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Biomedical subjects

N Beyers

Publications and source records attributed to N Beyers.

At least 91 records · Page 5Linked to original sources
PubMed1996

The 5-year outcome of multidrug resistant tuberculosis patients in the Cape Province of South Africa.

Little is known about the outcome of multidrug resistant (MDR) tuberculosis (TB) in developing countries. In this study, 443 patients with MDR-TB, defined as resistance to two or more antituberculosis drugs, were identified over the 2-year period 1987 and 1988 in the Cape Province of South Africa. The 5-year outcome of the 343 (77%) patients that could be traced by questionnaire was evaluated retrospectively during 1992 and 1993. Of these, 240 (70%) were resistant to both isoniazid (H) and rifampicin (R) with or without resistance to other first-line antituberculosis drugs and 103 (30%) were resistant to H or R and/or other antituberculosis drugs. Mortality was 116 (48%) and 28 (27%) in these groups respectively with a significantly greater risk of death in the first group. Only 114 (33%) of all the MDR-TB patients were cured after 5 years, 50 (15%) were respiratory disabled and 44 (13%) were still bacteriology positive. Twenty-four (7%) patients were lost during follow-up. Taking into account the high costs involved in treating MDR-TB patients and the scarce resources available in developing countries, more emphasis should be placed on direct observed therapy to cure newly diagnosed infectious drug sensitive tuberculosis patients, thus preventing MDR-TB rather than treating it.

Adolescent↗
PubMed1996

Genotyping of Mycobacterium tuberculosis with additional markers enhances accuracy in epidemiological studies.

Two highly polymorphic Mycobacterium tuberculosis genomic domains, characterized by hybridization to the oligonucleotide (GTG)5, were identified as potential DNA fingerprinting probes. These domains were cloned [pMTB484(1) and pMTB484(2K4), respectively] and shown to be useful for genotype analysis by Southern blotting. These probes were used to genotype geographically linked strains of M. tuberculosis previously shown to have identical IS6110 fingerprints. Subsequent DNA fingerprints generated with MTB484(1) and MTB484(2K4) showed a high degree of polymorphism, allowing subclassification of IS6110-defined clusters into composites of smaller clusters and unique strains. Correlation of the molecular data with patient interviews and clinical records confirmed the sensitivity of these probes, as contacts were established only within subclusters. These findings demonstrate the requirement for multiple probes to accurately classify M. tuberculosis strains, even those with high copy numbers of IS6110. The enhanced accuracy of strain typing should, in turn, further our understanding of the epidemiology of tuberculosis.

Bacterial Typing Techniques↗
PubMed1996

The use of a geographical information system (GIS) to evaluate the distribution of tuberculosis in a high-incidence community.

OBJECTIVE: To determine the geographical distribution of tuberculosis in the two Western Cape suburbs with the highest reported incidence of tuberculosis. DESIGN: Descriptive illustrative study. SETTING: Two adjacent Western Cape suburbs covering 2.42 km2 with a population of 34,294 and a reported tuberculosis incidence of > 1,000/100,000. SUBJECTS: All patients notified as having tuberculosis over a 10-year period (1985-1994). INTERVENTIONS: None OUTCOME MEASURE: The geographical distribution of the cases was determined using a geographical information system (GIS) and the National Population Census (1991). RESULTS: One thousand eight hundred and thirty-five of the 5,345 dwelling units (34.3%) housed at least 1 case of tuberculosis during the past decade and in 483 houses 3 or more cases occurred. These cases were distributed unevenly through the community, with the tuberculosis incidence per enumerator subdistrict (ESD) varying from 78 to 3,150/100,000 population. CONCLUSION: In a small area with a high incidence of tuberculosis, the cases are spread unevenly through the community and there are certain houses where tuberculosis occurs repeatedly. This information should be used to direct health services to concentrate on certain high-risk areas.

Adolescent↗
PubMed1996

Unexpectedly high strain diversity of Mycobacterium tuberculosis in a high-incidence community.

