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Biomedical subjects

P Ruff

Publications and source records attributed to P Ruff.

At least 19 recordsLinked to original sources
PubMed2006

Antibodies against six human herpesviruses in relation to seven cancers in black South Africans: a case control study.

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.

Journal Article↗
PubMed2004

Low socioeconomic status and risk for infection with human herpesvirus 8 among HIV-1 negative, South African black cancer patients.

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.

Adult↗
PubMed2002

Risk factors for oesophageal, lung, oral and laryngeal cancers in black South Africans.

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.

Adolescent↗
PubMed2001

A phase II trial of oral eniluracil/5-fluorouracil in patients with inoperable hepatocellular carcinoma.

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.

Administration, Oral↗
PubMed2000

The spectrum of HIV-1 related cancers in South Africa.

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.

Acquired Immunodeficiency Syndrome↗
PubMed2000

E- and P-selectin expression depends on the resuscitation fluid used in hemorrhaged rats.

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.

Animals↗
PubMed2000

Human neutrophil activation and increased adhesion by various resuscitation fluids.

OBJECTIVE: To determine whether activated neutrophils play a major role in secondary tissue injury after resuscitation in trauma. We hypothesized that human neutrophil activation and adhesion vary, depending on the type and amount of resuscitation fluid used. SETTING: University-based research facility. SUBJECTS: Ten healthy adult volunteers. DESIGN: Whole blood from volunteers was serially diluted in polypropylene tubes with various resuscitation fluids. Fluids tested were phosphate-buffered saline, normal saline, lactated Ringer's solution, dextran, hespan, 5% human albumin, 25% human albumin, 3.5% hypertonic saline, and 7.5% hypertonic saline. Neutrophil activation (intracellular oxidative burst activity with dichlorofluorescin diacetate staining) and adhesion (integrin cell surface expression of CD18) were measured with flow cytometry (fluorescence-activated cell sorting). Blood was diluted with hypertonic saline by controlling for sodium content equal to normal saline. dose-related increase in neutrophil oxidative burst activity as the result of dilution followed with crystalloid fluids and artificial colloids (dextran and hespan). The increase was 12-18 x baseline at the 75% dilution. The increase with 5% human albumin was only 2.2 x baseline, and 25% albumin did not demonstrate any increased intracellular activity. A similar significant increase in the neutrophil adhesion expression (CD18) occurred with artificial colloids (p<.05) and, to a lesser extent, with crystalloids, but not with albumin. Hypertonic saline caused a decrease in CD18 cell surface expression. CONCLUSIONS: This study suggests that the neutrophil activation and adhesion may vary, depending on the type of resuscitative fluid used. All artificial resuscitative fluids may not be similar or innocuous, as demonstrated by the dose-related increase in neutrophil activation and adhesion.

Adult↗
PubMed2000

A prospective randomized study of Chop versus Chop plus alpha-2B interferon in patients with intermediate and high grade non-Hodgkin's lymphoma: the International Oncology Study Group NHL1 Study .

UNLABELLED: The addition of a brief alpha interferon regimen to each CHOP induction cycle, plus one year of alpha interferon thrice weekly maintenance therapy, has no early effect on response rates or survival in patients with Intermediate or High grade cell NHL. BACKGROUND: The CHOP (Cyclophosphamide, Adriamycin. Vincristine, Prednisone) regimen is the most widely used first-line therapy for patients with Intermediate or High Grade (IG/HG) non-Hodgkin's lymphoma (NHL). Alpha 2b interferon (INF) enhances response rates and improves survival in low-grade NHL. The International Oncology Study Group (IOSG) conducted a prospective randomized study comparing CHOP alone or combined with INF in patients with IG/HG-NHL. The primary study aim was to compare the objective response rates in these patient cohorts. PATIENTS AND METHODS: Patients with a confirmed diagnosis of measurable NHL of International Working Formulation (IWF) groups D to H histology were randomized to receive CHOP alone or CHOP with 5Mu INF s.c. for 5 days on days 22 to 26 of each 28 day cycle with INF 5 million units (Mu) given three times per week subcutaneously for 52 weeks in those patients who responded to CHOP plus INF. RESULTS: The overall response rates were equivalent in both groups: CHOP alone (214 patients) 81% (complete 55%, partial 26%); CHOP plus INF (221 patients) 80% (complete 54%, partial 26%). At 36 months, the actuarial survival rate was equivalent in both groups. CONCLUSIONS: There is no apparent early advantage in terms of response or survival conferred by adding the study INF regimen to CHOP therapy for patients with IG/HG-NHL.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

Exon skipping truncates the PDZ domain of human erythroid p55 in a patient with chronic myeloid leukemia in acute megakaryoblastic blast crisis.

