Hb Genotype Research Articles

Hemoglobin Genotype Has Minimal Influence on the Physiological Response of Juvenile Atlantic Cod (Gadus morhua) to Environmental Challenges

Hemoglobin (Hb) polymorphism in cod is associated with temperature-related differences in biogeographical distribution, and several authors have suggested that functional characteristics of the various hemoglobin isoforms (HbIs) directly influence phenotypic traits such as growth rate. However, no study has directly examined whether Hb genotype translates into physiological differences at the whole animal level. Thus, we generated a family of juvenile Atlantic cod consisting of all three main Hb genotypes (HbI-1/1, HbI-2/2, and HbI-1/2) by crossing a single pair of heterozygous parents, and we compared their metabolic and cortisol responses to an acute thermal challenge (10 degrees C to their critical thermal maximum [CTM] or 22 degrees C, respectively) and tolerance of graded hypoxia. There were no differences in routine metabolism (at 10 degrees C), maximum metabolic rate, metabolic scope, CTM (overall mean 22.9 degrees +/- 0.2 degrees), or resting and poststress plasma cortisol levels among Hb genotypes. Further, although the HbI-1/1 fish grew more (by 15%-30% during the first 9 mo) when reared at 10 degrees +/- 1 degrees C and had a slightly enhanced hypoxia tolerance at 10 degrees C (e.g., the critical O(2) levels for HbI-1/1, HbI-2/2, and HbI-1/2 cod were 35.56% +/- 1.24% , 40.56% +/- 1.99%, and 40.20% +/- 1.19% air saturation, respectively), these results are contradictory to expectations based on HbI functional properties. Thus, our findings (1) do not support previous assumptions that growth rate differences among cod Hb genotypes result from a more efficient use of the oxygen supply-that is, reduced standard metabolic rates and/or increased metabolic capacity-and (2) suggest that in juvenile cod, there is no selective advantage to having a particular Hb genotype with regards to the capacity to withstand ecologically relevant environmental challenges.

An Evaluation of Pfmdr1 Mutations in Chloroquine Resistance: Effect of Host Factor

Background: Pfcrt and Pfmdr1 mutations have been reported to be associated with chloroquine resistance, but these reports have been inconsistent. Red cell factors, sickle cell trait, ABO blood group antigens and glucose-6-phosphate dehydrogenase (G6PD) deficiency are known to confer some degree of resistance against malaria parasite infection but their interplay with CQ resistance is yet unknown. This study therefore aims at evaluating the correlation of CQ resistance with Pfmdr1 mutation and certain host factors in humans. Methods: One hundred and twenty patients (1–15yrs) with acute uncomplicated falciparum malaria were enrolled into the study. They were administered standard doses of CQ and followed up for parasitological and clinical response for 14 days. Thick and thin blood films as well as filter paper blood samples were obtained from patients before enrolment and during follow up. Blood samples were collected in EDTA bottles for assessment of haematological parameters. DNA was extracted from filter paper using the methanol fixation method and used for Pfmdr1 and msp1 analyses by polymerase chain reaction. Results: Seventy patients were followed up to day 14.53% of the patients were cured, with a 47% failure rate to CQ. Although Pfmdr1Y86 was detected in majority of the patients (19/33) with clinical failure, this was not statistically significant (p > 0.05). 88% of the clinical failures was due to recrudescence and this was highly significant with treatment outcome (p = 0.000). No significant association was found between Pfmdr1 alleles and red cell factors. However, individuals with HbAA were found to be 2.3 times more likely to develop resistance to CQ treatment compared to those having HbAS. Conclusion: In conclusion, the prevalence of CQ resistance and Pfmdr1Y86 mutation was high in this malaria endemic setting. There was no clear influence of ABO, G6PD deficiency and Hb genotype on CQ resistance and Pfmdr1 mutation.

