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1.
S Afr J Surg ; 60(4): 229-234, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36477050

ABSTRACT

BACKGROUND: Data on colorectal cancer (CRC) diagnosis to treatment interval (DTI), an index of quality assurance in high-income countries (HICs) is lacking in South Africa. This study aimed to determine DTIs and their impact on CRC survival in a South African cohort. METHODS: Participants (n = 289) from the Colorectal Cancer in South Africa (CRCSA) cohort were identified for inclusion. The DTI was defined as the duration between the diagnosis and initial definitive treatment and categorised into approximate quartiles (Q1-4). The DTI quartiles were 0-14 days, 15-28 days, 29-70 days, and ≥ 71 days. Overall survival (OS) was illustrated using the Kaplan-Meier method and compared between DTI groups using Cox proportional hazards (PH) regression. RESULTS: There was no significant impact of the DTI (as quartiles) on overall CRC survival. The median length of time between DTI in this cohort was 29 days. Significant associations were identified between the DTI and self-reported ethnicity (p-value = 0.025), the site of the malignancy (colon vs rectum) (p-value < 0.0001), multidisciplinary team (MDT) review (p-value = 0.015) and the initial treatment modality (p-value < 0.0001). CONCLUSION: Prolonged DTIs did not significantly impact survival for those with CRC in the CRCSA cohort. Symptom to diagnosis time should be investigated as a determinant of survival.


Subject(s)
Colorectal Neoplasms , Humans , South Africa/epidemiology , Colorectal Neoplasms/therapy
2.
S Afr Med J ; 110(5): 382-388, 2020 Apr 29.
Article in English | MEDLINE | ID: mdl-32657722

ABSTRACT

BACKGROUND: The Colorectal Cancer South Africa (CRCSA) study is an observational cohort of patients with colorectal cancer (CRC) in Johannesburg, South Africa (SA). We found that the mean age at the time of CRC diagnosis was 56.6 years, consistent with studies from SA and sub-Saharan Africa. In high-income settings, comorbidity adversely affects CRC survival, and patients are substantially older at the time of CRC diagnosis. Given the younger age at CRC diagnosis in the CRCSA cohort, we hypothesised that comorbidity may be less prevalent and have little impact on CRC survival. OBJECTIVES: To determine the prevalence of comorbidity and whether comorbidity adversely affects overall survival (OS) of CRC patients. METHODS: Patients enrolled in the CRCSA study between January 2016 and July 2018 were included. The cohort comprised a convenience sample of adults with histologically confirmed CRC, treated at the University of the Witwatersrand Academic Teaching Hospital Complex. Demographic, clinical and histological variables were collected at baseline and participants were followed up for OS. The Charlson comorbidity index (CCI) scoring system was used to classify participants as 'no comorbidity' (CCI score 0) and '1 or more comorbidities' (CCI score ≥1). A descriptive analysis of the cohort was undertaken, while survival across comorbidity groups was compared by the Kaplan-Meier method and Cox proportional hazards (PH) regression models. Multivariable Cox PH regression was performed to examine the effect of comorbidity on survival (unadjusted) and then adjusted for variables. RESULTS: There were 424 participants, and the mean (standard deviation) age was 56.6 (14.1) years (range 18 - 91). Only 19.1% of participants had ≥1 comorbidities, of which diabetes mellitus was most frequent (12.3%), followed by chronic obstructive pulmonary disease (4.7%) and cardiovascular disease (3.1%). There was no significant difference in unadjusted and adjusted risk of death for the group with ≥1 comorbidities compared with those with no comorbidity. However, an incidental finding showed a significantly increased risk of death for those receiving potentially curative treatment later than 40 days after CRC diagnosis. CONCLUSIONS: In the CRCSA cohort from Johannesburg, comorbidity is uncommon, with no significant adverse effect on OS. If potentially curative treatment is initiated within 40 days of CRC diagnosis, OS could be improved. To fully understand the epidemiology of CRC in SA, population-based registries are essential, and future research should aim to identify health system failures that lead to delays in intervention beyond 40 days in patients with CRC.


