Hospital-acquired bloodstream infections in patients with cancer: current knowledge and future directions.

Patients with cancer experience higher rates of preventable harm from hospital-acquired bloodstream infections (haBSIs) and central-line-associated bloodstream infections (CLABSIs) compared with the general hospital population. The prevention of haBSIs and CLABSIs in patients with cancer is an urgent priority, and requires standardized surveillance and reporting efforts. The application of haBSI and CLABSI definitions, classification systems and surveillance strategies for patients with cancer is complex, and there is wide variation in clinical practice. Existing systems were not designed explicitly for patients with cancer, and have different strengths and weaknesses in the cancer setting. For these reasons, epidemiological estimates of haBSIs and CLABSIs in patients with cancer also require careful interpretation. This complexity can be a barrier to identifying appropriate targets for intervention and reducing preventable harm. This review provides an overview of key concepts and challenges in haBSI surveillance and prevention specific to patients with cancer. In addition, this review summarizes the strengths and weaknesses of commonly used surveillance definitions and denominators in the setting of cancer care; existing surveillance practice; epidemiology of haBSIs and CLABSIs; prevention strategies; and current knowledge gaps. A global collaborative effort to harmonize the surveillance of hospital-acquired infections in patients with cancer would be invaluable to improve the accuracy and utility of existing data, advance efforts to prevent hospital-acquired infections, and improve patient safety.

The barriers to linkage and retention in care for women living with HIV in an high income setting where they comprise a minority group.

Women comprise a minority population of individuals living with HIV in Australia, and are often poorly represented in research and clinical trials so their needs remain largely unknown. Data suggests that they are diagnosed later than men and start antiretroviral therapy at a lower CD4 cell count. This raises the question whether there are sex specific barriers to linkage and retention in care. This study analyzed 484 surveys received from clinicians collecting demographic, virological, and reproductive health data along with perceived barriers to linkage and retention in care. Most women (67%) were estimated to have been linked into care within 28 days of diagnosis. For women who were not linked into care for more than 28 days, the most commonly reason cited was fear of disclosure to others, followed by fear of disclosure to their partner. The main reasons given for non-retention in care were related to transport, carer responsibilities, financial pressure, health beliefs and concern about stigma or disclosure.

Anemia among HIV-Infected Patients Initiating Antiretroviral Therapy in South Africa: Improvement in Hemoglobin regardless of Degree of Immunosuppression and the Initiating ART Regimen.

Among those with HIV, anemia is a strong risk factor for disease progression and death independent of CD4 count and viral load. Understanding the role of anemia in HIV treatment is critical to developing strategies to reduce morbidity and mortality. We conducted a prospective analysis among 10,259 HIV-infected adults initiating first-line ART between April 2004 and August 2009 in Johannesburg, South Africa. The prevalence of anemia at ART initiation was 25.8%. Mean hemoglobin increased independent of baseline CD4. Females, lower BMI, WHO stage III/IV, lower CD4 count, and zidovudine use were associated with increased risk of developing anemia during follow-up. After initiation of ART, hemoglobin improved, regardless of regimen type and the degree of immunosuppression. Between 0 and 6 months on ART, the magnitude of hemoglobin increase was linearly related to CD4 count. However, between 6 and 24 months on ART, hemoglobin levels showed a sustained overall increase, the magnitude of which was similar regardless of baseline CD4 level. This increase in hemoglobin was seen even among patients on zidovudine containing regimens. Since low hemoglobin is an established adverse prognostic marker, prompt identification of anemia may result in improved morbidity and mortality of patients initiating ART.

Kaposi sarcoma-associated herpes virus and response to antiretroviral therapy: a prospective study of HIV-infected adults.

