the feasibility of determining the optimal MABP in individual infants. Methods: Twelve preterm infants (mean gestation 26.5 weeks) were studied over eighteen episodes (2 hours each) within median 3days(range 1-9 days)of life. ICM+ software4 was used to collect and analyse data from NIRO 200NX and DWL Doppler system as well as the physiological variables from the intensive care monitors. Using this data, mean flow index (Mx)2, total haemoglobin reactivity (THx)3 and tissue oxygenation index of dynamic autoregulation (TOx)2 were calculated as autoregulation indices. Results: Coherence analysis of tissue oxygenation index (TOI), total haemoglobin index (THI)and Fv was above 0.6 in ultralow frequency. TOx and THx correlated with Mx [(R=0.47, p=0.057) and (R=0.59, p=0.011) respectively] across individual recordings. ‘Optimal MABP’ was demonstrated in some individual recordings using Mxopt3 and TOxopt3. Conclusion: This is the first study assessing the indices of dynamic monitoring of cerebral autoregulation in preterm infants. Initial results suggest that NIRS derived cerebrovascular reactivity indices (THx, TOx) correlate well with Doppler derived index (Mx), and a non-invasive assessment of ‘optimal MABP’ is feasible in this population group.

A mathematical model is developed for the carbon monoxide (CO) uptake by the blood by taking into account the molecular diffusion, convection, facilitated diffusion and the non-equilibrium kinetics of CO with haemoglobin. The overall rate for the combination of CO with haemoglobin is derived by including the dissociation of CO from carboxyhaemoglobin (COHb). The resulting coupled system of nonlinear partial differential equation with physiologically relevant initial, entrance and boundary conditions is solved numerically. A fixed point iterative technique is used to deal with nonlinearities. The concentration of COHb in the blood is computed as a function of exposure time and ambient CO concentration. The COHb levels computed from our model are in good agreement with those measured experimentally. Also, results computed from our model give better approximation to the experimental values compared with the results from other models. The time taken by the blood COHb to attain 95 % of its equilibrium value is computed. The COHb concentration in the blood increases with the increase in ventilation rate, association rate coefficient of CO with haemoglobin and total haemoglobin content in the blood, and with the decrease in dissociation rate coefficient of CO with haemoglobin and mean capillary blood p O 2 . It is found that the COHb level in the blood is not affected significantly because of endogenous production of CO in the body under normal condition. However, the effect may be significant in the patients with haemolytic anaemia.

EDITOR,—During the past decade measurement of the glycated haemoglobin concentration has become the gold standard for assessing glucose control in diabetes.1 Eric S Kilpatrick and colleagues identified a discrepancy between measurements of total haemoglobin A1 and haemoglobin A1c, but our experience indicates that this may not apply to other laboratories. When we changed our analytical method to automated ion exchange chromatography (Glycomat, Ciba-Corning) we established our own reference range for a healthy population (n = …

We have shown in a pilot study an induction of fetal haemoglobin synthesis with rhEPO in anaemic patients with heterozygous beta-thalassaemia during pregnancy (1). A remarkable increase in F reticulocytes and F cells in our patients might confirm the hypothesis that high HbF is seen following intermittent administration of rhEPO due to the alternating exposures of the cells to high and low levels of EPO (2). These data are in accordance with results of McDonagh et al., who showed a significant increase of F reticulocyte production when rhEPO was given weekly and not daily (3). It is still an open question why there is a discrepancy between the increase of F reticulocytes/F cells and the variable increase of total HbF and total haemoglobin in these patients. This observation is in accordance with previous studies in patients with thalassemia and sickle cell disease, where the authors showed significant increases in F cells without changes in HbF or total hemoglobin. Concerning iron administration in these patients, iron should be considered, if iron stores are low during pregnancy and rhEPO would lead to functional iron deficiency without adequate supplementation (4).

