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.

The effects of increasing weekly doses of ascorbate on certain cellular and humoral immune functions in normal volunteers.

Certain functions of the blood neutrophils and lymphocytes from normal adult volunteers were evaluated after the ingestion of increasing doses of ascorbate. Serum immunoglobulins and levels of C'3 and total hemolytic complement were also measured. Enhancement of neutrophil motility to a chemotactic stimulus of endotoxin-activated autologous serum was observed in normal adult volunteers after the ingestion of 2 and 3 g ascorbate daily. No alteration was observed at lower doses. Other neutrophil functions evaluated that remained unaltered by ascorbate, were postphagocytic hexose monophosphate shunt activity and myeloperoxidase mediated iodination of ingested protein. Stimulation of lymphocyte transformation to the mitogens phytohaemagglutinin and concanavalin A was detected after the daily ingestion of 1, 2, and 3 g of ascorbate. Mitogen-induced protein synthesis was unaffected. Serum levels of IgG, IgA, IgM, C'3, and C'4 and total complement activity were unaltered by ascorbate.

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.

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.

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.

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.

An evaluation of four methods of 111In planar image quantification.

The accurate quantification of the in vivo distribution of 111In labeled platelets, other cells, and proteins with a scintillation camera is important in clinical and experimental medicine. Planar techniques of image quantification were therefore evaluated with the aim of improving on the accuracy, and simplifying the techniques currently in use. The attenuation of the 172- and 247-keV photons of 111In, singly and in combination, was determined for varying diameter flat sources (3.4 to 16.9 cm). The influence of region of interest (ROI) selection on the shape of the attenuation curves was also determined for five different ROI's. Defining the attenuation curves mathematically generated parameters of fit for three approaches to in vivo quantification, namely: a single exponential geometric mean approach that takes into account source size, depth-dependent, and depth-independent buildup factor approaches to account for the contribution of scatter. The accuracy of these techniques was ascertained and compared to the classical geometric mean method. This was done in a waxen phantom of a human thorax with a hollow liver and spleen. The results indicated that the depth-independent buildup factor is the best method; the error for quantification in the spleen was 0.8% +/- 2.2%. The classical geometric mean approach gave a corresponding error of 43.3% +/- 3.4%. Since the attenuation of the two energies of 111In differ, their ratio changes with depth. This phenomenon was investigated with the goal of determining whether the depth of an object can be estimated from one set of planar images. This was not successful.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

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.

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.

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.

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.

The in vitro effects of propranolol and atenolol on neutrophil motility and post-phagocytic metabolic activity.

Propranolol at concentrations of 1 x 10(-6) to 1 x 10(-4) M consistently increased neutrophil motility as measured in Boyden chambers. The effects were not due solely to stimulation of random migration and chemokinesis but also of directional motility. Propranolol, over a similar concentration range, caused inhibition of post-phagocytic cell metabolic activity (hexose monophosphate shunt, nitro-blue tetrazolium reduction and protein iodination) without any detectable effect on the ingestion rate of Candida albicans. Atenolol had no effect on any of these neutrophil functions. Both drugs were without effect on glycolysis and intracellular cyclic AMP levels. Propranolol however, at concentrations which stimulated cell motility, caused increased intracellular cyclic GMP levels. It is suggested that propranolol may stimulate neutrophil motility by promoting increased intracellular cyclic GMP levels or by decreasing neutrophil superoxide production.

Clinical aspects of chronic brucellosis.

Twenty-one patients with brucellosis wereinvestigated. Four patients with the classical manifestations of acute brucellosis presented no problems in diagnosis. The other 17 patients suffered from chronic disease and had no history of any acute episode of brucellosis. The most common symptoms in this group were tiredness, fatigue, depression, arthralgia and muscular pains. Abdominal pain and pain in the temperomandibular joints were marked in some patients. Most of these patients had been receiving psychiatric treatment. Clinical examination was largely negative, but lymphadenopathy was found in 9 cases. Brucella meningo-encephalitis was diagnosed in 7 patients who complained of severe headache. Problems in the diagnosis of chronic brucellosis with an insidious onset are discussed.

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.

