A quality assurance programme for cell salvage in cardiac surgery.

At the same time as cell salvage was introduced into our institution for all patients undergoing cardiac surgery with cardiopulmonary bypass, we established a supporting programme of quality assurance to reassure clinicians regarding safety and efficacy. Data collected in patients operated on between 2001 and 2007 included pre- and post-wash heparin concentration, haemoglobin concentration and free haemoglobin concentration. Cell salvage was used in 6826 out of a total of 7243 patients (94%). Post-wash heparin concentration was consistently low (always < 0.4 IU.ml(-1)). There was a significant decrease in post-wash haemoglobin concentration in 2003 compared to 2001, from a median (IQR [range]) of 19.6 (16.7-22.2 [12.9-25.5]) g.dl(-1) to 17.5 (13.6-20.8 [12.6-23.7]) g.dl(-1) (p < 0.015). In addition, there was a significant increase in free plasma haemoglobin in 2006 compared to 2001, from 0.5 (0.3-0.8 [0.1-2.6]) g.l(-1) to 0.8 (0.3-1.4 [0.3-5.2]) g.l(-1) (p < 0.001). This programme led to the detection of a change in operator behaviour in 2003 and progressive machine deterioration resulting in appropriate fleet replacement in 2006. You can respond to this article at http://www.anaesthesiacorrespondence.com.

Should we abandon the APTT for monitoring unfractionated heparin?

INTRODUCTION: The activated partial thromboplastin time (APTT) is commonly used to monitor unfractionated heparin (UFH) but may not accurately measure the amount of heparin present. The anti-Xa assay is less susceptible to confounding factors and may be a better assay for this purpose. MATERIALS AND METHODS: The validity of the APTT for monitoring UFH was assessed by comparing with an anti-Xa assay on 3543 samples from 475 patients (infants [n=165], children 1-15years [n=60] and adults [n=250]) receiving treatment dose UFH. RESULTS: Overall concordance was poor. The highest concordance (66%; 168/254) was seen in children. Concordance (51.8%) or discordance (48.4%) was almost equal in adult patients. Among adult patients whose anti-Xa level was within 0.3-0.7IU/mL, only 38% had an APTT in the therapeutic range whilst 56% were below and 6% were above therapeutic range. Children and adult patients with anti-Xa of 0.3-0.7IU/mL but sub- therapeutic APTT had significantly higher fibrinogen levels compared to those with therapeutic or supra-therapeutic APTT. CONCLUSIONS: When the anti-Xa level was 0.3-0.7IU/mL, the majority of samples from infants demonstrated a supra-therapeutic APTT, whilst adults tended to have a sub-therapeutic APTT. This may lead to under anticoagulation in infants or over anticoagulation in adults with risk of bleeding if APTT is used to monitor UFH. These results further strengthen existing evidence of the limitation of APTT in monitoring UFH. Discordance of APTT and anti-Xa level in adults and children may be due to elevation of fibrinogen level.

Pilot trial of a pentavalent pneumococcal polysaccharide/protein conjugate vaccine in Gambian infants.

BACKGROUND: Invasive pneumococcal disease is a major cause of mortality and morbidity in young children in developing countries. Pneumococcal polysaccharide/protein conjugate vaccines, which are likely to be immunogenic in the very young, offer a potential way for preventing these infections. Therefore a pilot safety and immunogenicity study of a five-valent conjugate vaccine has been undertaken in an area of rural Africa where invasive pneumococcal disease is prevalent. METHODS: Thirty Gambian infants were vaccinated with 3 doses of a five-valent pneumococcal conjugate vaccine containing 5 micrograms of type 6B, 14, 18, 19F and 23F polysaccharides conjugated to the diphtheria toxin mutant protein CRM197 at the ages of 2, 3 and 4 months; 30 infants received 2 doses at the ages of 2 and 4 months and 30 infants who received three doses of a Haemophilus influenzae type b vaccine acted as controls. Local and systemic reactions were recorded after vaccination and antibody titers were measured by an enzyme-linked immunosorbent assay. RESULTS: No serious local or systemic reactions to vaccination were recorded. Antibody responses to each component of the vaccine were demonstrated. One month after immunization with three doses of vaccine, antibody titers were 3 to 11 times higher than before vaccination (postvaccination titers ranged from 2.49 micrograms/ml for type 19 polysaccharide to 7.59 micrograms/ml for type 14). Elevated titers were well-maintained during the subsequent 4 months. Three doses of vaccine induced higher titers than did two doses. Antibody titers increased 2- to 3-fold over the period of immunization in children who received H. influenzae type b vaccine. CONCLUSIONS: A five-valent pneumococcal conjugate vaccine proved safe and immunogenic in Gambian infants. However, a vaccine containing a larger number of serotypes will be necessary to achieve a maximal clinical impact.

