Point-of-Care Assessment of Folate Status in Women of Reproductive Age Using a Fluorescence Lateral Flow Assay.

Folate is an essential vitamin to the development of a fetus in early pregnancy. Maternal folate supplementation around the time of conception has been shown to decrease the risk of neural tube defects (NTDs), a class of serious birth defects. The closure of the neural tube before the 28th day after conception necessitates that the folate intake must take place before most women know that they are pregnant. Therefore, screening women of reproductive age for folate status would allow for an improved understanding of the need for supplementation in women who could become pregnant as well as the effectiveness of current supplementation and fortification recommendations. Current folate assessment is limited to labbased assays which require expensive equipment, trained personnel, and are time-intensive. Our point-of-care diagnostic test quantifies levels of folate in human serum with the use of a lateral flow assay and a portable imaging device. We have designed an assay which uses fluorescent particles, folate binding protein, and antibodies to measure serum folate. This test could be used in resource-limited settings, where access to laboratory infrastructure is limited and where knowledge of folate status in women of reproductive age is lacking. By increasing our understanding of folate status around the world, we can improve implementation of folic acid supplementation and fortification and therefore reduce the risk of NTDs.

Vitamin B12 status in pregnant women and their infants in South India.

BACKGROUND/OBJECTIVES: Vitamin B12 deficiency during pregnancy has been associated with increased risk of adverse perinatal outcomes. However, few studies have investigated the burden and determinants of vitamin B12 status in young infants. This study was conducted to determine the associations between maternal and infant vitamin B12 status. SUBJECTS/METHODS: Pregnant women participating in a vitamin B12 supplementation trial in Bangalore, India, were randomized to receive vitamin B12 (50 µg) or placebo supplementation daily during pregnancy through 6 weeks postpartum. All women received 60 mg of iron and 500 µg of folic acid daily during pregnancy, as per standard of care. This prospective analysis was conducted to determine the associations between maternal vitamin B12 biomarkers (that is, plasma vitamin B12, methylmalonic acid (MMA) and tHcy) during each trimester with infant vitamin B12 status (n=77) at 6 weeks of age. RESULTS: At baseline (⩽14 weeks of gestation), 51% of mothers were vitamin B12 deficient (vitamin B12<150 pmol/l) and 43% had impaired vitamin B12 status (vitamin B12<150 pmol/l and MMA>0.26 µmol/l); 44% of infants were vitamin B12 deficient at 6 weeks of age. After adjusting for vitamin B12 supplementation, higher vitamin B12 concentrations in each trimester were associated with increased infant vitamin B12 concentrations and lower risk of vitamin B12 deficiency in infants (P<0.05). After adjusting for vitamin B12 supplementation, infants born to women with vitamin B12 deficiency had a twofold greater risk of vitamin B12 deficiency (P<0.01). Higher maternal folate concentrations also predicted lower risk of vitamin B12 deficiency in infants (P<0.05). Impaired maternal vitamin B12 status, which combined both circulating and functional biomarkers, was the single best predictor of infant vitamin B12 status. CONCLUSIONS: Impaired maternal vitamin B12 status throughout pregnancy predicted higher risk of vitamin B12 deficiency in infants, after adjusting for vitamin B12 supplementation. Future interventions are needed to improve vitamin B12 status periconceptionally, and to ensure optimal vitamin B12 status and health outcomes in pregnant women and their children.

PREDICTORS OF INCIDENT TUBERCULOSIS IN HIV-EXPOSED CHILDREN IN TANZANIA.

OBJECTIVE: To examine the predictors of tuberculosis infection in HIV-exposed children. DESIGN: A longitudinal cohort study nested within a randomised controlled trial. SETTING: Antenatal clinics in Dar-es-Salaam, Tanzania. SUBJECTS: Children born to 875 HIV-infected women in Tanzania. RESULTS: A total of 82 children developed tuberculosis during the follow-up period. In multivariate analyses, HIV infection was associated with a six-fold increase in risk of tuberculosis. Breastfeeding duration, child mid-upper arm circumference, and maternal CD4 T-cell counts were inversely related to risk of tuberculosis. In HIV-infected children, greater number of people eating at the same household meal and child CD8 T-cell counts were associated with increased risk of tuberculosis; higher maternal lymphocyte counts, increased duration of breastfeeding, and lower vitamin E levels were associated with reduced risk of tuberculosis. In HIV-uninfected children, breastfeeding duration and increased child mid-upper arm circumference were associated with reduced risk of tuberculosis. CONCLUSION: Breastfeeding duration, HIV status, maternal and child nutritional and immunological status were important predictors of child tuberculosis. Appropriate infant feeding and nutritional interventions could represent important adjuncts to prevent tuberculosis in children born to HIV-infected women in sub-Saharan Africa.