OBJECTIVE: To characterise Mycobacterium tuberculosis strains present in a community experiencing an epidemic, in order to establish whether a high rate of transmission results in low strain diversity. DESIGN: Sputum specimens collected for 18 months; IS6110-based DNA fingerprinting. SETTING: The communities of Ravensmead and Uitsig, Cape Town, South Africa. PARTICIPANTS: Three hundred and thirty-four pulmonary tuberculosis patients attending the Local Authority Health Care Clinic. MAIN OUTCOME MEASURE: DNA fingerprinting. RESULTS: A total of 334 M. tuberculosis isolates were characterised by IS6110-based DNA fingerprinting; 209 strains were identified, 199 having 5 or more insertions. Forty of these strains were present in 2 or more patients (clustering--126 patients in total), which indicates a recent transmission rate of 30%. The 163 unique strains suggest reactivation of latent infections. Computer analysis showed a high degree of strain diversity, and a common progenitor could only be linked to 33% of the strains. Clustering was shown in 50% of drug-resistant isolates. CONCLUSIONS: The low rate of transmission (30%) and the high degree of strain diversity (209 strains) was unexpected and unexplained, given the high burden of disease in this community. The clustering of drug-resistant strains suggests that transmission, rather than lack of compliance, drives the spread of antibiotic resistance in this community. Preliminary indications are that BCG vaccination, while having little effect on the incidence of tuberculosis in this community, may have altered the strain dynamics.

Adolescent↗
PubMed1995

Concentrations of interferon gamma, tumor necrosis factor alpha, and interleukin-1 beta in the cerebrospinal fluid of children treated for tuberculous meningitis.

Concentrations of interferon gamma (IFN-gamma) in the lumbar cerebrospinal fluid (CSF) of 30 children (mean age, 27 months) being treated for stage III (16 children) and stage II (14 children) tuberculosis meningitis (TBM) were determined by ELISA. Nine children with stage III TBM and six with stage II TBM received prednisone (4 mg/kg). Concentrations of IFN-gamma in 73 CSF specimens (18 from the first week of therapy, 20 from the second, 19 from the third, and 16 from the fourth) were determined. The mean concentrations were 780 pg/mL in the first week of therapy and 554 pg/mL, 529 pg/mL, and 269 pg/mL in the second, third, and fourth weeks, respectively. Tumor necrosis factor alpha (TNF-alpha) and interleukin-1beta (IL-1beta) concentrations in 56 specimens from 23 of these same children were determined by ELISA. The mean CSF TNF-alpha concentration in 12 specimens obtained during the first week of therapy was 17 pg/mL, and the mean was 11 pg/mL during each of the subsequent weeks (14 specimens were evaluated in the second week and 15 specimens in the third and fourth weeks of therapy). Mean IL-1beta concentrations in these same groups of specimens were 52 pg/mL, 43 pg/mL, 42 pg/mL, and 18 pg/mL. No correlation could be shown between cytokine concentration and stage of disease, and no differences existed between those who did and those who did not receive prednisone. A significant decline in IL-1beta concentrations was shown during the 4-week period, but none in TNF-alpha or IFN-gamma concentrations was noted. Persistently high CSF INF-gamma concentrations in cases of TBM (as in cases of aseptic meningitis but not bacterial meningitis) at the time of diagnosis suggest an immune response fundamentally different from that in bacterial meningitis.

Child↗
PubMed1995

TB or not TB? An evaluation of children with an incorrect initial diagnosis of pulmonary tuberculosis.

