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Biomedical subjects

R D Williams

Publications and source records attributed to R D Williams.

At least 55 records · Page 3Linked to original sources
PubMed1997

Accuracy of color Doppler sonography in assessing venous thrombus extension in renal cell carcinoma.

OBJECTIVE: Our objective was to evaluate the accuracy of color Doppler sonography for assessing tumor thrombus extension into the renal veins, the inferior vena cava, and the right side of the heart in patients with renal cell carcinoma. MATERIALS AND METHODS: Over the past 4.5 years, 44 patients with 46 renal cell carcinomas were examined with color Doppler sonography for the presence and extent of tumor thrombus in the renal veins, the inferior vena cava, and the right side of the heart. Examinations were performed after an equivocal CT scan in 34 patients and as a primary imaging technique in 10. Color Doppler sonographic findings were correlated with surgical-pathologic findings or findings from autopsies performed within 3 months of the Doppler study. Seven patients were excluded: two because of poor technical quality caused by body habitus and five because pathologic correlation was performed more than 3 months after the color Doppler sonographic examination. The remaining 39 renal vein and 37 caval Doppler examinations constituted the study material. Criteria used for the diagnosis of tumor thrombus included distention of the renal vein or the inferior vena cava by echogenic material and partial or complete absence of flow detected with color Doppler sonographic examination. RESULTS: Sixteen of 39 renal veins evaluated had pathology-proven tumor thrombus. Color Doppler sonography was 87% accurate with a sensitivity of 75%, a specificity of 96%, a positive predictive value of 92%, and a negative predictive value of 85%. In two false-positive cases, involvement was limited to intrarenal veins, causing no change in the surgical approach. Five of 37 inferior venae cavae evaluated had proven involvement by tumor thrombus. Color Doppler sonography was 100% accurate in assessing the presence and extent of inferior vena caval involvement by tumor thrombus. Extension into the right atrium and ventricle that was shown by this technique was proven by surgery in one case. The overall accuracy for detecting venous involvement for both the renal veins and the inferior vena cava was 93%, the sensitivity was 81%, and the specificity was 98%. CONCLUSION: In patients with renal cell carcinoma, color Doppler sonography appears to be fairly accurate in assessing tumor extension into the renal veins, the inferior vena cava, and the right side of the heart. Although CT is the primary imaging technique for staging renal cell carcinoma, color Doppler sonography may be used as a complementary technique for assessing venous extension in patients with an equivocal CT examination.

Carcinoma, Renal Cell↗
PubMed1997

Laparoscopic pelvic lymph node dissection following definitive radiotherapy for carcinoma of the prostate.

PURPOSE: Laparoscopic pelvic lymph node dissection is an effective and minimally invasive approach to the clinical staging of adenocarcinoma of the prostate. We report our experience with this technique in patients in whom full course pelvic radiotherapy had failed and who were being considered for salvage local therapy. MATERIALS AND METHODS: In 14 patients disease was staged by transperitoneal laparoscopic pelvic lymph node dissection performed for persistent adenocarcinoma of the prostate at least 20 months (average 49.5) following external beam radiotherapy and/or brachytherapy. All patients were healthy, had no evidence of metastatic disease and were considered to be candidates for salvage therapy. RESULTS: A total of 13 patients underwent successful laparoscopic pelvic lymph node dissection while 1 sustained an enterotomy requiring conversion to open surgery. The normal surgical planes were more difficult to dissect, with the obturator lymph node packets appearing smaller and more fibrotic than in nonirradiated patients, yielding an average of 7.1 total nodes. Average operative time was 167 minutes and postoperative hospitalization was comparable to reported series of nonirradiated patients. Four patients (28%) with metastatic pelvic lymph nodes underwent subsequent orchiectomy. Nine patients with negative lymph nodes underwent ultrasound guided transperineal placement of radioactive gold or palladium seeds. One patient underwent salvage radical retropubic prostatectomy. CONCLUSIONS: Laparoscopic pelvic lymph node dissection following full course pelvic irradiation is technically feasible, albeit more difficult than in nonirradiated patients. This approach appears to be an excellent minimally invasive technique for the clinical restaging of persistent adenocarcinoma of the prostate in patients being considered for salvage therapy.

