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Summary: Microinterferometry was used to determine the dry mass of α-chain precipitates in erythrocytes from four patients with homozygous β-thalassaemia. α-Chain precipitates represented on the average 40% of the total dry mass of cells with measurable amounts of precipitation. The maximum load of α-chain inclusions in a single cell was 75% of the dry mass. A linear correlation was established between the amount of total haemoglobin and non-α-chains in individual cells, and the amount of α-chain precipitation increased linearly with decreasing amounts of soluble haemoglobin, thus indicating an association between impaired haemoglobin production and lack of non-α-chains at undisturbed α-chain production. The mean ratio of the quantity of α/(β+γ+δ) chain in individual patients varied between 2.3 and 3.0. These ratios are lower than expected from synthetic rate studies, thus indicating the possibility of some precipitate degradation in vivo.

Glycosylated haemoglobin A1 levels were measured in 186 patients with diabetes mellitus and 108 non-diabetic controls. Forty-nine diabetics were considered well controlled with at least three blood glucose levels below 10 mmol/L, while 50 diabetic patients were poorly controlled with at least three blood glucose levels above 15 mmol/L. Mean glycosylated haemoglobin A1 levels for the 108 normal controls was 7.45% +/- 0.73%, for the well controlled diabetics, 10.7% +/- 2%, and for poorly controlled diabetics, 15.0% +/- 2.5% of total haemoglobin. In patients with the onset of diabetes after the age of 40 years, there was a significant difference between the haemoglobin A1 levels in those with diabetic retinopathy and those without complications. There was a significant association between haemoglobin A1 levels and the duration of the disease in diabetics controlled with insulin.

The swimming performance of triploid coho salmon (Oncorhynchus kisutch) was compared with diploid controls to assess the ability of these fish to survive if released into the wild. Triploid salmon had similar haematocrits to diploid salmon but they had lower total haemoglobin content in their blood. There was no difference in the maximum sustained swimming ability between triploid and diploid salmon.

One hundred and forty patients with diabetes mellitus were examined in the small mining town of Kalgoorlie, Western Australia. The primary object was to determine the incidence of retinopathy in the diabetic community. One hundred and thirty-eight sets of data were obtained. There were 69 males and 69 females. The diabetes was controlled with orally administered hypoglycaemic agents in 62 patients, in 58 patients with insulin, and in 18 by diet alone. Forty-six of the 138 volunteers (33%), were found to have retinopathy and this included eight of the 14 Aboriginals taking part in the survey. Glycosylated haemoglobin levels ranged from 8.1% to 18.8% (mean 11.7%; SD; 2.28%) of total haemoglobin concentration, and plasma glucose levels from 1.2 mmol/L to 27.3 mmol/L (mean, 9.5 mmol/L, SD, 5.06 mmol/L); there was a positive correlation between levels of glycosylated haemoglobin and plasma glucose (r = 0.63; P less than 0.001). Diabetics with retinopathy had a mean glycosylated haemoglobin level of 12.5% compared with 11.3% in those without this complication. Examination by treatment groups showed that patients with retinopathy whose disease was controlled with insulin had significantly higher levels of glycosylated haemoglobin compared with those without this complication (0.01 greater than P greater than 0.001). Patients whose disease was controlled with orally administered hypoglycaemic agents did not show this difference.

A new unstable haemoglobin, alpha(2)beta(2)15 Trp--Arg (Hb Belfast), with increased oxygen affinity has been found during the routine investigation of a long-stay psychiatric patient. It seemed to cause little haematological disorder. The reticulocytes synthesized normal and abnormal beta-chains at the same rate but in the circulating blood Hb Belfast amounted to only 27.5% of the total haemoglobin.

Haemoglobin Lepore was demonstrated in four members of a Turkish family. It was found in the heterozygote state and was associated with erythrocyte morphology similar to that observed in the beta thalassaemia trait. The average concentration of haemoglobin Lepore was 8.1% of the total haemoglobin. Structural analysis showed that the Lepore haemoglobin was the LeporeBoston type. This is the first reported instance of the occurrence of haemoglobin Lepore in Turkey.