Predictors for a positive blood culture in African children with pneumonia.

BACKGROUND: Blood culture isolation rates for children with pneumonia are generally low. Therefore it would be helpful if epidemiologic studies could identify children who have a higher than average chance of yielding a positive culture. METHODS: Simple clinical and laboratory predictors of a positive blood culture were investigated in 1222 children younger than 5 years of age with pneumonia who presented at rural dispensaries in The Gambia, West Africa. RESULTS: A high temperature (chi square for linear trend, 24.1; P < 0.0001), a rapid respiratory rate (chi square for linear trend, 6.33; P = 0.010), dehydration (odds ratio, 2.33; P < 0.001), nasal flaring (odds ratio, 2.06; P = 0.001), grunting (odds ratio, 4.01; P < 0.001), dullness to percussion (odds ratio, 2.31; P < 0.001), bronchial breathing (odds ratio, 2.61; P < 0.001) and diminished breath sounds (odds ratio, 2.07; P < 0.001) were positive predictors for a positive blood culture. Wheezing (odds ratio, 0.16; P < 0.001) and malaria parasitemia (odds ratio, 0.26; P = 0.008) were negative predictors. A combination of these findings were used to assess how the number of cultures taken might be reduced without substantially reducing the yield of positive cultures. For example it was found that exclusion of children with a temperature of < 38.0 degrees C and/or a respiratory rate of < 50/min and/or wheezing would have reduced the number of cultures taken by 55.6% but would have led to a loss of only 31.3% of positive cultures. CONCLUSION: Careful selection of children investigated by blood culture could help to reduce the work required during the preparations for and conduct of pneumococcal vaccine trials.

Safety and immunogenicity of a nonavalent pneumococcal vaccine conjugated to CRM197 administered simultaneously but in a separate syringe with diphtheria, tetanus and pertussis vaccines in Gambian infants.

BACKGROUND: Unrelenting high morbidity and mortality have mandated that immunogenic vaccines be used to combat pneumococcal disease in infants. OBJECTIVES: To evaluate the safety and immunogenicity of a nonavalent pneumococcal conjugate vaccine and the antigenic interaction when administered simultaneously with diphtheria, tetanus and pertussis vaccines. METHODS: Two hundred seven infants were randomized to receive three doses of either nonavalent protein conjugate pneumococcal vaccine (PnCV) or inactivated polio vaccine (IPV) at 2, 3 and 4 months of age with routine Expanded Program of Immunization vaccines as scheduled. Vaccinees were visited on Days 1, 2 and 7 to observe local and systemic adverse reactions. Blood was drawn before the first dose and 1 month after the third dose. Antibody concentrations in sera were measured by standardized enzyme-linked immunosorbent assay. Nasopharyngeal carriage of pneumococci was tested at 5 and 9 months of age. RESULTS: No serious reactions were observed. Local induration and tenderness were observed more commonly at the site of administration of diphtheria, tetanus and pertussis vaccines than at the site of administration of IPV or PnCV. Between 79 and 91% achieved >1 microg/ml antibody against specific pneumococcal serotypes. Antibody responses to diphtheria and pertussis antigens were similar in both groups; however, antibody response to tetanus toxoid was significantly lower in infants who received PnCV (geometric mean concentration, 11.1 vs. 17.4; P < 0.001). Nasopharyngeal carriage in PnCV-vaccinated children was reduced but not significantly different from those vaccinated with IPV. CONCLUSION: Simultaneous administration of PnCV with Expanded Program of Immunization vaccines is safe and immunogenic. immune response to the composite antigens is likely to confer protection.

