Health system costs of providing outpatient care for diabetes in people with TB in the Philippines.

BACKGROUND: Diabetes mellitus (DM) is a known risk factor for active TB. A key activity in the Philippines is to integrate TB services with other disease programmes, with a target of DM screening in 90% of TB cases. However, costs of providing DM outpatient services for TB patients are not well known. METHODS: We estimated the costs of providing integrated DM outpatient services within TB services from the health system perspective. Resources for outpatient DM services were valued using the bottom-up approach for capital goods, staff time and consumables. Resource quantities were obtained by interviewing 60 healthcare professionals in 11 health facilities in the Philippines. RESULTS: The mean cost per service ranged from USD0.53 for DM risk assessment to USD23.72 for oral glucose tolerance test. The cost per case detected for different algorithms varied from USD17.43 to USD80.81. The monthly cost per patient was estimated at USD8.95 to USD12.36. CONCLUSION: Our study provides the first estimates of costs for providing integrated DM outpatient services and TB care in a low- and middle-income country. The costs of DM detection in TB patients suggests that it may be useful to further investigate the cost-effectiveness and affordability of service delivery.

CONTEXTE: Le diabète (DM) est un facteur de risque bien établi pour la TB active. Aux Philippines, l'une des principales initiatives est d'intégrer les services de lutte contre la TB dans d'autres programmes de santé, dans le but de dépister le DM chez 90% des patients atteints de TB. Cependant, les coûts des services ambulatoires de traitement du DM pour les patients atteints de TB ne sont pas clairement définis. MÉTHODES: Nous avons évalué les coûts des services ambulatoires intégrés pour le traitement du DM dans le cadre des services de lutte contre la TB, du point de vue du système de santé. Les ressources pour les services ambulatoires de DM ont été évaluées en utilisant l'approche ascendante pour les biens d'équipement, le temps du personnel et les consommables. Les quantités de ressources ont été recueillies en interrogeant 60 professionnels de la santé dans 11 établissements de santé aux Philippines. CONCLUSION: Notre étude présente les premières estimations des coûts des services ambulatoires intégrés pour le traitement du DM et de soins de la TB dans un pays à revenu faible ou intermédiaire. Il est suggéré d'approfondir l'étude du rapport coût-efficacité et de l'accessibilité des services de détection de la DM chez les patients atteints de TB, compte tenu des coûts impliqués.

Effects of comorbidities on quality of life in Filipino people with tuberculosis.

BACKGROUND: We investigated health-related quality of life (HrQoL) in Filipino people undergoing TB treatment, and whether HrQoL was negatively impacted by comorbidity with undernutrition, diabetes (DM) and anaemia.METHODS: Adult participants were enrolled in public facilities in Metro Manila (three sites) and Negros Occidental (two sites). Multivariate linear regression was used to model the four correlated domain scores from a WHOQOL-BREF questionnaire (physical, psychological, social, environmental). A forward-stepwise approach was used to select a final multivariable model with inclusion based on global tests of significance at P < 0.1.RESULTS: In 446 people on drug-susceptible TB treatment, DM and moderate/severe anaemia were not associated with HrQoL. After adjustment for age, sex, education, food insecurity, treatment adherence, inflammation, Category I or II TB treatment, treatment phase, current side effects and inhibited ability to work, moderate/severe undernutrition (body mass index < 17 kg/m²) was associated with lower HrQoL (P = 0.003) with reduced psychological (coefficient: -1.02, 95% CI -1.54 to -0.51), physical (-0.62, 95% CI -1.14 to -0.09) and environmental domain scores (-0.45, 95% CI -0.88 to -0.01). In 225 patients with known HIV status in Metro Manila, HIV was associated with modestly reduced HrQoL (P = 0.014).CONCLUSION: Nutritional status and food insecurity represent modifiable risk factors for poor HrQoL that may be alleviated through interventions.

L-Glutamine in sickle cell disease.