Human p55, the major palmitoylated protein associated with the cytoplasmic face of the erythrocyte membrane, is believed to modulate interactions between protein 4.1 and glycophorin C. It is the prototype of a newly described family of signaling molecules that includes hD1g, the human homologue of the Drosophila discs-large tumor suppressor protein. Chronic myeloid leukemia is characterized by transformation to a fulminating acute leukemia, heralded by evolution of the Philadelphia chromosome positive genotype (Ph +) to further abnormalities. RT-PCR of p55 mRNA from a patient with acute megakaryoblastic CML revealed a 69 base pair deletion in the PDZ domain, corresponding to exon 5 of the p55 gene. The deletion of constitutive exon 5 not only marks the first abnormality of the p55 cDNA in human disease but also the first abnormality of a PDZ domain in human disease and may represent another genetic abnormality associated with CML in blast crisis.

Amino Acid Sequence↗
PubMed1999

Comparison of an orally disintegrating ondansetron tablet with the conventional ondansetron tablet for cyclophosphamide-induced emesis in cancer patients: a multicenter, double-masked study. Ondansetron Orally Disintegrating Tablet Emesis Study Group.

A total of 427 cancer patients receiving cyclophosphamide chemotherapy participated in this multicenter, double-masked, double-dummy, parallel-group, randomized study comparing the antiemetic efficacy and safety of an 8-mg conventional ondansetron tablet (OT, n = 212) taken twice daily with an 8-mg orally disintegrating ondansetron tablet (ODT, n = 215) taken twice daily for 3 days. In the primary efficacy analysis, complete or major control of emesis (0 to 2 emetic episodes) between days 1 and 3 was seen in 80% of OT and 78% of ODT patients. The 90% confidence interval for the differences between treatments was -8.6% to 4.4% (defined interval of equivalence, +/-15%), showing that the formulations were equivalent. In the secondary efficacy analysis, no significant differences were observed in the rates of complete control of emesis (no episodes of emesis) over 3 days (63% and 64% of the respective groups) and on day 1 (84% and 81%, respectively) and in the complete control of nausea over 3 days (37% and 43%, respectively) and on day 1 (59% and 61% of patients, respectively). The taste of ODT was acceptable to the majority of patients (89%) who received it. OT and ODT were both well tolerated. Thus 8 mg ODT twice daily represents a palatable, well-tolerated, and effective antiemetic treatment for the control of cyclophosphamide-induced emesis and nausea and provides equivalent treatment to OT 8 mg twice daily.

Administration, Oral↗
PubMed1999

Resuscitation with lactated Ringer's solution in rats with hemorrhagic shock induces immediate apoptosis.

BACKGROUND: We hypothesize that different resuscitative fluids may immediately affect the degree of apoptosis after hemorrhagic shock. METHODS: Rats (n = 35) were hemorrhaged 27 mL/kg over 5 minutes followed by 1 hour of shock, then resuscitation over 1 hour. The six treatment groups were sham hemorrhage, sham resuscitation, whole blood resuscitation, lactated Ringer's solution (LR) resuscitation with three times the volume bled, sham hemorrhage with LR infusion, and 7.5% hypertonic saline resuscitation (9.7 mL/kg). Liver and small intestine were harvested immediately after resuscitation. Apoptosis was evaluated by using in situ cell death detection method. RESULTS: Resuscitation with LR resulted in a significant increase in small intestinal and liver apoptosis. Animals that received LR infusion without hemorrhage had an increased level of apoptosis in the intestine. Apoptosis in the intestine was observed in both the mucosa and muscularis externa. There was no increase in apoptosis in either organ in the animals resuscitated with sham resuscitation, whole blood, and hypertonic saline compared with the sham hemorrhage group. CONCLUSION: Resuscitation with LR solution after hemorrhagic shock increased immediate cell death by apoptosis in both the small intestine and liver. There was no significant increase in apoptosis in the animals resuscitated with hypertonic saline, whole blood, or in unresuscitated animals. Thus, the type of resuscitation fluid used may affect the apoptotic cellular response to shock.

Animals↗
PubMed1999

Early up-regulation of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 expression in rats with hemorrhagic shock and resuscitation.

This study evaluated the effect of resuscitation fluids on intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). Sprague-Dawley rats (n = 36) were subjected to a 27 mL/kg hemorrhage over 5 min followed by a 1 h shock and 1 h resuscitation. Animals groups included: 1) cannulation only (Sham); 2) hemorrhage only (NR); 3) resuscitation with 1:1 shed blood (Blood); 4) resuscitation with 3:1 lactated Ringer's (81 mL/kg, 3LR+); 5) no hemorrhage but infusion with 3:1 lactated Ringer's (3LR); and 6) resuscitation with .36:1 hypertonic saline (7.5%, 9.7 mL/kg, HTS). At the end of resuscitation, the spleen and lung were harvested for detection of adhesion molecule mRNA and protein by RT-PCR and immunostaining. ICAM-1 and VCAM-1 expression exhibited the following pattern: 3LR+ > HTS approximate to 3LR > Blood approximate to NR approximate to Sham. VCAM-1 mRNA in the lung of the 3LR+ group was 2 or more times more than the groups of Sham, NR, Blood, and 3LR (p < .05). ICAM-1 and VCAM-1 mRNA in the spleen was significantly increased in the 3LR+ group compared with the groups of Sham, NR, and Blood (p < .05). Animals in the 3LR+ group showed enhanced staining for ICAM-1 in the pulmonary microvessels and in the marginal and trabecular areas of the spleen. Pulmonary edema and inflammatory cell infiltration were observed only in the 3LR+ group. In summary, resuscitation with LR following hemorrhagic shock induced immediate up-regulation of ICAM-1 and VCAM-1, which was associated with tissue injury. Thus, the type of resuscitation fluid used affected resuscitation injury.