The development of a simple purification method for two haemorphins, VV-haemorphin-7 (Val-Val-Tyr-Pro-Trp-Thr-Gln-Arg-Phe) and VV-haemorphin-4 (Val-Val-Tyr-Pro-Trp-Thr), from a total peptic haemoglobin hydrolysate is described. Cation-exchange chromatography on CM-Sephadex was used as a pre-fractionation step for the hydrolysate. VV-haemorphin-7 and VV-haemorphin-4 were eluted in two different fractions. The second and final purification step was hydrophobic-interaction chromatography on phenyl-Sepharose, which allowed the isolation of the two pure haemorphins. Haemoglobin and globin hydrolysates were compared as starting materials. For easy recovery of haemorphins and easy adjustment of conditions for final purification, a volatile buffer, ammonium acetate buffer, pH 6.5, was employed. This process, which allowed the preparation of pure haemorphins from a total protein hydrolysate, could be scaled up and used in the food industry.

Summary. The relationship between the irreversibly sickled cell (ISC) count and other haematological parameters has been investigated. Positive correlations occurred with the MCH, MCHC, and with two expressions of intracellular Hb S content. Since the ISC has a high MCHC, the positive correlations with MCHC and with factors derived from the MCHC may be difficult to evaluate. Negative correlations occurred with total haemoglobin and Hb F. The MCHC was found to affect the relationship between HbF and ISC count, a low MCHC being associated with, and probably determining, lower ISC counts at any level of Hb F. It is proposed that a low MCHC may inhibit ISC formation and the practical implicaions of this are discussed.

The total haemoglobin, foetal haemo-blobin and nucleated red blood cells were analysed in 34 infants born of toxaemic pregnancies and 58 healthy newborns. In the healthy infants, the respective mean values were 16.03 G.% 64.57% and 4.1/100 W.B.C. The corresponding figures for infants born of toxaemic mothers were 16.44 G.%, 79.85 % and 7.1/100 W.B.G. These differences were observed irrespective of gestational age, birth weight and crown to heel length. The total haemoglobin and foetal haemoglobin were higher in newborns of anaemic mothers and normal pregnancy in comparison to newborns of mothers with haemoglobin more than 7 G.%. The total haemoglobin and foetal haemoglobin were higher in small-for-date newborns in comparison to those appropriate-for-date.

A new A γ chain haemoglobin variant, haemoglobin F Victoria Jubilee, with an electrophoretic mobility slightly anodal to haemoglobin F Port Royal, was found in a Jamaican infant. The amino acid residue substitution of 80 Aspartic Acid → Tyrosine was associated with alanine in position 136. Haemoglobin F Victoria Jubilee constituted about 7.0% of the total haemoglobin F.

In a selected sample of patients with sickle cell-haemoglobin C (SC) disease, proliferative retinopathy (PSR) occurred in 90/243 (37%) patients, developed most frequently between the ages of 20 and 30 years, and affected 68% patients aged 45 years or over. Comparison of haematological indices in patients with and without PSR, after age-related effects were allowed for, indicated significant relationships with high mean cell volume in males and with low fetal haemoglobin in both sexes. A highly significant relationship with total haemoglobin level in males (as previously reported in SS disease) was shown in SC disease to be entirely secondary to a strong age-related trend in haemoglobin level.

A new haemoglobin has been found in Rovigo (Italy). This haemoglobin is an unstable variant of the alpha chain (alpha 53 (E 2) Ala → Asp), and is as fast moving as haemoglobin J. It represents a high percentage (35–49.5%) of the total haemoglobin. The amino acid composition of the new peptide is described.

The internationally standardized HiCN method for measuring the total haemoglobin concentration of the blood (c Hb * ) is based on the chemical composition of the haemoglobin molecule. If all haemoglobin measured in the blood by this method were active, i.e., capable of reversibly binding O2, the O2 binding capacity (β) would be 1.39 ml · g−1 The experimental values of β to be found in the literature vary over a wide range, values as low as 1.24 ml · g−1 being no exception. We determined β for 36 blood samples of healthy men, using for the determination of the O2 content 3 independent methods, i.e., a manometric, a polarographic and a chemical one. Before the measurements the blood was equilibrated with humidified pure O2 for 3 h. Appropriate corrections for dissolved O2 were made. The mean β was 1.368 ml · g−1, with a s.d. of 0.017 ml · g−1 (median 1.372 ml · g−1; range 1.322–1.387 ml · g−1). This mean β corresponds to 98.4% active haemoglobin. The inactive haemoglobin consisted of 0.7% HbCO, Hi and SHb (“dyshaemoglobin”) and 0.9% unidentified inactive haemoglobin. In 4 samples a high fraction of unidentified inactive haemoglobin was found (2.8–4.3%). Taking into account that in addition to this fraction a considerable amount of dyshaemoglobin (especially HbCO) may be present in the blood of normal men, it must be concluded that calculating the O2 carrying capacity of the blood by multiplyingc Hb * by a constant value of β, may be subject to an appreciable error. If β=1.39 ml · g−1 is used, the O2 carrying capacity of the blood may easily be found 10–15% too high.