Carboxyhaemoglobin concentrations were measured in 3487 subjects comprising 1255 non-smokers, 1933 cigarette smokers, 193 cigar smokers (39 primary, 154 secondary), and 106 pipe smokers (30 primary, 76 secondary). In cigarette smokers the mean carboxyhaemoglobin concentration was 4.78% of the total haemoglobin and 94.7% of smokers had a concentration greater than 1.7%. Primary cigar smokers had a much lower mean carboxyhaemoglobin concentration (0.93%), and only 10.3% had concentrations greater than 1.7%. Primary pipe smokers also had a low mean carboxyhaemoglobin concentration (1.36%) and none had a concentration above 1.7%. Secondary cigar smokers had a high mean concentration (6.80%) and 97.4% had values above 1.7%; the findings in secondary pipe smokers were similar--the mean concentration was 3.39%, 94.7% having values greater than 1.7%. The lower carboxyhaemoglobin concentrations in primary pipe and cigar smokers suggest that in general they do not inhale, and the raised concentrations in cigarette smokers who change to pipes or cigars suggest that they usually continue to inhale and to absorb large amounts of carbon monoxide and other constituents of tobacco smoke.

A colorimetric technique for the determination of carboxyhaemoglobin in blood is described. Carbon monoxide released from blood in a standard Conway unit reacts with palladous chloride/arsenomolybdate solution to produce a blue colour. Using 0·5 to 2 ml. of blood, the method will estimate carboxyhaemoglobin accurately at levels from 0·1% to 100% of total haemoglobin and in the presence of other abnormal pigments. A number of methods are available for the determination of carboxyhaemoglobin; none is accurate below a concentration of 1·5 g. carboxyhaemoglobin per 100 ml. but for most clinical purposes this is not important. For forensic purposes and occasionally in clinical use, an accurate determination of carboxyhaemoglobin below 750 mg. per 100 ml. may be required and no really satisfactory method is at present available. Some time ago when it was important to know whether a person who was found dead in a burning house had died before or after the fire had started, we became interested in developing a method which would determine accurately carboxyhaemoglobin at levels of 750 mg. per 100 ml.

IN 1966–67 a survey for electrophoretically abnormal haemoglobin variants was carried out in southern Arabia. Samples of venous blood were collected from 2,130 Arabs and examined for sickling and signs of thalassaemia, and the haemoglobins were screened by electrophoresis on cellulose acetate1. The subjects included 234 members of the Audhali tribe in whom three sickle cell trait carriers, five persons with β thalassaemia minor, and two with a similar haemoglobin variant were discovered; these two are the subject of this report. The variant moved on electrophoresis at alkaline pH behind haemoglobin A, but faster than haemoglobin S in the position of haemoglobin G. It amounted to 25 per cent of the total haemoglobin. It was found in two men from different Audhali villages, and there was no known blood relationship; it was not seen in any of the other fifteen tribes examined. One family study was possible, and in this case the variant was found in the father and one brother, but not in the mother of the propositus. In none of the four persons with this haemoglobin was anaemia found or any other abnormality of the blood.

A rapid and reproducible electrophoretic method for the separation and quantitation of haemoglobins on cellulose acetate is described. The accuracy of the method and its possible sources of error are discussed. The normal range for haemoglobin A(2) by this method is 1% to 3% of the total haemoglobin concentration. Blood samples from 32 thalassaemic patients showed haemoglobin A(2) values of 3.5% to 7%.

Livers from fed male rats were perfused in a non-recirculating system with undiluted rat blood containing 14 mM glucose. In these experiments there was a substantial uptake of glucose which was stimulated by insulin. Perfusion with blood containing carboxyhaemoglobin at a concentration of 40% of total haemoglobin lowered O2 consumption and abolished hepatic glucose uptake in control and insulin-infused livers, respectively. In experiments with rat erythrocytes resuspended in buffer to haematocrit values of 38 and 22%, O2 consumption and control and insulin-stimulated rates of glucose uptake were similar to corresponding perfusions with undiluted blood and blood containing carboxyhaemoglobin. It is concluded that serum factors are of relatively small importance and that hepatic glucose uptake is dictated by O2 supply.