BACKGROUND: The possible impact of coinfection with the Kaposi sarcoma-associated herpes virus (KSHV) on the response to antiretroviral therapy (ART) is unknown. Prospective studies are rare, particularly in Africa. METHODS: We enrolled a prospective cohort of HIV-infected adults initiating ART in Johannesburg, South Africa. The subjects were defined as seropositive to KSHV if they were reactive to either KSHV lytic K8.1 or latent Orf73 antigen or to both. The subjects were followed from ART initiation until 18 months of treatment. HIV viral load and CD4 counts were tested 6 monthly. Linear generalized estimating and log-binomial regression models were used to estimate the effect of KSHV infection on immunologic recovery and response and HIV viral load suppression within 18 months after ART initiation. RESULTS: Three hundred eighty-five subjects initiating ART from November 2008 to March 2009 were considered to be eligible including 184 (48%) KSHV+. The KSHV+ group was similar to the KSHV- in terms of age, gender, initiating CD4 count, body mass index, tuberculosis, and hemoglobin levels. The KSHV+ group gained a similar number of cells at 6 [difference of 10 cells per cubic millimeter, 95% confidence interval (CI): -11 to 31], 12 (3 cells per cubic millimeter, 95% CI: -19 to 25), and 18 months (24 cells per cubic millimeter, 95% CI: -13 to 61) compared with that gained by the KSHV- group. Adjusted relative risk of failure to suppress viral load to <400 copies per milliliter (1.03; 95% CI: 0.90 to 1.17) were similar for KSHV+ and KSHV- by 6 months on treatment. CONCLUSIONS: In a population with a high KSHV prevalence, HIV-positive adults coinfected with KSHV achieved similar immunologic and virologic responses to ART early after treatment initiation compared with those with KSHV-.

Gender differences in mortality and CD4 count response among virally suppressed HIV-positive patients.

BACKGROUND: Treatment outcomes for antiretroviral therapy (ART) patients may vary by gender, but estimates from current evidence may be confounded by disease stage and adherence. We investigated the gender differences in treatment response among HIV-positive patients virally suppressed within 6 months of treatment initiation. METHODS: We analyzed data from 7,354 patients initiating ART between April 2004 and April 2010 at Themba Lethu Clinic, a large urban public sector treatment facility in South Africa. We estimated the relations among gender, mortality, and mean CD4 response in HIV-infected adults virally suppressed within 6 months of treatment initiation and used inverse probability of treatment weights to correct estimates for loss to follow-up. RESULTS: Male patients had a 20% greater risk of death at both 24 months and 36 months of follow-up compared to females. Older patients and those with a low hemoglobin level or low body mass index (BMI) were at increased risk of mortality throughout follow-up. Men gained fewer CD4 cells after treatment initiation than did women. The mean differences in CD4 count gains made by women and men between baseline and 12, 24, and 36 months were 28.2 cells/mm(3) (95% confidence interval [CI] 22.2-34.3), 60.8 cells/mm(3) (95% CI 71.1-50.5 cells/mm(3)), and 83.0 cells/mm(3) (95% CI 97.1-68.8 cells/mm(3)), respectively. Additionally, patients with a current detectable viral load (>400 copies/mL) and older patients had a lower mean CD4 increase at the same time points. CONCLUSIONS: In this initially virally suppressed population, women showed consistently better immune response to treatment than did men. Promoting earlier uptake of HIV treatment among men may improve their immunologic outcomes.

Cohort profile: the Themba Lethu Clinical Cohort, Johannesburg, South Africa.

The Themba Lethu Clinical Cohort was established in 2004 to allow large patient-level analyses from a single HIV treatment site to evaluate National Treatment Guidelines, answer questions of national and international policy relevance and to combine an economic and epidemiologic focus on HIV research. The current objectives of the Themba Lethu Clinical Cohort analyses are to: (i) provide cohort-level information on the outcomes of HIV treatment; (ii) evaluate aspects of HIV care and treatment that have policy relevance; (iii) evaluate the cost and cost-effectiveness of different approaches to HIV care and treatment; and (iv) provide a platform for studies on improving HIV care and treatment. Since 2004, Themba Lethu Clinic has enrolled approximately 30,000 HIV-positive patients into its HIV care and treatment programme, over 21,000 of whom have received anti-retroviral therapy since being enrolled. Patients on treatment are typically seen at least every 3 months with laboratory monitoring every 6 months to 1 year. The data collected include demographics, clinical visit data, laboratory data, medication history and clinical diagnoses. Requests for collaborations on analyses can be submitted to our data centre.

The feasibility of using screening criteria to reduce clinic visits for stable patients on antiretroviral therapy in South Africa.