Socio-economic status, urbanization, and cardiometabolic risk factors among middle-aged adults in Tanzania.

OBJECTIVE: This study was conducted to examine the associations between socioeconomic status, urbanization, and cardio-metabolic risk factors in Tanzania. METHODS: Participants were 209 adults (45-66 years) in Dar es Salaam, Tanzania. A structured questionnaire was used to evaluate socioeconomic status and behavioral characteristics, including income, education, occupation, residence (urban, rural, mixed), dietary factors, and smoking. Blood samples were collected and analyzed to measure lipid profiles and fasting glucose levels. Cardiometabolic risk factors were defined using World Health Organization criteria. RESULTS: Urban residence and higher socioeconomic status were associated with decreased intake of traditional staple food (ugali), and increased consumption of meat products and beverages. Higher socioeconomic status was associated with a significant 3.5-kg/m2 higher BMI (p = 0.0001) and 8 cm higher waist circumference (p < 0.001), and a three-fold increase in the risk of obesity. Urban residence was associated with poorer lipid profile, including significantly higher total cholesterol, increased LDL cholesterol, but lower triglycerides, compared to rural residence. The prevalence of metabolic syndrome was high (38%), and was associated with increased socioeconomic status. CONCLUSION: Urban residence and higher socioeconomic status were important correlates of cardiometabolic risk factors, including obesity and poorer lipid profile. Primary prevention and health screening strategies are needed to target cardiometabolic risk factors in urban areas, to reduce the burden of cardiovascular disease in Tanzania.

Economic risk factors for HIV infection among women in rural Haiti: implications for HIV prevention policies and programs in resource-poor settings.

AIMS: The goals of this study were to (1) estimate the prevalence of HIV infection among women accessing services at a women's health center in rural Haiti and (2) to identify economic risk factors for HIV infection in this population. METHODS: Women who accessed healthcare services at this center between June 1999 and December 2002 were recruited to participate. The analysis was based on data from a case-control study of sexually transmitted diseases (STDs) in rural Haiti. HIV prevalence in the study population was 4%. RESULTS: In multivariate analyses, partner occupation was associated with HIV infection in women, with mechanic (OR 9.0, 95% CI 1.8-45) and market vendor (OR 4.2, 95% CI 1.6-11) reflecting the strongest partner occupational risk factors. Partner's occupation as a farmer reduced the risk of infection in women by 60% (95% CI 0.14-1.1). Factors indicating low socioeconomic status (SES), such as food insecurity (OR 2.0, 95% CI 0.75-5.6) and using charcoal for cooking (OR 1.7, 95% CI 0.72-3.8) suggested an association with HIV infection. CONCLUSIONS: Given pervasive gender inequality in Haiti, women's economic security often relies on their partners' income earning activities. Our findings show that although factors reflecting poverty are associated with HIV-positive status, stronger associations are observed for women whose partners indicated a more secure occupation (e.g., mechanic or market vendor). Policies and programs that expand access to education and economic opportunities for women and girls may have long-term implications for HIV prevention in Haiti and other resource-poor settings.

The epidemiology and prevention of burn injuries to firefighters.

From 1981 to 1991, 746 firefighters were treated for burn injuries at New York Hospital-Cornell Burn Center. The predominant anatomic areas of deep injury were the hands and lower extremities. An educational program was initiated that urges proper use of the protective gear as designed. A reduction in the number of burns to the hands subsequently was noted, but lower extremity burns persisted. Analysis of the lower extremity burns revealed that firefighters functioning as nozzle operators were particularly prone to injury because of inadequate lower extremity protection. Improved protection of the lower extremities with the introduction of bunker pants could reduce the incidence of the injuries and result in substantial cost savings for the City of New York.

