SCA-1 Labels a Subset of Estrogen-Responsive Bipotential Repopulating Cells within the CD24+ CD49fhi Mammary Stem Cell-Enriched Compartment.

Estrogen stimulates breast development during puberty and mammary tumors in adulthood through estrogen receptor-α (ERα). These effects are proposed to occur via ERα+ luminal cells and not the mammary stem cells (MaSCs) that are ERαneg. Since ERα+ luminal cells express stem cell antigen-1 (SCA-1), we sought to determine if SCA-1 could define an ERα+ subset of EpCAM+/CD24+/CD49fhi MaSCs. We show that the MaSC population has a distinct SCA-1+ population that is abundant in pre-pubertal mammary glands. The SCA-1+ MaSCs have less stem cell markers and less in vivo repopulating activity than their SCA-1neg counterparts. However, they express ERα and specifically enter the cell cycle at puberty. Using estrogen-deficient aromatase knockouts (ArKO), we showed that the SCA-1+ MaSC could be directly modulated by estrogen supplementation. Thus, SCA-1 enriches for an ERα+, estrogen-sensitive subpopulation within the CD24+/CD49fhi MaSC population that may be responsible for the hormonal sensitivity of the developing mammary gland.

Risk factors for HTLV-I among heterosexual STD clinic attenders

Human T-cell lymphotropic virus type 1 (HTLV-I) status was assessed in 994 patients attending a sexually transmitted disease (STD) clinic in Kingston, Jamaica, between November 1990 and January 1991 for a new STD complaint. Of 515 heterosexual men, 36 (7.0 percent) were HTLV-I seropositive, as were 38 (7.9 percent) of 479 women. HTLV-I seroprevalence increased with age in women. A history of blood transfusion was associated with HTLV-I in both sexes, significantly so in men [odds ratio (OR) 4.7, confidence interval (CI) 1.1-17 for men; OR 1.9, CI 0.6-5.0 for women]. Further analysis excluded all persons reporting a transfusion. On multiple logistic regression analysis, independent associations with HTLV-I infection in men were shown for marital status (OR 3.5, CI 1.2-10 for married/common law vs. single/visiting unions), agricultural occupation (OR 9.0, CI 2.0-41), bruising during sex (OR 2.9, CI 1.0-8.1), o 15 years at first sexual intercouse (OR 2.9, CI 1.0-8.2), and a positive test for hepatitis B surface antigen (OR 7.3, CI 1.2-52). In women, associations were shown for two or more sex partners in the 4 weeks prior to complaint (OR 4.9, CI 1.8-13), 11 or more lifetime sexual partners (OR 5.9, CI 1.3-27), aged < 15 years at first sexual intercouse (OR 2.3, 1.0-5.4), bruising during sex (OR 2.7, CI 1.1-6.6), microhaemagglutination-Treponema pallidum positivity (OR 3.6, CI 1.6-8.4), human immunodeficiency virus infection (OR 14, CI 2.1-92). STDs and bruising during sex may facilitate sexual transmission of HTLV-I, whereas sexual activity is a more important risk factor in women than men. Programs promoting safer sexual practices and controlling STDs may reduce HTLV-I infection in Jamaica (AU)

Haematological risk factors for pregnancy outcome in Jamaican women with homozygous sickle cell disease

OBJECTIVE; To examine the association between fetal outcome and the steady state haematology of mothers with homozygous sickle cell disease. DESIGN; A retrospective observational study. The data were taken from the dockets, kept at the Sickle Cell Clinic at the University Hospital of the West Indies or two peripheral clinics operated by the staff of the MRC Laboratories. SUBJECTS; All women aged 14 years or older with homozygous sickle cell disease who had experienced at least one pregnancy in the period 1977 to 1986. MAIN OUTCOME MEASURES; Three fetal outcomes including miscarriages, perinatal deaths, and birthweight. RESULTS; There were 270 singleton pregnancies in 175 women with an overall fetal wastage of 32.2 percent. There was a significant increased risk of perinatal death with low maternal fetal haemoglobin level, but there was no haematological associations with miscarriages or birthweight. CONCLUSIONS: These data suggest that maternal steady-state haemoglobin has little influence on fetal outcome, with the exception that mothers with high HbF levels are less prone to perinatal deaths. Further study is required to investigate acute haematological changes associated with pregnancy. (AU)