OBJECT: The aim of the study was to identify diagnoses that are confused with pulmonary tuberculosis in children. DESIGN: Prospective, investigative clinical study. SETTING: Tertiary care teaching hospital and an urban tuberculosis clinic in an area with a very high incidence of pulmonary tuberculosis (> 800 new cases/100,000/year). PATIENTS: Children suspected of having tuberculosis, children followed up for pulmonary infiltrates with eosinophilia and children with congenital pulmonary anomalies were investigated. INTERVENTION(s). None. OUTCOME MEASURE: Pulmonary tuberculosis was diagnosed using modified World Health Organisation criteria and the diagnoses of those children not suffering from pulmonary tuberculosis were analysed. RESULTS: Of the 354 children initially suspected of suffering from tuberculosis 71 (20%) were found to be suffering from other pulmonary disease, viz. pneumonia or bronchopneumonia (29%), bronchopneumonia with wheezing (18%), and asthma with lobar or segmental collapse (12%). Of 14 children suffering from pulmonary infiltrates with peripheral eosinophilia 6 (43%) were initially incorrectly diagnosed and treated for tuberculosis. Of 54 children with congenital pulmonary anomalies, 8 (15%) were treated for tuberculosis before the correct diagnosis was made. Congenital anomalies most often confused with tuberculosis were unilateral lung hypoplasia, bronchogenic cyst and tracheal bronchus with an anomalous lobe. CONCLUSIONS: The criteria for diagnosing tuberculosis in children is complicated in areas with a high incidence of tuberculosis and poor socio-economic circumstances where many children presenting with conditions other than tuberculosis will be in contact with an adult case of pulmonary tuberculosis. The commonest conditions confused with tuberculosis are pneumonia, bronchopneumonia and asthma. Pulmonary infiltrates with peripheral eosinophilia and congenital lung abnormalities should be considered especially if the children have an atypical clinical picture or do not respond to tuberculosis treatment.

Child↗
PubMed1995

Respiratory tuberculosis in childhood: the diagnostic value of clinical features and special investigations.

During a 16-month period children presenting to a pediatric outpatient facility from an area with a high tuberculosis incidence (> 400/100,000) and suspected of having respiratory tuberculosis (TB) were evaluated for close contact with adult pulmonary tuberculosis, weight loss, symptom duration, respiratory signs, lymphadenopathy and hepatosplenomegaly and by chest radiography and tuberculin testing (Mantoux or tine). Probable tuberculosis was diagnosed in 258 children and was confirmed in 109 (42%) patients with a mean age of 31 months by culture of Mycobacterium tuberculosis from gastric aspirate or another source. Eleven children with confirmed TB had a normal chest radiograph. After review of special investigations, clinical course and follow-up of the remaining 149 children, 86 children (58%) with a mean age of 32.4 months were considered to have probable TB and 63 (42%) with a mean age of 27 months not to have TB. Significantly fewer children in the "not TB" group than in the confirmed and probable TB groups had a close adult pulmonary tuberculosis contact (13 (21%) and 95 (49%), respectively; P < 0.01). There was no difference between the "not TB" group and the confirmed and probable TB groups in the proportion presenting with weight loss, cough or other respiratory symptoms, a symptom duration > 2 weeks, the presence of bronchial breathing, wheeze, hepatomegaly or splenomegaly or peripheral lymphadenopathy. Final diagnoses in the "not TB" group included bacterial or viral pneumonia or bronchopneumonia in 37, asthma often accompanied by segmental collapse in 9 and cavitating pneumonia in 3 children.(ABSTRACT TRUNCATED AT 250 WORDS)

Child↗
PubMed1994

Value of the lateral chest radiograph in tuberculosis in children.

The value of the lateral chest radiograph, often considered a useful adjunct in the detection of hilar adenopathy, was evaluated in a prospective study of 449 children assessed for tuberculosis. Of these children 298 presented to the hospital with signs and symptoms suggestive of tuberculosis, while 151 were investigated in a regional clinic solely because they were in close contact with an adult household member on treatment for tuberculosis. Tuberculosis was confirmed by culture in 176 of the 449 children (39%). In 40 of these (23%) hilar adenopathy was visible on frontal and lateral view, in 19 of the 176 confirmed cases (11%) only on a frontal view and in 22 (13%) on a lateral view only. Probable tuberculosis was diagnosed in a further 140 of the 449 children (31%), and hilar adenopathy was visible on frontal and lateral views in 39 of these children (28%), on the frontal view only in 8 (6%) and on the lateral view only in 27 (19%). In the symptomatic children investigated in the hospital, and the asymptomatic children investigated in the clinic, hilar adenopathy was detected on the lateral chest radiograph only in 36 (12%) and 14 (9%) cases respectively. Lateral chest radiographs will considerably improve the accuracy of the diagnosis of childhood tuberculosis.