Summary. The rheological properties of erythrocytes of four patients with haemoglobin Koln (Hb Koln) disease were studied. Filtration of erythrocytes through polycarbonate sieves with a pore diameter of 5 μm and viscosity measurements of erythrocytes suspensions with a PCV of 80% were carried out. The rheological properties of erythrocytes of two of the patients were severely altered. In both patients an increased haemoglobin attachment to erythrocyte membranes resulting in a decreased filtration rate of erythrocytes was found. One of these cases had been splenectomized some years before. About half of the erythrocytes of this patient contained large Heinz bodies. Erythrocytes of this patient showed a decreased filtration rate and an increased viscosity. Moreover, erythrocytes of healthy adults containing Heinz bodies after incubation with acetylphenylhydrazine showed a decreased filtration rate as well as an increased viscosity. Membranes of erythrocytes of the other patients contained haemoglobin in an amount within the normal range of haemoglobin content of membranes of healthy adults. Erythrocytes of these patients showed normal rheological properties. The haemolytic process in these patients was only mild. We suggest that the amount of total haemoglobin attached to the erythrocyte membrane corresponds to the percentage of the unstable Hb Koln present in the erythrocytes of the particular patient.

A comparison was made between the results of a standard 75 g oral glucose tolerance test and total haemoglobin A1 in 168 subjects referred by their general practitioners for the diagnosis of diabetes mellitus. The subjects were classified as having normal, impaired or diabetic glucose tolerance using WHO criteria. Of 108 subjects with normal glucose tolerance only three had haemoglobin A1 concentrations over 8%. Of 10 with impaired glucose tolerance two had haemoglobin A1 concentrations over 8%. Of 47 with diabetic responses, eight had haemoglobin A1 concentrations below 9%. There was a significant difference between the haemoglobin A1 concentration when fasting and that 2 hours after the glucose load in the subjects with a diabetic glucose tolerance response, but no significant difference between the two values in the other subjects.

The time course of the transition from HbF to HbA production in the postnatal period has been studied. The description is based on the time-dependent pattern of total haemoglobin and of HbF observed in an 8 months follow-up of 25 premature newborns. The absolute amount of HbF decreases exponentially from birth to approximately 25 weeks (from 15.56 +/- 0.48 g/dl to 0.66 +/- 0.08 g/dl), at a weekly rate of approximately 16%. On the other hand, HbA shows a biphasic pattern: first it decreases slightly from birth to 6 weeks (from 4.09 +/- 0.32 g/dl to 2. 63 +/- 0.33 g/dl); afterwards it increases exponentially at a weekly rate of 5% up to a plateau value, until HbF is almost completely replaced by HbA. Therefore the total haemoglobin decreases exponentially from birth to approximately constant for the next 6 weeks, and thereafter it increases very slowly. From these data, two distinct phases of postnatal erythropoiesis can be identified: the first (from birth to 6 weeks) is characterized by a decrease in the total amount of haemoglobin produced whereas in the second there is an alteration in the relative proportions of HbF and HbA being synthesized.

Summary Haematological indices, including total haemoglobin, mean cell haemoglobin concentration, red cell count, mean cell volume, mean cell haemoglobin, reticulocytes, and serum iron values, in a cohort of 243 randomly selected Negro children with normal haemoglobin genotype, followed from birth to 5 years, are reported. Total haemoglobin fell rapidly from high levels at birth to a plateau at 2–6 months; a secondary fall occurred after 6 months and a gradual increase after 18 months. The red cell count also fell rapidly, but increased after 2 months to a plateau and then slowly declined from age 1–5. Mean cell volume and mean cell haemoglobin fell continuously from birth to the lowest values at 15 months and then progressively increased to the age of 5 years. Serum iron levels were low at one year of age (mean 9.7 μmol/1) increasing slowly by age 4 and sharply by age 5. Mean cell haemoglobin concentration fell gradually to 1–1 years and then increased progressively to age 5. Values for Hb, MCHC, MCV, and MCH were consistently and often significantly lower in males before the age of 2 years, compatible with greater depletion of iron stores. Serum iron values were generally lower in males but there was no sex difference at one year when highly significant differences in Hb, MCHC, MCV, and MCH occurred. The cause of sex differences in early haematological development is currently unclear.