Subject(s)
Colorectal Neoplasms/mortality , Comorbidity , Adolescent , Adult , Aged , Aged, 80 and over , Cohort Studies , Colorectal Neoplasms/therapy , Female , Humans , Kaplan-Meier Estimate , Longitudinal Studies , Male , Middle Aged , Proportional Hazards Models , Sampling Studies , South Africa/epidemiology , Young Adult
3.
S Afr Med J ; 110(4): 271-273, 2020 Mar 30.
Article in English | MEDLINE | ID: mdl-32657737

ABSTRACT

Trastuzumab was added to the South African Essential Medicines List (EML) in 2017 for the adjuvant management of human epidermal growth factor receptor 2 (HER2)-positive early breast cancer. However, access has remained inconsistent, as some provinces continue to regard trastuzumab as unaffordable within the contexts of their respective oncology budgets. The intention of providing access to trastuzumab through its inclusion on the EML, therefore, has not been met. The National EML Committee (NEMLC) recently reviewed newly published peer-reviewed information investigating the impact of a shorter trastuzumab treatment period on both clinical efficacy and safety. On account of this review, and with a view to improving access while reducing cost and toxicity, the NEMLC has revised the duration of trastuzumab therapy, i.e. from 12 months to 6 months in the adjuvant management of early HER2-positive breast cancer. This article explores and reports on the data used to make this policy amendment.


Subject(s)
Antineoplastic Agents, Immunological/therapeutic use , Breast Neoplasms/drug therapy , Drugs, Essential , Duration of Therapy , Health Policy , Mastectomy , Policy Making , Trastuzumab/therapeutic use , Antineoplastic Agents, Immunological/economics , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Budgets , Cardiotoxicity/etiology , Chemotherapy, Adjuvant , Female , Health Services Accessibility , Humans , Mastectomy, Segmental , Neoplasm Staging , Receptor, ErbB-2/metabolism , South Africa , Trastuzumab/economics
4.
Eur J Public Health ; 27(1): 173-178, 2017 02 01.
Article in English | MEDLINE | ID: mdl-28177503

ABSTRACT

Background: To describe breast cancer (BC) incidence and mortality by ethnicity in South Africa (SA). Methods: Sources of data included the South African National Cancer Registry (NCR) pathology-based reports (1994­2009) and Statistics South Africa (SSA) mortality data (1997­2009). Numbers of cases, age-standardised incidence rates (ASIR) and lifetime risk (LR) were extracted from the NCR database for 1994­2009. Age-specific incidence rates were calculated for five-year age categories. The direct method of standardisation was employed to calculate age-standardised mortality rates (ASMR) using mortality data. Results: Between 1994 and 2009, there were 85 561 female BC. For the Black, Coloured and Asian groups, increases in ASIR and LR were observed between 1994 and 2009. In 2009, the ASIR for the total population, Blacks, Whites, Coloureds and Asians were 26.9, 18.7, 50.2, 40.9 and 51.2 per 100 000, respectively. For Asians, an increase in proportion of BC as a percentage of all female cancers was observed between 1994 and 2002 (11.1%) and continued to increase to 2009 (a further 4.5%). Whites and Asians presented higher incidences of BC at earlier ages compared with Blacks and Coloureds in 2009. In 1998, there were 1618 BC deaths in SA compared with 2784 deaths in 2009. ASMR between 1997 and 2004 increased but stabilised thereafter. Conclusion: This paper demonstrated that SA BC incidence rates are similar to other countries in the region, but lower than other countries with similar health systems. Ethnic differences in BC trends were observed. However, the reasons for observed ethnic differences are unclear.


Subject(s)
Breast Neoplasms/ethnology , Breast Neoplasms/epidemiology , Ethnicity/statistics & numerical data , Mortality/trends , Adult , Age Distribution , Aged , Asian People/statistics & numerical data , Black People/statistics & numerical data , Breast Neoplasms/pathology , Female , Humans , Incidence , Middle Aged , Mortality/ethnology , Registries , South Africa/epidemiology , White People/statistics & numerical data
5.
S. Afr. med. j. (Online) ; 106(6): 607-610, 2016.
Article in English | AIM (Africa) | ID: biblio-1271106

ABSTRACT

BACKGROUND AND OBJECTIVES:Cancer is emerging as a critical public health problem in South Africa (SA). Recognising the importance of research in addressing the cancer burden; the Ministerial Advisory Committee on the Prevention and Control of Cancer (MACC) research working group undertook a review of the current cancer research landscape in SA and related this to the cancer burden.METHODS:Academic and research institutions in SA were contacted to provide information on the titles of all current and recently completed (2013/2014) cancer research projects. Three MACC research working group members used the project titles to independently classify the projects by type of research (basic; clinical and public health - projects could be classified in more than one category) and disease site. A more detailed classification of projects addressing the five most common cancers diagnosed in males and females in SA was conducted using an adapted Common Scientific Outline (CSO) categorisation.RESULTS:Information was available on 556 cancer research projects. Overall; 301 projects were classified as clinical; 254 as basic science and 71 as public health research. The most common cancers being researched were cancers of the breast (n=95 projects) and cervix (n=43); leukaemia (n=36); non-Hodgkin's lymphoma (n=35) and lung cancer (n=23). Classification of the five most common cancers in males and females in SA; using the adapted CSO categories; showed that the majority of projects related to treatment; with relatively few projects on prevention; survivorship and patient perspectives.CONCLUSION:Our findings established that there is a dearth of public health cancer research in SA