Child↗
PubMed1994

Delay in the diagnosis, notification and initiation of treatment and compliance in children with tuberculosis.

SETTING: The mortality and morbidity from childhood tuberculosis may be influenced by the delay from the time of first symptoms until the start of and compliance with treatment. OBJECTIVE: This study investigated these delay periods and the compliance with therapy in children with tuberculosis. DESIGN: During the study period there were 49 children with probable and 123 with confirmed pulmonary tuberculosis (WHO criteria). The mean period from first symptoms until presentation was 4.3 weeks, from presentation until notification 5 weeks and from notification until therapy 0.9 weeks. 16% of children notified as having tuberculosis never received therapy. Significantly fewer children in the urban squatter communities received therapy than in urban settled (P = 0.02), rural agricultural (P = 0.0001) and rural settled (P = 0.09) communities. 12% of children did not complete their therapy. CONCLUSION: The delay in presentation ('patient delay') was shorter than the delay in diagnosis ('doctor delay'). Failure to trace children and to complete therapy was particularly likely to occur in urban squatter communities. Easier access to health care facilities may shorten the 'patient delay' while greater awareness of tuberculosis and proper investigation of children may shorten the 'doctor delay'.

Child↗
PubMed1994

Oligonucleotide (GTG)5 as a marker for Mycobacterium tuberculosis strain identification.

Culture of Mycobacterium tuberculosis provides no information on the identity of a strain or the distribution of such a strain in the community. Strain identification of M. tuberculosis can help to address important epidemiological questions, e.g., the origin of an infection in a patient's household or community, whether reactivation of infection is endogenous or exogenous in origin, and the spread and early detection of organisms with acquired antibiotic resistance. To research this problem, strain identification must be reliable and accurate. Although genetic identification techniques already exist, it is valuable to have genetic identification techniques based on a number of genetic markers to improve the accurate identification of M. tuberculosis strains. We show that oligonucleotide (GTG)5 can be successfully applied to the identification of M. tuberculosis strains. This technique may be particularly useful in cases in which M. tuberculosis strains have few or no insertion elements (e.g., IS6110) or in identifying other strains of mycobacteria when informative probes are lacking.

Adult↗
PubMed1994

Erythrocyte and polymorphonuclear cell transit time and concentration in human pulmonary capillaries.

Pulmonary capillary transit times were examined in patients who required lung resection by use of 99mTc-labeled macroaggregates (99Tc-MAA) and chromium-labeled erythrocytes (51Cr-RBC) to measure regional blood flow and volume in the resected lung. Cell flow (cells.ml-1.s-1) to each resected lung sample was determined by multiplying the number of polymorphonuclear leukocytes (PMN) per milliliter of circulating blood by the blood flow to that sample. Capillary blood volume was obtained by multiplying the morphometrically determined fraction of pulmonary blood in capillaries by the total 51Cr-RBC volume in each sample. Cell concentrations (cells/ml) in capillary blood were calculated morphometrically, and capillary transit times were obtained by dividing cell concentration by cell flow. The results show that PMN transit times were 60-100 times longer than the RBC transit times, with a 22% overlap between their distributions. We conclude that PMN are concentrated with respect to RBC in pulmonary capillary blood because of differences in their transit times and that these long transit times provide an opportunity for PMN-endothelial interactions.

Blood Flow Velocity↗
PubMed1993

Tuberculosis in infants less than 3 months of age.