OBJECTIVES: South African HIV care providers are exploring ways to reduce the intensity of patient visits while maintaining high quality of care. We used routinely collected data to model whether a simple screening tool could identify stable patients who would not need to see a doctor during a scheduled medical visit. DESIGN: We identified stable and nonstable visits from January 2007 to September 2011 at a large HIV clinic in Johannesburg, SA. Stable medical visits were defined as having all of the following: stable CD4 count, undetectable viral load, stable weight, not pregnant, no comorbidity, no regimen change within three months, and normal laboratory results for hemoglobin, alanine aminotransferase, and creatinine clearance. METHODS: We assessed the sensitivity and specificity of nonstable visits at predicting indicators of disease progression or needing additional care: (1) ART regimen change and (2) follow-up visits in <2 and <4 weeks from previous visit. RESULTS: Stable visits had a sensitivity of 88.9% (95% confidence interval: 88.2 to 89.7) and a specificity of 44.8% (44.5 to 44.1) at predicting ART therapy changes, and a sensitivity of 72.6% (71.8 to 73.4) and specificity of 45.1% (44.8 to 45.4) for predicting a follow-up visit interval of <2 weeks and similar results for predicting a follow-up visit interval of <4 weeks. CONCLUSIONS: Our retrospective analysis suggests an approach to potentially reduce the number of medical visits while missing few visits in which changes in regimen or additional care would be needed. Evaluation of our criteria in a primary care setting is needed to determine whether they could safely reduce visits.

Poorer ART outcomes with increasing age at a large public sector HIV clinic in Johannesburg, South Africa.

BACKGROUND: As the current HIV-positive population ages, the absolute number of patients >50 years on treatment is increasing. METHODS: We analyze the differences in treatment outcomes by age category (18-29, 30-39, 40-49, 50-59, and ≥ 60) among 9139 HIV-positive adults initiating ART in South Africa. RESULTS: The adjusted hazard ratios (HRs) for all-cause mortality increased with increasing age, with the strongest association in the first 12 months of follow-up among patients 50 to 59 years (HR 1.67; 95% confidence interval [CI]: 1.24-2.23) versus those <30 years. However, patients 50 to 59 years were less likely to be lost during 24 months on antiretroviral therapy ([ART] HR 0.75; 95% CI: 0.59-0.94) versus patients <30 years. By 6 and 12 months on treatment, older patients were less likely to increase their CD4 count by ≥ 50 cells/mm(3). CONCLUSION: Although older patients are at higher risk of mortality and have poorer immunological responses than their younger counterparts, they are more likely to adhere to care and treatment in the first 24 months on ART.

Prevalence and predictors of kaposi sarcoma herpes virus seropositivity: a cross-sectional analysis of HIV-infected adults initiating ART in Johannesburg, South Africa.

BACKGROUND: Kaposi sarcoma (KS) is the most common AIDS-defining tumour in HIV-infected individuals in Africa. Kaposi sarcoma herpes virus (KSHV) infection precedes development of KS. KSHV co-infection may be associated with worse outcomes in HIV disease and elevated KSHV viral load may be an early marker for advanced HIV disease among untreated patients. We examined the prevalence of KSHV among adults initiating antiretroviral therapy (ART) and compared immunological, demographic and clinical factors between patients seropositive and seronegative for KSHV. RESULTS: We analyzed cross-sectional data collected from 404 HIV-infected treatment-naïve adults initiating ART at the Themba Lethu Clinic, Johannesburg, South Africa between November 2008 and March 2009. Subjects were screened at ART initiation for antibodies to KSHV lytic K8.1 and latent Orf73 antigens. Seropositivity to KSHV was defined as positive to either lytic KSHV K8.1 or latent KSHV Orf73 antibodies. KSHV viremia was determined by quantitative PCR and CD3, 4 and 8 lymphocyte counts were determined with flow cytometry. Of the 404 participants, 193 (48%) tested positive for KSHV at ART initiation; with 76 (39%) reactive to lytic K8.1, 35 (18%) to latent Orf73 and 82 (42%) to both. One individual presented with clinical KS at ART initiation. The KSHV infected group was similar to those without KSHV in terms of age, race, gender, ethnicity, smoking and alcohol use. KSHV infected individuals presented with slightly higher median CD3 (817 vs. 726 cells/mm3) and CD4 (90 vs. 80 cells/mm3) counts than KSHV negative subjects. We found no associations between KSHV seropositivity and body mass index, tuberculosis status, WHO stage, HIV RNA levels, full blood count or liver function tests at initiation. Those with detectable KSHV viremia (n = 19), however, appeared to present with signs of more advanced HIV disease including anemia and WHO stage 3 or 4 defining conditions compared to those in whom the virus was undetectable. CONCLUSIONS: We demonstrate a high prevalence of KSHV among HIV-infected adults initiating ART in a large urban public-sector HIV clinic. KSHV viremia but not KSHV seropositivity may be associated with markers of advanced HIV disease.