Obstetric and Gynecological History in Sickle Cell Disease Females

Pregnancy in sickle cell disease (SCD) has been associated with complications and adverse outcomes for mother and child and thus warrants specialized clinical care. There is bidirectional impact between pregnancy and SCD. Only a small number of previous studies of pregnancy outcomes in SCD patients have been published, and some have been based on nationwide diagnosis queries rather than direct patient queries. An increased incidence of spontaneous abortion, pregnancy-induced hypertension, infections, pre-term labor, and low birth weight was noted in those reports. The aim of the present study was to identify and describe the characteristics and outcomes of pregnancy and other gynecological events in our current patients with SCD. We hypothesized that these women experience a higher frequency of pregnancy-related complications and earlier onset of menopause than the general population. One hundred adult female SCD patients from the Duke University Medical Center sickle cell clinic were included in this study. Sixty five were homozygous for hemoglobin (Hb) SS, 22 had Hb SC and 13 had other Hb genotypes. A standard questionnaire was developed, and patients were interviewed either personally or by telephone after obtaining IRB-approved informed consent. Most of the data reported here comes from patient interviews. Medical records were reviewed only to confirm Hb genotype and age. The mean age of individuals included in the study was 38.7± 13 years (range 19–75 yr). Sixty-seven of 100 reported a history of regular menses. The median age at menopause was 45 yr (range 27 to 58) as compared to 49.3 yr in the general African American population (AA) (Bromberger, Am J Epidemiol. 1997). Twenty-five percent of the patients were never pregnant, 92% of those (23 out of 25) stated they did so by choice. Seventy-five patients reported a total of 158 pregnancies; there were 111 live births and 3 still-births. One tubal pregnancy was terminated. Patients reported a total of 43 abortions: 28 were spontaneous, and 15 were induced. Twenty-seven (36%) patients have had at least one abortion. Of women with a history of pregnancy, 57 (76%) reported unplanned pregnancies. Mean gestational age was 35.9 ± 5 weeks. Maternal complications evaluated included: thrombosis in 6 patients (8%), five in the lower limb and one in the lungs; and pregnancy-induced hypertension in 10 (13%) patients. The rate of live births was 0.7. The prevalence of low birth weight was higher than in the AA population (26.3% vs. 13.2%, respectively) and the mean birth weight was lower than the AA population (2595.5 vs. 3089 g, respectively) (David et al, NEJM. 1997). The mean birth weight for women who increased their use of pain medications during pregnancy was lower than that for women who continued on the same pain medication regimen, those who took less medication, and those who did not use pain medication (2045, 2743, 2758, and 2924 g, respectively, p < 0.02). The babies of patients in the first group were more likely to stay longer in the hospital (p = 0.006). We conclude that obstetrical and gynecological outcomes in SCD patients differ significantly from and are in general worse than for the AA population, especially for menstrual history, onset of menopause, prevalence of low birth weight and mean birth weight. Moreover, increased use of pain medications in pregnancy was associated with lower birth weight. This finding is troublesome and deserves further study.

Omega-3 Fatty Acid Deficiency in Sickle Cell Disease Correlates with Clinical Severity and Has Therapeutic Implications.

Background: Clinical illness in SCD results not only from the β-globin gene mutation, but also from other genetic and environmental factors acting in concert. The biological basis of individual variation in the severity of SCD is not fully understood. Our previous study revealed that WBCs from people with severe SCD express high levels of the adhesion molecules L-selectin (CD62L) and αMβ2 integrin (CD11a/18) in steady state. These cell membrane proteins mediate leukocyte adherence to vascular endothelium and facilitate vaso-occlusion: a fundamental pathological process in SCD. The lipid composition of cell membranes affects the level of expression of adhesion molecules on the membrane, its structural integrity and function. Abnormalities of plasma and erythrocyte lipids in SCD had been recognised. However, there is little information on lipid composition of leukocyte and platelet membranes in SCD, and its relationship with clinical severity.Objectives: To analyse the membrane fatty acid (FA) composition of blood mononuclear cells and platelets in SCD, find out if the degree of lipid abnormalities in RBCs affects the Hb level, and whether differences in FA composition of blood cells relate to clinical severity.Study Design & Methods: The fatty acid (FA) composition of blood cells and plasma in 71 HbSS and 9 HbSC steady-state patients were compared with those of 58 healthy, racially-matched, HbAA controls with similar age and sex distribution. To minimise the confounding effects of differences in dietary patterns, patients were compared with controls living in the same environment. We excluded cigarette smokers, SCD patients with other diseases, HbF levels ≥ 10%, and blood transfusion or pregnancy in the previous 3 months. Hb genotype was determined by electrophoresis or High Performance Liquid Chromatography. The manifestations of SCD were ascertained in each patient by clinical assessment. FA composition of cell membranes and plasma was analysed as described by Folch et al. The statistical package SPSS for Windows (SPSS Ltd, Woking, UK) was used for data analyses.Results: Mononuclear leukocytes, platelets, plasma and erythrocytes of SCD patients showed deficiency of omega-3 FA relative to matched HbAA controls (p< 0.05). Steady-state Hb level in SCD patients showed strong direct correlation with the proportion of omega-3 FA in RBCs (p< 0.01). HbSS patients had significantly lower amounts of omega-3 FA compared with HbSC individuals in erythrocytes (p< 0.001) and plasma (p< 0.05). The deficiency of omega-3 FA was significantly greater in patients with complications of SCD in comparison to those who had none (p< 0.005).Therapeutic Implications: The findings suggest that steady-state Hb level in SCD patients might be improved by administration of omega-3 FA. That HbSC patients are also deficient in omega-3 FA suggests that they might derive clinical benefit from therapy with these naturally occurring substances; as previously demonstrated in a pilot clinical trial involving HbSS individuals. Considering that omega-3 fatty acids are generally consumed as food across the world, more widely available and affordable, safer and have less side-effects compared to hydroxyurea or blood transfusion, it is appropriate to assess their efficacy in SCD in a large clinical trial.