Adenocarcinoma↗
PubMed1996

Activation domains of transcription factors mediate replication dependent transcription from a minimal HIV-1 promoter.

Transcription from a minimal HIV-1 promoter containing the three Sp1 binding sites and TATA box can be activated without Tat by template DNA replication. Here we show that this activation can also be mediated by recombinant GAL4 fusion proteins containing the activation domains of Sp1, VP16 or CTF (or by full-length GAL4) targeted to the HIV-1 promoter by replacing the Sp1 sites with five GAL4 binding sites. Thus Sp1 is not unique in its ability to mediate replication activated transcription, although the degree of processivity elicited by the different activators varied significantly from strongly processive (GAL4-VP16) to relatively non-processive (GAL4-Sp1 or -CTF). Processive GAL4-VP16-activated transcription, but not efficient initiation, required multiple GAL4 binding sites. In the presence of Tat, transcription with GAL4-SP1 and GAL4-CTF was further activated (principally at the level of processivity) but GAL4-VP16-potentiated transcription was only slightly stimulated. The Tat-dependent switch from non-processive to fully processive transcription was particularly marked for GAL4-Sp1, an effect which may be relevant to the selection of Sp1 binding sites by the HIV-1 promoter.

Base Sequence↗
PubMed1996

Human immunodeficiency virus type 1 Rev-dependent effects on the late gene expression of recombinant human adenovirus.

Both human adenovirus type 5 (Ad5) and human immunodeficiency virus (HIV-1) encode functions (E1b 55K/E4 orf6 and Rev respectively) which are needed for the efficient cytoplasmic accumulation of late viral mRNAs and which act post-transcriptionally. The similarity between these two regulatory systems was explored by constructing recombinant Ad5 carrying either one or both of the two components of the HIV-1 system (Rev and its RNA target sequence, RRE) and analysing the effects on Ad5 gene expression. In the presence of a functional Ad5 regulatory system, the HIV-1 system had no detectable effect on Ad5 gene expression. When the Ad5 system was rendered inoperative by mutation, the HIV-1 Rev/RRE system brought about a modest increase in the cytoplasmic accumulation of RRE-containing mRNAs. This was not sufficient to complement effectively the defect due to the Ad5 mutation. These data suggest that HIV-1 Rev acts on a similar pool of nuclear RNA to that targeted by Ad5 E1b 55K/E4 orf6 but functions inefficiently in the situation studied here. Effects were also observed on the accumulation of certain Ad5 mRNAs from which the RRE had been removed by splicing. No change was observed in the balance of production of differentially spliced mRNAs from the RRE-containing primary transcript when Rev was present. These observations are therefore more consistent with a mode of action for Rev that involves commitment of nuclear RNAs to transport than with models in which Rev acts as an inhibitor of splicing.

Adenoviruses, Human↗
PubMed1996

Paclitaxel in advanced urothelial carcinoma: its role in patients with renal insufficiency and as salvage therapy.

PURPOSE: We evaluated the role of paclitaxel in patients with advanced urothelial carcinoma and renal insufficiency or as second line therapy for metastatic disease. MATERIALS AND METHODS: Nine patients with advanced urothelial carcinoma received 175 to 250 mg./m2. paclitaxel intravenously as a 24-hour infusion. Six patients had renal insufficiency with a median serum creatinine of 2.25 mg./dl. (range 1.9 to 3.2) and 3 with normal renal function were treated after disease progression following 1 to 2 prior chemotherapy regimens. RESULTS: Of 9 patients 5 (56%) achieved a partial response, including 4 of 6 with renal insufficiency. Toxicity was primarily hematological with 4 patients experiencing febrile neutropenia. There was no adverse impact on renal function. CONCLUSIONS: Paclitaxel as a single agent represents an effective therapeutic alternative for patients with advanced transitional cell carcinoma of the urothelium and renal insufficiency precluding cisplatin or gallium nitrate based chemotherapy. Additionally, paclitaxel appears to be effective in patients in whom prior cisplatin based therapy failed.