Ferroportin (Q248H) mutations in African families with dietary iron overload.

BACKGROUND: Dietary iron overload found in sub-Saharan Africa might be caused by an interaction between dietary iron and an iron-loading gene. Caucasian people with ferroportin gene mutations have iron overload histologically similar to that found in African patients with iron overload. Ferroportin is also implicated in the hypoferremic response to inflammation. The prevalence of the ferroportin Q248H mutation, unique to African people, and its association with dietary iron overload, mean cell volume (MCV) and C-reactive protein (CRP) were examined in 19 southern African families. METHODS: Polymerase chain reaction (PCR) and restriction enzyme digestion were used to identify the Q248H mutation. Statistical analysis was carried out to correlate the presence of the mutation with markers of iron overload and inflammation. RESULTS: We identified three (1.4%) Q248H homozygotes and 53 (24.1%) heterozygotes in the families examined in the present study. There was no increased prevalence of the mutation in index subjects or their families. Logistic regression showed significantly higher serum ferritin concentrations with the mutation. The mean cell volume (MCV) was significantly lower, and the serum CRP significantly higher in subjects who carried the mutation. CONCLUSIONS: The present study of 19 families with African iron overload failed to show evidence that the ferroportin (Q248H) mutation is responsible for the condition. Logistic regression, correcting for factors influencing iron status, did show increased ferritin levels in individuals with the mutation. The strong association with low MCV suggests the possibility that the ferroportin (Q248H) mutation might interfere with iron supply, whereas the elevated serum CRP might indicate that the ferroportin mutation influences the inflammatory response in African populations.

Ascorbic acid deficiency, iron overload and alcohol abuse underlie the severe osteoporosis in black African patients with hip fractures--a bone histomorphometric study.

Osteoporosis and femoral neck fractures (FNF) are uncommon in black Africans although osteoporosis accompanying iron overload (from traditional beer brewed in iron containers) associated with ascorbic acid deficiency (oxidative catabolism by iron) has been described from sub-Saharan Africa. This study describes histomorphometric findings of iliac crest bone biopsies and serum biochemical markers of iron overload and of alcohol abuse and ascorbic acid levels in 50 black patients with FNFs (29 M, 21 F), age 62 years (40-95) years (median [min-max]), and in age- and gender-matched black controls. We found evidence of iron overload in 88% of patients and elevated markers of alcohol abuse in 72%. Significant correlations between markers of iron overload and of alcohol abuse reflect a close association between the two toxins. Patients had higher levels of iron markers, i.e., siderin deposits in bone marrow (P < 0.0001), chemical non-heme bone iron (P = 0.012), and serum ferritin (P = 0.017) than controls did. Leukocyte ascorbic acid levels were lower (P = 0.0008) than in controls. The alcohol marker mean red blood cell volume was elevated (P = 0.002) but not liver enzymes or uric acid. Bone volume, trabecular thickness, and trabecular number were lower, and trabecular separation was greater in patients than in controls, all at P < 0.0005; volume, surface, and thickness of osteoid were lower and eroded surface was greater, all at P < 0.0001. There was no osteomalacia. Ascorbic acid deficiency accounted significantly for decrease in bone volume and trabecular number, and increase in trabecular separation, osteoid surface, and eroded surface; iron overload accounted for a reduction in mineral apposition rate. Alcohol markers correlated negatively with osteoblast surface and positively with eroded surface. Relative to reported data in white FNF patients, the osteoporosis was more severe, showed lower osteoid variables and greater eroded surface; FNFs occurred 12 years earlier and were more common among men. We conclude that the osteoporosis underlying FNFs in black Africans is severe, with marked uncoupling of resorption and formation in favor of resorption. All three factors--ascorbic acid deficiency, iron overload, and alcohol abuse--contributed to the osteoporosis, in that order.

The potential role of NaFeEDTA as an iron fortificant.