The Landscape of Thrombophilia in Sickling Disorders: Unfamiliar Terrain.

Sickling disorders have long been suspected of decreasing physiologic thresholds for thrombosis, and the sickling process in tissue of being abetted by elements of the hemostatic system. The landscape of the presumed hypercoagulable state, however, has been ill-defined and differences among sickling disorders with regard to its characteristics, if any, undelineated. Learning how this landscape may reflect the pathophysiology of the sickling process may help guide further study of the interactions among the vasculature and the varieties of abnormal erythrocytes resulting from these hemoglobinopathies and define new opportunities to ameliorate the clinical manifestations of "sickle cell disease."Methods: Using laboratory strategies developed to characterize thrombophilia in non-sickling patients with thrombosis, modified for a largely non-European population, 144 patients with sickling disorders were prospectively evaluated for predisposition to thrombosis. A standard group of hemostatic studies was performed using patient samples obtained during steady-state "non-sickling" conditions, by skilled venepuncturists working consistently with this patient group.Genotypes included: HbSS 96/144 (67%); Hb SC 26/144 (18%;) Hb SSTh; 14/144 (9.5%); Hb S/AThal 8/144 (5.5%). 49/144 (34%) patients (pts) received regular automated erythrocytapheresis for prior stroke, recurrent acute chest syndrome or severe pain episodes > 6/yr.Results: As expected, 2/144 (1.4%) of pts were heterozygous for the Factor V Leiden mutation, 0/144 for the Prothrombin 20210 mutation, and 20/144 (14%) heterozygous, 1/144 (<1%) homozygous for the MTHFR C677T mutation despite homocysteine levels > 12 ng/dL in 38/144 patients (26%). Protein S activity levels were <65% in 83/144 (58%) pts with commensurate free Protein S levels. Total Protein S levels varied widely with no correlation to sickling genotypes, suggesting -as with homocysteine levels -dietary variation. Hb SC genotype was strongly associated with von Willebrand antigen (vWA) levels > 175%, frequently with lesser vWFactor activity (vWF) levels, whereas Hb SSt and SThal more frequently exhibited normal vWA/vWF profiles. Factor VIII activity varied widely, exhibiting no correlation to vWF antigen or activity levels in any of the Hb genotypes. Other thrombophilic conditioners, e.g. antithrombin III activity/Ag, Factor VIII activity, plasmnogen activator inhibitor, and b2-glycoprotein I antibodies were either normal or varied as expected in a " normal," e.g European population, with no correlation to Hb genotype.Conclusions: Thrombophilia in patients with sickling disorders appears to have varied contributors: Hb SC appears most thrombophilic with levels of vWF antigen suggestive of vascular dysfunction and supportive of intravscular platelet adhesion a aggregation. Other genotypes exhibit variable phenotypes, with Hb SThal exhibiting the least thrombogenic phenotype from a aboratory assessment perspective. vWF antigen and Protein S abnormalities emphasize the likely role of inflammation and vascular dysfunction but the dysjunction of vWF and Factor VIII activity hint at greater complexity. Further study of these phenomena and the inclusion of platelet function studies may yield additional insights as to the interaction of sickling erythrocytes, their products and vascular/hemostatic interactions. For now, routine thromboprophylaxis in patients with SC disease appears essential, and likely important in all other genotypes except Hb SThal.

