Preservation of deformability (filterability) of sickle cells by BW12C during progressive deoxygenation

S ummary . venous blood from patients with sickle-cell disease in the steady state or in crisis was progressively deoxygenated in vitro to study the effect of BW12C, a new compound designed to stabilize haemoglobin in the oxy-conformation, on the deformability (filterability) of washed erythrocytes. At a final concentration of 1·5 mM, BW12C significantly increased erythrocyte deformability, compared with no added compound, at all levels of deoxygenation below normal arterial PO₂. At concentrations of 3·0 and 5·0 mM, BW12C prevented any significant reduction of erythrocyte deformability, or increase in sickled cells, with deoxygenation down to PO₂ values below the normal venous level. These in vitro results demonstrate the considerable potential, as an anti-sickling agent, of this novel compound.     

Uptake and release of transferrin and iron by mitogen-stimulated human lymphocytes

Phytohaemagglutinin stimulation of human peripheral blood lymphocytes resulted in the expression of transferrin receptors and the uptake of iron into the cells. As assessed from the resistance of the ¹²⁵I label to pronase, transferrin was rapidly bound and internalized at 37°C, while at 4°C 85% of the ¹²⁵I label remained on the cell surface and was degraded by the pronase. Over 94% of the ¹²⁵I label associated with and subsequently released from the cells was acid precipitable, indicating that transferrin was not degraded during its uptake and release. After reincubation for 1 h in fresh medium 70% of the cell associated ¹²⁵I-transferrin was released. In contrast, less than 30% of the ⁵⁹Fe was released, showing that iron was removed from transferrin and retained by the cells.
Concentration dependent binding of ¹²⁵I-transferrin estimated at 37°C occurred with an apparent K_a of 5·7±1·1 × 10⁷l mol⁻¹ (mean ± SD, n = 4) indicating little variation between cells from different individuals, although the number of transferrin molecules associated with the cells varied greatly from 6·2 × 10⁴/cell to 1·4 × 10⁵/cell. The rate of iron uptake from ⁵⁹Fe and ¹²⁵I labelled transferrin at 37°C by the cells from different subjects was also very variable, with a range between 0·46 and 2·27 pg Fe/min/10⁶ cells ( n = 6). However, iron uptake did not correlate with the amount of transferrin bound. This suggests that transferrin uptake and the release of iron from the transferrin to the interior of the cell are controlled independently.     

Haematological reconstitution following high dose and supralethal chemo-radiotherapy using stored, non-cryopreserved autologous bone marrow

S ummary . Eighteen patients with small cell carcinoma of the lung received high dose cyclophosphamide (180–200 mg/kg) intensification following five pulses of 'CHOP' chemotherapy (cyclophosphamide 750 mg/m² i.v., adriamycin 50 mg/m² i.v., vincristine 1·4 mg/m² i.v., prednisolone 40 mg orally for 5 d). They received infusions of autologous bone marrow which had been stored at 4°C for 34 h. Pancytopenia was predictable in onset and its duration acceptable. Recovery of neutrophils to greater than 1·0 × 10⁹/l was achieved in 17·5 ± 0·9 d (mean ± SEM) and platelets to greater than 100 × 10⁹/l in 17·5 ± 0·8 d. Four patients with acute myeloid leukaemia in complete remission received intensification with the supralethal combination of cyclophosphamide and total body irradiation followed by infusion of autologous marrow which had been stored at 4°C for 54 h. Haematological reconstitution in these patients was acceptable but slower (greater than 1·0 × 10⁹/l neutrophils between days 26 and 40; greater than 20 × 10⁹/l platelets between days 23 and 77). Except in one case, normal peripheral counts were attained in all patients.
It is concluded that bone marrow stored at 4°C for up to 54 h is a simple and practical source of viable stem cells which have the capacity for acceptable haematological reconstitution.     