L-Glutamine is a conditionally essential amino acid required for synthesis of the pyridines for nucleotides, including nicotinamide adenine dinucleotide (NAD) and glutathione, as well as glutamate, and becomes essential during oxidative stress exposure. The NADH:[NAD⁺ + NADH] (redox) ratio in sickle red blood cells (RBCs) is lower than in normal RBCs, consistent with oxidative stress, therefore glutamine availability is important in sickle cell disease (SCD). RBC glutamine levels vary between SCD studies but the ratio glutamine:glutamate was inversely related to tricuspid regurgitant jet velocity in one. Oral L-glutamine was associated with an increase in NADH and reduction in RBC endothelium adhesion in small studies of SCD patients. In a sickle mouse model, glutamine levels were directly related to cerebral blood flow. Phase II and III randomized, double-blind, controlled trials of L-glutamine 0.6 g/kg/day compared with placebo in children and adults with SCD and = 2 episodes of pain in the previous year provide evidence that L-glutamine is safe and associated with a reduction in painful episodes and in hospitalizations. However, L-glutamine was only tolerated in two-thirds of patients, anemia and hemolysis did not improve and there are few data on mortality and organ complications. Future studies should investigate the effect of other amino acids and total protein intake.

Nocturnal haemoglobin oxygen desaturation in urban and rural East African paediatric cohorts with and without sickle cell anaemia: a cross-sectional study.

Low haemoglobin oxygen saturation (SpO2) predicts complications in children with sickle cell anaemia (SCA) in the North but there are few data from Africa, where the majority of the patients reside. We measured daytime and overnight SpO2 in children with SCA in routine follow-up clinic, and controls without symptoms of SCA, comparing rural (Kilifi, Kenya) and urban (Dar-es-Salaam, Tanzania) cohorts. Daytime SpO2 was lower in 65 Tanzanian children with SCA (TS; median 97 (IQR 94-100)%); p<0.0001) than in 113 Kenyan children with SCA (KS; 99 (98-100)%) and 20 Tanzanian controls (TC; 100 (98-100)%). Compared with 95 Kenyan children with SCA, in 54 Tanzanian children with SCA and 19 TC who returned for overnight oximetry, mean (KS 99.0 (96.7-99.8)%; TS 97.9 (95.4-99.3)%; TC 98.4 (97.5-99.1)%; p=0.01) and minimum nocturnal SpO2 (92 (86-95)%; 87 (78.5-91)%; 90 (83.5-93)% p=0.0001) were lower. The difference between children with SCA persisted after adjustment for haemoglobin (p=0.004). Urban Tanzanian children, with and without SCA, experience greater exposure to low daytime and night-time SpO2 compared with rural Kenyan children with SCA. Possible explanations include differences in the prevalence of obstructive sleep apnoea or asthma, alterations in the oxyhaemoglobin desaturation curve or cardiovascular compromise, for example, to shunting at atrial or pulmonary level secondary to increased pulmonary artery pressure. The fact that non-SCA siblings in the urban area are also affected suggests that environmental exposures, for example, air pollution, nutrition or physical exercise, may play a role. Further studies should determine aetiology and clinical relevance for the SCA phenotype in children resident in Africa.

Nocturnal haemoglobin oxygen saturation variability is associated with vitamin C deficiency in Tanzanian children with sickle cell anaemia.

AIM: To compare pulse oximetry in children with sickle cell anaemia (SCA) and controls and test the hypothesis that vitamin C deficiency (VCD; <11.4 µmol/L) is associated with nocturnal haemoglobin oxygen desaturation in SCA. METHODS: We undertook nocturnal and daytime pulse oximetry in 23 children with SCA (median age 8 years) with known steady-state plasma vitamin C concentrations and 18 siblings (median 7 years). RESULTS: Median nocturnal delta 12 s index (delta12 s), a measure of haemoglobin oxygen saturation (SpO(2)) variability, was 0.38 (interquartile range 0.28-0.51) in SCA and 0.35 (0.23-0.48) in controls, with 9/23 and 6/18, respectively, having a delta12 s >0.4, compatible with obstructive sleep apnoea (OSA). Eleven of twenty-three with SCA had VCD; logged vitamin C concentrations showed a 66% decrease per 0.1 unit increase in delta12 s ([95% CI -86%, -15%]; p=0.023) and delta12 s >0.4 was associated with VCD (odds ratio 8.75 [1.24-61.7], p=0.029). Daytime and mean nocturnal SpO(2) were lower in SCA but there was no association with vitamin C. CONCLUSION: Obstructive sleep apnoea (OSA), detected from nocturnal haemoglobin oxygen saturation variability, is common in Tanzanian children and associated with vitamin C Deficiency in SCA. The direction of causality could be determined by comparing OSA treatment with vitamin C supplementation.