Subject(s)
Academic Medical Centers , Neoplasms/prevention & control , Public Health , Research , South Africa
6.
Ann Oncol ; 25(7): 1346-1355, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24718886

ABSTRACT

BACKGROUND: The Panitumumab Randomized trial In combination with chemotherapy for Metastatic colorectal cancer to determine Efficacy (PRIME) demonstrated that panitumumab-FOLFOX4 significantly improved progression-free survival (PFS) versus FOLFOX4 as first-line treatment of wild-type (WT) KRAS metastatic colorectal cancer (mCRC), the primary end point of the study. PATIENTS AND METHODS: Patients were randomized 1:1 to panitumumab 6.0 mg/kg every 2 weeks + FOLFOX4 (arm 1) or FOLFOX4 (arm 2). This prespecified final descriptive analysis of efficacy and safety was planned for 30 months after the last patient was enrolled. RESULTS: A total of 1183 patients were randomized. Median PFS for WT KRAS mCRC was 10.0 months [95% confidence interval (CI) 9.3-11.4 months] for arm 1 and 8.6 months (95% CI 7.5-9.5 months) for arm 2; hazard ratio (HR) = 0.80; 95% CI 0.67-0.95; P = 0.01. Median overall survival (OS) for WT KRAS mCRC was 23.9 months (95% CI 20.3-27.7 months) for arm 1 and 19.7 months (95% CI 17.6-22.7 months) for arm 2; HR = 0.88; 95% CI 0.73-1.06; P = 0.17 (68% OS events). An exploratory analysis of updated survival (>80% OS events) was carried out which demonstrated improvement in OS; HR = 0.83; 95% CI 0.70-0.98; P = 0.03 for WT KRAS mCRC. The adverse event profile was consistent with the primary analysis. CONCLUSIONS: In WT KRAS mCRC, PFS was improved, objective response was higher, and there was a trend toward improved OS with panitumumab-FOLFOX4, with significant improvement in OS observed in an updated analysis of survival in patients with WT KRAS mCRC treated with panitumumab + FOLFOX4 versus FOLFOX4 alone (P = 0.03). These data support a positive benefit-risk profile for panitumumab-FOLFOX4 for patients with previously untreated WT KRAS mCRC. KRAS testing is critical to select appropriate patients for treatment with panitumumab.


Subject(s)
Antibodies, Monoclonal/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Colorectal Neoplasms/drug therapy , Adult , Aged , Aged, 80 and over , Antibodies, Monoclonal/adverse effects , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Female , Fluorouracil/administration & dosage , Fluorouracil/adverse effects , Genes, ras , Humans , Leucovorin/administration & dosage , Leucovorin/adverse effects , Male , Middle Aged , Neoplasm Metastasis , Organoplatinum Compounds/administration & dosage , Organoplatinum Compounds/adverse effects , Panitumumab , Quality of Life
7.
J Dent Res ; 92(7 Suppl): 37S-42S, 2013 Jul.
Article in English | MEDLINE | ID: mdl-23690352

ABSTRACT

One in four adults reports a clinically significant fear of dental injections, leading many to avoid dental care. While systematic desensitization is the most common therapeutic method for treating specific phobias such as fear of dental injections, lack of access to trained therapists, as well as dentists' lack of training and time in providing such a therapy, means that most fearful individuals are not able to receive the therapy needed to be able to receive necessary dental treatment. Computer Assisted Relaxation Learning (CARL) is a self-paced computerized treatment based on systematic desensitization for dental injection fear. This multicenter, block-randomized, dentist-blind, parallel-group study conducted in 8 sites in the United States compared CARL with an informational pamphlet in reducing fear of dental injections. Participants completing CARL reported significantly greater reduction in self-reported general and injection-specific dental anxiety measures compared with control individuals (p < .001). Twice as many CARL participants (35.3%) as controls (17.6%) opted to receive a dental injection after the intervention, although this was not statistically significant. CARL, therefore, led to significant changes in self-reported fear in study participants, but no significant differences in the proportion of participants having a dental injection.