The painful crisis of homozygous sickle cell disease: clinical features

The details of onset, perceived precipitating factors, associated symptoms, and pain distribution in the painful crisis of homozygous sickle cell (SS) disease have been prospectively recorded in 183 painful crises in 118 patients admitted to a day-care centre in Kingston, Jamaica. Painful crises developed most frequently between 3 p.m. and midnight, most commonly affected patients aged 15-29 years, affected the sexes equally, and were not obviously influenced by menstrual cycle. Of the perceived precipitating factors, skin cooling occurred in 34 percent, emotional stress in 10 percent, physical exertion in 7 percent, and pregnancy in 5 percent of women of child-bearing age. Cold as a precipitant was not less common in patients with more subcutaneous fat. Pain affected the lumbar spine in 49 percent, abdomen in 32 percent, femoral shaft in 30 percent, and knees in 21 percent. There was a highly significant excess of bilateral involvement in limb and rib pain. Recurrent painful crises occurred in 40 patients but showed no evidence of involving similar sites on successive occasions. Abdominal painful crises were associated with abdominal distention in 18 ( 31 percent) and with referred rib pain in a further 15 (26 percent) of crises. Fever was common even in apparently uncomplicated painful crises, suggesting that fever is characteristic of the painful crisis itself after and not necessarily indicative of infection. Following investigation and treatment in a day-care centre, over 90 percent of patients returned home (AU)

Rising HIV-1 prevalence among sexually transmitted disease clinic attenders in Jamaica: traumatic sex and genital ulcers as risk factors

Between November 1990 and January 1991, status of human immunodeficiency virus (HIV) infection was assessed for 522 men and 484 women attending the Comprehensive Health Centre in Kingston, Jamaica, for a new sexually transmitted disease (STD) complaint. Prevalence of HIV type 1 (HIV-1) infection was 3.1 percent (31 of 1,006), a tenfold rise in seroprevalence in 4.5 years. Nineteen of 517 (3.7 percent) heterosexual men, 3 of 5 (60 percent) homosexual/bisexual men, and 9 of 484 (1.9 percent) women were infected with HIV. In heterosexual men, factors associated with HIV infection after age adjustment included present complaints of genital ulcers [odds ratio (OR) 7.3; 95 percent confidence interval (CI) 1.4-72], past history of genital ulcer (OR)4.3; CI, 1.4-12), positive MHATP syphilis serology (OR, 3.4; CI, 1.1-10), sex with a prostitute in the past month (OR, 3.8; CI, 1.1-11). Three or more sex partners in the month prior to the complaint (OR, 3.6; CI, 1.0-12), and bruising during sex (OR, 4.0; CI, 1.4-13). On multiple logistic regression analysis, independent associations with HIV infection were shown for bruising during sex (OR, 3.0; CI, 1.1-8.3), positive MHATP syphilis serology (OR,3.2; CI, 1.1-9.5), and history of genital ulcer (OR 2.9; CI, 1.0-8.0). (AU)

Laser photocoagulation for proliferative retinopathy in sickle haemoglobin C disease

The effect of sectoral, scatter laser photocoagulation on proliferative sickle retinopathy (PSR) was investigated by reviewing florescein angiograms of 88 sickle cell-haemoglobin C patients enrolled in a controlled, randomised trial. Follow-up was for a median period of 2.9 years. Complete infarction of all PSR in an eye occurred in 7 of 74 treated eyes and 2 0f 60 control eyes. Treatment resulted in significantly greater regression (decrease in number and size of PSR lesions) in eyes of patients aged <25 years at enrollment but not in eyes of patients> or = 25 years at enrollment. Infarction of the individual PSR lesions was significantly more common in treated eyes. Treated PSR was significantly more likely to infarct if small (< 15 degrees circumferential involvement) and if flat rather than elevated. New PSR was significantly less likely to develop in treated eyes.