Ethylene diamine tetraacetic acid (EDTA) is a hexadentate chelator, which can combine with virtually every metal in the periodic table. CaNa2EDTA and Na2EDTA (ADI 2.5 mg EDTA/kg body weight/day) are widely used as sequestering agents in canned products, while NaFeEDTA is a promising iron fortificant. Binding of EDTA with iron is favored in the acid milieu of the stomach, irrespective of whether the EDTA is administered as CaNa2EDTA, Na2EDTA, or NaFeEDTA, but in the more alkaline medium of the duodenum the iron is exchanged, in part, with other metals. The iron released from EDTA is absorbed by the normal physiological mechanisms. When NaFeEDTA is present in a meal, the iron moiety exchanges with the intrinsic food iron and the EDTA partially protects the iron in this common non-heme iron pool from the effects of inhibitors of iron absorption, such as phytates and polyphenols. When iron is added as NaFeEDTA to an inhibitory meal, it is two to three times better absorbed than is iron added as ferrous sulfate. It also has a similar effect on the intrinsic food iron in the meal. Fortification with NaFeEDTA is most efficacious when administered with cereal- and legume-based diets but offers no advantages over other fortificants when added to meals of high bioavailability. Its potential as a fortificant has been confirmed in five extended fortification trials carried out in developing countries. There is no evidence that NaFeEDTA in the dose range proposed for food fortificants (5 to 10 mg iron daily) will have any direct toxic effects. Na2EDTA and CaNa2EDTA have proved safe over a number of years, while the Joint FAO/WHO Expert Committee on Food Additives concluded in 1999 that NaFeEDTA "could be considered safe when used in supervised fortification programs". Animal and human studies, including the results of two fortification trials, suggest that NaFeEDTA has little or no effect on overall zinc metabolism. Indeed, if anything, it increases zinc and possibly copper absorption. Data on potentially toxic metals, such as lead mercury, aluminum, and manganese, are limited but the evidence that is available is uniformly negative thus far. Further studies in this field are desirable. The long-term potential of NaFeEDTA fortification to cause iron overload is conjectural but the available evidence suggests that homeostatic controls would prevent excess iron accumulation in the normal population. NaFeEDTA, which is pale yellow in color, causes fewer organoleptic changes in a number of stored vehicles, including cereals, than do other soluble iron salts. Other potential vehicles include condiments, several of which have been successfully used in fortification trials. What is currently lacking is a consolidated body of published evidence on the stability of NaFeEDTA during processing, storage, and household cooking in widely consumed food vehicles, coupled with standardized testing of consumer acceptance of each fortified vehicle. While NaFeEDTA seems to be an appropriate fortificant for developing countries, its cost is about six to eight times that of ferrous sulfate in terms of equivalent amounts of iron. Its better absorption (a factor of 2-3) might make it possible to halve the daily fortification level but, it still remains expensive and there is a pressing need for food grade NaFeEDTA at more affordable prices. Another possible option is the use of other salts of EDTA (Na2EDTA or Ca Na2EDTA) together with a soluble source of iron, such as ferrous sulfate. The combination has been shown to be as effective as NaFeEDTA when the EDTA:Fe molar ratio is between 1:2 and 1:1. This approach is, however, only feasible with vehicles that are stored for short periods because of ferrous sulfate's propensity to cause organoleptic changes. The search for an iron source that is more stable but at the same time available to combine with EDTA has been unsuccessful thus far. Target populations for fortification with NaFeEDTA include all those that subsist on cereal- and legume-based diets, with the most appropriate vehicles being cereal products and condiments. The fortification of infant milk and cereal formulas with NaFeEDTA does not seem appropriate, since the amounts of NaFeEDTA required for effective fortification would be close to the acceptable daily intake (ADI) of 2.5 mg EDTA/kg body weight/day.

Basal endocrine status in African dietary iron overload.

Endocrine disturbances, notably diabetes, have been well described as a complication of iron overload due to hereditary hemochromatosis and beta-thalassemia. Dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis has also been well documented. The pattern of iron loading in African iron overload with saturated transferrin is similar to that seen in hereditary hemochromatosis. In addition, many symptoms ascribed to pituitary dysfunction are common to both conditions. The present study was undertaken to assess whether a similar pattern of endocrine dysfunction occurs in African iron overload. Thirty subjects with African iron overload and transferrin saturation >50%, plus 30 age and sex matched normal controls were studied. An iron profile, fasting plasma glucose, cortisol, DHEA-S, LH, FSH, growth hormone, prolactin, TSH, and FT4 levels were measured in all 60 subjects as well as testosterone in the males and estradiol in the females. Iron loading in the subjects with increased transferrin saturation ranged from moderate to severe. No significant differences were found in the mean testosterone, estradiol, LH, DHEA-S, growth hormone, prolactin, or TSH levels between the subjects and normal controls. In female subjects, although within the normal range, the mean FSH level was significantly higher, probably due to their being somewhat older and in a more advanced stage of menopause than the control females. Mean cortisol concentrations were increased in both genders in the patient group, significantly so in the females; however, values were within the reference range. We conclude therefore that there appears to be no major impairment of endocrine function in the basal state in African iron overload subjects with moderate to severe degrees of iron loading.