Improved leucoreduction of red blood cell units prepared after a 24-h hold with the platelet-rich plasma method using newly developed filters

Background and Objectives  A previous study indicated that the extension of whole blood (WB) storage from 8 to 24 h at 20–24 °C before the processing of platelet-rich plasma (PRP)-depleted red blood cell (RBC) units had a negative effect on the efficacy of leucoreduction filters. In this study, we further characterized the phenomenon and tested the leucoreduction capacity of two newly developed filters.
Materials and Methods  Whole blood was stored at 20–24 °C and processed at 4-h intervals between 8 and 24 h postcollection. Components were leucoreduced before storage. Efficacy of novel filters to leucoreduce 24-h-hold PRP-depleted RBC units was also evaluated.
Results  Using a conventional filter, the mean residual white blood cell (WBC) counts in leucoreduced PRP-depleted RBCs were comparable in units prepared within 12 h from collection but gradually increased upon extended preprocessing storage from 0·36 ± 0·03 at 12 h to 0·46 ± 0·21, 0·76 ± 0·54 and 1·72 ± 1·76 × 10⁶ per unit at 16, 20 and 24 h, respectively. However, the mean residual WBC content in 24-h-hold RBCs was reduced to 0·60 ± 0·39 × 10⁶ and 0·46 ± 0·13 × 10⁶ per units using RC2D and the prototypes B-1582 rev B filters, respectively.
Conclusion  For PRP-depleted RBC units, the extension of the WB room temperature storage from 8 to 24 h before processing is likely to require the introduction of newly developed filters having an increased leucoreduction capacity in order to meet the maximal residual WBC guideline in the RBCs.     

Analysis of Heat-damaged Erythrocyte Clearance Curves

S ummary . The rate of clearance from the blood of heat-damaged erythrocytes (HDE) is used routinely as a quantitative assessment of splenic function. The time taken for the value at 3 min to fall by 50% ( t _0-5) is usually taken as the index of function. The clearance of HDE is dependent on three processes: splenic blood flow, splenic HDE extraction ratio and intrasplenic transit time of 'unextracted'HDE, returning to the circulation. Exponential analysis of the clearance curve can resolve these three functions. Simple methods of analysis, however, such as t _0-5, which are applied directly to the curve, may be weighted in favour of any one of them. In this paper, a large number of clearance curves have been analysed and the components of splenic function resolved. The t _0-5, the percentage fall in HDE between 8 and 28 min ( C ₂₀), the rate constant at 8 min ( K ₈) and the rate constant of the tail of the curve (α₂) have been correlated with these components. K ₈ showed a close correlation with splenic blood flow, and α₂ with the rate of HDE phagocytosis. In general, the correlation between the various components of splenic function was better with C ₂₀ than with t _0-5. This is explained predominantly by the fact that the t _0-5 includes liver clearance. The t _0-5 should therefore be used with caution as an estimate of splenic function, which can be usefully assessed by applying alternative simple methods of analysis described.     

Cholecystokinin-Stimulated Monocytes Produce Inflammatory Cytokines and Eicosanoids

Objectives : Plasma cholecystokinin increases with enteral feeding. Cholecystokinin increases intracellular calcium in lymphocytes/monocytes and is a lymphocyte co-mitogen. We hypothesize that decreased cholecystokinin production with "bowel rest" and parenteral nutrition may be beneficial in inflammatory bowel disease by down-regulating gut immune/inflammatory mechanisms. The majority of cells observed in mucosa of inflammatory bowel disease are monocytes and neutrophils. Cholecystokinin effect was therefore measured on monocyte production of proinflammatory mediators (tumor necrosis factor α, interleukin-1 β, intcrteukin-6) and neutrophil chemotaxins/activators (interleukin-8, granulocyte-macrophage colony stimulating factor, and leukotriene B₄). Methods : Peripheral blood monocytes (0.5 ± 10⁶) from healthy donors in 1 mL of RPMI 1640 plus 5% fetal calf serum were cultured for 24 h in 5% CO₂ at 37±C with 5 μg/mL endotoxin, 1 ± 10-⁻⁷ M cholecystokinin, or no agonist. Supernatants were analyzed by ELISA for cytokines and leukotriene B₄. Results : Endotoxin-stimulated monocytes produced 1130 pg/mL tumor necrosis factor versus 81 pg/mL for cholecystokinin, 612 pg/mL interleukin-1 versus 10 pg/mL, 694 pg/mL interIeukin-6 versus 30 pg/mL, 4531 pg/mL of interleukin-8 versus 3848 pg/mL, 21 pg/mL granulocytemacrophage colony stimulating factor versus 9 pg/mL, and 21 pg/mL leukotriene B₄ versus 12 pg/mL. Controls produced no cytokines/eicosanoids (N = 8, p < 0.001). Conclusion : Cholecystokinin increase with enteral feeding may up-regulate gut immune response. Cholecystokinin suppression with parenteral alimentation may decrease inflammatory mediator production.     

