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Biomedical subjects

S D Graham

Publications and source records attributed to S D Graham.

At least 19 recordsLinked to original sources
PubMed1995

Intravesical suramin in the prevention of transitional cell carcinoma.

OBJECTIVES: To examine the effects of intravesical suramin on N-methyl-N-nitrosurea (MNU)-induced bladder tumors in Fischer 344 rats. METHODS: Multiple cohorts of female rats received four biweekly intravesical instillations of MNU. A control group received no other treatment, the experimental group received 25 mg/kg intravesical suramin twice a week beginning at week 6. RESULTS: After 18 weeks from the first instillation of MNU, 60% to 65% of control animals developed papillary transitional cell carcinoma, compared with only 0% to 10% of the suramin-treated animals (P = 0.01 to P = 0.0007). There was no local or systemic toxicity observed. CONCLUSIONS: Intravesical suramin is an effective chemopreventative therapy for transitional cell carcinoma in vivo with minimal toxicity.

Administration, Intravesical↗
PubMed1995

Normal range prostate-specific antigen versus age-specific prostate-specific antigen in screening prostate adenocarcinoma.

OBJECTIVES: Prostate-specific antigen (PSA) has become the most useful serum tumor marker in the diagnosis and screening of prostate adenocarcinoma. The currently cited reference range of normal (0 to 4.0 ng/mL monoclonal) lacks both the sensitivity and specificity to be universally accepted as a screening test, and alternatives to serum PSA have been proposed, such as PSA density, PSA velocity, and age-adjusted PSA. Age-adjusted PSA takes into account the facts that as men grow older the prostate enlarges and that screening should have maximum sensitivity in younger men and maximum specificity in older men. METHODS: A population of 4,710 men with no known history of prostate adenocarcinoma underwent 5,629 examinations by transrectal ultrasound of the prostate (TRUS) from 1987 to 1994. This population consists of Mobile Urology Group, Mobile, Alabama, and Emory University, Atlanta, Georgia, patient databases. We have examined our data to determine the sensitivity, specificity, and positive predictive values for normal range PSA (0 to 4 ng/mL) versus age-specific PSA values. RESULTS: A total of 2040 patients had an abnormal digital rectal examination (DRE) and 3581 procedures were performed for an elevated PSA and a normal DRE. Biopsies were performed in 2,657 patients with 945 (35.6%) positive for cancer. Criteria for biopsy included elevated PSA (more than 4 mg/mL), PSA density more than 0.15 abnormal DRE, or suspicious TRUS. Patients were grouped according to decade: group 1 (ages 40 to 49 years, n = 183), group 2 (ages 50 to 59 years, n = 1018), group 3 (ages 60 to 69 years, n = 2358), and group 4 (ages 70 to 79 years, n = 1687). CONCLUSIONS: Use of the age-specific range for PSA increases the sensitivity in younger men more likely to benefit from treatment, and decreases the biopsy rate in older patients who may not be candidates for aggressive treatment. Age-adjusted PSA is the most valuable for patients over the age of 70 years of whom 22% would be spared TRUS with biopsy.

Adenocarcinoma↗
PubMed1995

Microvascular invasion in prostate cancer correlates with pathologic stage.

