Measuring HIV- and TB-related stigma among health care workers in South Africa: a validation and reliability study.

SETTING: Recent evidence indicates that human immunodeficiency virus (HIV) and tuberculosis (TB) related stigma act as a key barrier to the utilisation of associated occupational health services by South African health care workers (HCWs). It also highlights a dearth of appropriate tools to measure HIV and TB stigma among HCWs. OBJECTIVE: To test four scales measuring different aspects of stigma: respondent's external stigma (RES) and others' external stigma (OES) towards TB as well as HIV across different professional categories of HCWs. DESIGN: The current study employs data from a study on HIV and TB stigma among HCWs, a cluster randomised controlled trial for the collection of data among 882 HCWs in the Free State Province of South Africa. Confirmatory factor analyses and structural equation modelling were used to assess the validity and reliability of the scales. RESULTS: All four scales displayed adequate internal construct validity. Subsequent analysis demonstrated that all four scales were metric-invariant, and that the OES scales were even scalar-invariant across patient and support staff groups. The scales displayed good reliability and external construct validity. CONCLUSION: Our results support the use of the scales developed to measure TB and HIV stigma among HCWs. Further research is, however, needed to fine tune the instruments and test them across different resource-limited countries.

Long-term Care of Children and Adolescents with Intellectual Disabilities and Severe Physical Abnormalities

Objective: This study sets out to review the clinical profile and treatment program of children and adolescents with intellectual disability in Waverley Care Center (WCC). Method: A retrospective review was done of users from January to December 2004. Reviewed parameters included age; gender; length of stay; DSM IV diagnoses; current medical treatment; and level of functioning and mobility according to the Therapeutic Classification System for Children (TCS). Results: A total of 179 users were receiving care. Although the mean age of users was 14 to 15 years; their ages ranged from 3 to 34 years. The gender ratio of users was 1 (female) to 1.6 (male). The average length of stay was 6.73 years and the range of stay from 0.5 to 29 years. Attention deficit hyperactivity disorder was diagnosed in eight children and pervasive disorders were suspected in some. Intellectual impairment ranged from severe to profound. Specific interventions with regard to severe physical impairments were made by occupational therapy and physiotherapy

Adjunctive thalidomide therapy of childhood tuberculous meningitis: possible anti-inflammatory role.

The objective of this study was to determine the safety and tolerability of the immunomodulatory agent thalidomide as adjunct therapy in children with tuberculous meningitis. Children with stage 2 tuberculous meningitis received oral thalidomide for 28 days in a dose-escalating study, in addition to standard four-drug antituberculosis therapy, corticosteroids, and specific treatment of complications such as raised intracranial pressure. Clinical and laboratory evaluations were carried out. Fifteen patients (median age, 34 months) were enrolled. Thalidomide was administered via nasogastric tube in a dosage of 6 mg/kg/day, 12 mg/kg/day, or 24 mg/kg/day. The only adverse events possibly related to the study drug were transient skin rashes in two patients. Levels of tumor necrosis factor-alpha in the cerebrospinal fluid decreased markedly during thalidomide therapy. Clinical outcome and neurologic imaging showed greater improvement than that experienced with historical controls. Thalidomide appeared safe and well tolerated in children with stage 2 tuberculous meningitis and could have important anti-inflammatory effects. These promising results have led us to embark on a randomized, double-blind, placebo-controlled trial of the efficacy of thalidomide in tuberculous meningitis.

Quantifying the radiation dosage to individual skeletal lesions treated with samarium-153-EDTMP.