Risk factors in HIV infection in STD clinic attenders in Kingston, Jamaica - abstract

Between November, 1990 and January, 1991, 522 males and 484 females attending the Comprehensive Health Centre in Kingston, Jamaica, for a new STD complaint were assessed for HIV status. Overall prevalence of HIV infection was 3.1 percent (31/1,006). Nineteen of 513 (3.7 percent) heterosexual males, three of five (60 percent) homosexual males and nine of 484 (1.9 percent) females were HIV-infected. On univariate analysis, factors associated with HIV infection in heterosexual males included present complaint of genital ulcer Odds Ratio, (OR) 7.3, CI 1.4,72; past history of genital ulcer OR 4.3, CI 1.4, 12.2, positive MHATP OR 3.4, CI 1.1, 10.1; sex with a prostitute in the past four weeks OR 3.8, CI 1.1, 11.2; three or more sex partners in the four weeks prior to complaint OR 3.6, CI 1.0, 12.0; and bruising during sex OR 4.0, CI 1.4, 13.0, (all OR adjusted for age). On multivariate analysis, independent effects of association for HIV infection in heterosexual males were shown for bruising during sex OR 3.1, CI 1.1, 8.9; positive MHATP OR 3.4, CI 1.1, 10.3, and history of genital ulcer OR 2.6, CI 0.9, 7.4. Among females, there was an association between the following variables and HIV infection: history of "bad blood" (syphilis) OR 6.6, CI 1.4, 30.3, gonorrhoea (culture positive) OR 12.2, CI 2.1, 72, HTLV-I seropositivity OR 6.2, CI 0.9, 32, perception of risk of AIDS (test for trend p = 0.01), history of stillbirth OR 7.6, CI 1.3, 43 and abnormality of the cervix OR 15.3, p = 0.008 (these associations must be interpreted with caution in view of the small number of HIV-infected females). The eight-fold rise in HIV prevalence among STD attenders in 4« years indicates that there are no grounds for complacency concerning the HIV epidemic in Jamaica(AU)

Stroke in a cohort of patients with homozygous sickle cell disease

Strokes occurred in 17 of 310 children with homozygous sickle cell disease who were followed from birth, representing an incidence of 7.8 percent by the age of 14 years. Two children had subarachnoid hemorrhage, one having resolution of symptoms after aneurysm surgery and another dying of a presumed second hemorrhage 14 days later. The remaining 15 strokes were presumed to be cerebral infarction, although autopsy, angiographic, or computed tomographic evidence was available in only 8 children. There were 6 deaths, 2 in the acute events and 4 after recurrence, which occurred in 6 (46 percent) of 13 patients who survived the initial episode. There were 10 recurrent episodes at a median interval of 9 months after the initial event. Steady-state hematologic data revealed significantly higher leukocyte counts than in control subjects without strokes at age 1 year and in the last study preceding the stroke. The initial stroke coincided with an acutely lowered hemoglobin value in 5 patients (3 aplastic crises, 1 acute splenic sequestration, 1 probable pulmonary sequestration) and with painful crises in another 7 patients. We conclude that a high leukocyte count and an acute decrease of hemoglobin are risk factors for stroke in patients with homozygous sickle cell disease.(AU)

Two different forms of homozygous sickle-cell disease - abstract

Haematological, clinical and some molecular genetic features have been compared in two groups of patients with homozygous sickle-cell (SS) disease in Saudi Arabia, 33 patients from the Eastern Province (eastern) and 30 from the South Western Province (Western). Eastern patients all had the Asian haplotype of DNA polymorphisms within the beta globin gene cluster whereas Western patients were more variable but predominantly of the Benin haplotype. Eastern patients had significantly more deletional alpha thalassaemia, higher levels of total haemoglobin and foetal haemoglobin, and lower of HBA, mean volume reticulocytes, and platelets. Clinically, Eastern patients had a greater persistence of splenomegaly, less dactylitis, less acute chest syndrome, a more normal body build and greater subscapular skin fold thickness. Painful crises occurred with equal frequency in both groups. Avascular necrosis of the femoral head was common in both groups. The disease in the Eastern province has many mild features consistent with the higher HbF levels and more frequent alpha thalassaemia but bone pathology (painful crises, avascular necrosis of the femoral head, osteomyelitis) remains common. The disease in the West is more severe, consistent with the Benin haplotype suggesting an African origin (AU)