Vitamin A supplementation increases ratios of proinflammatory to anti-inflammatory cytokine responses in pregnancy and lactation.

Vitamin A supplementation reduces child mortality in populations at risk of vitamin A deficiency and may also reduce maternal mortality. One possible explanation for this is that vitamin A deficiency is associated with altered immune function and cytokine dysregulation. Vitamin A deficiency in pregnancy may thus compound the pregnancy-associated bias of cellular immune responses towards Th-2-like responses and exacerbate susceptibility to intracellular pathogens. We assessed mitogen and antigen-induced cytokine responses during pregnancy and lactation in Ghanaian primigravidae receiving either vitamin A supplementation or placebo. This was a double-blind, randomized, placebo-controlled trial of weekly vitamin A supplementation in pregnant and lactating women. Pregnancy compared to postpartum was associated with a suppression of cytokine responses, in particular of the proinflammatory cytokines interferon (IFN)-gamma and tumour necrosis factor (TNF)-alpha. Mitogen-induced TNF-alpha responses were associated with a decreased risk of peripheral parasitaemia during pregnancy. Furthermore, vitamin A supplementation was significantly associated with an increased ratio of mitogen-induced proinflammatory cytokine (IFN-gamma) to anti-inflammatory cytokine (IL-10) during pregnancy and in the postpartum period. The results of this study indicate that suppression of proinflammatory type 1 immune responses and hence immunity to intracellular infections, resulting from the combined effects of pregnancy and vitamin A deficiency, might be ameliorated by vitamin A supplementation.

The efficacy of external ultrasound-assisted liposuction: a randomized controlled trial.

BACKGROUND: Use of high-intensity, high-frequency external ultrasound before liposuction has been reported to enhance the ease of fat extraction, increase the amount of fat extracted, and decrease patient discomfort during liposuction. OBJECTIVE: The purpose of this study was to compare the effect of application of high-intensity continuous wave ultrasound to extremely low-intensity ultrasound (placebo) prior to tumescent liposuction. METHODS: A total of 19 patients (25 sites) completed the double-blind study. We used a split treatment area design so that each patient could serve as their own control. After tumesing the treatment area, a 3 W/cm2 continuous wave 1 MHz ultrasound was applied for 10 minutes. The placebo control was treated with 0.3 W/cm2 1 MHz for 10 minutes. Traditional tumescent liposuction followed ultrasound application. Doctors completed a visual analog scale rating the following: rate of extraction, degree of resistance to cannula movement, and color of fat. Patients also completed a questionnaire after the procedure and at 1 month postoperatively. Histologic samples of the fat treated with external ultrasound were taken from two patients. RESULTS: In 14 of 19 patients the doctors graded either no difference between treatment and control sides or found a better response on the nontreated side in rate of fat removal and resistance to cannula advancement giving a P value of .0096. Only 5 of 19 aspirates were graded as differing in redness between treatment and control sides. Four of these were more red on the control side and one was more red on the treatment side. Therefore 15 of 19 had no better result with treatment, giving a P value of .0022. Seven patients graded the sensation during suctioning and/or postoperative course as better on the control side, four graded these variables as better on the treatment side, four showed no difference between the two sides, and four had mixed results. This gives only 4 of the 19 patients showing any advantage in treatment with a P value of .0022. CONCLUSION: When the placebo effect is eliminated, there is no advantage to the application of external ultrasound prior to liposuction.

Characteristics of systemic antibody responses of nonhuman primates to cell envelope and cell wall antigens from periodontal pathogens.