UNLABELLED: Samarium-153ethylenediaminetetramethylenephosphonate (EDTMP) is used in the treatment of painful skeletal lesions. This study attempted to quantify the radiation dosage to individual lesions on both the macroscopic and microscopic level. METHODS: A gamma camera-based quantification technique was adapted and refined for 153Sm. The accuracy of the technique was determined by using a realistic phantom. The activity and volume of lesions as well as normal bone were determined and used to estimate the radiation dosages to these regions. Two patients died of unrelated causes shortly after receiving 153Sm-EDTMP. This made it possible to compare the gamma camera results with direct measurements. It also allowed for autoradiographic examination of the lesions. Finally, the microscopic radiation dosages were estimated. RESULTS: The phantom study indicated that the quantification technique was off, on average, by 4.1% (s.d. = 8.1%). The absolute activity concentration of trabecular bone was found to be approximately 0.22 MBq/g, and that of cortical bone was found to be approximately 0.1 MBq/g, regardless of the dosage administered. The corresponding concentrations for lesions were between 3 and 7 times higher than that of normal bone, with no apparent ceiling. From these results, the macroscopic radiation dosage could be estimated. The dosage to normal bone varied between 0.9 and 3.9 cGy x kg/MBq, and that of the lesions varied between 5.2 and 27.1 cGy x kg/MBq. The autopsy results confirmed that the gamma camera technique was accurate. The autoradiography showed clearly that the activity was associated with the surface of the bone. From these findings, the microscopic radiation dosage distribution was estimated for cortical and trabecular bone as well as osteoblastic lesions. The variation in the microscopic dosage compared to the macroscopic dosage was quite large. Microscopic dosages, when compared to the macroscopic dosages, were as high as 965% and as low as 14.9%. CONCLUSION: The techniques used have been proven to be accurate. The activity in normal bone may be at a ceiling value for all the administered doses, which could explain the small variation. This is not true for the lesions. The large variation in dosages on a microscopic scale, combined with the ceiling in normal bone, may explain the lower than expected toxicity and relatively quick relapse of the patients.

Ribosomal DNA-polymerase chain reaction assay discriminates between Anopheles quadriannulatus and An. merus (Diptera: Culicidae).

A ribosomal DNA polymerase chain reaction technique (rDNA-PCR) that distinguishes the 5 more common and widespread members of the Anopheles gambiae complex failed to consistently identify specimens of Anopheles merus Dönitz collected in South Africa and Tanzania. When the original rDNA-PCR assay was applied to field-collected specimens or specimens from laboratory colonies established from these populations, bands diagnostic of both An. merus and An. quadriannulatus (Theobald) were amplified from all individual specimens. However, all the specimens tested had the polytene chromosome banding morphology or the superoxide dismutase isozyme that were diagnostic for An. merus. Replacement of the original An. quadriannulatus-specific primer with a new primer derived from another region of the rDNA intergenic spacer resulted in an alternative rDNA-PCR assay that accurately and consistently differentiated among specimens of An. merus, An. quadriannulatus, and An. arabiensis Patton. Anopheles gambiae Giles also may be distinguished by this assay if high percentage agarose gels or gels of other matrices with better resolving powers are used.

Dose response relationship and multiple dose efficacy and toxicity of samarium-153-EDTMP in metastatic cancer to bone.

INTRODUCTION: The optimal dose of samarium-153-EDTMP (153Sm-EDTMP) for effective palliation of painful metastases to bone is under investigation. It is not known whether increased doses of 153Sm EDTMP will lead to better and longer pain and tumour control and survival. Multiple dose efficacy and toxicity is of importance as most Patients will require prolonged support for pain. METHODS: Twenty-eight (28) patients were treated with 0.75 mCi/kg, 35 patients with 1.5 mCi/kg and 19 patients with 3 mCi/kg in three sequential Phase I-II trials. Multiple doses were given to patients on the 0.75 mCi/kg and 1.5 mCi/kg dose levels. RESULTS: At all dose levels adequate pain control was achieved in 78-95% of patients. The duration of pain control was 40-56 days with the best results in the 1.5 mCi/kg group (56 days). There is no evidence that increasing dose leads to better and longer pain control, tumour response and survival, but toxicity is increased. Multiple doses can be given with acceptable toxicity and pain control, however, only 38% of patients will qualify for multiple treatments. CONCLUSION: 153Sm-EDTMP provides adequate and safe palliation but multiple doses can only be given in 38% of patients. There is not a clear dose-response relationship. The length of pain control is satisfactory but not ideal and hospitalisation for 4 days every 6-8 weeks is a disadvantage. Further research is required to combine 153Sm-EDTMP with cytostatics and to administer it on an out patient basis.