Subject(s)
Computer-Assisted Instruction/methods , Dental Anxiety/prevention & control , Desensitization, Psychologic/methods , Injections/psychology , Patient Education as Topic , Adolescent , Adult , Aged , Dental Care/psychology , Female , Follow-Up Studies , Humans , Male , Middle Aged , Needles/adverse effects , Pamphlets , Relaxation Therapy , Single-Blind Method , Young Adult
8.
S Afr Med J ; 101(11): 840-6, 2011 Nov 01.
Article in English | MEDLINE | ID: mdl-22272968

ABSTRACT

INTRODUCTION: Chronic myeloid leukaemia (CML) is a chronic myeloproliferative disorder characterised by a chromosomal translocation between the long arms of chromosomes 9 and 22 [corrected] resulting in the formation of the BCR-ABL fusion gene. The management of CML has undergone major changes over the past decade. Novel treatment approaches have had a dramatic impact on patient outcomes and survival. Nevertheless, these outcomes can only be achieved in the context of expert management, careful monitoring of disease response, appropriate management of adverse events and timeous adjustments to therapy when responses are not achieved within stated time-frames. AIM: With the advent of novel treatments providing molecular responses, both the monitoring and management of CML have become more complicated. The aim of these recommendations was to provide a pragmatic yet comprehensive roadmap to negotiate these complexities. METHODS: Recommendations were developed based on local expert opinion from both the academic and private medical care arenas after careful review of the relevant literature and taking into account the most widely used international guidelines. About five meetings were held at which these recommendations were discussed and debated in detail. RESULTS: A comprehensive set of recommendations was compiled with an emphasis on diagnosis, investigation, treatment and monitoring of disease. Careful attention was given to circumstances unique to South Africa, funding constraints, availability and access to laboratory resources, as well as the effects of concurrent HIV infection. CONCLUSION: Most patients with CML can live a reasonably normal life if their disease is appropriately managed. These recommendations should be of value to all specialists involved in the treatment of haematological disorders.


Subject(s)
Leukemia, Myelogenous, Chronic, BCR-ABL Positive/therapy , Adult , Benzamides , Comorbidity , Dasatinib , Disease Management , HIV Infections/epidemiology , Humans , Imatinib Mesylate , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/diagnosis , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/epidemiology , Piperazines/administration & dosage , Piperazines/therapeutic use , Protein Kinase Inhibitors/administration & dosage , Protein Kinase Inhibitors/therapeutic use , Protein-Tyrosine Kinases/antagonists & inhibitors , Pyrimidines/administration & dosage , Pyrimidines/therapeutic use , South Africa , Thiazoles/administration & dosage , Thiazoles/therapeutic use , Treatment Outcome
9.
S Afr Med J ; 101(12): 900-6, 2011 Nov 28.
Article in English | MEDLINE | ID: mdl-22273034

ABSTRACT

INTRODUCTION: Myelodysplastic syndromes (MDS) encompass a heterogeneous group of clonal haematopoietic disorders characterised by chronic and progressive cytopenias resulting from ineffective haematopoiesis. Treatment is complicated by differences in disease mechanisms in different subgroups, variable clinical phenotypes and risk of progression to acute myeloid leukaemia. RATIONALE: Changes in disease classification, prognostic scoring systems, the availability of novel treatment options and the absence of South African guidelines for the diagnosis and management of these complex disorders underpinned the need for the development of these recommendations. METHODS: These recommendations are based on the opinion of a number of experts in the field from the laboratory as well as clinical settings and came from both the private and institutional academic environments. The most recent literature as well as available guidelines from other countries were discussed and debated at a number of different meetings held over a 2-year period. RESULTS: A comprehensive set of recommendations was developed focusing on risk stratification, supportive management and specific treatment. Novel agents and their indications are discussed and recommendations are made based on best available evidence and taking into account the availability of treatments in South Africa. CONCLUSION: Correct diagnosis, risk stratification and appropriate therapeutic choices are the cornerstones of success in the management of patients with myelodysplastic syndromes.


Subject(s)
Myelodysplastic Syndromes/therapy , Practice Guidelines as Topic , Algorithms , Anemia/therapy , Disease Progression , Ferritins/blood , Hematinics/therapeutic use , Humans , Immunosuppressive Agents/therapeutic use , Iron Chelating Agents/therapeutic use , Myelodysplastic Syndromes/blood , Myelodysplastic Syndromes/classification , Prognosis , Risk Assessment , South Africa
10.
Br J Cancer ; 98(9): 1586-92, 2008 May 06.
Article in English | MEDLINE | ID: mdl-18362941