An abnormal, fast-moving haemoglobin was observed in 5 healthy subjects of a family from Calabria (southern Italy). In all these carriers the abnormal haemoglobin, which structural studies identified as Hb Norfolk (α257(E6) GIy→Aspβ2) [4], occurs at a level averaging 33% of the total haemoglobin. Biosynthetic studies showed no evidence for unbalance of the globin chain synthetic ratio. In order to account for the observed percentages of Hb Norfolk, current concepts about the α-globin chain genetic system are reviewed, and different genie arrangements which would be in agreement with the experimental findings are discussed.

Significant increases in total haemoglobin concentrations, and microhaematocrit values were associated with acclimation of rainbow trout and goldfish to increased temperature. Goldfish held at 2°C were characterized by two haemoglobin components, whereas those acclimated to 20° and 35°C exhibited three. Nine haemoglobin variants were observed in trout at 2°, 10° and 18°C. The data provide evidence that both species selectively alter the concentrations of specific haemoglobin fractions during the thermoacclimatory process.

The physical working capacity of adult Liberian males, living in areas with different malario-metric indices, was studied by bicycle ergometry and placed in relation to total haemoglobin. No major differences were found between fanners living in holo-endemic areas and mining company workers living in meso-endemic areas. This implies that there is no major impact of malaria on physical work capacity in these age groups. Likewise, no difference was found between the Liberian material and Swedish male normals in the relation between physical working capacity and total haemoglobin.

A structured treatment and teaching programme for non-insulin-treated non-insulin-dependent (type 2) diabetes was evaluated prospectively in general practice. The four group sessions were mainly conducted by paramedical personnel. 65 patients from five general practices were assessed at the start of the programme and 50 (mean age 65 years, diabetes duration 7 years) completed the 1 year follow-up (intervention group). The control group consisted of 49 patients (mean age 63 years, diabetes duration 7 years) from three other general practices without the programme. In the intervention group the percentage of patients receiving sulfonylureas fell from 68% at the start of the study to 38% after 1 year (mean difference 30%, 95% confidence interval [CI] 16-44%); the mean weight loss was 2.7 kg (95% CI 1.6-3.8 kg), and non-fasting triglycerides were reduced by 0.77 mmol/1 (95% CI 0.35-1.19 mmol/l); and glycosylated haemoglobin remained unchanged (7.1% of total haemoglobin). In the control group none of these indices was changed during the study year, and 10% of patients started insulin treatment. The structured treatment and teaching programme improved the overall quality of patient care in elderly non-insulin-dependent diabetic patients treated by general practitioners.

A new alpha chain variant Hb Spanish Town, α27 Glutamic acid - Valine, was detected in the cord blood of a Jamaican Negro infant. In the mother the adult component (α2Spanish Townβ2) has an electrophoretic mobility between haemoglobins S and F at alkaline pH and measures 11.0–12.0% of the total haemoglobin.

Human blood haemolysates containing ethylene glycol (final volume fraction 0.35) were prepared and stored at -20 degrees C (in the liquid state) up to 372 days. During the whole period, the total haemoglobin concentration (assayed in the material by means of the reference HiCN method) was found to be stable; spectral analysis also failed in detecting any deterioration, Hi formation being low. Good stability was also recorded on storage at 2-4 degrees C for 15 days, but only for 1-2 days at room temperature. The stabilised haemolysate is suggested as a material for long-term control of accuracy in hemoglobinometry.

Finnstrom, O., Gothefors, L. and Zetterlund, B. (Departments of Paediatrics, University Hospitals, Linkoping and Umea, Sweden). Studies on maturity in newborn infants. VII. Foetal haemoglobin. Acta Paediatr Scand, 64:404, 1975.–Cord blood from 125 newborns of various gestational ages has been analysed for the ratio foetal haemoglobin to total haemoglobin, using an alkali denaturation method. The quotient, percentage of foetal haemoglobin divided by birth weight correlates well with gestational age. Thus the percentage of foetal haemoglobin in cord blood can be used as a method for estimating maturity in newborn infants. Foetal haemoglobin has been compared with other methods for maturity assessments and seems to give the same precision in estimating gestational age as the best of these, which is the scoring of external characteristics. However, the latter method is considerably less time-consuming and more suitable for routine use.