Animals↗
PubMed1998

A phase II study of oral clofazimine in unresectable and metastatic hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma is highly refractory to most chemotherapeutic agents. Clofazimine, a riminophenazine compound used to treat leprosy since 1962, inhibits various cancer cell lines, including hepatocellular carcinoma cell lines, via phospholipase A2 dependant processes. Clofazimine also inhibits p170-glycoprotein, the mdr1 gene product. PATIENTS AND METHODS: Thirty patients (26 males and four females) with unresectable (25) or metastatic (5) hepatocellular carcinoma received oral clofazimine 600 mg daily for two weeks, followed by 400 mg daily until progression or death. RESULTS: There were three responses (10%)--one of a soft tissue metastasis, and two of local disease, with 13 patients disease stabilizing for up to 20 months. The overall median survival was 13 weeks. Adverse events included hyperpigmentation, eczematous skin rashes and palpitations. CONCLUSIONS: Although only three patients had an objective response (10%), the 13 patients with stable disease for up to 20 months, and an overall median survival of 13 weeks, suggest that clofazimine, or other riminophenazine compounds may prove to be of value in hepatocellular carcinoma.

Administration, Oral↗
PubMed1997

Association between human immunodeficiency virus type 1 infection and cancer in the black population of Johannesburg and Soweto, South Africa.

A case-control study of 913 black cancer patients (aged 15-50 years) was undertaken to measure the association between human immunodeficiency (HIV) infection and cancers believed to have an infective aetiology. Controls were patients with cancers believed not to be infective in origin. The prevalence of HIV in the controls of 7.3% (24 of 325) was similar to the background HIV seropositivity in this population. Odds ratios (ORs) and 95% confidence intervals (CI) adjusted for age, year of diagnosis, marital status and sex were calculated. There was a strong association between HIV infection and Kaposi's sarcoma (KS), with 27 of 33 cases being HIV seropositive, OR = 61.8 (95% CI 19.7-194.2) and an elevated association with non-Hodgkin's lymphoma (NHL), with 27 of 40 cases being HIV seropositive [OR = 4.8 (95% CI 1.5-14.8)]. The elevated odds ratio for KS associated with HIV infection accords with the observed increases in the incidence of KS in several sub-Saharan African countries where the prevalence of HIV is high. The odds ratio for NHL associated with HIV infection was lower than that reported in developed countries, and the reason for this is not clear. No other cancers, including cervical and liver cancers, showed significantly elevated odds ratios associated with HIV infection.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Low serum testosterone and a younger age predict for a poor outcome in metastatic prostate cancer.

Carcinoma of the prostate gland is one of the most common malignancies in males. This study was undertaken to determine which factors predict the course and outcome of patients treated with first line hormonal manipulation. A total of 144 patients with Stage D2 prostate cancer who received androgen deprivation therapy were studied. Pretreatment parameters analyzed were age, performance status, analgesia usage, concurrent disease, histologic differentiation, hemoglobin, leukocyte and platelet count, serum creatinine, alkaline phosphatase, lactate dehydrogenase, prostate specific antigen, total and prostatic acid phosphatase, serum testosterone, follicle stimulating and luteinizing hormone levels, number of metastatic sites and bone scan grade. Only initial serum testosterone (> 10 nmol/l) had a positive impact on response (p = 0.0304), whereas age older than 60 years had a positive impact on time to progression (16 vs. 11 months, p = 0.0414). Both serum testosterone (26 vs. 20 months, p = 0.003), and age (28 vs. 17 months, p = 0.036) had a significant influence on overall survival. Low testosterone, indicating androgen independence, and a younger age, seem to result in a more aggressive disease and a poorer prognosis in advanced prostate cancer.

Age Factors↗
PubMed1996

SSCP analysis of the tyrosine kinase domain of the insulin receptor gene: polymorphisms detected in South African black and white subjects.

The frequency of DNA polymorphisms in the tyrosine kinase domain (exons 17-21) of the insulin receptor gene was assessed in 30 black and 30 white South Africans, using single-stranded conformation polymorphism and direct sequencing analysis. A comparison of the frequencies of the normal versus the combined polymorphic alleles, found only in exon 17, showed a significant difference between black and white groups (P = 0.037).

Adult↗