OBJECTIVE: To determine the incidence of microvascular invasion in prostatic carcinoma and its correlation with other prognostic factors. DESIGN: Evaluation of the frequency and extent of microvascular invasion by routine light microscopy in 210 whole-mounted radical prostatectomies with cancer. RESULTS: Microvascular invasion was identified in 111 (53%) of 210 specimens. Focal microvascular invasion (involvement of fewer than three high-power fields) was present in 42 cases (20%); extensive microvascular invasion (involvement of three or more high-power fields) was present in 69 cases (33%). Capsular perforation was present in 43% and 62% of cases with focal and extensive microvascular invasion, respectively. Seminal vesical involvement was observed in 23% and 47% of cases with focal and extensive microvascular invasion, respectively. Lymph node metastases were only observed in cases with microvascular invasion and were present in 7% and 23% of cases with focal and extensive invasion, respectively. There was also a strong positive correlation of microvascular invasion with surgical margin status, Gleason score, and cancer volume. Tumors ranged in volume from 0.14 cc to 47.25 cc (mean, 9.09 cc), and the volume in cases without microvascular invasion was lower than in those with invasion (mean, 5.4 cc and 12.7 cc, respectively); also, the volume in cases with focal invasion was lower than in those with extensive invasion (mean, 9.4 cc and 16.1 cc, respectively). CONCLUSIONS: Microvascular invasion in prostatic carcinoma correlates positively with virtually all measures of pathologic stage. Its presence should be reported in all prostate specimens according to the Cancer Committee of the College of Americans Pathologists.

Disease Progression↗
PubMed1995

Conservative renal surgery. Has it a role in renal cell carcinoma?

Conservative renal surgery is a viable alternative for patients in whom preservation of renal function is important. The long-term survival is similar to that of radical nephrectomy, especially in low-grade malignancies. The technique is unproven in patients with a normally functioning contralateral renal unit, although it may be an option in small, peripheral, low-grade lesions.

Carcinoma, Renal Cell↗
PubMed1994

Serum PSA adjusted for volume of transition zone (PSAT) is more accurate than PSA adjusted for total gland volume (PSAD) in detecting adenocarcinoma of the prostate.

OBJECTIVE: This study evaluates the accuracy of comparing serum prostate-specific (PSA) levels in the range between 4.1 ng/mL and 10.0 ng/mL (monoclonal) to the volume of the transition zone (TZ) of the prostate and total gland volume as a predictor of a positive biopsy. METHODS: Using sonographic voluming of the entire prostate and of the TZ, prostate-specific antigen density (PSAD) and prostate-specific antigen density of the TZ (PSAT) were calculated in 21 biopsy-positive patients and 38 biopsy-negative patients. Biopsy was directed at sonographically suspicious areas and did not include sextant biopsies. RESULTS: A statistically significant association was determined between a positive biopsy and gland volume, TZ volume, and PSAT. The association of a positive biopsy with PSA and PSAD was not statistically significant. CONCLUSIONS: PSAT is more accurate in predicting a positive biopsy than is PSAD for PSA levels between 4.1 ng/mL and 10.0 ng/mL.

Adenocarcinoma↗
PubMed1994

Methoxypsoralen phototherapy of transitional cell carcinoma.

OBJECTIVES: The goal of this research was to assess whether methoxypsoralen compounds in combination with ultraviolet light were effective in preventing cellular proliferation in an in vitro model of human transitional cell carcinoma. METHODS: Three methoxypsoralen compounds, 5-methoxypsoralen (5-MOP), 8-methoxypsoralen (8-MOP), and 4'-aminomethyl 4,5'-8'-trimethylpsoralen (AMT), were added in vitro to T-24 transitional cell carcinoma cells. Psoralens directly bind to DNA, cross-linking the strands when exposed to ultraviolet light and thereby prevent cellular division. RESULTS: In vitro activity was demonstrated utilizing AMT and ultraviolet radiation at 320 to 340 nm, preventing cellular proliferation in T-24 transitional cell carcinoma. CONCLUSIONS: Methoxypsoralen compounds in combination with ultraviolet light are effective in preventing proliferation of bladder carcinoma cells in vitro. This therapy may prove to be effective in clinical early stage transitional cell carcinoma and warrants further assessment.

5-Methoxypsoralen↗
PubMed1992

Critical assessment of prostate cancer staging.

Staging of prostatic adenocarcinoma is a systematic classification of the extent of disease based on clinical and pathologic criteria. This classification determines treatment and reflects ultimate expected clinical outcome. The technologic changes in diagnostic modalities need to be incorporated into the staging classification and a better assessment of biologic hazard of each individual tumor needs to be developed to further refine current treatment of prostate cancer.