Iron deficiency and the developing world.

The dietary intake of iron in underdeveloped countries is based mainly on non-hem iron which is absorbed to a lesser degree that hem iron and is subjected to many interferences from inhibitors generally present in the diets, such as phenols, phytates, fibers, etc. Food fortification with iron is considered to be the best and cheapest long-term approach for correcting the deficiency. The iron source selected for this purpose has to be soluble, and of high bioavailability, even in a diet rich in inhibitors. Ferrochel may prove to be this type of compound.

The ratio of serum transferrin receptor and serum ferritin in the diagnosis of iron status.

Laboratory tests used in the diagnosis of iron status lack specificity in defining iron deficiency anaemia (IDA) and anaemia of inflammation (AI). The serum transferrin receptor (sTfR) may provide more information in this regard. The iron status of 561 pre-school children was determined and classified using the conventional measurements. The value of the concentration of sTfR, the ratio of sTfR (microg/ml) to LogSF (microg/l) (TfR-Index), and the Log of the ratio of sTfR (microg/l) to SF (microg/l)--(LogTfR:Fer ratio), in the classification of the iron status were determined by comparing their distributions across the classification of iron status. Although there were significant differences in sTfR and TfR-Index across the categories of iron status, there was considerable overlap. All subjects with iron deficiency had LogTfR:Fer ratio > 2.55, whereas in all subjects classified as AI it was < 2.55, thus clearly separating the two. The LogTfR:Fer ratio was not able to exclude IDA in the presence of inflammation. However, in cases of combined IDA and AI the LogTfR:Fer ratio was < 2.55 but increased to > 2.55 after resolution of the inflammation. This novel method of calculating the LogTfR:Fer ratio may provide a more precise classification of the iron status of children.

Clinical and genetic heterogeneity in hereditary haemochromatosis: association between lymphocyte counts and expression of iron overload.

To identify a new marker of expression of disease, independent of HFE genotype in patients with hereditary haemochromatosis (HHC), the total peripheral blood lymphocyte counts were analysed according to iron status in two groups of subjects with HFE mutations. The groups consisted of 38 homozygotes for C282Y, and 107 heterozygotes for the C282Y or compound heterozygotes for C282Y and H63D. For control purposes, total lymphocyte counts and iron status were also examined in 20 index patients with African dietary iron overload, a condition not associated with HFE mutations, and in 144 members of their families and communities. Mean lymphocyte numbers were lower in C282Y homozygous HHC index subjects with cirrhosis and higher iron stores than in those without cirrhosis and with lower iron burdens [(1.65 +/- 0.43) x 10(6)/mL vs. (2.27 +/- 0.49) x 10(6)/mL; p = 0.008]. Similarly, mean lymphocyte counts were significantly lower in C282Y heterozygotes and C282Y/H63D compound heterozygotes with iron overload and increased serum ferritin concentrations compared to those with normal serum ferritin concentrations (p < 0.05). Statistically significant negative correlations were found, in males, between lymphocyte counts and the total body iron stores, either in C282Y homozygous HHC patients (p = 0.031 in a multiple regression model dependent on age) and in C282Y heterozygotes or C282Y/H63D compound heterozygotes with iron overload (p = 0.029 in a simple linear model). In contrast, lymphocyte counts increased with increasing serum ferritin concentrations among the index subjects with African iron overload (r = 0.324, not statistically significant) and among the members of their families and communities (r = 0.170, p = 0.042). These results suggest that a lower peripheral blood lymphocyte count is associated with a greater degree of iron loading in HFE haemochromatosis but not in African iron overload, and they support the notion that the lymphocyte count may serve as a marker of a non-HFE gene that influences the clinical expression of HFE haemochromatosis.