The haemoglobin of Chironomus is dissolved in the haemolymph of the larva. It was determined that only a negligible haemoglobin turnover takes place and the amount of haemoglobin synthesis during the fourth larval instar could be calculated. By means of cytophotometrical methods, haemoglobin specific absorption could be found only in the oenocytes. Specific immunological methods have also been used to identify the haemoglobin-synthesising tissue and again only the oenocytes gave positive results. The oenocytes are arranged as 4 large cells on each side of the abdominal segments. The measured haemoglobin content of single oenocytes is in good agreement with the calculations of their haemoglobin content and indicates that synthesis in only 60 cells could account for the total haemoglobin production.

The coupling of glucose to haemoglobin is dependent on time, concentration and pH. The optimum pH is 7.4 (Niederau etal., 1980). The process is not catalyzed enzymatically and is relatively slow. Although aldimine is formed by attachment of the sugar to the N-terminal β-chain of haemoglobin, glucose can be split off again by an increase in blood acidity or, for example, by processes occurring during dialysis (Niederau etal., 1980). A stable ketoamine is only formed by a prolonged process of molecular transformation according to Amadori (Fig. 26).

The DIAMAT TM (Bio-Rad) analyser is a microprocessor-operated HPLC system using a silica-based weak cation exchange column with three phosphate buffers of increasing ionic strength as the step gradient mobile phase. A dual wavelength detector measures absorbance at 415 and 690 nm; each sample is completely processed in 8 minutes. The instrument effectively separates and quantifies HbF in a discrete peak. We have verified that the HbF assay is linear up to about 65% values. We calculated within-run imprecision for n = 20 in 3 different haemolysed blood samples; the results are shown below as percent of total haemoglobin: A) Mean = 1.06 SD = 0.048 CV% = 4.5 B) Mean = 1.90 SD = 0.041 CV% = 2.1 C) Mean = 8.93 SD = 0.047 CV% = 0.5 Between-run imprecision for similar samples (n = 18) was: D) Mean = 3.74 SD = 0.20 CV% = 5.5 E) Mean = 9.94 SD = 0.15 CV% = 1.5 Accuracy was assessed in different series by correlating Hb values (y) with those obtained by the alkali denaturation test (x). The regression line equation was y = 1.03 x - 0.33 (r = 0.999, n = 62). The DIAMAT TM instrument also reveals the presence of any HbS and calculates its peak area correctly, as we found by electrophoretic reassay in heterozygous subjects. We also noted the presence of other abnormal haemoglobins characterized by specific retention times.

Within the last 40 years many attempts have been made to measure the arterial oxygen saturation (Sao2). The arterial oxygen saturation is defined as the amount of oxyhaemoglobin (HbO2) expressed as a percentage or as a fraction of the amount of total haemoglobin (THb) including haemoglobin (Hb) plus carboxy- haemoglobin (HbCO), oxyhaemoglobin (HbO2) and methaemoglobin (MetHB) under physiological as well as clinical conditions.

MOST structural variants of human haemoglobin occur in smaller amounts than HbA in the peripheral blood of heterozygous subjects. Abnormal haemoglobins with mutations in the β chain usually comprise 35–45% of the haemoglobin in haemolysates. In contrast, haemoglobins with abnormal α chains generally amount to only 20–25% of the total haemoglobin. This difference in the proportion of α and β chain variants is thought to reflect the fact that in some populations there are two α loci and only one out of four α globin genes is affected in a heterozygote, whereas one out of two β globin alleles is abnormal in a subject with a β varient1,2. Certain unstable haemoglobins with critical alterations in β-chain structure also constitute a much smaller proportion of the total circulating haemoglobin than HbA. The low concentration of these abnormal haemoglobins is the result of accelerated preferential destruction3–7. We report here a new unstable β variant, Hb Bushwick, which was detected in an intact form constituting only 1–2% of the total circulating haemoglobin. Evidence was found for rapid postsynthetic destruction of the abnormal β chain. In spite of this accelerated loss of the product of one of the two β alleles, the affected erythrocytes contained normal amounts of haemoglobin.

The frequency of alpha-thalassaemia in Cyprus was determined with studies of haemoglobin Bart's in 1200 Greek Cypriot and 132 Turkish Cypriot newborn babies. Of the Greek newborns, 12.4%, and of the Turkish newborns, 6.8% had raised Hb Bart's (from 0.6% to 12.9% of the total haemoglobin) suggesting that they were carriers of either alpha-thalassaemia-1 or alpha-thalassaemia-2 genes. The findings suggest that the population of Cyprus has the highest frequencies of alpha-thalassaemia among Caucasian people.