Acid Phosphatase↗
PubMed1992

Suramin inhibits growth factor binding and proliferation by urothelial carcinoma cell cultures.

Suramin is a polyanionic compound recently noted to inhibit growth factor action and proliferation of several types of neoplastic cells in vitro. Data from clinical trials show antineoplastic activity against some prostatic and adrenal cortical carcinomas. Suramin is excreted unmetabolized into the urine suggesting possible application in treatment of urothelial carcinoma and prompting us to examine the drug's effect on growth factor binding and cell proliferation by two urothelial carcinoma cell lines. Half-maximal inhibition of 125I-epidermal growth factor (EGF) binding to T24 and HT1376 cells was produced by suramin concentration of approximately 300 and 100 microM, respectively. The corresponding value for 125I-insulin-like growth factor 1 (IGF1) binding was 60 microM for both cell lines. Inhibition of T24 and HT1376 growth was virtually complete at suramin concentrations in the range achievable clinically.

Animals↗
PubMed1992

The detection of African horse sickness virus antigens and antibodies in young Equidae.

Four ponies were each inoculated with a different serotype of African horse sickness virus (AHSV) which had been passaged through cell culture in order to achieve attenuation. Three of the ponies died suddenly after showing mild clinical signs, the fourth pony remained clinically normal and was killed at day 38. Infectious AHSV was isolated from blood samples collected at intervals from all four ponies. Positive antigen ELISA reactions were only observed with blood samples from two of the ponies on the two days preceding death. Specific AHSV antibodies were detected by ELISA in serum samples from the other two ponies although one eventually died. African horse sickness viral antigens were detected by ELISA in post-mortem tissue samples collected from all four ponies. No infectious virus could be detected in tissue samples taken post-mortem from the pony which survived African horse sickness (AHS) infection. In the event of a suspected outbreak of AHS it is recommended that sera and heparinized blood should be tested for specific antibodies and AHSV antigen respectively. When available, post-mortem tissues, including spleen, heart, lung and liver, should also be tested for AHSV antigen. Although the ELISA used for the detection of AHSV antigen is highly sensitive and specific, negative ELISA results should be confirmed by virus isolation attempts.

African Horse Sickness↗
PubMed1992

Immunology of the bladder.

Immunobiology techniques that once were the domain of research are increasingly being applied in the clinic. Transitional epithelium of the bladder undergoes some recognized immunologic changes as it becomes malignant, and their detection may have prognostic value. Examples of such changes are deletion of the ABO(H) blood group antigens, inappropriate expression of Lewis antigens, loss of beta-2 microglobulin and the MHC class 1 heavy chain, and alterations in the production of cellular adhesion molecules and integrins. Other possibly useful markers are ras oncogene products, Thomsen-Friedenreich antigen, epidermal growth factor receptor, and perhaps antigens unique to transitional-cell carcinoma.

Antigens, Neoplasm↗
PubMed1991

ABO(H) antigens and beta-2 microglobulin in transitional cell carcinoma. Predictors of response to intravesical bacillus Calmette-Guerin.

The response of patients with superficial transitional cell carcinoma of the bladder (STCB) to intravesical chemotherapy is variable; some patients enjoy a long period without recurrence, whereas others have recurrence of tumor within 2 years of removal of the primary lesion. Previously, others have demonstrated that the loss of normal cell surface antigens, such as ABO(H) blood group antigens or beta-2 microglobulin (B2M) has been correlated with more aggressive behavior by tumor. In this study, using immunohistochemical techniques, the authors evaluated the initial pretreatment biopsy specimen of bladder tumors for the presence of ABO(H) antigens and B2M. Data from this sample patient population, all with biopsy-proven STCB, indicate that expression of these two markers is predictive of a therapeutic response to prophylactic intravesical bacillus Calmette-Guerin (BCG) (Tice strain) after resection, and that expression of the two markers is of greater predictive value than expression of either antigen alone.