Loss of Red Blood Cell Viability Associated with Limited Thermal Inactivation of Extracellular HIV-1

The effects of incubation at mildly elevated temperatures on HIV-1 inactivation and in vitro red blood cell properties were investigated. Red cells (55% Hct) were leukodepleted (3 log₁₀) by filtration, maintained at 45 or 47°C for 4 or 8 h, and then stored at 4°C. Hemolysis was twice that of controls after 42-day storage for samples treated for 4 h at 45°C, and five times larger for samples heated at 47°C. There was also a significant increase in the rate of potassium loss, an early decrease in ATP levels, and an initial drop in pH for samples treated at either temperature. Larger differences were observed for samples exposed to these elevated temperatures for 8 h. Osmotic deformability curves obtained by ektacytometry showed dramatic decreases in red cell deformability at both temperatures and for both time periods. HIV-1 inactivation in red cells treated at 45°C (approximately 0.25 log₁₀/h) was considerably less than that obtained in tissue culture medium (1–2 log₁₀/h). Since the decrease in red cell deformability is likely to indicate reduced red cell function and survival, and the rate of HIV-1 inactivation is low, mild heat treatment is not an adequate process for viral inactivation of red cell products.     

Isoferritins in normal leucocytes

Monocytes, lymphocytes and polymorphs were separated from the peripheral blood of normal human subjects. Ferritin concentrations were determined with antibodies to both human spleen and heart ferritins. The heart type ferritin concentration in monocytes was 38·4±21·6 fg/cell (mean ±SD), in lymphocytes 8·6±6·6 fg/cell and in polymorphs 3·2±2·4 fg/cell. Spleen type ferritin concentrations (fg/cell) were 15·6±7·0 in monocytes, 6·6±5·7 in lymphocytes and 7·0±4·6 in polymorphs. The mean heart/spleen ferritin ratios were 2·8/1 for monocytes, 2·0/1 for lymphocytes and 0·6/1 for polymorphs. The cell extracts were also subjected to anion exchange chromatography. Heart type ferritin eluted at a higher chloride ion concentration than spleen type ferritin. Both H and L subunits were synthesized by mononuclear cells when incubated with ³H-leucine. Human leucocytes contain a wide range of isoferritins and ferritin concentrations may be considerably underestimated in conventional assays for serum ferritin which employ antibodies to liver or spleen ferritin.     

PEDIATRICS

Eduardo Ibarguen-Secchia , MD. *   * Pediatric Digestive Care, San Antonio, TX.
Purpose: To determine safety, tolerability and comfort of use of carbon dioxide for insufflation during colonoscopy in children.
Methods: After informed consent, a total of 84 consecutive patients undergoing colonoscopy were randomized to use either air or CO₂ insufflation. Ages ranged from 6 years to 16 years (mean 12). End tidal carbon dioxide was recorded before the examination, at 2 minute intervals during the examination and 10 minutes after it. General anesthesia was used for sedation in all cases. Pain at 5 and 15 minutes after the procedure was measured using a ten-point analog scale.
Results: Pain scores at 5 minutes after the examination were 5.2 ± 0.3 for the air group and 4.8 ± 0.2 for the CO₂ group (no significant difference). At 15 minutes the score were 2.8 ± 0.3 for the air group and 0.7 ± 0.3 for the CO₂ group (significant at P < 0.05). End tidal CO₂ in both groups was no different.
Conclusion: Using CO₂ for insufflation during colonoscopy is safe and improves patient comfort. Patients who received CO₂ insufflation during their colonoscopy experienced less post-procedure discomfort. There was no evidence of CO₂ retention based on end tidal carbon dioxide monitoring.     

Binding and uptake of exogenous isoferritins by cultured human erythroid precursor cells

Summary. The interaction of extracellular human isoferritins with normal erythroid precursors developing in a two-phase liquid culture was studied. Cells at the stage of polychromatic normoblasts exhibited substantial specific binding of radio-iodinated placental isoferritins. Considerably more acidic isoferritin was bound than basic isoferritin. The binding of ferritin was significantly higher at 37°C than at 4°C. All of the ¹²⁵I-acidic isoferritin bound at 4°C, but only part of that bound at 37°C, could be dislodged by the addition of a 500-fold excess of non-labelled acidic isoferritin. Acidic isoferritin displaced radio-iodinated acidic isoferritin from the erythroid cells more efficiently than intermediate or basic isoferritins. Kinetic analysis suggests a dissociation constant ( K _d) of 3·9 × 10^-8 m for acidic ferritin and 3·7 × 10^-7 m for basic isoferritin. The average number of binding sites for acidic isoferritin was 1·3 × 10⁵ per cell. The results point to specific binding and receptor-mediated internalization for predominantly acidic isoferritin by developing human erythroid cells.     