Blood samples from 24 non-diabetics and 26 diabetics were analysed using both thin layer iso-electric focusing and ion-exchange chromatography. Using iso-electric focusing it was found that about 10% of haemoglobin Alc (0.7—1.2% of total haemoglobin) could be removed by a preceding incubation of the erythrocytes in saline at 37°C for 6 h. When glucose was added to the incubation medium in a final concentration of 25 mmol/l no decline was seen in the concentration of haemoglobin Alc. Using similar treatment of erythrocytes identical results were obtained by the two methods. A reference interval for normal subjects (age range 6 months to 65 years) was established for the iso-electric focusing method using non-incubated samples.

A healthy 20-year-old woman, belonging to the Kgalagadi tribe of Botswana, has been found to possess a variant Haemoglobin A2 as her only minor haemoglobin component. Fingerprinting and amino-acid analysis have shown that it is Haemoglobin A2′ (δ16 Gly→Arg). The one parent available for study is heterozygous for the HbδA2′ allele and the variant haemoglobin accounts for 3% of the total haemoglobin in the proband. It is reasoned that the proband is, therefore, homozygous for the HbδA2′ allele. No haematological abnormalities were evident.

Summary. It is shown that, when oxygen and haemoglobin are diffusing through haemoglobin solutions, the concentration of total haemoglobin will be constant, independent of the reaction scheme of haemoglobin with oxygen. Solutions of transport equations for the cases of oxygen uptake in a stationary and in a moving flat film of haemoglobin solution are given. The influence of the diffusion of haemoglobin is shown. Advancing front equations, corrected for physically dissolved oxygen, are derived by formal integration of the transport equations. It is shown that ~hese derived formulas are good approximations of the solutions of the transport equations when the diffusion of haemoglobin is neglected.

Haemoglobin Constant Spring is an unusual variant which comprises only 1–2% of the total haemoglobin in heterozygotes. It has α-chains which are 172 residues long instead of the normal 141, and when it is inherited together with an α-thalassaemia gene it gives rise to haemoglobin H disease.

The determination during life of the total volume of blood contained in the living body is usually effected by Haldane’s method. This consists in first estimating the percentage hæmoglobin content of the blood and then determining the total hæmoglobin content of the circulating fluid, the latter being effected by administering a known volume of carbon monoxide and observing the extent to which the hæmoglobin of the red cells is in combination with this gas. Copeman and Sherrington determined the volume of the blood in the living body by injecting a measured volume of 0⋅75-per-cent. solution of sodium chloride (sp. gr. 1⋅0046) and observing the resulting fall in specific gravity of the blood. Recently, while making an investigation upon hæmoglobinæmia, we found it necessary to make estimations of the total amount of blood in the living body. This we carried out by: (1) making a hæmocrit estimation of the relative proportions, by volume, of red cells and plasma; (2) injecting a known quantity of dissolved hæmoglobin into the blood stream and determining the degree of the resulting hæmoglobinæmia, from which the amount of plasma present can be calculated. The method employed thus consists of two procedures, namely the estimation: (1) of the percentage (by volume) of plasma contained in the blood (A ); and (2) of the total volume of plasma contained in the body (B). The total volume of the blood is B/A × 100.

Experimentally, blood Po2 varies in vitro with temperature as follows: P O 2 at temperature T 1 P O 2 at temperature T 1 = 10 f ( T 1 − T 2 ) This paper investigates the theoretical dependence of f on the temperature-range under consideration, oxyhaemoglobin saturation, total haemoglobin concentration and blood acid-base state, f depends only slightly on the temperature-range; it varies, however, markedly with oxyhaemoglobin saturation. With a normal haemoglobin concentration and acid-base state, the mean value of f is 0.0045 at full saturation, it increases rapidly with increasing desaturation to 0.0300 at a saturation of 90%, and then approaches asymptotically a final value of 0.0306 at saturations below 80%. Changes in acid-base state and haemoglobin concentration alter the value of f at intermediate saturations but not at either extreme. A fall in pH (respiratory changes being more potent than non-respiratory) or in haemoglobin concentration decreases f. Opposite changes have the reverse effect. Agreement between the theoretically derived values and experimental data from the literature is good within the limits of experimental error of the latter.