A portable reflectance instrument for the rapid quantification of cutaneous haemoglobin and melanin is presented. Light emitting diodes (LEDS) are used to illuminate the skin and a silicon photodiode to detect the light diffusely reflected from the surface. Reflectance measurements are made at only three wavelengths and the problems of pigment quantification consequent upon this are discussed. In addition to quantification of haemoglobin and melanin, qualitative information on the redox state of the blood may also be obtained. Measurements made on a port wine stain, which had been treated with 576 nm CW laser radiation at times between 1 and 6 months previously, provided information on the vascular response to this thermal injury. Despite the treated area visually appearing normal at 6 months post-treatment the measured levels of deoxygenated and total haemoglobin were still markedly higher than those in the adjacent uninvolved skin. The cutaneous pigment indices are insensitive to skin movement and almost all body sites are suitable for measurement.

Haematological characteristics have been compared in 29 subjects with heterozygous beta0 thalassaemia and in 33 subjects with heterozygous beta+ thalassaemia, identified by the type of sickle cell-beta thalassaemia among close relatives, in a Jamaican Negro population. Total haemoglobin, MCV and MCH were significantly lower in the beta0 type but the level of Hb A2 was not significantly different. Individual values for MCV, MCH and Hb A2 in the beta+ type occasionally overlapped those in the normal population casting doubt on the adequacy of these criteria in identifying all cases of heterozygous beta+ thalassaemia. The haematological differences are those which would be expected on theoretical grounds. The inability to confidently differentiate the two types of heterozygous beta thalassaemia has implications for genetic counselling. The inability to distinguish heterozygous beta+ thalassaemia from normals on any single haematological index suggests that surveys depending on estimations of Hb A2 or on MCV alone may have underestimated the prevalence of the beta+ thalassaemia gene.

A survey of haemoglobin variants undertakin in an Italian community (Polesine) has revealed the presence of haemoglobin Hasharon (alpha2 47 Asp yields His beta2) in 108 subjects from 40 families. The variant accounted for 30 to 40% of the total haemoglobin. In subjects doubly heterozygous for Hb Hasharon and beta thalassaemia, the proportion was 17 to 19%. Though there was some evidence that the variant was unstable in vitro, there was no obvious haemoglobinopathy in vivo.

Eighty newborns of various birth weights and gestational age ranging from 28 to 45 weeks were studied. There were 26 preterm, 41 term and 13 post-term infants. The average values of total and foetal haemoglobin in males and females were studied and there was no significant difference in the two sexes. Total haemoglobin tended to rise with advancing gestation. On the contrary, foetal haemoglobin showed a gradual fall with advancing gestational age. Correlation between gestational age and birth weight and foetal haemoglobin could not be established. Foetal haemoglobin in preterm, term and post-term newborns was 83.93, 68.59 and 60.03% respectively. It was concluded that foetal haemoglobin can be used as one of the indices for determining the maturity.

Haematological indices were studied from birth to 9 years in a representative sample of 195 children with a normal haemoglobin (AA) genotype subdivided according to the number of alpha globin genes. These were 5 homozygotes for alpha-thalassaemia 2 (two-gene group), 60 heterozygotes for alpha-thalassaemia 2 (three-gene group), and 130 with a normal alpha globin gene complement (four-gene group). HbF and HbA2 showed no differences between the groups. Compared to the four-gene group, the three-gene group tended to have significantly lower levels of total haemoglobin, MCHC, MCV, and MCH, and higher levels of red cell count. These differences became apparent with increasing age in the order of MCV, RBC, MCHC, and total haemoglobin. The data suggested that haematological differences were more marked in the two-gene group but with the small numbers available, the differences were not significant.