Evaluation of samarium-153 and holmium-166-EDTMP in the normal baboon model.

Bone-seeking radiopharmaceuticals such as ethylenediaminetetramethylene phosphonate (EDTMP) complexes of samarium-153 and holmium-166 are receiving considerable attention for therapeutic treatment of bone metastases. In this study, using the baboon experimental model, multicompartmental analysis revealed that with regard to pharmacokinetics, biodistribution, and skeletal localisation, 166Ho-EDTMP was significantly inferior to 153Sm-EDTMP and 99mTc-MDP. A more suitable 166Ho-bone-seeking agent should thus be sought for closer similarity to 153Sm-EDTMP to exploit fully the therapeutic potential of its shorter half-life and more energetic beta radiation.

The polymerase chain reaction method as a tool for identifying members of the Anopheles gambiae complex (Diptera:Culicidae) in northeastern Tanzania.

Polymerase chain reaction (PCR) primers developed at the Centers for Disease Control in Atlanta for the identification of members of the Anopheles (Cellia) gambiae Giles complex were tested on material collected in the Bagamoyo and Muheza districts of northeastern Tanzania. Part of the sample from Bagamoyo was chromosomally identified and correlated with the PCR identifications. This sample contained 170 Anopheles arabiensis, 328 An. gambiae, and 58 Anopheles merus, of which 121, 237, and 54 specimens, respectively, were identified with both PCR and chromosomes. Three specimens identified chromosomally as An. merus gave only the PCR fragment characteristic for Anopheles quadriannulatus, but on retesting gave the correct result. The Muheza sample consisted of 771 An. arabiensis, 852 An. gambiae, 43 An. merus, and 4 specimens producing the fragment characteristic for An. quadriannulatus. Because An. quadriannulatus has never been recorded from mainland Tanzania and due to the high number of specimens that produced no result (193), it is probable that DNA degradation led to misidentification of An. merus specimens as An. quadriannulatus. The overall probability of correct identification by PCR was 99.685% at first testing, which compares favorably with other genetic methods currently in use.

Samarium-153-EDTMP for palliation of ankylosing spondylitis, Paget's disease and rheumatoid arthritis.

Samarium-153-EDTMP is an effective agent for palliation of widespread skeletal metastases because it concentrates in bone metastases which have an osteoblastic component. Similar concentration in areas of osteoblastic activity in ankylosing spondylitis, Paget's disease and rheumatoid arthritis suggests a possible new treatment approach. Three patients with ankylosing spondylitis, one patient with Paget's disease and one patient with rheumatoid arthritis were treated with 153Sm-EDTMP. Objective and subjective improvement was noted, especially in ankylosing spondylitis patients. Samarium-153-EDTMP has disease-modifying potential in ankylosing spondylitis and Paget's disease and has palliative value in resistant rheumatoid arthritis. Further trials to determine optimal dose, treatment scheduling, long-term disease-modifying potential and toxicity are needed.

Shewanella (Pseudomonas) putrefaciens bacteremia.

Shewanella (Pseudomonas) putrefaciens is a rare pathogen in humans, and to our knowledge only 13 cases of S. putrefaciens bacteremia have ever been reported in the literature. In this retrospective study we describe 28 cases of S. putrefaciens bacteremia: 16 in premature and 1-day-old neonates, 9 in adults, and 3 in children younger than 1 year of age. All the babies presented with respiratory distress and/or pneumonia. Six of the adults had associated traumatic lesions of the lower extremity, and of the eight patients who died of sepsis, six were neutropenic. Polymicrobial bacteremia was seen in 18 cases. Three syndromes of bacteremic infection with S. putrefaciens appear to exist: the first is associated with prematurity and congenital pneumonia; the second with ulceration of the lower extremities; and the third (which is more fulminant), with an underlying debility. The findings in these 28 cases confirm the fact that S. putrefaciens can invade the bloodstream; however, the presence of concurrent bacteremia makes it difficult to determine the pathogenic role of this organism in septicemia.