The immune response of the primate, Macaca fascicularis, to cell envelope (CEA) or cell wall (CWA) antigens of several periodontal pathogens was examined to develop a strategy to interfere with ligature-induced periodontitis. Animals were parenterally immunized with CEA of either Porphyromonas gingivalis, Prevotella intermedia or a combination of CEA/CWA of Campylobacter rectus, Fusobacterium nucleatum and Actinomyces viscosus. Serum samples were taken every 2-4 weeks over a 4-month period, which included a 13-week interval with molar teeth ligated. All of the nonhuman primates in the study exhibited baseline levels of IgG, IgM and IgA antibody to formalinized whole cells of the bacteria. These levels increased significantly following immunization and were elevated above baseline throughout the remainder of the experiment. The largest change in antibody responses was seen in IgA antibody levels of P. gingivalis and C. rectus (42-fold above baseline), IgM antibody to P. intermedia, (41-fold increase) and IgG antibody to F. nucleatum and A. viscosus (32 and 63-fold increases). Moreover, the nonhuman primates exhibited differences in isotype response levels to whole microorganisms compared with the cell envelope antigens. These findings demonstrate the capacity of these nonhuman primates to produce an active immune response to microorganisms chronically colonizing the subgingival microbiota. Additionally, it appears that the bacteria may exhibit some unique differences in their immunogenicity as detected by the nonhuman primate and may contribute to the ability of the immune responses to effectively interact with these pathogens.

Treatment of melasma with Jessner's solution versus glycolic acid: a comparison of clinical efficacy and evaluation of the predictive ability of Wood's light examination.

BACKGROUND: Melasma can be resistant to topical therapy. OBJECTIVE: Our purpose was to evaluate the efficacy of superficial peels in conjunction with topical tretinoin and hydroquinone in patients with melasma and to evaluate the ability of Wood's light examination to predict response to treatment. METHODS: We measured increased light reflectance in melasma areas with a colorimeter. Clinical observations were scored through an index designed to weigh numerically homogeneity, intensity of color, and area of melasma. RESULTS: Colorimetric analysis showed an average lightening of 3.14 +/- 3.1 on the glycolic acid-treated side and 2.96 +/- 4.84 on the Jessner's solution-treated side. There was no statistically significant difference between the right and left. There was an overall decrease in melasma area and severity of 63%. CONCLUSION: Superficial peels hasten the effects of topical therapy in melasma. Wood's light examination did not help predict response to treatment.

Long-term efficacy and safety of Jessner's solution and 35% trichloroacetic acid vs 5% fluorouracil in the treatment of widespread facial actinic keratoses.

BACKGROUND: Few studies have examined the long-term efficacy of fluorouracil (FU) or chemical peels for the treatment of actinic keratoses (AK). Our earlier work examined the efficacy and safety of a medium-depth chemical peel compared with the standard regimen of topical FU in the treatment of widespread facial AK through 12 months. OBJECTIVES: To determine long-term efficacy of both treatments by extending our observations through 32 months. METHODS: Fifteen patients with severe facial actinic damage were treated on the left side with a single application of Jessner's solution and 35% trichloroacetic acid and on the right side with twice daily applications of 5% FU cream for 3 weeks. Parameters evaluated at 1, 6, 12, and 32 months included counts of visible AK, random skin biopsies from both treatment areas, development of intercurrent neoplasms, and surveys assessing sun exposure. RESULTS: Eight patients were available for reevaluation at 32 months. Both treatment sides showed a reduction in mean number of AK at 12 months followed by an increase in mean AK number between 12 and 32 months. Improvements in biopsies of clinically actinically damaged skin were seen in keratinocytic atypia, hyperkeratosis, parakeratosis, and inflammation at all treatment times during the study with both treatments. Three squamous cell carcinomas developed in the patients after initial treatment; one developed on the side treated with the peel, and two developed on the side treated with fluorouracil. Surveys failed to demonstrate an association between sun exposure and clinical response. CONCLUSION: Based on these findings, patient with widespread actinic keratoses treated with medium-depth chemical peel or with 5% FU should be reevaluated yearly or every 1.5 years for reappearance of AK and retreatment.

Preliminary characterization of the role of protein serine/threonine phosphatases in the regulation of human lung mast cell function.