Nasopharyngeal carriage of pneumococci in Gambian children and in their families.

BACKGROUND: Nasopharyngeal carriage of pneumococci is prevalent among children in developing countries but little is known about the relationship of nasopharyngeal carriage to invasive disease or about the way in which pneumococci spread within households. OBJECTIVES: To determine the prevalence of nasopharyngeal carriage in healthy and sick Gambian children and to investigate transmission within households. METHODS: Nasopharyngeal swabs were obtained by the per nasal route and cultured for pneumococci on selective media. Pneumococci were serotyped with the use of latex particles coated with type-specific antisera. RESULTS: Pneumococci were isolated from the nasopharynx of 73 (90.1%) of 81 children with invasive pneumococcal disease, 86 (76.1%) of 113 healthy, age-matched control children and 911 (85.1%) of 1071 sick children. Pneumococci belonging to serotypes 1, 14 and 12 were isolated significantly more frequently from cases than from matched controls. In 43 (76.8%) of 56 children with invasive disease, pneumococci isolated from the nasopharynx and from the blood or other sterile site belonged to the same serotype. Pneumococci of the same serotype as the bacterium responsible for invasive disease in a child were obtained from 72 (8.5%) of 843 family members, most frequently from young siblings of the case patients. CONCLUSION: Nasopharyngeal carriage of pneumococci is more prevalent among young Gambian children than among adults and invasive infections are probably acquired more frequently from siblings than from parents. However, further studies are needed to confirm this hypothesis with more discriminating markers than polysaccharide serotyping.

A glycoprotein pneumococcal conjugate vaccine primes for antibody responses to a pneumococcal polysaccharide vaccine in Gambian children.

BACKGROUND: Streptococcus pneumoniae is a major cause of acute respiratory infections and acute bacterial meningitis in children. Pneumococcal polysaccharide vaccines are poorly immunogenic in this highly vulnerable group, but protein polysaccharide conjugate vaccines are likely to be more effective. OBJECTIVES: To determine whether immunization of infants with a pneumococcal conjugate vaccine induces immunologic memory. METHODS: Eighty-four Gambian children, who had been vaccinated previously with two or three doses of a pentavalent pneumococcal conjugate vaccine (CRM197) or with a Haemophilus influenzae type b (Hib) conjugate vaccine were immunized when approximately 2 years old with a 23-valent pneumococcal polysaccharide vaccine, and a blood sample was obtained 10 days later. Pneumococcal antibody titers in prevaccination and postvaccination sera were measured by enzyme-linked immunosorbent assay and by an opsonophagocytic assay. RESULTS: On revaccination with a pneumococcal polysaccharide vaccine, children who had previously received pneumococcal conjugate vaccine had higher antibody concentrations to each of the five polysaccharide components of the conjugate vaccine than did control children. For type 6B polysaccharide, which is poorly immunogenic in young children, postvaccination antibody concentrations were 0.37, 27.6 and 50.9 microg/ml in children who had received no previous pneumococcal immunization or two or three doses of conjugate vaccine, respectively. Type 14 antibodies produced after revaccination were of high avidity and had opsonic activity. CONCLUSION: Vaccination of young infants with two or three doses of a pneumococcal conjugate vaccine primes the immune system to respond strongly and rapidly on subsequent exposure to pneumococcal polysaccharide.

Management of severe malarial anaemia in Gambian children.