Pediatric burns. An overview.

This article describes the management of burn injuries in children. It begins with an epidemiologic description of pediatric burns. Attention is given to emergency care, burn wound evaluation, operative management, and rehabilitative goals.

Resuscitation of the thermally injured patient.

This article briefly reviews the pathophysiology of burn wounds as a basis for a more detailed discussion on the resuscitation of burn patients with lactated Ringer's solution or other regimens. The complications resulting from such resuscitation are also reviewed.

Comparison of an occlusive and a semi-occlusive dressing and the effect of the wound exudate upon keratinocyte proliferation.

Three consecutive studies were performed in 58 patients evaluating the effect of occlusion on the healing of partial-thickness wounds. Mirror-image donor sites were covered with the occlusive hydrocolloid dressing (HCD) (DuoDerm) and compared to fine mesh gauze, and the HCD was subsequently compared to a semi-occlusive dressing of polyurethane film, (Op-site). In addition, partial-thickness burn wounds were covered with the HCD and the remaining burn wound was treated with silver sulfadiazine. The donor sites and burn wounds treated with HCD healed significantly faster than those covered with fine mesh gauze or silver sulfadiazine (p less than 0.001) and with less pain. The HCD and polyurethane film were equivalent. There were no clinical infections with the wounds that were occluded. The exudate collected beneath the DuoDerm and Op-site on donor sites was added to the tissue culture system and resulted in a modest increase in keratinocyte proliferation. However, the exudate from burn wounds under HCD resulted in a marked increase in cell proliferation (p less than 0.001).

Occult diaphragmatic injury from stab wounds to the lower chest and abdomen.

Ninety-five patients with stab wounds to the lower chest and abdomen underwent routine abdominal exploration. Eighteen of these patients had diaphragmatic injury and in five patients it was the only injury found. Isolated diaphragmatic injury in asymptomatic patients cannot be reliably delineated by either serial physical examination or peritoneal lavage. Delayed recognition of incarcerated diaphragmatic hernia after stab wounds to the lower left chest and upper abdomen has an associated mortality rate of 36%. The anatomic area of concern can be defined as stab wounds that penetrate the left side of the chest below the fourth intercostal space anteriorly, the sixth intercostal space laterally, and the tip of the scapula posteriorly. Exploratory laparotomy is necessary in these patients until a reliable nonoperative method is established that can exclude injuries to the diaphragm.

Use of vascular clips to approximate skin grafts.

During excisions of acute burn wounds, attention to aesthetic detail often is secondary to the goal of rapid gross coverage. Expeditious approximation of adjacent skin grafts has long presented a problem to surgeons. Some surgeons simply place the grafts next to each other, relying on the intervening areas to "scar in". Others use staples to hold grafts together. These staples, however, can become buried under healed grafts and can cause "foreign body" reactions in the months and years ahead. In addition, staples cause bleeding beneath the newly placed grafts, contributing to hematoma formation. Still other surgeons suture or tape adjacent pieces of skin graft together, a tedious exercise. The cosmetic result of these techniques is often less than optimal resulting in the unfortunately familiar "patchwork quilt" appearance of grafts interweaved among scars. Vascular clips have proven to be useful for holding adjacent pieces of skin graft together.

Mafenide-induced pseudochondritis.

Wound infections following burns of the ear can result in the devastating complication of chondritis, requiring resection of cartilage. To prevent this, it has become common practice to dress the burned ear with mafenide acetate. We have observed six hypersensitivity reactions to the mafenide that occurred following several weeks of continuous use of the drug. The reaction mimics chondritis, causing edematous, erythematous, pruritic ears with a profuse serous exudate. There is no associated fever, systemic signs, or pain on motion of the cartilage. Treatment consists of stopping the mafenide. Recovery occurs within 72 hours. Differentiating between chondritis, with its required surgical and antibiotic treatment, and a hypersensitivity reaction is necessary to avoid further iatrogenic injury.

Grafting of cultured allogeneic epidermis on second- and third-degree burn wounds on 26 patients.