1. Okadaic acid, a cell permeant inhibitor of protein serine/threonine phosphatases (PPs), attenuated the IgE-dependent release of mediators from human lung mast cells (HLMC). The concentration of okadaic acid required to inhibit by 50% (IC50) the IgE-dependent release of histamine was 0.2 microM. Okadaic acid also inhibited the IgE-mediated generation of prostaglandin D2 (PGD2) and sulphopeptidoleukotrienes (sLT) with IC50 values of 0.2 microM and 0.6 microM respectively. 2. The IgE-mediated generation of histamine, PGD2 and sLT was inhibited by okadaic acid and two analogues of okadaic acid, okadaol and okadaone, with the following rank order of activity; okadaic acid > okadaol > okadaone. This order of activity for the inhibition of mediator release parallels the activity of these compounds as inhibitors of isolated PPs. 3. Extracts of HLMC liberated 32P from radiolabelled glycogen phosphorylase and this PP activity was inhibited by the PP inhibitors (all at 3 microM), okadaic acid (73 +/- 4% inhibition, P < 0.0005), okadaol (26 +/- 7% inhibition, P < 0.05) and okadaone (8 +/- 7% inhibition, P = 0.52). The rank order of activity of okadaic acid > okadaol > okadaone parallels the activity of these compounds as inhibitors of isolated PPs. 4. Dephosphorylation of radiolabelled glycogen phosphorylase by extracts of HLMC was inhibited by 15 +/- 3% (P < 0.001) by a low (2 nM) concentration of okadaic acid and by 88 +/- 4% (P < 0.0005) by a higher (5 microM) concentration of okadaic acid. Because 2 nM okadaic acid may act selectively to inhibit PP2A whereas 5 microM okadaic acid inhibits both PP1 and PP2A, these data suggest that both PP1 and PP2A are present in HLMC. 5. Inhibitor 2, a PP1-selective inhibitor, attenuated (71 +/- 3% inhibition, P < 0.05) PP activity in extracts of HLMC suggesting that HLMC contain PP1 and that it may constitute 71% of the phosphorylase PP activity in extracts of HLMC. 6. Radiolabelled casein, a PP2A-restricted substrate, was dephosphorylated by extracts of purified HLMC and this activity was inhibited (81 +/- 8% inhibition, P < 0.005) by 2 nM okadaic acid suggesting that PP2A is resident in HLMC. 7. Collectively, these data suggest that both PP1 and PP2A are resident in HLMC. However, although the data suggest that okadaic acid regulates responses in HLMC by interacting with PPs, it has not been possible to determine whether either PP1 or PP2A or both PPs are involved in the okadaic acid-induced inhibition of mediator release from HLMC.

A comparison of the efficacy and safety of Jessner's solution and 35% trichloroacetic acid vs 5% fluorouracil in the treatment of widespread facial actinic keratoses.

BACKGROUND AND DESIGN: We compared the efficacy and safety of a medium-depth chemical peel with those of the standard regimen of topical fluorouracil in the treatment of widespread facial actinic keratoses (AK). Fifteen patients with severe facial actinic damage and similar numbers of AK on both sides of the face were treated on the left side with a single application of Jessner's solution and 35% trichloroacetic acid and on the right side with twice daily applications of 5% fluorouracil cream for 3 weeks. Evaluations were conducted before treatment and at 1, 6, and 12 months after treatment. Visible AK were counted, random skin biopsies performed, adverse effects monitored, and patients questioned about preference and perception of efficacy. RESULTS: Both treatments reduced the number of visible AK by 75% and produced equivalent reductions in keratinocyte atypia, hyperkeratosis, parakeratosis, and inflammation, with no significant alteration of preexisting solar elastosis and telangiectasia. Except for erythema that lasted 3 months in one patient, no untoward side effects were observed with the chemical peel. The majority of patients preferred the peel over fluorouracil because of the single application and less morbidity. CONCLUSION: The medium-depth peel induced by Jessner's solution and 35% trichloroacetic acid is a useful alternative therapeutic option for widespread facial AK, particularly for poorly compliant patients, because it equals fluorouracil in efficacy while being superior in terms of the convenience of a single application with little associated morbidity.

Pemphigus erythematosus in a five-year-old child.