The channel ratio method of scatter correction for radionuclide image quantitation.

The accuracy of quantitation of radionuclide distributions in human tissue with the scintillation camera is decreased by attenuation and scatter of photons. If scatter correction is applied satisfactorily, narrow beam attenuation can be applied. In this article, a scatter correction technique, the channel ratio (CR) method, is introduced. The CR scatter correction method is proposed for quantitation of the radionuclide distribution in organs. The improvement in the geometrical resolution was measured and examples of clinical images are presented. In this method, the change in the ratio of counts from two symmetrical adjacent energy windows straddling the energy photopeak was used to eliminate the contribution of scattered photons during imaging with 99mTc. The theory and methods for the empirical affirmation are described. To apply the CR scatter correction method, two constants, the ratio of primary photons G and the ratio of scattered photons H in the same windows, were determined. Different sized sources in varying depths of water were imaged. When the source activities were quantified after scatter correction with the CR method, the measurements ranged from 96%-108% in comparison to the reference value in 100 mm water. The scatter fraction increased from 0.20 in 10 mm water to 1.44 in 200 mm water. The geometrical resolution expressed as full width at tenth maximum in 150 mm water improved by 30.4% and was restored to the value of the geometrical resolution in air. The CR scatter correction method is a simple method to correct for scatter in order to facilitate accurate quantitation of the radionuclide distribution during imaging with a scintillation camera.

Thalassemia: lung function with reference to iron studies and reactive oxidant status.

Pulmonary function tests were performed in 15 thalassemic patients (age 5 years 8 months to 18 years 6 months), receiving both regular transfusions and desferrioxamine, to determine the presence and nature of any abnormalities in lung function. Reactive oxidant production from neutrophils was measured simultaneously to ascertain if a causal relationship existed between free radical production and tissue damage in the lungs. Mean total lung capacity, mean residual volume, and mean forced vital capacity were significantly reduced, indicating a restrictive pattern of lung function abnormality. In addition, the carbon monoxide diffusion was low, and hypoxemia was present in 6 of 13 patients tested. These pulmonary function abnormalities did not correlate with age, cumulative volume of transfusion, or serum ferritin levels. In addition, neutrophil reactive oxidant status did not correlate with these or with pulmonary function parameters. These results indicate that neutrophil-derived oxygen free radicals do not appear to be a major cause of lung function abnormalities in thalassemics.

Passive smoking by humans sensitizes circulating neutrophils.

The proinflammatory effects of passive inhalation of cigarette smoke were investigated by exposing a total of 16 healthy, young nonsmokers (mean age 29 +/- 1.4 yr, 11 women and five men) to actively smoking individuals in a poorly-ventilated room. Neutrophil functions were measured before and after 3 h of exposure to cigarette smoke. Passive cigarette smoking was associated with increased leukocyte counts (mean increase 33%, p less than 0.005), chemotaxis (57%, p less than 0.001), and release of reactive oxidants (71%, p less than 0.005) by stimulated neutrophils. These results were confirmed in a second study designed to eliminate the possible complicating effects of serial venepuncture. Plasma concentrations of the proinflammatory cytokines interleukin-1 (IL-1) alpha, IL-1 beta, IL-6, and tumor necrosis factor alpha (TNF alpha) were not affected by passive smoking. These results indicate that inhalation of sidestream tobacco smoke promotes systemic priming of neutrophils. These potentially proinflammatory events may induce oxidant-mediated tissue damage and carcinogenesis in the lungs of passive smokers.

Comparison of the pro-oxidative interactions of flunoxaprofen and benoxaprofen with human polymorphonuclear leucocytes in vitro.