A halothane-induced biochemical defect in muscle of normal and malignant hyperthermia-susceptible Landrace pigs.

Muscle adenosine triphosphate (ATP), glucose-6-phosphate, phosphocreatine, and pH were measured in nine malignant hyperthermia (MH)-susceptible and 14 MH-resistant Landrace pigs. Muscle biopsies were taken before (under barbiturate anesthesia) and after exposure to halothane. When compared to levels during barbiturate anesthesia, exposure to halothane had no immediate effect on muscle ATP levels in either MH-susceptible or -resistant pigs. However, once malignant hyperthermia developed in susceptibe pigs ATP levels decreased significantly. In both susceptible and resistant pigs halothane increased muscle glucose-6-phosphate and decreased muscle phosphocreatine and pH significantly below control levels observed during barbiturate anesthesia. In susceptible pigs these changes were significantly more marked than were the changes produced in resistant pigs. These data indicate that the effect of halothane on muscle metabolism is similar in both MH-resistant and -susceptible pigs. The results suggest that the effect of halothane is to inhibit aerobic metabolism by preventing mitochondrial dehydrogenation of pyruvate. Inhibition is complete in susceptible pigs but only retarded in resistant pigs. In susceptible pigs the consequent lactacidosis, hyperthermia, and reduction in ATP synthesis contribute to the development and maintenance of rigidity.

The use of transfer factors in the treatment of multiple sclerosis: a case report.

A 23-year-old woman suffering from multiple sclerosis (MS) was given a course of 6 injections (0.5 U) of mumps transfer factor (TF) at 2-weekly intervals. The patient's symptoms improved dramatically and during the 10 months since treatment was instituted, no exacerbations have occurred. The possible aetiological role of paramyxoviruses in MS and the use of TF in the treatment of the disease are discussed. MS is however, a disease of exacerbations and spontaneous remissions, and despite our promising findings in this patient we wish to refrain from hailing mumps TF as a possible cure for this notorious disease.

Studies on a naturally occurring R factor harbouring a chromosomal nutritional marker.

A naturally occurring R factor which carried resistance determinants to tetracycline and chloramphenicol as well as a marker for lactose fermentation was found in a strain of Klebsiella pneumoniae isolated from sewage. The TcCmlac+ factor was transferred by conjugation to E. coli K12. It showed no recombination or stable coexistence with R factors of the fi- class. Studies in recombination-deficient (rec-) strains of E. coli K12 showed that the TcCmlac+ factor is an autonomously replicating plasmid. Preparative ultracentrifugation and electron microscopic studies revealed the presence of more than one molecular species. Average contour lengths for two of these species were 11,20 +/- 1,55 mum and 16,14 +/- 1,45 mum, which correspond to molecular weights of about 23,18 X 10(6) and 34,63 X 10(6) daltons, respectively.

Effects of sulfamethoxazole and trimethoprim on human neutrophil and lymphocyte functions in vitro: in vivo effects of co-trimoxazole.

The effects of sulfamethoxazole and trimethoprim individually and in combination on in vitro neutrophil random migration, chemotaxis to autologous endotoxin-activated serum and the synthetic chemotactic tripeptide N-formyl-L-methionyl-L-leucyl-L-phenylalanine, phagocytosis and postphagocytic Nitro Blue Tetrazolium reduction, glycolysis, hexose monophosphate shunt activity, myeloperoxidase-mediated protein iodination, hydrogen peroxide production, and degranulation were assessed. The effects on lymphocyte mitogen-induced transformation were also evaluated. It was found that the test agents individually and in combination at high concentrations (> 100 microgram/ml) caused the inhibition of neutrophil postphagocytic myeloperoxidase-mediated protein iodination, which was related to the interference with H2O2 formation as the enzyme per se was unaffected. Both agents caused the inhibition of lymphocyte transformation at high concentrations (> 100 microgram/ml). In vivo studies before and after the ingestion of co-trimoxazole by three individuals showed no inhibition of any of the neutrophil functions tested. The inhibition of lymphocyte transformation was observed in one individual after the ingestion of the chemotherapeutic agent. These findings indicate that the concentrations which inhibit neutrophil H2O2 production and lymphocyte transformation in vitro are not attainable in vivo.