ABSTRACT

Demographic and lifestyle information from 9690 black patients diagnosed with cancer or cardiovascular disease was collected in an ongoing case-control study in Johannesburg, South Africa. Compared to never smokers, the odds ratio (OR) for lung cancer among current smokers was 16.3 (95% confidence interval (CI), 9.6-27.6) for men and 6.4 (95% CI, 4.0-10.4) for women. The corresponding OR for other smoking-related cancers was 4.6 (95% CI, 3.7-5.7) among men and 1.9 (95% CI, 1.6-2.2) among women, and for cardiovascular disease, 3.4 (95% CI, 2.1-5.4) among men and 1.5 (95% CI, 1.1-2.1) among women. Risks were higher among smokers than former smokers, and all risk estimates increased with increasing levels of smoking duration and intensity. Non-electric domestic fuel was associated with approximately 60% increase in the risk of smoking-related cancer, but not cardiovascular disease. Risks for cancers of cervix, oesophagus, oral cavity/pharynx, stomach, larynx, pancreas and anogenital region, as well as squamous cell carcinoma of skin were all significantly higher among current than never-smokers, with ORs ranging from 1.5 for cervix (95% CI, 1.2-1.8) to 14.7 for larynx (95% CI, 7.2-30). The risks of tobacco-related disease reported here are similar to that currently observed in Western countries, even though cigarette consumption is relatively low in this population.


Subject(s)
Black People/statistics & numerical data , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/etiology , Neoplasms/epidemiology , Neoplasms/etiology , Smoking/adverse effects , Smoking/epidemiology , Urban Population/statistics & numerical data , Adult , Age Distribution , Age Factors , Aged , Aged, 80 and over , Case-Control Studies , Confidence Intervals , Female , Humans , Incidence , Life Style , Male , Middle Aged , Odds Ratio , Prevalence , South Africa/epidemiology
11.
Infect Agent Cancer ; 1: 2, 2006 Sep 14.
Article in English | MEDLINE | ID: mdl-17150131

ABSTRACT

BACKGROUND: Infections with certain human herpesviruses have been established as risk factors for some cancer types. For example, Epstein-Barr Virus is considered a cause of Burkitt's lymphoma and other immunosuppression related lymphomas, Hodgkin lymphoma, and nasopharyngeal cancer. Several other human herpesviruses have been linked to cancers but the totality of evidence is inconclusive. METHODS: We conducted a systematic sub-study from within an ongoing case control study of adult black South Africans to investigate the relationship between antibodies to six human herpesviruses and seven cancer groups that may be caused by infectious agents. Subjects had incident cancers of the oral cavity (n = 88), the cervix (n = 53), the prostate (n = 66), Hodgkin lymphoma (n = 83), non-Hodgkin lymphoma (n = 80), multiple myeloma (n = 94) or leukaemia (n = 203). For comparison, patients with other cancers (n = 95) or cardiovascular disease (n = 101) were randomly selected from within the study. Patients were interviewed and their blood was tested for IgG antibodies against HSV-1, HSV-2, VZV, EBV-EBNA, CMV and HHV-6 using enzyme linked immunosorbent assays. Because these viruses are highly prevalent in this population, optical density results from the assays were used as an indirect, quantitative measure of antibody level. RESULTS: There was significant variation in the mean log antibody measures for HSV-2, VZV, CMV and HHV-6 between the disease groups. However, none of the specific cancer groups had significantly higher mean log antibody measures for any of the viruses compared to either control group. In a more detailed examination of seven associations between cancers and herpesviruses for which there had been prior reports, two statistically significant associations were found: a decreasing risk of myeloid leukaemia and an increasing risk of oral cancer with increasing tertiles of antibodies against HHV-6 compared to all other patients (p-trend = 0.03 and 0.02, respectively). Odds ratios for the top tertile compared to the bottom tertile were 0.58 (95%CI 0.3-1.0) for myeloid leukaemia and 2.21 (95% CI 1.1-4.3) for oral cancer. CONCLUSION: In this population, using these tests for IgG, neither mean antibody measure nor high antibody measure against human herpesviruses 1-6 was strongly associated with any of the seven cancer groups. However, we may not have had sufficient power to detect weak associations or associations with a sub-type of cancer if they were present.