At concentrations of 3.75 micrograms/ml and greater the non-steroidal anti-inflammatory drugs, benoxaprofen and to a lesser extent flunoxaprofen, caused dose-related spontaneous activation of both luminol- and lucigenin-enhanced chemiluminescence in human polymorphonuclear leucocytes (PMNL) in vitro. Flunoxaprofen- and benoxaprofen-mediated activation of oxidant release by PMNL was increased by UV-radiation. Pre-incubation of PMNL with sub-stimulatory concentrations of both drugs greatly enhanced the release of reactive oxygen species on subsequent exposure of the cells to various standard stimuli of membrane-associated oxidative metabolism. The protein kinase C inhibitor, H-7, and the phospholipase A2 inhibitor, BPB, both prevented drug-mediated activation of superoxide generation by PMNL. Flunoxaprofen-mediated stimulation of PMNL membrane-associated oxidative metabolism is, like benoxaprofen, due to apparent activation of protein kinase C. These findings establish the pro-oxidative properties of flunoxaprofen.

Investigation of the effects of oral administration of vitamin E and beta-carotene on the chemiluminescence responses and the frequency of sister chromatid exchanges in circulating leukocytes from cigarette smokers.

Sixty asymptomatic cigarette smokers were randomly allocated into three treatment groups. Smokers in Group 1 received 900 international units of Vitamin E (VE) daily for 6 wk, whereas 40 mg of beta-carotene (BC) daily was administered to those in Group 2 for the same period. Subjects in Group 3 were treated with a matched placebo. Plasma levels of VE and BC as well as circulating leukocyte counts, sister chromatid exchanges (SCEs), and the luminol-enhanced chemiluminescence (LECL) responses of blood phagocytes activated with phorbol myristate acetate (PMA) and FMLP with cytochalasin B (FMLP/CB) were measured prior to the administration of the antioxidant/placebo after 4 and 6 wk of supplementation and 12 wk after cessation of treatment. SCEs and leukocyte counts remained unchanged throughout the trial in all three treatment groups. Administration of VE for 4 wk was accompanied by decreased FMLP/CB-activated (p less than 0.005) and PMA-activated (p less than 0.005) LECL responses. However, with PMA as stimulant, the inhibition of LECL was transient, with partial recovery observed after 6 wk despite continued administration of VE. Administration of BC was associated with progressive inhibition of both FMLP/CB-activated (p less than 0.05 and p less than 0.01 after 4 and 6 wk, respectively) and PMA-activated (p less than 0.025 after 6 wk) LECL. No alterations in LECL responses were observed in Group 3 (placebo). VE appeared to inhibit the generation of oxidants by activated phagocytes, whereas BC scavenged oxidants generated by the myeloperoxidase/H2O2/halide system.

Investigation of the role of phagocytes and anti-oxidant nutrients in oxidant stress mediated by cigarette smoke.

In this study we have correlated the plasma levels of the anti-oxidant vitamins C and E, and beta-carotene with smoking histories, the release of reactive oxidants from circulating phagocytes and spirometry in asymptomatic cigarette smokers. Smoking histories, the generation of reactive oxidants by activated phagocytes and spirometric abnormalities were strongly inter-correlated. However, plasma levels of the anti-oxidant nutrients did not correlate with any of the other measured parameters. These findings indicate that plasma levels of vitamins C and E, and beta-carotene are apparently not predictive of predisposition to oxidant-mediated-spirometric abnormalities in cigarette smokers.

Methicillin resistance and beta-lactamase production in Staphylococcus aureus.

Staphylococcus aureus isolates were either sensitive, resistant or partially resistant (minimum inhibitory concentration 90 of 4 micrograms/ml) to methicillin. Low-level methicillin resistance was shown to be due to beta-lactamase production. The clinical significance of this beta-lactamase-mediated resistance is still unclear, so it is recommended that these strains should, at present, be regarded as methicillin-resistant.