The optimum management of children with severe malarial anaemia is still uncertain. Hence, we have undertaken a study to determine whether iron treatment is as effective at restoring haemoglobin levels one month after presentation as blood transfusion without iron treatment in children with moderately severe malarial anaemia. Two hundred and eighty-seven children with a packed cell volume (PCV) < 15% and malaria infection were recruited into the study; 173 children were assigned to receive blood transfusion because they had a PCV < 12% and/or signs of respiratory distress and the remaining 114 children were allocated at random to receive either blood transfusion (58) or treatment with oral iron (56) for 28 d. Twenty-four children died, 23 in the most severely anaemic group. Fifteen children (65%) died before transfusion was given and most deaths occurred within the first 4 h of admission. One child died in the iron treatment group and 10 subsequently required transfusion. Among the severely anaemic children, those with respiratory distress were at greater risk of death than those without respiratory distress. After 28 d, haematological restoration was significantly better in children who had received iron than in those treated by blood transfusion (P = 0.02). Children who received malaria chemoprophylaxis after discharge from hospital had fewer episodes of malaria and subsequent admissions to a hospital or health centre than those who did not. Children with severe anaemia and clinical signs of respiratory distress must be identified quickly and transfused as soon as possible. However, for less severely anaemic children who are clinically stable, iron therapy offers an alternative to transfusion provided such children can be kept under surveillance and transfused subsequently should this become necessary.

Geographical variation in prevalence of hypertension within The Gambia.

Hypertension has become an important public health problem for sub-Sahara Africa. In a previous nationwide study, we observed a high degree of geographical variation in the prevalence of diastolic hypertension. Geographical variation provides essential background information for the development of community randomised trials could suggest aetiological mechanisms, inform control strategies and prompt further research questions. We designed a follow-up study from the nine high-prevalence communities, and from 18 communities where hypertension was found least prevalent (controls). In each community, 50 households were randomly selected. In each household, an (unrelated) man and woman were enrolled. The risk for hypertension (blood pressure > or =160/95 mm Hg) was higher in the high prevalence communities compared to the control villages (adjusted OR = 1.7, 95% CI 1.3-2.2). The observed coefficient of variation in hypertension prevalence, k, was 0.30. Thus we confirmed significant geographical variation in prevalence of hypertension over time, which has implications for planning of interventions.

Blood pressure patterns and cardiovascular risk factors in rural and urban gambian communities.

Hypertension is emerging as an important public health problem in sub-Saharan Africa. We studied blood pressure (BP) patterns, hypertension and other cardiovascular risk factors in a rural and an urban area of The Gambia. A total of 5389 adults (> or =15 years) were selected by cluster sampling in the capital Banjul and a rural area around Farafenni. A questionnaire was completed, BP, pulse rate, height and weight were recorded. Glucose was measured 2 h after a 75 g glucose load among participants > or =35 years (n = 2301); total cholesterol, triglycerides, creatinine and uric acid were measured among a stratified subsample (n = 1075). A total of 7.1% of the study participants had a BP > or =160/95 mm Hg; 18.4% of them had a BP > or =140/90 mm Hg. BP was significantly higher in the urban area. BP increased with age in both sexes in both areas. Increasing age was the major independent risk factor for hypertension. Related cardiovascular risk factors (obesity, diabetes and hyperlipidaemia) were significantly more prevalent in the urban area and among hypertensives; 17% of measured hypertensives were aware of this, 73% of people who reported to have been diagnosed as hypertensive before had discontinued treatment; 56% of those who reported being on treatment were normotensive. We conclude that hypertension is no longer rare in either urban or rural Gambians. In the urban site hypertension and related cardiovascular risk factors were more prevalent. Compliance with treatment was low. Interventions aimed at modifying risk factors at the population level, and at improving control of diagnosed hypertension are essential to prevent future increases of cardiovascular morbidity and mortality. In view of limited resources and feasibility of intervention in rural Gambia, these could initially be directed towards urbanised populations.

Meningococcal antibody titres in infants of women immunised with meningococcal polysaccharide vaccine during pregnancy.

Seventy five Gambian women were immunised with a single dose of a group A+group C meningococcal polysaccharide vaccine during the last trimester of pregnancy. IgG antibody titres were measured in mothers and in their infants by an enzyme-linked immunosorbent assay (ELISA). All women had a good response to vaccination and maternal antibodies were high at the time of delivery (23.2 micrograms/ml for group A antibodies and 14.3 micrograms/ml for group C antibodies). However, only a proportion of this antibody crossed the placenta; cord blood:maternal antibody ratios were 30% for group A antibody and 44% for group C antibody, respectively. Considerable variability in cord blood:maternal blood ratios was seen between individuals. This could not be related to age, parity, or ethnic group. Mean group A and group C cord blood:maternal blood ratios were lower in women with serological evidence of syphilis than in seronegative women, and diminished transfer of group A antibody was noted in women with active malarial infection of the placenta. Antibody titres declined rapidly in infants and by the age of 3-4 months these had reached control values. Maternal immunisation may give infants some protection against group A and group C meningococcal disease but only during the first few months of life.