The clinical and radiological features in 38 infants less than 3 months of age with tuberculosis proved by culture are described and may aid early diagnosis of this often fatal condition. Respiratory symptoms, cough in 33 (87%) and tachypnoea in 31 (82%), were the commonest presenting symptoms. Twenty five infants (66%) had hepatomegaly and 20 (53%) splenomegaly. Mantoux testing gave an induration of > 15 mm in three of 17 (18%) infants. In a further five a Tine test gave confluent response. Chest radiography in 27 infants showed miliary tuberculosis in seven (26%) and hilar or paratracheal adenopathy in 14 (52%) and 10 (37%) respectively. Compression of either the bronchi or trachea or both was noted in 15 (56%). Detection of this complication was aided by high kilovolt radiographs. A culture of Mycobacterium tuberculosis was obtained from gastric aspirate in 35 (92%) infants, but positive cultures were also obtained from cerebrospinal fluid, tracheal or bronchial aspirate and liver and lymph node biopsy. Of 30 mothers evaluated seven (23) had previously unsuspected pulmonary tuberculosis.

Female↗
PubMed1993

Comparison of neutrophil and capillary diameters and their relation to neutrophil sequestration in the lung.

Neutrophils [polymorphonuclear leukocytes (PMNs)] are sequestrated in the lung capillary bed because PMNs are delayed with respect to red blood cells (RBCs) as they pass through these microvessels. The present study examines circulating PMN size in relation to the distribution of capillary segment diameters in human, dog, and rabbit lungs and compares the shape of PMNs in suspension to that found within the pulmonary capillaries. The data show that 61, 67, and 38% of the capillary segments are narrower than the mean diameter of spherical PMNs in the rabbit, dog, and human, respectively. They also show that PMNs deform from a spherical to an ellipsoid shape in the pulmonary capillaries of all three species. These findings are consistent with previous studies showing that the pulmonary circulation restricts the passage of PMNs through the lungs and suggest that PMNs are delayed because they must deform to pass through restrictions encountered in the pulmonary capillary bed. We conclude that the discrepancy between PMN and pulmonary capillary size and the decreased deformability of PMNs with respect to RBCs are major determinants of the delay that PMNs experience with respect to RBCs in the pulmonary circulation.

Animals↗
PubMed1986

Vitamin D and mineral metabolism in normal pregnancy and in the normal fetus.

Metabolic bone diseases in neonates are being recognized with increasing frequency but, despite extensive research, the pathophysiology of neonatal osteopenia remains unclear. This review briefly summarizes vitamin D and mineral metabolism in the normal non-pregnant human adult, and then addresses the adaptations that occur during pregnancy and fetal life.

Adult↗
PubMed1986

Metabolic bone disease in preterm infants.

Small preterm infants often develop osteopenia with or without rickets and with or without fractures. Whether these bone abnormalities all form part of the same disease process with a wide spectrum of presentation or whether each abnormality represents a different disease is as yet unclear. Bone mineralization depends largely on adequate supplies of calcium and phosphate. The normal intra-uterine accretion of these minerals is higher than can be achieved by feeding preterm babies postnatally with breastmilk or conventional formulas. Supplementation with calcium, phosphorus and vitamin D is needed to prevent the development of 'neonatal osteopathy'. The main action of vitamin D in the preterm baby is probably to increase the intestinal absorption of calcium and phosphorous, although it may, together with other calciotrophic hormones, have a more specific effect on bone growth.

Acidosis↗
PubMed1984

Value of C reactive protein measurement in tuberculous, bacterial, and viral meningitis.

The value of C reactive protein measurement in the differential diagnosis of meningitis was assessed in a population where tuberculous meningitis is prevalent. C reactive protein was measured serially with a sensitive radioimmunoassay in sera from 31 children with bacterial meningitis, 15 with tuberculous meningitis (6 with miliary tuberculosis), and 28 with viral meningitis. Concentrations of C reactive protein in patients with tuberculous meningitis lay between those of patients with bacterial and viral meningitis--a finding which detracts from the virtually absolute discrimination C reactive protein measurement allows between bacterial and viral meningitis. In all but two of the patients with tuberculous meningitis, C reactive protein concentrations fell rapidly after treatment began and became normal after 10 days. This fall did not, however, exclude the development of hydrocephalus as a complication. Measurement of C reactive protein remains a useful additional parameter in the diagnosis and management of the various types of meningitis.

Adolescent↗