Association between ABO, Rheus blood group systems and haemoglobin genotype among confirmed HIV/AIDS-TB co-infected patients in Enugu urban, Nigeria

The distribution of ABO, Rhesus blood group and haemoglobin (Hb) genotypes was investigated among 320 confirmed human immunodeficiency virus I & II (HIV)/acquired immunodeficiency syndrome (AIDS) with tuberculosis (TB) co-infected patients. One Hundred and Sixty (160) healthy HIV I & II negative age and sex-matched population were used as controls for this study. Patients and controls were from the same environment and their blood groups and Hb genotypes were determined by the standard tube and electrophoresis methods respectively. The statistical analysis of the results revealed statistically significant association (P<0.01) between Hb-genotype among female patients and female controls chi-squared = 6.099, P<0.01, and also between patient and control groups of both sexes chi-squared = 7.4561, p<0.01 only. We conclude that HIV I & II/AIDs with TB co-infection among Nigerians so far studied appear to show no association in the distribution of ABO, Rhesus blood group and Hb-genotype prevalence. Hence they cannot be said to have either protective nor predisposing characteristics.

Hemoglobin F Concentration as a Function of Age in Kuwaiti Sickle Cell Disease Patients

Objective: This study aimed to document the transition of hemoglobin (Hb) F levels from early childhood to adulthood in Kuwaiti sickle cell disease patients, investigating its relationship to sex, Hb genotype and coexistence of α-thalassemia trait. Subjects and Methods: The following parameters were extracted from the patients’ records: age, sex, Hb, mean corpuscular volume, mean corpuscular Hb, red blood cell count, Hb F, Hb S, Hb A₂ and α-globin genotype. Hb quantitation was performed with cation exchange HPLC, while α-globin genotype was determined by PCR. Results: Records were available for 149 patients, made up of 94 SS and 55 Sβ⁰thal; 83 males and 66 females, aged 3 months to 60 years (mean 10.5 ± 1.8). The mean Hb F level in the whole population was 21.5 ± 8.1% and was not significantly different between males and females, and SS or Sβ⁰thal. When the age groups were analyzed, the Hb F level was highest (28.9 ± 10.9%) in those below 5 years. Indeed, patients ≤2 years had a mean level of 31.9 ± 13.0%. There was no significant difference in the Hb F levels in SS patients with or without coexistent α-thal trait. Conclusions: Kuwaiti sickle cell disease patients below 5 years of age have close to 30% Hb F and this is probably a major reason why they usually do not present before this age, unlike patients elsewhere who present within the first year of life.

Cancer Incidence in Sickle Cell Disease. Howard University, 1996–2004.

There are no prospectively collected data on cancer incidence and mortality in patients with sickle cell disease. This information would be a useful baseline for cancer surveillance, particularly in sickle patients exposed to potentially carcinogenic interventions such as hydroxurea administration and stem cell transplantation. A review of cancer cases among 696 adult sickle cell patients (mean age 28.8 y) at Howard University for the years 1986–1995 (2,684 patient-years, pt. yrs.) estimated the cancer incidence and mortality at 1.74 and 1.04 per 1000 pt. yrs, respectively (Am J Hematol 1997; 55:188). These figures were comparable to those reported for adult African American patients of similar age in the SEER database.Because sickle cell patients are now surviving longer, we examined again the cancer incidence and mortality at our institution for the years 1996 – 2004. In determining the patient-years of observation we assumed that if a patient was seen at least once during a given calendar year, the patient had been observed for that whole year. A total of 677 adult sickle cell patients (mean age 35.1 ± 12.5 y) were followed from 1996 through 2004 (2,317 pt.yrs.). There were 54.5 % females and 45.5 % males; the Hb genotype distribution was SS=70.5%, SC=19.2%, S-Thal=9.7%, and other=1%. The table shows the characteristics of 7 sickle cell patients who developed cancer during the study period. Their ages ranged between 38 and 64 years. All but one (Pt. 7) were female and all but one (Pt. 2) had Hb SS. Patients 1 and 3 had been treated with hydroxyurea.Based on these cases, the estimated cancer incidence was 3.02 per 1000 patient years, still below the upper 95% confidence limit in the 1986–1995 estimate (4.3 per 1000 patient years). Two additional cancer patients were seen at our institution, one with prostate cancer and the other with metastatic breast cancer. They were not included in the incidence estimate since they were specifically referred to our institution because of the cancer diagnosis. The current incidence of cancer in adult sickle cell patients at our institution is not increasing appreciably even though they are getting older and some are taking hydroxyurea.PatientAge (y)SexHb typeCancer type143FSSCervical carcinoma in situ238FSCHodkin's disease364FSSUterine carcino-sarcoma443FSSMetastatic adeno-ca., primary unknown557FSSRenal adenocarcinoma648FSSBreast cancer738MSSAnaplastic B-cell lymphoma (HIV)