In vitro platelet ageing at 22°C is reduced compared to in vivo ageing at 3 7°C

Summary .In these studies, platelet ageing during in vitro at 22°C was compared with in vivo ageing using isotope labelling. Paired fresh and 5-d-stored platelets had a mean residual life-span (MRL) of 4–8 ± 0–7d and 3–2 ± 0–9 d, respectively. After 2–1 ± 0–4 d in vivo circulation, the MRL of the fresh platelets was equivalent to that of the 5-d-stored in vitro platelets. This suggests that platelet ageing for 5 d in vitro at 22°C corresponds to 2–1 d in vivo ageing at 37°C. Thus, the relative ageing at 22°^CC in vitro was (2.1 d/ 5d) = 0–42 of that at 37°C in vivo. A similar ageing ratio (0–44) was obtained by measurement of the decrease in MRL during storage at 22°C of platelets stored for 1, 5, 7, 10 and 14 d relative to the decrease in MRL of fresh platelets in vivo.
ATP turnover rate at 22°C was compared to the rate of 37°C by measurement of the rates of platelet oxygen consumption and lactate production in vitro. In vitro ATP turnover at 22°C versus 37°C, was found to be 10–5 ± 10 versus 21–6 ± l.4/μmol/10¹²plts/min, respectively. Thus, the ATP turnover ratio (0–48) at these two temperatures suggests that the relative decrease in ageing at 22°C compared to 37°C is similar to the relative decrease in metabolic rate at this temperature.     

The Effect of Cimetidine on Gastrin Release in Ulcer Disease

Summary: The effect of cirnetidine on gastrin release in ulcer disease. M. G. Korman. J. Hansky and J. Waugh, Aust. N.Z. J. Med., 1979, 9, pp. 367–369.
The effect of a single dose of 400 mg of the H₂-receptor antagonist cimetidine on protein meal stimulated immunoreactive gastrin was assessed in ten patients with gastric ulcer and ten patients with duodenal ulcer. In gastric ulcer patients, serum gastrin (mean±SE) rose from 34±2·2 pmol∖l^-1 to a peak of 80±5·0 pmol∖l^-1 at 45 minutes without and from 36±2·2 to 107±8·0 pmol∖l^-1 at 60 minutes with cimetidine; in duodenal ulcer it rose from 26±3·0 to 47±5·1 pmol∖l^-1 at 45 minutes without and 26±3·2 to 52±5·1 pmol∖l^-1 at 60 minutes with cimetidine. Integrated gastrin responses in gastric ulcer were 4900±800 pmol∖l^-1 720 minutes without and 7000±900 pmol∖l^-1 720 minutes with cimetidine and 1560±300 pmol∖l^-1 720 minutes without and 2620±400 pmol∖l^-1 720 minutes with cimetidine in duodenal ulcer patients. These gastrin increases after cimetidine are comparable to those achieved with continuous intragastric neutralisation with alkali.     

Effects of Autoclave Sterilization on the Physical Properties of Storage Bags and Granulocyte Function

Abstract. Autoclave sterilization altered the leaching of plasticizer, CO₂ gas permeability, surface area and the surface wettability of bag films. These changes affected granulocyte cell counts and functions during storage. Four types of polyvinyl chloride bags, with di-(2-ethylhexyl)phthalate (DEHP) or tri-(2-ethylhexyl)trimellitate (TOTM) as plasticizer, with or without treatment by glow discharge (H2), were sterilized with ethylene oxide (EO) or autoclaving (AC). The greatest amounts of plasticizer leached from DEHP-EO bags. TOTM plasticizer did not leach into plasma. CO₂ gas permeability was greater with TOTM than DEHP. AC sterilization decreased the surface area of bags. Wettability of film surfaces was greatest with H₂-TOTM-EO. After storage in these bags for 24 and 48 h at 22 °C, the granulocyte cell counts and functions were greatest in H₂-TOTM-EO bags with the nonleaching plasticizer, higher CO₂ gas permeability and higher wettable surface due to glow-discharge treatment. The H₂-TOTM-EO bag was useful as a granulocyte storage container.     