Adult↗
PubMed1996

Management of prostate and bladder cancer in the elderly.

The management of prostate and bladder cancer in the elderly will increasingly require clinicians to judge the impact on comorbidity and toxicity of the proposed therapy in order to make sound management decisions. As PSA-based screening has rapidly increased, physicians are increasingly challenged to decide the upper age limits for such screening and therapy. Bladder cancer management in the elderly differs little from that offered to the younger patient and the new therapeutic developments may improve the risk-to-benefit ratio of treating advanced disease. It is clear that as the US population ages, management of prostate and bladder cancer will become an increasingly common dilemma for the urologic practitioner.

Age Factors↗
PubMed1996

The effect of exogenous testosterone on total and free prostate specific antigen levels in healthy young men.

PURPOSE: We evaluated the effect of exogenous testosterone administration on serum total and free prostate specific antigen (PSA) in healthy young men. MATERIALS AND METHODS: Nine volunteers received either 100, 250 or 500 mg. testosterone by intramuscular injection each week for 15 weeks. Blood was drawn every other week for 28 weeks and at week 40. Serum total and free PSA, and total and free testosterone were measured and compared to baseline values. RESULTS: Significant elevations in total and free testosterone occurred but no significant change in serum total and free PSA was detected. CONCLUSIONS: Serum PSA is not responsive to elevated serum testosterone levels in healthy young men. PSA metabolism in the normal prostate is unclear but our findings may have implications for differentiation of pathological conditions of the human prostate.

Adult↗
PubMed1996

Staging of incidentally detected prostate cancer: role of repeat resection, prostate-specific antigen, needle biopsy, and imaging.

Numerous studies have confirmed the distinct biological behavior of two subsets of prostate cancer diagnosed incidentally after either transurethral resection (TURP) or open prostatectomy for presumed benign prostatic hyperplasia (BPH). Focal, low-grade lesions are associated with a low risk for clinical progression and are designated as stage T1a or A1. These cases have traditionally been managed conservatively with close clinical observation. In contrast, multifocal, high-volume, or high-grade tumors are associated with a more aggressive clinical course and are designated as stage T1b or A2. Early definitive intervention is usually advocated for these latter patients. Therefore, accurate pathological assignment to either stage T1a or T1b is crucial for selection of appropriate management options. A variety of methods for staging patients with incidentally detected prostate cancer have been proposed, including detailed histological analysis, repeat TURP or transurethral biopsy, serial prostate-specific antigen (PSA) analysis, and imaging with either transrectal ultrasound (TRUS) or magnetic resonance (MRI) techniques. This article critically examines the clinical utility of these staging modalities for patients with incidentally detected prostate cancer.

Biopsy, Needle↗
PubMed1995

Postradical orchiectomy hemorrhage: should an alteration in staging strategy for testicular cancer be considered?

We report 3 cases of postradical orchiectomy hemorrhage from separate institutions. The retroperitoneal and pelvic hematoma formed as a complication of orchiectomy can be misinterpreted to represent metastatic disease on postoperative staging computed tomography scans. As a result of inaccurate information obtained from these evaluations, significant alterations in patient management will result. Prevention and early recognition of this complication are crucial if unnecessary treatment is to be avoided.

Adult↗
PubMed1995

Treatment of renal cell carcinoma in von Hippel-Lindau disease: a multicenter study.

A total of 65 patients with von Hippel-Lindau disease underwent surgery for renal cell carcinoma (54 bilaterally and 11 unilaterally) at 8 medical centers. Only 1 patient presented with metastatic disease. Radical nephrectomy and nephron sparing surgery were performed in 16 and 49 patients, respectively. Mean posttreatment followup was 68 months. The 5 and 10-year cancer-specific survival rates for all patients were 95% and 77%, respectively. The corresponding rates for patients treated with nephron sparing surgery were 100% and 81%, respectively. Of the latter patients 25 (51%) had postoperative local tumor recurrence but only 2 had concomitant metastatic disease. Survival free of local recurrence was 71% at 5 years but only 15% at 10 years. End stage renal failure occurred in 15 patients (23%): 6 underwent renal transplantation (5 are alive with satisfactory renal function and no evidence of malignancy) and 9 were treated with chronic dialysis (6 are free of tumor). Our results indicate that nephron sparing surgery can provide effective initial treatment for patients with renal cell carcinoma and von Hippel-Lindau disease. These patients must be followed closely, since most will eventually have locally recurrent renal cell carcinoma. When removal of all renal tissue is necessary to achieve control of malignancy, renal transplantation can provide satisfactory replacement therapy for end stage renal disease.