Effects of hydroxyurea treatment on cerebral oxygenation in adult patients with sickle cell disease: an open-label pilot study

In patients with sickle cell disease (SCD), cerebral oxygen saturation (rSO(2)) has been reported to be below normal and to increase after red blood cell transfusion. This study was designed to determine the effects of long-term and short-term hydroxyurea (HU) treatment on cerebral oxygenation in patients with SCD. This open-label pilot study was conducted at the Department of Anesthesiology and the Center for Sickle Cell Disease, College of Medicine, Howard University, Washington, DC. Adult African American outpatients with SCD and hemoglobin (Hb) genotype HbSS (homozygous sickle Hb) who were receiving long-term (>6 months) HU treatment (15-30 mg/kg . d PO) or who had never received this treatment (control group) were enrolled. Patients in the treated and control groups were matched for age, sex, race, and Hb genotype. Cerebral oximetry (near-infrared spectroscopy) was performed to determine rSO(2) index. In a separate analysis to determine the effects of short-term HU treatment on cerebral oxygenation, hospitalized patients with SCD and vaso-occlusive crisis (VOC)receiving long-term therapy with HU were enrolled. We performed cerebral and pulse (fingernail) oximetry to determine rSO (2)index and arterial oxygen saturation (SpO(2)) after the administration of a single oral dose of HU (500-mg tablet) alone and again after dosing concomitantly with inhaled oxygen. The study enrolled 11 patients in the HU group (6 women, 5 men; mean [SD] age, 37 [8] years) and 20 controls (8 women, 12 men; mean [SD] age, 35 [6] years). Mean (SD) rSO(2) index was significantly increased (but still low) in patients receiving long-term HU treatment compared with controls (46.1% [6.6%] vs 41.2% [7.6%]; P< 0.025). Hb concentration (9.6 [1.4] g/dL vs 8.5 [1.2] g/dL; P< 0.027), hematocrit (28% [3%] vs 24% [4%]; P < 0.028), and mean corpuscular volume (102% [7%] vs 89% [8%]; P < 0.027) also were significantly higher in the HU group compared with controls. In 8 patients with SCD and VOC (6 men, 2 women; mean [SD] age, 28 [5] years), single-dose HU, either alone or in combination with inhaled oxygen, did not significantly affect cerebral oxygenation, and SpO(2) failed to correlate with rSO(2) index in these patients. The results of this open-label pilot study in patients with SCD suggest that the low cerebral oxygenation in these patients is significantly improved but not normalized with long-term HU treatment. A single dose of HU, either alone or in combination with inhaled oxygen, did not appear to influence cerebral oxygenation in patients with VOC.

A new classification of osteomyelitis for developing countries

The term osteomyelitis (OSM) was first coined by Nelaton in 1844. Waldvogel et al, Cierny-Mader, May et al classifications of OSM from developed countries and Meier et al's from Nigeria have been described. This new classification was developed to highlight significant pathology seen in developing countries not covered by existing classifications. A prospective study. University of Ilorin Teaching Hospital, Ilorin, Nigeria. All OSM patients treated from January 1998 to June 2000. Age, sex, clinical features, radiographs and treatment offered were analysed. Five stages were recognised: stage 0 (potential OSM with bone contamination), stage I (early or acute OSM), stage II (intermediate OSM with subperiosteal abscess), stage III (lateorchronic OSM with sequestrum and subdivided into IIIa 'curable', IIIb 'controllable', IIIc 'complicated'). Stage IV (compound OSM) with joint involvement: IVa, if anatomical and IVb if physiological. Patients' haemoglobin (Hb) status is added to the staging, for example stage II (Hb SS). All 271 patients comprising 198 males and 73 females (M: F = 2.7: 1) with age range 2-48 years (mean 29.4 +/- 12.2) were studied. Only 93 patients had Hb genotype done; only 42 had Hb S. The stage O had 184 patients (120 open fractures and 64 bone operations). Stage I had nine patients, stage II 19 patients, stage III 51 patients and stage IV eight. This new staging incorporates pre-emptive OSM seen in developing countries where certain practices, if unchecked lead to OSM. The severity of OSM featuring florid disease not common in the developed world, and for which existing classifications did not accommodate, is included.