The haematology of homozygous sickle-cell disease - abstract

The purpose of the study was to investigate age- and sex-related variations in the haematology of older patients with SS disease, in order to determine haematological characteristics possibly favouring survival. Steady state haematology was available in 181 patients aged 40-73 years. There appeared to be no consistent sex differences in any of the indices examined. Longitudinal analyses were performed for the 133 patients with at least two observations, using analysis of covariance (ANCOVA) methods. Highly significant declines in total haemoglobin (Hb), platelet counts and absolute reticulocyte count were displayed in both sexes. Overall, Hb levels decreased by approximately 0.076 gm/dl/year in females and 0.113 gm/dl/year in males. Significant increases occurred in HbA, HbF and MCV in females only. The total nucleated count (NBC) fell with age, although the decline was only significant in females. These observations are consistent with a progressive bone marrow failure which is not explained by the commonly occurring renal impairment in older SS patients since the changes persisted in analyses confined to the 84 patients with normal creatinine levels (C=120 æmol/l). The mechanism for this bone marrow failure is currently unknown. The prevalence of homozygous alpha thalassaemia in the study group (4.4 percent) was similar to that in the overall SS population, providing no evidence that this may lead to improved survival, as has been suggested (AU)

Stroke in a cohort study of patients with homozygous sickle-cell disease - abstract

The features of 16 strokes occurring in a cohort of 310 children with homozygous sickle-cell (SS) disease followed from birth have been reviewed. The incidence was 6.9 percent by the age of 14 years. Recurrences occurred in 7/15 (47 percent) subjects surviving the first attack. Of the 14 recurrences 13 were within two years of the initial episode and the median interval was 9 months. Six children died, one during the initial episode and 5 during recurrences. The pathological basis was subarachnoid haemorrhage in 2, infarction in 7 and unknown in 7. The stroke group had significantly lower red cell counts and higher total nucleated counts in their preceding steady state haematology. The stroke was associated with an acute lowering of haemoglobin level in 5 patients (3 aplastic crises, 1 acute splenic sequestration, 1 unexplained), and with painful crises in 5 patients. These observations are the first in a representative sample of patients followed from birth and indicate a lower incidence of initial stroke and of recurrence than presented in other reports. The association with acute anaemia and with painful crisis has not been previously recognised, and suggests new directions for research in this complication (AU)

Prophylactic penicillin in young chidlren with homozygous sickle-cell diseases: lack of effect on manifestations other than pneumococcal septicaemia - abstract

This study investigates the effects of prophylactic penicillin in young children with homozygous sickle-cell (SS) disease, on clinical manifestations other than the known effect of preventing pneumococcal septicaemia. Thirty-nine patients received monthly injections of intramuscular penicillin for the 30-month period between age 6 and 36 months (treatment group) and 36 SS patients were followed without penicillin prophylaxis (control group). The features investigated included common manifestations before the age of 3 years such as haematological abnormalities, dactylitis, acute chest syndrome, acute splenic sequestration, and growth delay. No significant differences were found between the two groups in haematology, the incidence of dactylitis, acute chest syndrome, or acute sequestration during the study period, or in attained weight and height at age 3 years or at 8 years. Prophylactic penicillin given as monthly IM injections has no beneficial effect for children under 3 years with homozygous sickle-cell disease, other than the known effect of preventing pneumococcal sepsis (AU)

The red cell distribution width in sickle cell disease: is it of clinical value?