12.
Int J Gynecol Cancer ; 16(4): 1614-9, 2006.
Article in English | MEDLINE | ID: mdl-16884375

ABSTRACT

The purpose of this study was to evaluate the maximum tolerated dose (MTD) of weekly cisplatin in a sample population of South African patients with cervical carcinoma, when given in combination with radical pelvic irradiation. Patients with cervical carcinoma stage IB2-IIIB (without hydronephrosis) received up to six cycles of cisplatin at weekly intervals. Groups consisting of three patients each were treated at each of the three predetermined dose levels of cisplatin (20, 25, and 30 mg/m(2)). Eighteen patients were treated and evaluated for toxicity. All the patients who received 20 mg/m(2) (n = 3) and 25 mg/m(2) (n = 3) cisplatin had no dose-limiting toxicity (DLT). Four of the 12 patients who were given cisplatin 30 mg/m(2) experienced DLT with rising serum creatinine and declining creatinine clearance. The minimum creatinine clearance was 22 mL/min. The highest serum creatinine was 174 mumol/L. This study showed that a weekly dose of 25 mg/m(2) of cisplatin was the MTD when used in combination with pelvic irradiation for this sample of patients. This dose is lower than the recommended dose of cisplatin 40 mg/m(2)/week. The patients in this study may have reduced tolerance to higher doses of cisplatin, when compared to patients from Western countries.


Subject(s)
Antineoplastic Agents/therapeutic use , Cisplatin/therapeutic use , Pelvis/radiation effects , Uterine Cervical Neoplasms/drug therapy , Uterine Cervical Neoplasms/radiotherapy , Adult , Aged , Combined Modality Therapy , Dose-Response Relationship, Drug , Female , Humans , Maximum Tolerated Dose , Middle Aged , Neoplasm Staging , Treatment Outcome , Uterine Cervical Neoplasms/pathology
13.
Nanotechnology ; 17(7): S189-94, 2006 Apr 14.
Article in English | MEDLINE | ID: mdl-21727413

ABSTRACT

Force microscopy experiments with the pendulum geometry are performed with attonewton sensitivity (Rugar et al 2004 Nature 43 329). Single-crystalline cantilevers with sub-millinewton spring constants were annealed under ultrahigh-vacuum conditions. It is found that annealing with temperatures below 500 °C can improve the quality factor by an order of magnitude. The high force sensitivity of these ultrasoft cantilevers is used to characterize small magnetic and superconductive particles, which are mounted on the end of the cantilever. Their magnetic properties are analysed in magnetic fields as a function of temperature. The transition of a superconducting sample mounted on a cantilever is measured by the detection of frequency shifts. An increase of dissipation is observed below the critical temperature. The magnetic moment of ferromagnetic particles is determined by real time frequency detection with a phase-locked loop (PLL) as a function of the magnetic field. The dissipation between the probing tip and the sample is another important ingredient for ultrasensitive force measurements. It is found that dissipation increases at separations of 30 nm. The origins of this type of dissipation are poorly understood. However, it is predicted theoretically that adsorbates can increase this dissipation channel (Volokitin and Persson 2005 Phys. Rev. Lett. 94 086104). First experiments are performed under ultrahigh vacuum to investigate this type of dissipation. Long-range dissipation is closely related to long-range forces. The distance dependence of the contact potential is found to be an important aspect.

14.
Epidemiol Infect ; 132(6): 1191-7, 2004 Dec.
Article in English | MEDLINE | ID: mdl-15635980

ABSTRACT

Between January 1994 and October 1997, we interviewed 2576 black in-patients with newly diagnosed cancer in Johannesburg and Soweto, South Africa. Blood was tested for HIV-1 and HHV-8 antibodies and the study was restricted to 2191 HIV-1 antibody-negative patients. We examined the relationship between infection with HHV-8 and sociodemographic and behavioural factors using unconditional logistic regression models. Of the 2191 HIV-1 negative patients who did not have Kaposi's sarcoma, 854 (39.1%) were positive for antibodies against the latent nuclear antigen of HHV-8 encoded by orf73 in a immunofluorescence assay. Infection with HHV-8 was independently associated with increasing age (P trend = 0.02). For females, independent risk factors also included working in a paid domestic capacity (OR 1.63, 95% CI 1.09-2.44, P = 0.02), defining occupational status as economically non-active unemployed (OR 1.70, 95% CI 1.06-2.72, P = 0.03), having a state pension or being on a disability grant (OR 1.49, 95% CI 1.05-2.11, P = 0.02), using oral contraceptives (OR 1.43, 95% CI 1.03-1.99, P = 0.03) and having a delayed age at menarche (P trend = 0.04). The relationship between these variables and HHV-8 antibody status requires further, prospective study.