Spectrum of Hemoglobinopathies in Orissa, India

Five hundred and 20 cases (279 males; 241 females), referred for anemia, with a wide age range, from different parts of the state of Orissa, India, were investigated to evaluate the extent of the prevalence of hemoglobinopathies (sickle cell disorders and thalassemias) by analyzing the associated hemoglobin (Hb) profiles, Hb genotypes, as well as the clinical and hematological parameters. We found sickle cell trait (Hb AS) in 131 cases (62 males; 69 females), homozygous sickle cell anemia in 49 cases (34 males; 15 females) and Hb S‐β thalassemia (S‐β‐thal) in 17 cases (nine males; eight females). There were also 46 cases (32 males; 14 females) of β‐thal major, 103 cases (51 males; 52 females) of β‐thal trait, six cases (four males; two females) of Hb E trait [β26(B8)Glu→Lys; GAG→AAG], and 17 cases (12 males; five females) of Hb E‐β‐thal (E‐β‐thal). A large proportion of these anomalies were found among the general caste people rather than among the tribal population which constitutes 22% of the total population in this state. Hb E was found mainly in higher castes like Khandayat and Karan, residing in the coastal region of Orissa. This study provides comprehensive data on the spectrum of hemoglobinopathies in this state.

Poor Acceptance Rate for Semen Donors to a Private Cryobank in Nigeria

A retrospective analysis of sixty one prospective donors who visited the cryobank in person from August 1999 to December 2001 was done. The study evaluated the acceptance rate of prospective semen donors and semen characteristics in order to assess the fertility potential of the supposedly normal population of young men. The outcome of the various screening processes--history taking, infection screening, blood grouping and Hb genotype assessment, semen analyses (pre-freeze and post-thaw), and post-quarantine (six months after production of last sample) infection--was analysed. Out of the 61 enquiries, 9 (14.8%) donors were recruited, 7 (77.8%) of whom were less than 25 years old. Fourteen (22.9%) donors had sperm concentrations greater than 60' 10(6) ml, 31 (50.8%) had motility greater than 60% and 17 (27.8%) had normal forms greater than 30%. Six (9.8%) of the donors were unable to masturbate and thus were disqualified, while only one donor (6.1%) failed to show up for a re-test after the completion of the quarantine period. Twenty one (38.2%) donors had low semen values based on the WHO reference value. We conclude that a high proportion of prospective semen donors may have suboptimal semen parameters, and that using strict criteria, poor acceptance rates for donors is observed in a semen donation programme.

Acute Chest Syndrome in Adults With Sickle Cell Disease

Acute chest syndrome (ACS) is a frequent and potentially severe pulmonary illness in sickle cell disease (SCD). The aim of the study was to report the clinical features and outcome of consecutive ACS episodes in adult patients in a French SCD center. All patients were treated according to an uniform therapeutic protocol applying transfusion only in the more severe clinical form of ACS. There were 107 consecutive episodes in 77 adult patients (mean age, 29 +/- 7 years; 78% hemoglobin [Hb] SS; 14% Hb SC; and 8% Hb Sbeta + thalassemia) over a 6-year period. Seventy-eight percent of our patients had an associated vaso-occlusive crisis that preceded the chest signs in half of the cases. Comparison between acute and baseline levels showed a statistically significant difference in Hb levels (drop of 1.6 to 2. 25 g/dL depending on Hb genotype), WBC count (increase of 9.2 +/- 8. 3 x 10(9)/L); platelet count (increase of 67 +/- 209 x 10(9)/L); and lactate dehydrogenase values (increase of 358 +/- 775 IU/L) in ACS patients. Hypercapnia was detected in 42% of patients without sign of narcotic abuse. We identified a high percentage of alveolar macrophages containing fat droplets in 31 of 43 (77%) patients who underwent BAL. Bacterial culture findings were almost always negative, but were performed after starting antibiotic therapy that was administered in 96 episodes. Transfusion was required in 50 of 107 ACS events (47%). Five patients died, and all were transfused. These results confirm that fat embolism is probably a frequent mechanism of ACS in adult patients. However, fat embolism was not associated with a more severe clinical course, suggesting that bronchoscopy and BAL have little impact on the management of these patients. Restricting transfusion to the most severe ACS cases does not seem to increase the mortality rate.