Adolescent↗
PubMed1995

Trends in the AIDS epidemic among men who reported sex with men in New York City: 1981-1993.

New York City is a major urban epicenter of the AIDS epidemic in the United States, and has reported nearly one fifth of the nation's cases. This paper chronicles trends in the AIDS epidemic among men who have sex with men (MSM) from 1981 through 1993 in New York City. Annual AIDS incidence and cumulative deaths are described, results of survival analysis by race/ethnicity for three time periods are reported, and the effects of the epidemic on premature mortality are shown from the beginning of the epidemic through 1993. Among 25,812 cases reported in MSM, 52% were white, 25% were black and 21% were Hispanic. AIDS incidence among whites has been declining since 1987 and is continuing to increase among minorities. Survival has been improving over time among all groups analyzed, but a persistent differential in survival between different race and ethnic groups is found, with whites surviving longer than minorities. Overall, nearly one half a million person years of life before age 65 were lost among MSM between 1981 and 1993. A rapid increase in AIDS cases among men born 1970-79 who were diagnosed after 1988 suggests a new wave of the epidemic may be occurring, and continued efforts in AIDS education and prevention among MSM entering the age of sexual activity is required.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Functional consequences of posttranslational isomerization of Ser46 in a calcium channel toxin.

The venom of the funnel-web spider Agelenopsis aperta contains several peptides that paralyze prey by blocking voltage-sensitive calcium channels. Two peptides, omega-Aga-IVB (IVB) and omega-Aga-IVC (IVC), have identical amino acid sequences, yet have opposite absolute configurations at serine 46. These toxins had similar selectivities for blocking voltage-sensitive calcium channel subtypes but different potencies for blocking P-type voltage-sensitive calcium channels in rat cerebellar Purkinje cells as well as calcium-45 influx into rat brain synaptosomes. An enzyme purified from venom converts IVC to IVB by isomerizing serine 46, which is present in the carboxyl-terminal tail, from the L to the D configuration. Unlike the carboxyl terminus of IVC, that of IVB was resistant to the major venom protease. These results show enzymatic activities in A. aperta venom being used in an unprecedented strategy for coproduction of necessary neurotoxins that possess enhanced stability and potency.

Agatoxins↗
PubMed1994

Conservative surgical therapy of localized renal cell carcinoma in von Hippel-Lindau disease.

BACKGROUND: Renal cell carcinoma is a frequent cause of morbidity and mortality in patients with von Hippel-Lindau disease. METHODS: A review was conducted of 10 patients with von Hippel-Lindau disease and localized renal tumors, who underwent renal parenchyma-sparing surgery. Four patients had recurrences, requiring a total of 16 operations. Patients were followed for recurrence by computed tomography. RESULTS: The mean follow-up for these patients was 62 months (range, 11-118 months). Seventy-two tumors were resected, including 36 tumors not seen by preoperative imaging studies. This was accomplished primarily by enucleation or partial nephrectomy when anatomically feasible. No patient required dialysis, and the mean serum creatinine at follow-up was 1.2 mg/dl (range, 0.9-1.7). Of the 10 patients, 2 died, one of primary lung cancer with recurrent renal cell carcinoma found at autopsy, and one of metastatic renal cell carcinoma. Another patient with probable recurrent tumor was being observed at the time of this writing. The other seven patients were alive and without evidence of renal cancer. CONCLUSION: Although the risk of recurrence is high, these patients may be treated with parenchyma-sparing renal surgery and enjoy a prolonged survival, and avoid the complications of dialysis or transplantation.

Adult↗