Twenty-six individuals with second- and third-degree burn wounds have been grafted with cultured allogeneic epidermal cells. These epidermal cell grafts were grown in culture from cadaver skin according to a technique which we have developed. After being grafted with cultured allogeneic epidermal cells, superficial wounds, e.g., donor sites, healed within 7 days, compared to 14 days for mirror image control sites. Deep second-degree burn wounds which were excised before grafting with cultured cells healed in a mean time of 10 days. Deep second-degree burn wounds which were not excised before grafting healed in a mean time of 14 days. The cultured cells produced rapid healing in 11 of the 12 patients with deep second-degree burn wounds. The deep second-degree wounds grafted with cultured allogeneic epidermal cells healed with results which were comparable to the deep second-degree wounds which were autografted. Grafts of cultured allogeneic epidermal cells placed on full-thickness, or third-degree burn, wounds did not grow well.

Human keratinocyte culture. Identification and staging of epidermal cell subpopulations.

Stratification of human epidermal cells into multilayered sheets composed of basal and suprabasal layers (resembling the stratum germinativum and stratum spinosum of the epidermis) was studied in a dermal component-free culture system. Although no stratum corneum developed in vitro, this culture system provided a method to study early events in human keratinocyte differentiation. Multiparameter flow cytometric analysis of acridine orange-stained epidermal cells from these cultures revealed three distinct subpopulations differing in cell size, RNA content, and cell cycle kinetics. The first subpopulation was composed of small basal keratinocytes with low RNA content and a long generation time. The second subpopulation consisted of larger keratinocytes, having higher RNA content and a significantly shorter generation time. Finally, the third subpopulation contained the largest cells, which did not divide, and represent the more terminally differentiated keratinocytes. This in vitro approach provides discriminating cytochemical parameters by which the maturity of the epidermal cell sheets can be assessed prior to grafting onto human burn patients.

Respiratory care of the burn patient.

The vast majority of respiratory disorders in thermally injured patients arise from associated inhalation injuries. The major forms of these injuries are carbon monoxide poisoning, injury to the upper airway, and pulmonary parenchymal damage. One hundred per cent oxygen, initiated at the scene of the accident, is the single most effective treatment of carbon monoxide toxicity, which must be assessed by carboxyhemoglobin determinations. Respiratory tract damage is identified by fiberoptic bronchoscopy and xenon ventilation-perfusion scintigrams. The compromised airway is protected by tracheal intubation, and respiratory failure is treated with assisted ventilation and supplemental oxygen. Pulmonary infection requires specific antibiotics based on isolated organisms and their sensitivities to antimicrobials. The upper respiratory tract of patients requiring long-term intubation should be assessed by fiberoptic bronchoscopy and other modalities to prevent fatal late airway occlusion.

Grafting of burn patients with allografts of cultured epidermal cells.

Epidermal cells from cadaver skin grown in culture into confluent sheets of stratified cells were grafted on to partial thickness burn wounds in three patients. The burn areas covered with these allogeneic cultured epidermal allografts were tangentially excised deep second-degree burns which routinely would have been covered with split-thickness autografts. The burn wounds grafted with cultured allografts healed within three days and remained healthy for the 9 months of observation. Since epidermal cell cultures may be grown continuously, cultured allografts may serve as alternative biological dressings, or grafts, for deep second-degree burn wounds. They produce accelerated healing and an excellent cosmetic result, and they reduce the need for split-thickness autografts.

Continent anal ileostomy with mucosal proctectomy: a bloodless technique using a surgical ultrasonic aspirator in dogs.

At present, mucosal proctectomy with ileo-anal anastomosis is a difficult, time-consuming operation involving much blood loss, often associated with impaired postoperative continence. A new operation has been devised in our department in which a surgical ultrasonic aspiratory, the CUSATM System (Cavitron Corporation) was used to fragment directly and strip bloodlessly mucosa from the rectal wall in 20 dogs as part of a simple ileo-anal sleeve anastomosis. All dogs were closely followed for up to 10 months. The only operative mortality occurred in the first dog where the upper rectum sloughed because the superior haemorrhoidal artery was divided. Preoperative weight was regained within the first 2 months. Initially stools were loose and frequent. Within 2 weeks the daily stool count was 5-6 with gradual thickening to semisolid consistency by 6 weeks. Finally 3-4 normal stools were passed daily. Postoperatively, all dogs remained contingent.