The Frequency and Clinical Significance of Structural Haemoglobin Variants in Donor Blood at University of Maiduguri Teaching Hospital

The Haemoglobin (Hb) genotypes of 1672 healthy blood donors at the university of Maiduguri Teaching hospital (UMTH) during the year 1999 were analysed. Hb AA, AS and SC were detected in 78.94%, 21% and 0.06% of the donor population respectively. There is the need for strict application of Hb electrophoresis on all donor blood in order to detect rare cases of mild forms of sickle cell disease who may present as donors. All blood banks should label their blood units with the appropriate tags to indicate the Hb genotype (Hb AA or Hb AS) status of the donor; and clinicians must indicate on transfusion request forms whenever the use of Hb AA rather than HbAS blood is specifically indicated as may be the case in the management of sickle cell disease patients on exchange transfusion. In this way we can improve the efficacy of transfusion therapy in sickle cell disease and related conditions (Nig J Surg Res 2000; 2:127-130) KEY WORDS: Haemoglobin Electrophoresis, Blood Donor

Prevalence of and risk factors for anemia in young children in southern Cameroon.

Anemia during childhood remains a major public health challenge in sub-Saharan Africa. To determine the prevalence of and the main risk factors for anemia in young children, we conducted a longitudinal survey in Ebolowa in southern Cameroon. Children were enrolled in two cohorts and followed during a three-year period: the first cohort was composed of 122 children from 0 to 36 months of age and the second cohort was composed of 84 children from 24 to 60 months of age. The two cohorts were followed weekly for symptomatic malaria, monthly for both symptomatic and asymptomatic malaria, and every six months for hematologic data; the children were grouped into six-month age groups. The prevalence of anemia (hemoglobin [Hb] level < 11 g/dl) was the highest in the six-month-old age group (47%) and the age-related evolution clearly showed a decrease in the prevalence from three years of age. Thus, 42% of the children less than three years of age were anemic, while 21% of the children between three and five years of age were anemic. The lowest mean +/- SD Hb content (10.7 +/- 2.1 g/dl) was observed in the six-month-old children and a regular improvement in the Hb level occurred from six months to three years of age. A stabilization was observed at a level of approximately 12 g/dl. At any age, there was no difference in mean Hb levels between children with AS and AA Hb genotypes. Hookworm infection was diagnosed in two children in the study population. Results of a multivariate analysis showed that placental malaria infection was the strongest risk factor for anemia in the six-month-old children (odds ratio [OR] = 3.6; 95% confidence interval [CI] = 1.1-12.3) and was independent of the frequency of parasitemia, parasitemia at the time of Hb measurement, or microcytosis. In the one-year-old age group, microcytosis was a significant factor related to anemia (OR = 2.8, 95% CI = 1-7.8) pointing out the role of iron deficiency at this age. Parasitemia at the time of Hb measurement was significantly associated with anemia in all age groups (except in 54- and 60-month-old groups). Strategies to decrease the prevalence of anemia in young children in southern Cameroon should include chemoprophylaxis for pregnant women, prevention of acquired malaria infection in both pregnancy and infancy, and prevention of nutritional iron deficiency.

Genetic specificity of stress-induced anemia in rats.

There is a genetic difference in rat hemoglobin (Hb) beta-chain structure, with alternate alleles, A and B, at a single locus. This study was designed to find out whether marrow sensitivity due to gamma exposure and experimentally induced anemia in age-matched adult rats is entirely strain specific or is a combination of both strain and Hb genotype. Eight strains of inbred and outbred rats comprising AA and BB types were examined. The data indicate that there is a relationship between marrow sensitivity and Hb genotypes in response to erythropoietic stress caused by three techniques.