Es wird uber die ersten Erfahrungen mit einer neuen Kohlenoxydinhalationsmethode zur Bestimmung des Gesamthamoglobins (HbT) an Blutkranken berichtet. Die Untersuchungen an Gesunden ergaben einen Gesamthamoglobingehalt von 7,8 g/kg fur Frauen und 9,78 g/kg fur Manner. HbT-Bestimmungen an Kranken mit Polyzythamie, pernizioser Anamie, Tumoranamien und Eisenmangelanamien zeigen, das sich der Grad der Hamoglobinzu- oder -abnahme in den Hamoglobinkonzentrationsbestimmungen oft nur sehr unzuverlassig widerspiegelt. Bei intravenoser Eisentherapie wurde an Kranken mit Eisenmangelanamie eine tagliche Hamoglobinzunahme von 4,7 g gemessen. Die Eisenutilisation errechnet sich daraus mit 16 mg je Tag. The carbon monoxide method of determining total haemoglobin was used in normal subjects (40 men between 18 and 27 years and 20 women aged between 17 and 30 years) and patients with various blood diseases (nine with cancer, five with leukaemia, two with reticulosis, 16 with iron-deficiency anaemia and three with megaloblastic anaemia). HbT was 7.8 g./kg. in normal women and 9.78 g./kg. in normal men. HbT determinations in patients with polycythaemia, pernicious anaemia, anaemia associated with cancer and iron-deficiency anaemia showed that the degree of haemoglobin increase or decrease was not well reflected by changes in haemoglobin concentration. Patients with iron-deficiency anaemia given iron intravenously had an average daily increase in total haemoglobin of 4.7 g. Iron utilization was thus calculated to be 16 mg. per day. La importancia de la determinacion de hemoglobina total (HbT) para el enjuiciamiento del transcurso de afecciones hematologicas Se informa acerca de las primeras experiencias hechas con un nuevo metodo de inhalacion de oxido de carbono para la determinacion de la hemoglobina total (HbT) en enfermos de la sangre. De los estudios en personas sanas resultaron un contenido de hemoglobina total de 7,8 grs./kg. en cuanto a las mujeres y otro de 9,78 grs./kg. para los hombres. Determinaciones de HbT en enfermos con policitemia, anemia perniciosa, anemias tumorales y anemias por deficiencia de hierro muestran, que el grado del aumento o de la disminucion de hemoglobina se refleja en las determinaciones de concentracion de hemoglobina a menudo solo de un modo muy poco fidedigno. Con ferroterapia intravenosa se midio en enfermos con anemia por deficiencia de hierro un aumento de hemoglobina diario de 4,7 grs. La utilizacion de hierro se computa con 16 mgrs. por dia.

SYNOPSIS A male infant was cyanosed for the first 3 months of life, associated with methaemo-globin concentrations which fell from 15% of the total haemoglobin concentration initially to near-normal levels. Large cephalhaematomata were present at birth. The child developed normally except for left-handedness and retardation of speech development. At 3 years, the methaemoglobin concentration was 3%, and the erythrocytic diaphorase activity approximately 40-50% of normal. Family studies suggested that the patient was heterozygous for an autosomal mutant gene. The pathogenesis of methaemoglobinaemia in diaphorase deficiency is discussed.

Summary Two new methods for determination of the relative rates of synthesis of haemoglobins F and A are described. One method is based on the relative rates of appearance of intravenously injected radioiron into circulating HbF and HbA. The other is based on estimates of the relative content of HbF and HbA in circulating reticulo-cytes. The two methods show good agreement. The relative rate of synthesis of HbF and HbA was measured in 19 infants aged between 0 and 20 weeks. At birth, the relative synthetic rate of HbF was about 50–65 % of the total haemoglobin synthesis. After birth there was a gradual decrease in the relative rate of HbF synthesis, but, even at the age of 100–140 days, about 5 % of the total haemoglobin synthesis consisted of foetal haemoglobin.