Subject(s)
HIV Infections/complications , Herpesviridae Infections/etiology , Herpesviridae Infections/transmission , Herpesvirus 8, Human/pathogenicity , Social Class , Adult , Aged , Cross-Sectional Studies , Female , Fluorescent Antibody Technique , HIV-1/pathogenicity , Humans , Immunocompromised Host , Incidence , Male , Middle Aged , Neoplasms/complications , Neoplasms/virology , Risk Factors , South Africa/epidemiology
15.
Br J Cancer ; 86(11): 1751-6, 2002 Jun 05.
Article in English | MEDLINE | ID: mdl-12087462

ABSTRACT

The authors used data collected from 1995 to 1999, from an on-going cancer case-control study in greater Johannesburg, to estimate the importance of tobacco and alcohol consumption and other suspected risk factors with respect to cancer of the oesophagus (267 men and 138 women), lung (105 men and 41 women), oral cavity (87 men and 37 women), and larynx (51 men). Cancers not associated with tobacco or alcohol consumption were used as controls (804 men and 1370 women). Tobacco smoking was found to be the major risk factor for all of these cancers with odds ratios ranging from 2.6 (95% CI 1.5-4.5) for oesophageal cancer in female ex-smokers to 50.9 (95% CI 12.6-204.6) for lung cancer in women, and 23.9 (95% CI 9.5-60.3) for lung cancer and 23.6 (95% CI 4.6-121.2) for laryngeal cancer in men who smoked 15 or more grams of tobacco a day. This is the first time an association between smoking and oral and laryngeal cancers has been shown in sub-Saharan Africa. Long-term residence in the Transkei region in the southeast of the country continues to be a risk factor for oesophageal cancer, especially in women (odds ratio=14.7, 95% CI 4.7-46.0), possibly due to nutritional factors. There was a slight increase in lung cancer (odds ratio=2.9, 95% CI 1.1-7.5) in men working in 'potentially noxious' industries. 'Frequent' alcohol consumption, on its own, caused a marginally elevated risk for oesophageal cancer (odds ratio=1.7, 95% CI 1.0-2.9, for women and odds ratio=1.8, 95% CI 1.2-2.8, for men). The risks for oesophageal cancer in relation to alcohol consumption increased significantly in male and female smokers (odds ratio=4.7, 95% CI=2.8-7.9 in males and odds ratio=4.8, 95% CI 3.2-6.1 in females). The above results are broadly in line with international findings.


Subject(s)
Black People , Laryngeal Neoplasms/epidemiology , Lung Neoplasms/epidemiology , Mouth Neoplasms/epidemiology , Adolescent , Adult , Aged , Alcohol Drinking/adverse effects , Case-Control Studies , Educational Status , Female , Geography , Humans , Laryngeal Neoplasms/etiology , Life Style , Lung Neoplasms/etiology , Male , Middle Aged , Mouth Neoplasms/etiology , Risk Factors , Sex Characteristics , Smoking/adverse effects , South Africa/epidemiology , Surveys and Questionnaires
18.
Eur J Cancer ; 37(11): 1352-8, 2001 Jul.
Article in English | MEDLINE | ID: mdl-11435064

ABSTRACT

Only a minority of patients with hepatocellular carcinoma (HCC) may benefit from curative treatments, whereas there is no standard therapy for the remaining patients. The objective of this multicentre, open label phase II study was to estimate the objective tumour response rate of a 28-day regimen of oral eniluracil/5-fluorouracil (5-FU) in patients with chemotherapy-naïve, or anthracycline-refractory, inoperable HCC. 45 patients received courses of twice daily oral 5-FU (1.0 mg/m(2)) and eniluracil (10 mg/m(2)) for the first 28 days of each 5-week course. Patients were assessed at regular intervals to determine the tumour response and to evaluate toxicity. Patients were followed-up for a minimum of 6 months. No patient showed a partial or complete tumour response, and 18 patients (40%) had a best response of stable disease (95% confidence interval (CI) 25%, 55%). The median duration of progression-free survival (PFS) was 13.7 weeks (95% CI 10.0-20.0 weeks), and the median duration of overall survival (OS) was 50.3 weeks (range 1.1-64.1+ weeks). The combination of eniluracil/5-FU was well tolerated and had an acceptable safety profile. Only 7 patients (16%) reported at least one adverse event (AE) of grade 3 or 4 intensity considered reasonably attributable to the study medication. In conclusion, oral eniluracil/5-FU had minimal, if any, activity in patients with inoperable HCC, but the safety profile was acceptable.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Hepatocellular/drug therapy , Liver Neoplasms/drug therapy , Administration, Oral , Adult , Aged , Female , Fluorouracil/administration & dosage , Fluorouracil/adverse effects , Follow-Up Studies , Humans , Male , Middle Aged , Survival Rate , Uracil/administration & dosage , Uracil/adverse effects , Uracil/analogs & derivatives
19.
J Surg Res ; 94(2): 145-52, 2000 Dec.
Article in English | MEDLINE | ID: mdl-11104654