The haemoglobin (Hb) patterns of 345 Shiite Saudi Arab cord bloods were examined by alkaline starch-gel electrophoresis. A fast-moving component, identified by structural analysis as Hb Bart's, was found in 52% of cases, the highest incidence of this variant yet recorded. The levels of Hb Bart's ranged from 0.5 to 16% of the total haemoglobin. The relative rates of synthesis of the alpha, beta and gamma-chains, measured by [3H]leucine incorporation, were estimated in 12 newborn Arab infants. There was an excellent correlation between the amount of Hb Bart's and the alpha/non-alpha-globin-chain production ratio. Furthermore there was a significant correlation between the level of Hb Bart's and morphological abnormalities of the red cells and the mean cell haemoglobin (MCH). These findings indicate that elevated levels of Hb Bart's in this population are due to the presence of alpha thalassaemia. The absence of hydrops fetalis and the rarity of Hb-H disease despite the intense inbreeding in this population, points to an alpha-thalassaemia genotype that is, in terms of phenotypic expression, intermediate between the heterozygous state for alpha-thalassaemia I and Hb-H disease. A possible molecular basis for this genotype is suggested.

Eight insulin-treated diabetic patients in good glycaemic control were studied as out-patients with frequent determinations of stable glycosylated haemoglobin (HbA1c) before, during and after 1 week of induced poor glycaemic control. Stable HbA1c was determined by cation exchange chromatography after elimination of the labile fraction by incubation in saline (0.15 mol/l). The increase in mean blood glucose was significant on the first day of reduced insulin therapy and greatest after 1 week (6.9 +/- 3.9 mmol/l above basal values). Stable HbA1c increased significantly on day 7 of the reduced insulin treatment. The increase represented, on average, 0.009% of total haemoglobin per mmol/l increase in mean blood glucose per 24 h during the period of induced hyperglycaemia. After restoring insulin therapy, a significant decrease in blood glucose was achieved on day 1 and after 2 days, the blood glucose level was similar to before the study. There was no significant decrease in stable HbA1c within the first 2 weeks of improved glycaemia.

HAEMOGLOBIN A2, the minor component of normal adult haemoglobin, amounts to about 2.5 per cent of the total haemoglobin; it can be distinguished from the major adult component, haemoglobin A1, by its electrophoretic and chromatographic properties. Recent investigations have shown that haemoglobin A2 consists of two types of polypeptide chains: the α-chain, identical with the α-chain of haemoglobins A1 and F, and the δ-chain, which differs in constitution from the corresponding chains of haemoglobin A1, (the β-chain) and F (the γ-chain)1,2. A two-fold increase of the normal percentage of haemoglobin A2 occurs in the usual type of β-chain thalassaemia trait, prevalent in Greece3, while a decrease is observed in haemoglobin-H disease. A decrease of the A2 fraction down to 1 per cent has been observed as a reversible phenomenon in iron-deficiency anaemia4. Traces of haemoglobin A2 can be detected in cord blood haemoglobin by the application of special techniques.

Twenty-five patients of ages 39–72 years, with a maximum ventilatory capacity (MVVF) of ≤35% of the predicted values, were classified into a respiratory insufficiency (R) and a comparison (C) group according to the clinical progress of the disease. With the patients in their habitual state, the total haemoglobin (THb, g), the pulmonary and systemic pressures, cardiac output (Q, 1/min) and pulmonary (PVR) and systemic (SVR) vascular resistance in (mmHg/1)ċmin were measured at rest and during work.The mean values and S.E.M. in groups R and C were as follows: for THb 7.4±0.3 and 8.6±0.5 g/kg, blood volume 59.1±2.0 and 64.9±2.8 ml/kg, SaO2 86.2±2.2 and 90.4±1.4%, aO2 48.5±2.5 and 53.2±2.6 ml/l, pulmonary arterial mean pressure 31±2 and 26±2 mmHg, PVR 4.7±0.5 and 3.2±0.3 (mmHg/l) ċ min, arterial mean pressure 105±4 and 102±4 mmHg, SVR 23.1±1.2 and 23.9±1.8 (mmHg/l) ċ min. Q was 4.5 ± 0.2 in the R-group male patients and 4.7 ± 0.3 l/min in the females, and 4.5 ± 0.3 in the C-group male patients and 3.5 ...

A minor haemoglobin component consisting of freeα-chains is regulary present in haemolysates of human cord and adult blood. The isolation is achieved by chromatography on DEAE-Sephadex A50 in Tris-HCL-KCN buffer at pH 8.63. In normal adults the amount is in the range between 0.034 and 0.090 (mean 0.061) percent, in fullterm newborns between 0.042 and 0.101 (mean 0.075) percent of the total haemoglobin mass. Freeα-chains are missing in premature infants. In inherited deficiencies ofβ-chain production the amount of freeα-chains in highly increased.