Paraneoplastic autoimmune phenomena in patients with myelodysplastic syndromes: response to immunosuppressive therapy

Summary. Single oral dose pharmacokinetics of the iron chelator deferiprone (L₁) were studied in 24 patients with chronic iron overload and correlated with 24h urinary iron excretion (UIE) and creatinine clearance. Absorption of L₁ was rapid with a t _1/2 of 22·2 pL 17·7 (mean pL SD) min. The elimination half-life (el t _1/2) of the drug was 91·1 pL 33·1 min and of its metabolite, L₁-glucuronide (L₁G) 147·7pL 52·0 min. Creatinine clearance of the patients correlated significantly with the elimination t _1/2 of L₁G ( r = -0·79, P = 0·002). There was also a significant correlation between 24 h UIE in the 14 patients studied and L₁ versus time area under the curve (AUC) ( P = 0·007). The total amount of L₁ recovered in urine in 24 h comprised 77·9 pL 13·3% of the L₁ dose. L₁ efficiency (the 24 h UIE divided by the amount of iron the oral dose of L₁ is capable of binding) in the 14 patients was 3·8 pL 1·9%. These data show for the first time that the urinary elimination of L₁G is influenced by the renal function of the patient. Although no significant accumulation of L₁ and L₁G will occur in most of the patients if L₁ is given more than once daily, in some patients with impaired renal function, L₁G may accumulate.     

Leucine and Glucose Turnover in Chronic Alcoholics During Early Abstinence and After an Ethanol Load

We studied leucine turnover using a primed infusion of [1-¹⁴C]- l -leucine and glucose turnover using a primed infusion of [6-³H]- d -glucose in five alcoholic patients without liver damage and five age-matched controls. Infusions were maintained for 6 hr, and at the end of the 3rd hour, a 0.8 g/kg iv ethanol load was administered in 20 min. Leucine flux, nonoxidative disposal and oxidation rates, and glucose rate of appearance were calculated during the 3rd and 6th hours of infusion. Ethanol disappearance rate and the percentage completely metabolized to CO₂ and H₂O in 3 hr were also calculated. Compared with controls, alcoholics had significantly higher basal leucine flux (55.6 ± 12 vs. 37.3 ± 9.3 μ m /m²/min) and nonoxidative disposal (48.7 ± 8.7 vs. 31.1 ± 7.5 μ m /m²/min). No differences were observed in basal glucose appearance rates in alcoholics and controls (397.6 ± 115.2 vs. 349.4 ± 120.6 μ m /m²/min). Compared with controls, alcoholics had a higher alcohol disappearance rate (2.72 ± 0.59 vs. 1.84 ± 0.43 m m /kg/min) and percentage of ethanol metabolized to CO₂ and H₂O in 3 hr (40.6 ± 10.2 vs. 22.9 ± 6.9%). After the ethanol load, both leucine turnover and glucose rate of appearance decreased significantly only in alcoholics. There was a positive correlation between the change in leucine flux and ethanol disappearance rate and percentage metabolized to CO₂ and H₂O in alcoholics.     

Pathogen reduction technology (Mirasol®) treated single-donor platelets resuspended in a mixture of autologous plasma and PAS

Background and Objectives  Mirasol^® pathogen reduction technology (PRT) for platelet concentrates uses riboflavin and ultraviolet light. Previously, we described increased metabolism and activation for PRT platelets stored in 100% plasma. To improve platelet quality, we resuspended platelets in a mixture of plasma and platelet additive solution (PAS).
Materials and Methods  Single-donor platelets were resuspended in plasma and split into an untreated control and a PRT-treated single product. One hundred and fifty millilitre PAS (SSP+) was added to both. Over 7 days, we assayed pH, glucose consumption-, lactate production rate and CD62p with and without TRAP.
Results  On day 5, PRT units showed a significantly lower pH (7·087 ± 0·105 vs. 7·288 ± 0·200) accompanied by a higher lactate production (0·104 ± 0014 vs. 0·063 ± 0·017 mmol/10¹²/h) and glucose consumption rate (0·039 ± 0005 vs. 0·028 ± 0·009 mmol/10¹² platelets/h). CD62p expression was higher in treated units (44·5 ± 13·0 vs. 16·5 ± 7·6%).
Conclusion  In comparison to PRT platelets resuspended in 100% plasma, a mixture of plasma and PAS improves pH and platelet metabolism but not platelet activation. Prolonged shelf-life for up to 7 days may be possible.     