Fibrinolytic activity in women on oral contraceptive pills: Variation due to haemoglobin genotype

Plasma fibrinogen levels and euglobulin lysis time (ELT) were determined in 84 women with haemoglobin genotype AA (HbAA) and in 38 with haemoglobin genotype AS (HbAS), aged 17–35 years, who were on oral contraceptive pills (OCP). The control group included 23 HbAA and 27 HbAS age-matched, apparently healthy women, who had regular menstruation and no history of OCP usage. The controls showed statistically significant elevations in fibrinogen levels in women with genotype HbAS (+ 13%; P<0.05) compared with women with genotype HbAA. Among OCP users, the difference in fibrinogen levels (+ 5%) between HbAS and HbAA women was not statistically significant. The elevation in fibrinogen levels which was restricted to the HbAA women, was probably caused by OCP use, and may be dependent on the Hb genotype. In contrast, the observed elevations in euglobulin lysis time among OCP users ( P<0.005) were independent of Hb genotype. Thus, while OCP may constitute a risk factor for the development of thromboembolism in women, the S-gene may confer partial protection against this development in women who have the HbAS genotype.

Is there a relationship between haemoglobin genotype and the innate resistance to experimental Haemonchus contortus infection in Merino lambs?

Responses to a single or repeated infection with 7000 infective larvae of Haemonchus contortus were studied in an experiment using a total of 106 3-month-old lambs with AA, AB or BB haemoglobin (Hb) genotypes. Results were assessed by faecal egg counts, adult worm counts, haematocrit values, haemoglobin concentrations, total serum protein and serum antibody IgG 1 and IgA ELISA titres. None of these parameters showed a strong relationship to the Hb type. The prevalence of low responder (>500 worms) and of high responder (<50 worms) animals in groups AA, AB and BB Hb types was 3.8 and 34.6, 20.6 and 35.2, 28.1 and 43.7%, respectively, suggesting that the responsiveness to nematode infection is under the control of gene(s) not closely linked with those determining the Hb genotype. Worm counts of a primary infection are nor subject to variation than those of a secondary infection. There is a strong relationship between adult worm counts and faecal egg counts taken close to the time of slaughter. In living animals low and high responder discrimination can be based on individual faecal egg counts around 50 days after a secondary infection. Haematocrit values proved to be of little value in the low and high responder selection. In this regard neither Hb concentration nor total serum protein values are of practical significance. In 3-month-old lambs primary infection induced partial immunity which could prevent the establishment of a part of the secondary infection, irrespective of the presence or absence of the primary worm population. The development of immunity was not associated with an increase of serum IgG 1 and IgA antibody levels. Specific antibody production was not influenced by Hb types. Mean antibody levels of low responder lambs showed no difference from those of high responders. Thus, serum IgG 1 and IgA levels are of no predictive value in identifying lambs which are genetically resistant to Haemonchus infection.

Increased incidence of hepatitis B markers in children with sickle-cell anemia.

Screening of 143 children 6 months to 12 years of age with sickle-cell anemia showed that 39.2% were HBsAg-positive as compared with 19.3% of the 161 control children of the same age group, who had Hb genotype AA (chi 2 = 14.7383; P less than 0.001). Fifty percent of the HbSS children under the age of 1 year were HBsAg-positive as opposed to 4.3% of the control group (chi 2 = 9.1955; P less than 0.001), while 28.6% of patients were HBsAg-positive at the age of 4 years compared with only 7.4% of the controls at the same age. The incidence of anti-HBc in both groups was similar. Markers of HBV infection (HBsAg + anti-HBc) were, however, on the whole higher in the patients with sickle-cell anemia [88/118 (74.6%)] than in the controls [54/88 (61.3%; P less than 0.005)].

Plasma cortisol in sickle cell disease.

The plasma cortisol levels of 108 children aged 1-16 years with various Hb genotypes (AA, AS and SS) were measured. The mean plasma cortisol levels of both the AS and SS groups (during steady state) fell within the normal range but the mean of the SS group is significantly lower than the AA group. In fact, 9 of the sickle cell children had plasma cortisol levels below the normal range while no child in the HbAS and HbAA groups had plasma cortisol below the normal range. These results indicate that in sickle cell disease, there is low cortisol production while the secretion is increased during painful crisis.