A quantitative paper electrophoresis method for the separation of haemoglobins A and A(2) is described. The possible sources of error and the accuracy of the method have been investigated. The normal range for haemoglobin A(2) by this method is 1.3% to 4.3% of the total haemoglobin concentration. Good clinical correlation has so far been obtained.

Experiments with several aminophenols showed that 4-dimethylaminophenol and 4-methylaminophenol most rapidly produced controlled amounts of ferrihaemoglobin in the blood of various species in vitro and in vivo. The rapid reaction of 4-dimethylaminophenol and 4-methylaminophenol was also observed after intravenous injection in humans. Doses which oxidize 30 to 40% of the haemoglobin produce the half-maximal ferrihaemoglobin concentration in 1 and 2 min respectively without any immediate effect on the cardiovascular system. Sodium nitrite in doses of 4 mg/kg recommended for the treatment of cyanide poisoning was found to oxidize slowly about 7% of the haemoglobin, 10 min being taken for producing half the maximal amount of ferrihaemoglobin, i.e. 3.5% of the total haemoglobin. Nitrite caused a decrease in arterial blood pressure in all experiments and orthostatic collapse of several test persons. The rate of ferrihaemoglobin reduction in humans was determined. An amount of ferrihaemoglobin equal to about 8% of the total haemoglobin is reduced each hour, when the ferrihaemoglobin concentration amounts to more than 10% of the total haemoglobin.

HAEMOGLOBIN S is found in a concentration of 35–45 per cent of the total haemoglobin in most individuals with sickle cell trait under non-stress conditions1,2. It is believed that the relative concentrations of the heterogenic haemoglobins, haemoglobin S and haemoglobin A, in these individuals remain fairly constant throughout life. However, on rare occasions, changes in these relative concentrations have been demonstrated. In 1956, Zuelzer, Neel and Robinson3 described an 8-month-old infant with sickle cell trait and severe iron-deficiency anaemia in whom haemoglobin S could not be demonstrated by paper electrophoresis until the anaemia had been corrected with iron therapy. More recently, Heller, Yakulis, Epstein and Friedland4 have described a patient with sickle cell trait and coexistent megaloblastic anaemia in whom the haemoglobin S concentration increased from an initial level of 10.6 per cent to a concentration of 38.5 per cent following therapy with folic acid.

Blood oxygen affinity curves of Large White pigs were determined by a polarographic technique. The whole blood P50 values at pH 7.40 (37 °C) for adult i.e. non-pregnant, maternal and foetal (80–100 days gestation) pigs were 34.2 (S.D. ± 2.2 mm Hg), 35.0 (S.D. ± 2.6 mm Hg) and 22.0 mm Hg (S.D. ± 1.2 mm Hg) respectively. The difference between the adult and maternal P50 values was not significant but the foetal P50 was significantly different from both these values (P < O.001). The Bohr shifts of the adult and foetal bloods were determined at O.20 pH intervals from pH 7.00 to 7.60. The Bohr factors (Δlog PO2/ΔpH) calculated from these data were -O.43 and -O.45 for adult and foetal bloods respectively. Variations in adult and foetal P50 at the same pH were not related to individual variations in oxygen capacity or total haemoglobin concentration.

Summary The steady state haematological characteristics observed in 1071 patients with homozygous sickle cell (SS) disease aged 5–66 years are presented. Cross sectional studies indicated that HbA2 levels were consistently higher in males but no age related change was apparent. Fetal haemoglobin levels were consistently higher in females and fell significantly in males between the 5–9 and 10–14 year age groups. Total haemoglobin was significantly higher in females before age 15 and higher in males after 20 years, a dramatic age related rise occurring in males between the 10–14 and 25–29 year age groups, and a fall in patients aged 40 years and over. The mean cell volume was consistently greater in females after 15 years and a marked age related rise occurred in both sexes between the 5–9 and 25–29 year age groups. Counts of irreversibly sickled cells were consistently higher in males. Reticulocytes fell significantly with age, while platelets and total bilirubin fell significantly after the age of 15 years. Longitudinal studies confirmed the increase in total haemoglobin levels in males over the ages 10–14 years, and a significant fall in males after the age of 30 years. Such studies also confirmed the fall in HbF in males aged 5–14 years, the increase in MCV in both sexes aged 5–29 years, and the fall in platelet counts in both sexes over the age of 20 years. These observations provide ‘normal’values for patients seen elsewhere and also contribute to an understanding of factors determining the haemoglobin indices in SS disease.