ABO Blood-Group System↗
PubMed1991

Randomized study of interleukin 2 (IL-2) alone vs IL-2 plus lymphokine-activated killer cells for treatment of melanoma and renal cell cancer.

The purpose of this study was to evaluate the efficacy and safety of a continuous-infusion interleukin 2 (IL-2) regimen for patients with metastatic melanoma and renal cell cancer. To investigate the contribution of adoptively transferred lymphokine-activated killer cells, patients were randomized to receive either IL-2 alone or IL-2 plus lymphokine-activated killer cells. Twenty-three patients with renal cell carcinoma and 20 with melanoma were entered into the protocol. There were no objective responses noted in the 38 assessable patients (20 with renal cell carcinoma, 18 with melanoma). Most patients demonstrated progressive disease following one 31-day cycle of weekly continuous-infusion IL-2. Grade I and II toxic reactions, including fever, rash, anorexia, and weight gain, were common and treated symptomatically. Significant in vivo stimulation of lymphokine-activated killer and natural killer cell activity was noted in most patients. This continuous-infusion IL-2 regimen with or without lymphokine-activated killer cells was ineffective in the treatment of melanoma and renal cell carcinoma.

Adult↗
PubMed1991

Antibodies in horses, mules and donkeys following monovalent vaccination against African horse sickness.

A total of 256 sera collected from three species of domesticated equidae in four different Spanish provinces were examined 1-4 months after the administration of attenuated monovalent African horse sickness virus (AHSV) serotype 4 vaccine. Approximately 10% of the sera were negative by ELISA, virus neutralization, agar gel immuno-diffusion and complement fixation tests. Similar negative reactions were recorded with sera from two ponies after experimental primary vaccination. The rapid rise in antibodies in sera from these two ponies, after a second dose of vaccine, suggested they would probably have been immune to challenge. It is therefore suggested that the apparent absence of antibodies against AHSV in some animals after primary vaccination may not necessarily indicate a total lack of protection.

African Horse Sickness↗
PubMed1991

Renal cell carcinoma with inferior vena caval involvement.

Renal cell carcinoma extends into the lumen of the inferior vena cava in approximately 4% of patients at the time of diagnosis. Surgical removal of the intracaval tumor thrombus with radical nephrectomy is the preferred treatment for this malignancy. From January 1977 to June 1990, 31 such patients were examined for combined problems of renal carcinoma and intracaval tumor extension. Twenty-six of these patients underwent radical nephrectomy and vena caval thrombectomy. Ten patients had tumor thrombus confined to the infrahepatic vena cava, 11 had retrohepatic caval involvement, and 5 had extension to the level of the diaphragm or into the right atrium. Surgical approach was dictated by the level of caval involvement. Control of the suprahepatic vena cava plus temporary occlusion of hepatic arterial and portal venous inflow were necessary in some cases; cardiopulmonary bypass was required for transatrial removal of more extensive tumors. Five of the 26 patients had evidence before operation of distant metastatic disease; none of these survived beyond 12 months. The 5-year actuarial survival rate of the 21 patients without known preoperative metastatic disease was 57%. Complete surgical excision of all gross tumor appears to be critical for long-term survival in these patients.

Adolescent↗
PubMed1990

Enucleation of tumor versus partial nephrectomy as conservative treatment of renal cell carcinoma.

In patients with renal insufficiency, solitary kidney, or bilateral renal malignancies, conservative surgery for renal cell carcinoma has been suggested. The authors treated 17 such patients with either enucleation of tumor or partial nephrectomy. Overall survival from disease in this series was 58.8%. Seventy percent of patients undergoing enucleation and 42.9% undergoing partial nephrectomy survived with a mean follow-up period of 5 years. Survival or local recurrence rate after enucleative surgery is an effective treatment of renal carcinoma in selected patients, and despite concerns about tumor invasion of the pseudocapsule, the clinical data do not indicate any difference in survival. There was no significant difference between enucleation of tumor and partial nephrectomy regarding morbidity, mortality, or recurrence rate.

Adult↗