Application of the intravenous glucose tolerance test and the minimal model to patients with insulinoma: insulin sensitivity (Si) and glucose effectiveness (Sg) before and after surgical excision

Background  The unmodified frequently sampled intravenous glucose tolerance test (FSIGT) has not previously been used to assess insulin/glucose kinetics in patients with insulinoma.
Objective  To measure insulin sensitivity (Si) and glucose effectiveness (Sg) by means of the FSIGT in patients with insulinoma, before and after surgical removal of the tumour.
Subjects and methods  FSIGTs were performed in five patients, before and approximately 3 months post-surgery, and in 11 controls. Si and Sg were estimated using Minimal Model computer analysis of dynamic glucose and insulin data.
Results  Si was lower in insulinoma patients before, compared with after surgery (3·37 ± 0·62 vs. 6·24 ± 1·09 SE [×10⁻⁴] min⁻¹µU⁻¹ ml, P  < 0·05). Sg was similar in patients pre- and post-surgery (3·0 ± 0·67 vs. 2·4 ± 0·6 [×10⁻²] min⁻¹, NS).
Conclusions  Insulin sensitivity improves after excision of an insulinoma. Glucose effectiveness is not influenced by chronic hyperinsulinaemia and hypoglycaemia.     

Differential Coating of Human Red Blood Cells with C4 or C3 in a Low Ionic Strength Medium

An EDTA-containing, low ionic strength medium, pH 5.1, can be used for incubation of blood to obtain coating of red blood cells with C4 or C3. The coating achieved depends on incubation temperature (4 or 37°C) and on whether or not CaCl₂ or MgCl₂ is added to the medium. The optimal concentration of EDTA appears to be 2 m M under the present conditions. This is equimolar to the final concentration of the added CaCl₂/MgCl₂. The choice between CaCl₂ and MgCl₂ depends on whether blood without anticoagulant or ACD blood is employed. Coated cells keep satisfactorily for 5 weeks at 4°C in Alsever's solution as well as after freezing and thawing. C3-coated cells can be converted to C3dcoated ones by incubation in normal, compatible, EDTA-containing serum at 37°C.     

Plasma kallikrein clearance by the liver of chronic carbon tetrachloride-treated rats

Abstract We have previously reported that the endocytosis of rat plasma kallikrein (RPK) by hepatocytes is a calcium-independent and beta-galactoside-dependent mechanism. We now report the clearance of RPK by the liver of four groups of rats: normal, inflamed (48 h ex-turpentine) and two groups chronically treated with CCl₄ (52 mg/kg per week, intragastrically, for 9-12 weeks). Each liver was isolated, exsanguinated and perfused at 37°C with 30 mL of BSA-Krebs-Henseleit-bicarbonate medium containing 10 nmol/L RPK. Although all rats received the same mild CCl₄ treatment, the liver histology showed that they evolved either to severe hepatitis (serum alanine aminotransferase [ALT] 4852 ± 885 U/L, parenchymatous necrosis in the perivenous region) or to compensated cirrhosis (serum ALT 209 ± 42 U/L, vigorous fibrous encircling regeneration nodules); neither jaundice nor ascites was noted. The results show that serum albumin was not altered among the groups and that: the acute-phase response by itself (inflamed group) increased RPK clearance rate (3.01 ± 0.59 mL/min) as compared with the normal group (1.85 ± 0.14 mL/min); the CCl₄ treatment, although induced an acute-phase response, decreased ( P < 0.01) RPK clearance rates (0.80 ± 0.11 mL/min hepatitis group and 0.98 ± 0.10 mL/min cirrhosis group). These findings suggest that the hepatic clearance rate of plasma kallikrein is an early indicator of liver injury.     

Haemoglobin A1 in Diabetes Mellitus

Summary: Haemoglobin A₁ in diabetes mellitus. P. C. Bartley and T. E. Hambling
HbA₁ was measured by a rapid method in a routine hospital laboratory. The normal range of 5·0–8·5% compares favourably with other studies. Patients with uncontrolled diabetes had levels of HbA₁ of up to 20·5% while well controlled patients had levels of HbA₁ in the normal range. The level of HbA₁ is relatively stable in normal subjects and does not correlate with age, sex or weight. There was a correlation (p < 0·001) with a 1–2 hour postprandial, post-insulin blood sugar in insulin dependent diabetics. There was a relationship between type of therapy and HbA₁ level at presentation. From the study of two ketoacidotic patients, it is apparent that the level of HbA₁ decreases about six weeks after the decrease in blood sugar. It is concluded that the measurement of HbA₁ is a useful adjunct in the assessment of diabetic control.