Influence of placental malaria infection and maternal hypergammaglobulinaemia on materno-foetal transfer of measles and tetanus antibodies in a rural west African population.

Placental malaria infection jeopardizes pregnancy outcome, and its influence may also impair the transplacental transfer of some antibodies. Two hundred and thirteen Gambian mother-baby pairs were studied to determine the influence of placental malaria infection and maternal hypergammaglobulinaemia on transplacental transfer of measles and tetanus antibodies in Gambian population. Placental blood and tissue were collected for placental malaria diagnosis. Cord and maternal sera were tested for total IgG concentration by laser nephelometry and for IgG antibody to tetanus toxoid and measles by ELISA. The prevalence of placental malaria infection was 51.1%. Mothers whose placentae were parasitized had a significantly higher mean total serum IgG (22.0 g/L vs 11.3 g/L, p < 0.001) and measles antibody level (4.02 IU/mL vs 1.21 IU/mL, p < 0.01), but not tetanus antibody, than mothers with non-parasitized placentae. Results of multiple regression analysis showed that placental malaria infection and maternal hypergammaglobulinaemia were associated with the reduction of 72% (95% CI 67.84) and 86% (95% CI 76.91) in transplacental transfer of measles antibody respectively but did not influence the transfer of tetanus antibody. It is concluded that the combined influence of placental malaria infection and maternal hypergammaglobulinaemia is significantly associated with the transfer of impaired measles antibody in this population.

Genetic linkage of mild malaria to the major histocompatibility complex in Gambian children: study of affected sibling pairs.

PIP: Case-control studies have indicated that genes for the major histocompatibility complex influence the presentation and outcome of severe Plasmodium falciparum disease. To assess the role of genetic factors in mild malaria, an analysis was conducted in 217 pairs of Gambian twins (mean age, 5.3 years) concordant for this phenotype. The twins were monitored weekly during three rainy seasons (1991-93) for fever and P. falciparum infection. This surveillance produced a total of 40 pairs of twins who were concordant for clinical malaria; none had severe disease. In the 22 of these 40 families with complete information, 11 had two shared alleles (expected value, 5.5), 10 shared one allele (expected value, 11.0), and 1 shared no allele (expected value, 5.5). If a locus is genetically linked to disease, affected siblings will share a higher than expected number of alleles identical by descent at that locus. Sharing of major histocompatibility complex alleles was not increased among the 13 pairs of dizygous twins who were discordant for malaria. These findings confirm the importance of genetic factors to the risk of uncomplicated malaria.^ieng

Comparison between thromboelastography and conventional coagulation tests after cardiopulmonary bypass surgery in the paediatric intensive care unit.

INTRODUCTION: Following paediatric cardiac surgery using cardiopulmonary bypass (CPB), there is a risk of significant postoperative bleeding. A number of risk factors are associated with postoperative bleeding including; age, complexity of the surgery, dilution and consumption of clotting factors. We conducted a prospective audit comparing different coagulation tests used following paediatric CPB to determine whether thromboelastography (TEG) on the intensive care unit or routine laboratory coagulation assays including fibrinogen are better at assessing bleeding and bleeding risk. METHODS: Tests on arrival in paediatric intensive care unit (PICU) included the following: fibrinogen, prothrombin time, activated partial thromboplastin time, full blood count and TEG. Bleeding was measured in the first 1-4 h via chest drain loss. Bleeding was considered significant if ≥5 ml/kg/h. RESULTS: Of 107 patients admitted to PICU, 23/107 were considered to be bleeding during the first hour. Fibrinogen concentration had the best correlation with the amount of first-hour blood loss (r(s) = 0.52), followed by APTT (r(s) = 0.44) and TEG MA (r(s) = 0.34). TEG parameter TEG MA correlated with platelet count (r(s) = 0.68) and fibrinogen (r(s) = 0.66). CONCLUSIONS: Thromboelastography did not show better correlation with postoperative bleeding than conventional clotting tests. TEG parameter maximum amplitude correlates with platelet count and fibrinogen.