The red cell distribution width (RDW) has been studied during the clinical steady state in 1121 patients with homozygous sickle cell (SS) disease, 344 with sickle cell-haemoglobin C (SC) disease, 68 with sickle cell-beta+ thalassaemia, 49 with cell beta§ thalassaemia and in 130 control subjects with a normal (AA) genotype. The mean RDW was moderately increased in Sbeta+ thalassaemia and SC disease and markedly increased in Sbeta§ thalassaemia and SS disease. In SS, SC and Sbeta§ thalassaemia genotypes, lower RDW values occurred in females and with alpha thalassaemia. The RDW correlated negatively with total haemoglobin, mean cell haemoglobin concentration, mean cell volume and fetal haemoglobin (HbF) and positively with reticulocyte count in SS disease. A low RDW was associated with higher weight and less frequent dactylitis, painful crisis, acute chest syndrome, acute splenic sequestration and hospital admissions. A low RDW in SS disease is consistent with a high total haemoglobin, high HbF, low reticulocyte count, alpha thalassaemia and a more mild clinical course. (AU)

Comparison of homozygous sickle cell disease in Northern Greece

The clinical and hematological features of homozygous sickle cell (SS) disease were compared in 30 Greek and 310 Jamaican patients. Deletional O-thallassaemia, which modifies SS disease, is rare among Greek patients, so only Jamaican patients with four O-globin genes were included in the control group. Greek patients had higher total haemoglobin concentration and red cell counts, and lower mean cell haemoglobin concentration (MCHC) and reticulocyte counts. They also had a more normal body build and more adults had persistent splenomegaly. Fewer had a history of leg ulceration or priapism but more reported acute chest syndrome. The comparitively mild disease in Greek patients is consistent with less haemolysis and sickling and therefore less bone marrow expansion. In the absence of amelioriating factors such as high HbF concentration or O-thalassaemia, these findings may be explained by the low MCHC. (AU)

Nocturnal enuresis in sickle cell haemoglobinopathies

The prevalence of nocturnal enuresis (wet at least two nights a week) was investigated in children, aged 8, who were being followed up as part of a prospective cohort study. There were 175 children with homozygous sickle cell disease, 106 with sickle cell haemoglobin C disease, and 150 controls with a normal haemoglobin genotype. In homozygous sickle cell disease, 48 boys (52 percent) and 31 girls (38 percent) were enuretic, a significantly higher prevalence than in those with sickle cell haemoglobin C disease - five boys (10 percent) and 11 girls (20 percent) - or in normal children - 16 boys (22 percent) and 13 girls (17 percent). There was no significant difference between children with sickle cell haemoglobin C disease and the normal genotype. Boys with homozygous sickle cell disease were significantly more likely to be enuretic if they came from large families; there was a similar trend for girls with homozygous sickle cell disease, although it did not reach significance. Enuresis was more common in boys with homozygous sickle cell disease who had low concentrations of fetal haemoglobin and in girls with sickle cell haemoglobin C disease who had high mean corpuscular haemoglobin concentrations. Similar associations were not shown for girls with homozygous sickle cell disease or boys with sickle cell haemoglobin C disease. (AU)

Risk factors for proliferative sickle retinopathy

The prevalence, incidence, and risk factors associated with proliferative sickle retinopathy (PSR) were investigated in 786 patients with homozygous sickle cell (SS) disease and 533 patients with sickle cell hemo globin C (SC) disease. PSR was more common in SC disease, in which there was a significant predominance of males, and it increased with age in both genotypes. In SC disease the risk of developing PSR was highest between 15 and 24 years in males, between 20 and 39 years in females, and in SS disease between 25 and 39 years in both sexes. PSR tended to be bilateral, especially in SC disease. There was no evidence of familial clustering of PSR in SC siblings, and insufficient numbers of SS siblings were available to test for clustering. Haematological risk factors associated with PSR in SS disease were a high haemoglobin in males and a low fetal haemoglobin in both sexes and in SC disease, a high mean cell volume, and a low fetal haemoglobinin females. (AU)