A 5-year-old girl had pemphigus erythematosus based on clinical and immunohistologic criteria. The rare occurrence in childhood of the pemphigus group of disorders, and of pemphigus erythematosus in particular, is discussed. We also review current knowledge concerning the delineation of the different pemphigus subsets and the treatment of pemphigus erythematosus.

A spectrum of inflammatory metastasis to skin via lymphatics: three cases of carcinoma erysipeloides.

We report a case in which carcinoma erysipeloides was the first sign of the primary malignancy in a patient with a rare form of prostate carcinoma (mixed adenosquamous type) and two cases in which carcinoma erysipeloides was a marker of tumor recurrence in two patients with breast carcinoma. The value of recognizing the distinctive inflammatory manifestation of carcinoma erysipeloides and the significance of dermal lymphatic involvement in this form of skin metastasis are discussed.

Propagation of small bowel migrating motor complex activity fronts varies with anastomosis type.

Fasting small intestine motility (migrating motor complex or MMC) occurs in humans and dogs in four phases. Activity fronts during phase III consist of high amplitude contractions propagating aborally and are interrupted by transection of the small intestine. To study the effect of anastomosis type on MMC propagation six dogs underwent resection of a 15-cm segment of bowel 45 cm distal to the ligament of Treitz and single layer hand sewn end-to-end (EE) anastomosis. Single layer end-to-side (ES) or side-to-side (SS) anastomoses were hand sewn 15 cm distal to the transection in six other dogs. Eight force transducer strain gauges were placed at 10-cm intervals about each anastomosis. At least 7 days after operation, small bowel contractions were recorded in fasted animals, and recordings were visually inspected. Only 1 of 36 activity fronts propagated across the end-to-end anastomosis within 45 days of surgery. However, after 60 days 25 of 39 phase III activity fronts propagated. There was no propagation of MMC activity across the ES anastomosis and only 10% of activity fronts propagated across the SS anastomosis. We conclude phase III MMC activity front propagation is interrupted by small bowel transection. Propagation regenerates after EE anastomosis, but not after ES or after SS anastomoses, even after prolonged healing.

Salivary IgA responses to Porphyromonas gingivalis in the cynomolgus monkey. 1. Total IgA and IgA antibody levels to P. gingivalis.

Porphyromonas gingivalis has been associated with the subgingival plaque of advancing disease lesions in various types of periodontitis. Additionally, this species of oral microorganism has been found to increase dramatically in ligature-induced periodontitis in nonhuman primates (Macaca fascicularis) and has recently been shown to induce progressing disease when implanted into the subgingival plaque in this animal model. Although systemic antibody responses have been demonstrated to P. gingivalis in both human and nonhuman primate with periodontitis, no information is available on the oral secretory IgA antibody response to this bacteria. This report describes the methods for reproducible collection of salivary secretions from cynomolgus monkeys and the development of methods for analyzing salivary IgA levels and specific IgA antibody in the saliva reactive with P. gingivalis. Purification of monkey salivary IgA allowed quantification of IgA using an enzyme-linked immunosorbent assay (ELISA). Estimation of total IgA levels in saliva showed approximately a 20% greater level of IgA in whole versus parotid saliva from a group of 13 monkeys, with a 2-3 fold variation in levels among this group of animals. Naturally occurring salivary IgA antibody to P. gingivalis, as measured by ELISA, were routinely detectable but low in whole saliva; however, many of the parotid saliva specimens collected exhibited negligible levels of antibody to this microorganism. The IgA antibody in whole saliva showed nearly an 18-fold variation among the samples from the monkeys. Correlational analyses indicated that, although there was a positive relationship between antibody levels in whole and parotid saliva, the majority of natural IgA antibody in whole saliva appears to be derived from other sources.(ABSTRACT TRUNCATED AT 250 WORDS)

Grouping of beta-haemolytic streptococci by agglutination.

Streptococcal grouping sera, diluted and absorbed to remove cross-reactions, were bound to staphylococci and used to group trypsinised beta-haemolytic streptococci by coagglutination. The results compared well with those obtained using the Phadebact streptococcal grouping kit. The same sera bound to staphylococci without prior dilution and absorption could be used to group enzyme extracts of haemolytic streptococci by slide agglutination, the results again comparing favourably with those of the Phadebact kit.