ABSTRACT

BACKGROUND: E- and P-selectins are adhesion molecules that effect neutrophil-mediated reperfusion injury. Our hypothesis was that the expression of E- and P-selectins is dependent on the type of fluid used for resuscitation and that lactated Ringer's (LR) solution would result in an early upregulation of these molecules. METHODS: Male Sprague-Dawley rats (n = 36) were subjected to a 27 ml/kg hemorrhage over 5 min followed by a 1-h shock period and 1-h of resuscitation. The animals were randomized into the following resuscitation groups: (1) sham; (2) hemorrhage, no resuscitation; (3) whole blood (27 ml/kg); (4) 3:1 lactated Ringer's (81 ml/kg); (5) sham hemorrhage, infusion of lactated Ringer's (81 ml/kg); (6) 7. 5% hypertonic saline (9.7 ml/kg). Immediately after resuscitation, the spleen and lung were harvested for measurement of E- and P-selectin mRNA expression with reverse transcriptase- polymerase chain reaction (RT-PCR), and protein expression with immunostaining. RESULTS: LR resuscitation and LR infusion without prior hemorrhage significantly increased the E- and P-selectin mRNA in the lung and spleen. Immunostaining demonstrated that the adhesion molecule expression was mainly located in perivascular/peribronchial areas in the lung, and the marginal and trabecular areas in the spleen. Pulmonary edema and inflammatory cell infiltration were observed only in the animals that were hemorrhaged and resuscitated with LR. No resuscitation and resuscitation with whole blood caused no significant increase in selectin expression. CONCLUSION: LR resuscitation and LR infusion without hemorrhage are associated with early increased expression of E- and P-selectin molecules in the lung and spleen.


Subject(s)
Blood Transfusion , E-Selectin/genetics , Fluid Therapy/methods , Gene Expression Regulation , P-Selectin/genetics , Shock, Hemorrhagic/physiopathology , Shock, Hemorrhagic/therapy , Animals , Blood Pressure , Gene Expression Regulation/drug effects , Hemoglobins/analysis , Isotonic Solutions/pharmacology , Lactates/blood , Lung/pathology , Lung/physiopathology , Male , Pulmonary Edema/etiology , Pulmonary Edema/prevention & control , RNA, Messenger/analysis , Rats , Rats, Sprague-Dawley , Resuscitation/methods , Reverse Transcriptase Polymerase Chain Reaction , Ringer's Lactate , Saline Solution, Hypertonic/pharmacology , Shock, Hemorrhagic/blood , Spleen/pathology , Spleen/physiopathology , Transcription, Genetic/drug effects
20.
Int J Cancer ; 88(3): 489-92, 2000 Nov 01.
Article in English | MEDLINE | ID: mdl-11054682

ABSTRACT

Despite the high prevalence of infection by the Human Immunodeficiency Virus (HIV) in South Africa, information on its association with cancer is sparse. Our study was carried out to examine the relationship between HIV and a number of cancer types or sites that are common in South Africa. A total of 4,883 subjects, presenting with a cancer or cardiovascular disease at the 3 tertiary referral hospitals in Johannesburg, were interviewed and had blood tested for HIV. Odds ratios associated with HIV infection were calculated by using unconditional logistic regression models for 16 major cancer types where data was available for 50 or more patients. In the comparison group, the prevalence of HIV infection was 8.3% in males and 9.1% in females. Significant excess risks associated with HIV infection were found for Kaposi's sarcoma (OR=21.9, 95% CI=12.5-38.6), non-Hodgkin lymphoma (OR=5.0, 95%CI=2.7-9.5), vulval cancer (OR=4.8, 95%CI= 1.9-12.2) and cervical cancer (OR= 1.6, 95%CI= 1.1-2.3) but not for any of the other major cancer types examined, including Hodgkin disease, multiple myeloma and lung cancer. In Johannesburg, South Africa, HIV infection was associated with significantly increased risks of Kaposi's sarcoma, non-Hodgkin lymphoma and cancers of the cervix and the vulva. The relative risks for Kaposi's sarcoma and non-Hodgkin lymphoma associated with HIV infection were substantially lower than those found in the West.


Subject(s)
Acquired Immunodeficiency Syndrome/complications , HIV-1 , Neoplasms/epidemiology , Adolescent , Adult , Aged , Female , Humans , Lymphoma, AIDS-Related/epidemiology , Male , Middle Aged , Prevalence , Sarcoma, Kaposi/epidemiology , South Africa/epidemiology , Uterine Cervical Neoplasms/epidemiology
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