Iron deficiency and the developing world

The dietary intake of iron in underdeveloped countries is based mainly on non-hem iron which is absorbed to a lesser degree that hem iron and is subjected to many interferences from inhibitors generally present in the diets, such as phenols, phytates, fibers, etc. Food fortification with iron is considered to be the best and cheapest long-term approach for correcting the deficiency. The iron source selected for this purpose has to be soluble, and of high bioavailability, even in a diet rich in inhibitors. Ferrochel may prove to be this type of compound.

Maximal exercise testing in late gestation: fetal responses.

OBJECTIVE: To determine the fetal response to and safety of maximal maternal exercise in the third trimester. METHODS: Twenty-three active women with uncomplicated pregnancies (singleton gestations) underwent maximal exercise testing in late gestation using a progressive maximal cycle ergometer protocol. Fetal heart rate (FHR) responses were monitored and classified using National Institute of Child Health and Human Development guidelines. Statistical analyses involved use of the Student t test, repeated measures analysis of variance with Tukey-Kramer multiple comparisons posttest, and the chi(2) test. RESULTS: There was an increase in baseline FHR in the 20-minute posttest period compared with the 20-minute pretest period. There were significantly fewer accelerations in the second posttest 10-minute segment compared with the second pretest 10-minute segment. Variability was reduced in both posttest periods compared with the first 10-minute pretest period. Time to reactivity increased after testing. Mild tachycardia was noted in two tracings and bradycardia occurred in a fetus with previously undiagnosed growth restriction. There were no abnormal neonatal outcomes. CONCLUSION: Maximal exercise testing in late gestation led to minimal changes in FHR. Fetal bradycardiac responses were not seen in appropriate for gestational age fetuses, suggesting that brief maximal maternal exertion for research or diagnostic purposes is safe in this group.

Fractured neck of femur in black patients: a prospective study.

We explored the role of iron overload, deficiency of vitamin C and alcohol abuse in the aetiology of cervical and intertrochanteric fractures of the neck of the femur as a result of minor trauma. We studied prospectively 72 patients (45 men, 27 women). Levels of serum iron markers, vitamin C and alcohol markers were measured. Consumption of alcohol was estimated using questionnaires. The findings were compared with those of an age- and gender-matched control group. The mean age of the men was 59.5 years and of the women 66.9 years, with a male predominance. In the men, iron overload, as shown by high levels of serum ferritin (p < 0.001) and deficiency of vitamin C (p < 0.03), as well as abuse of both Western and the traditional type of alcohol, appear to be important aetiological factors. In women, alcohol abuse was also common, but iron markers and levels of vitamin C did not differ significantly from the control group.

Measurements of iron status and survival in African iron overload.

INTRODUCTION: Dietary iron overload is common in southern Africa and there is a misconception that the condition is benign. Early descriptions of the condition relied on autopsy studies, and the use of indirect measurements of iron status to diagnose this form of iron overload has not been clarified. METHODS: The study involved 22 black subjects found to have iron overload on liver biopsy. Fourteen subjects presented to hospital with liver disease and were found to have iron overload on percutaneous liver biopsy. Eight subjects, drawn from a family study, underwent liver biopsy because of elevated serum ferritin concentrations suggestive of iron overload. Indirect measurements of iron status (transferrin saturation, serum ferritin) were performed on all subjects. Histological iron grade and hepatic iron concentration were used as direct measures of iron status. RESULTS: There were no significant differences in either direct or indirect measurements of iron status between the two groups. In 75% of these subjects the hepatic iron concentration was greater than 350 micrograms/g dry weight, an extreme elevation associated with a high risk of fibrosis and cirrhosis. Serum ferritin was elevated in all subjects and the transferrin saturation was greater than 60% in 93% of the subjects. Hepatomegaly was present in 20 of the 22 cases and there was only a moderate derangement in liver enzymes except for a tenfold increase in the median gamma-glutamyl transpeptidase concentration. There was a strong correlation between serum ferritin and hepatic iron concentrations (r = 0.71, P = 0.006). After a median follow-up of 19 months, 6 (26%) of the subjects had died. The risk of mortality correlated significantly with both the hepatic iron concentration and the serum ferritin concentration. CONCLUSIONS: Indirect measurements of iron status (serum ferritin concentration and transferrin saturation) are useful in the diagnosis of African dietary iron overload. When dietary iron overload becomes symptomatic it has a high mortality. Measures to prevent and treat this condition are needed.