Lipid-laden bronchoalveolar macrophages in asthma and chronic cough.

BACKGROUND: The presence of lipids in alveolar macrophages (AMs) may impair their phagocytic response, and determine airway inflammation and obstruction. OBJECTIVE: To determine the factors such as severity of asthma, chronic cough, airway inflammation and obesity that may influence the presence of lipids in lung macrophages. METHODS: Bronchoalveolar lavage fluid (BALF) was obtained from 38 asthmatics (21 severe and 17 mild/moderate), 16 subjects with chronic cough and 11 healthy control subjects. The presence of lipids in macrophages was detected using an Oil-red-O stain and an index of lipid-laden macrophages (LLMI) was obtained. RESULTS: LLMI scores were higher in healthy subjects (median 48 [IQR 10-61]) and the severe asthma group (37 [11.5-61]) compared to mild/moderate asthmatics (7 [0.5-37]; p < 0.05 each). Subjects reporting a history of gastro-oesophageal reflux disease (GORD) had higher LLMI values (41.5 [11.3-138] versus 13 [0-39.3], p = 0.02). There was no significant correlation between LLMI and chronic cough, BAL cell differential counts, FEV1, FEV1/FVC or body mass index (BMI). CONCLUSIONS: The reduced LLMI in mild/moderate asthma may be related to lower incidence of GORD. However, this was not related to the degree of airflow obstruction, obesity or airway inflammation.

A retrospective analysis of the impact of azithromycin maintenance therapy on adults attending a UK cystic fibrosis clinic.

BACKGROUND: Azithromycin is widely used as an immunomodulatory agent in the treatment of cystic fibrosis with previous literature documenting improvements in lung function and a reduction in infective exacerbations. The maximal study period in adults has been six months. METHODS: 81 adult patients taking continuous azithromycin were retrospectively identified. Percentage predicted FEV(1) and courses of intravenous antibiotics were examined at yearly intervals two years prior to and two years after azithromycin initiation. RESULTS: FEV(1) deteriorated in the two years before starting azithromycin by a mean of 2.02% per year. In the year following initiation, FEV(1) increased by 1.15% (P=0.01). However, a mean 2.58% reduction was observed in year two. There was no statistically significant effect on courses of intravenous antibiotics. CONCLUSIONS: Azithromycin resulted in an improved FEV(1) at year one. This effect was not sustained beyond the first year of treatment.

Blood pressure control in the Hypertension in the Very Elderly Trial (HYVET).

To report blood pressure control in the Hypertension in the Very Elderly Trial, a placebo-controlled trial of hypertensive (systolic blood pressure (SBP) 160-199 mm Hg, diastolic blood pressure (DBP) <110 mm Hg) participants over the age of 80 years, given treatment in three steps: indapamide slow release 1.5 mg alone, indapamide plus 2 mg perindopril and indapamide plus 4 mg perindopril. The difference in control between participants with combined systolic and diastolic hypertension (SDH, DBP90 mm Hg) and those with isolated systolic hypertension (ISH, DBP<90 mm Hg) is determined together with the effects of increments in the treatment regimen. At 2 years, the active treatment lowered blood pressure by 16.5/6.9 mm Hg more than that on placebo in participants with SDH and by 19.3/4.8 mm Hg more in those with ISH. The 2-year falls in pressure on placebo alone were 13.2/8.5 mm Hg in SDH and 8.2/1.5 mm Hg in ISH participants. With full titration of active treatment, 62% of SDH participants achieved goal SBP (<150 mm Hg) by 2 years and 71% of those with ISH. The corresponding results for DBP control (<80 mm Hg) were 40 and 78%. The addition of active perindopril 2 mg roughly doubled the percentage controlled, as did increasing to 4 from 2 mg. Blood pressure control was good with ISH and better than with SDH. The fall in SBP accounted for the observed 30% reduction in strokes, but the 21% reduction in total mortality and 64% reduction in heart failure were greater than predicted.