Maternal haemoglobin A1c (HbA1c) values were measured before the end of the 15th week of gestation in 142 pregnancies in women with insulin dependent diabetes. In pregnancies complicated by fetal malformations (n = 17) the mean initial HbA1c value was 9.5 (SD 1.8)% of the total haemoglobin concentration, which was significantly (p less than 0.001) higher than in pregnancies without malformations (8.0 (SD 1.4)%; n = 125). HbA1c values did not differ between pregnancies complicated by minor and major fetal malformations, but the rate of malformations showed a positive relation to the HbA1c value in early pregnancy (chi 2 = 11.9; p = 0.001). Fetal malformations occurred in six out of 17 pregnancies (35.3%) in mothers whose initial HbA1c value was 10% or more, in eight out of 62 pregnancies (12.9%) in mothers with initial values between 8.0% and 9.9%, and in only three out of 63 pregnancies (4.8%) in mothers with an initial value below 8.0%. These data support the hypothesis that the increased incidence of fetal malformations in mothers with insulin dependent diabetes is associated with maternal hyperglycaemia during organogenesis. Hence diabetic women who are planning to have a child--especially those with a high HbA1c value--should receive intensified metabolic control.

The effects of stopping smoking for 48 hours on factors governing the availability of oxygen from the blood--that is, carboxyhaemoglobin (COHb), haemoglobin-oxygen (HbO2) affinity, and haemoglobin concentration--were measured in women in the last trimester of pregnancy. Three groups were studied: smokers, smokers who stopped smoking for 48 hours, and non-smokers. The 22 smokers had higher initial COHb values and greater HbO2 affinity than the 10 non-smokers, but their total haemoglobin concentrations were also higher, so that their oxygen availability was not significantly reduced. In the 11 smokers who stopped the reduction in COHb and decrease in HbO2 affinity led to a significant increase of 8% in "available oxygen" in 48 hours. Since even small improvements in oxygen delivery to the tissues may confer critical benefit to the fetus, particularly during labour or when exposed to general anaesthesia, smoking should be discouraged for 48 hours before elective deliveries. The same consideration might reasonably be applied to patients undergoing general anaesthesia for all elective operations.

PAULING introduced the term ‘molecular disease’ for the hereditary condition of sickle cell anaemia, in which the clinical signs in both the heterozygous carriers with the sickling trait, and the homozygous patients with the anaemia, are explained by the fraction of abnormal haemoglobin molecules present1. Only a part of the total haemoglobin is the abnormal type in the heterozygote with one abnormal gene, whereas nearly all the haemoglobin is the abnormal type in the homozygote with two abnormal genes. An extension of this concept of molecular disease leads to the prediction that in hereditary diseases associated with the loss of activity of an enzyme, the asymptomatic heterozygotes should be identifiable by having less than the normal amount of the enzyme primarily involved in the disease2.

HopKiNS–1 haemoglobin (haemoglobin Ho–1) was originally described in twelve members of a large kindred in 1958 by Smith and Torbert1. In this investigation the abnormal haemoglobin was estimated to make up about 50 per cent of the total haemoglobin in affected heterozygotes. Although the β chain has been established as the site of amino-acid substitution by the recombination of haemoglobin sub-units2, the nature and exact locus of the substitution have not yet been elucidated. Because haemoglobin Ho–1 is of the rapidly migrating haemoglobin I type electrophoretically, and therefore differs from haemoglobin A by two charges per abnormal chain, it can therefore be presumed that the mutation in haemoglobin Ho–1 involves the substitution of an acidic for a basic amino-acid.

IN a previous publication1 the finding of a new type of sheep haemoglobin was reported. This has a slower rate of migration on starch gels than the A and B haemoglobins. It was first found in highly anaemic lambs where its relative amount of total haemoglobin showed great variation. For these reasons it was called abnormal and tentatively given the symbol N. Blunt and Evans2 reported a new haemoglobin in sheep with haemoglobin A type and made anaemic by experimental bleedings. This new type was electrophoretically similar to haemoglobin B.