Improved survival at low lung function in cystic fibrosis: cohort study from 1990 to 2007.

OBJECTIVES: To evaluate the survival of patients with cystic fibrosis whose lung function has deteriorated to a forced expiratory volume in one second (FEV(1)) below 30% predicted in the recent treatment era and to explore factors associated with any change in survival. Design Cohort study. SETTING: Adult cystic fibrosis unit in London. PARTICIPANTS: 276 patients (147 (53%) male) whose FEV(1) was first observed to be less than 30% predicted between 1 January 1990 and 31 December 2003. MAIN OUTCOME MEASURE: Survival during follow-up to 31 December 2007 in two year sub-cohorts. RESULTS: Median survival improved from 1.2 years in the 1990-1 group to 5.3 years in the 2002-3 group, with a marked improvement in survival from 1994. The use of nebulised recombinant human DNase was significantly associated with a reduced risk of death (hazard ratio 0.59, 95% confidence interval 0.44 to 0.79). Significantly increased risks were associated with a body mass index under 19 (hazard ratio 1.52, 1.10 to 2.10), long term oxygen therapy (3.52, 2.49 to 4.99), and nebulised antibiotics (1.84, 1.05 to 3.22). CONCLUSION: A marked improvement has occurred in the survival of patients with cystic fibrosis with an FEV(1) less than 30% predicted. Secondary analyses suggest that some of this improvement may be due to use of recombinant human DNase.

Twin children in The Gambia: evidence for genetic regulation of physical characteristics in the presence of sub-optimal nutrition.

It has been demonstrated that physical growth characteristics are subject to genetic regulation. However, in developing countries, environmental factors such as food availability and frequent infections are associated with growth faltering which is particularly marked in infancy. We have conducted anthropometric measurements of a cohort of twin children aged less than 14 years living in a rural area of The Gambia to ascertain the extent to which genetic factors influence physical growth in the presence of a sub-optimal diet. Almost 25% of the children were more than 2SD below the median of the reference population in terms of their height-for-age Z score, indicating a marked level of undernutrition. Nevertheless, the within-pair variances were significantly less for monozygous than for dizygous twin pairs for the following variables: height, head circumference and body mass index (p < 0.01); weight (p < 0.02) and mid upper arm circumference (p < 0.1), indicating that there is a strong genetic influence on growth regulation despite the sub-optimal nutrition.

PIP: At the Medical Research Council (MRC) field station serving villages in the Upper River Division (URD) of The Gambia in April 1991, health workers took anthropometric measurements and a blood sample from 39 pairs of monozygous (MZ) twins and 115 pairs of same-sexed dizygous (DZ) twins who had been living together and lived together at the time of the survey. All the twins were less than 14 years old. Researchers wanted to determine whether genetic factors influence physical growth in the presence of a suboptimal diet and infectious diseases, especially diarrhea and malaria. The study was conducted at the end of the dry season when food availability was limited. The frequency distribution curves of height-for-age (HAZ) and weight-for-height (WHZ) for the study population were left of the distribution curve for the US National Center for Health Statistics' reference population. This leftward shift suggests that the twins were undernourished at the time of the survey and for a prolonged time, resulting in growth stunting. 17.8% of the children had a WHZ score that was less than or equal to two standard deviations below the median of the reference population. 24.6% had an HAZ score less the median of the reference population. Stunting was most common in children younger than 2 years old. No significant difference between the 2 total variances of the 2 twin types existed. On the other hand, except for skinfold thickness, the within-pair variances were significantly less for MZ than for DZ twin pairs (height, head circumference, and body mass index [p 0.01); weight [p 0.02], and mid-upper arm circumference [p 0.1]). The environmental constraints (i.e., suboptimal diet and presence of infections) may have concealed the genetic influences of skinfold thickness. These findings suggest that genetic factors influence height, head circumference, body mass index, weight, and mid-upper arm circumference.