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Biomedical subjects

J A Vaccaro

Publications and source records attributed to J A Vaccaro.

At least 19 recordsLinked to original sources

Implication of the tRNA initiation step for human immunodeficiency virus type 1 reverse transcriptase in the mechanism of 3'-azido-3'-deoxythymidine (AZT) resistance.

There is a lack of correlation between biochemical studies and the observed clinical resistance of AIDS patients on long-term AZT therapy. Mutant HIV-1 reverse transcriptase in the viral isolates from these patients shows a 100-fold decrease in sensitivity to AZT whereas little or no difference is observed in kinetic parameters in vitro using steady-state kinetic analysis. A pre-steady-state kinetic analysis was used to examine the binding and incorporation of 2'-deoxythymidine 5'-triphosphate (dTTP) and 3'-azido-3'-deoxythymidine 5'-triphosphate (AZTTP) by wild-type HIV-1 reverse transcriptase and a clinically important AZT-resistant mutant form of the enzyme (D67N, K70R, T215Y, K219Q) utilizing a physiologically relevant RNA 18-mer/RNA 36-mer primer-template substrate. It was determined that with this RNA/RNA substrate there is a 2.6-fold increase in the selection for incorporation of the natural nucleotide dTTP over the unnatural nucleoside analogue AZTTP by AZT-resistant reverse transcriptase as compared to its wild-type form. This observation indicates that the tRNALys initiation step plays an important role in the development of drug resistance. Furthermore, this result implies that the structural basis of AZT resistance in HIV-1 reverse transcriptase involves the conformation of the RNA-DNA junction (formed upon attachment of a deoxynucleotide to the RNA primer). Taken together, these observations suggest a new pharmacological basis for the development of more effective and novel AIDS drugs.

DNA Primers

Mechanism of reconstitution of brewers' yeast pyruvate decarboxylase with thiamin diphosphate and magnesium.

Reconstitution of apo-pyruvate decarboxylase isozymes (PDC, EC 4.1.1.1) from Saccharomyces carlsbergensis was investigated by determination of the steady-state kinetics of the reaction with thiamin diphosphate (TDP) and Mg2+ in the presence and absence of substrate (pyruvate) or allosteric effector (pyruvamide). Reconstitution of the PDC isozyme mixture and alpha 4 isozyme (alpha 4-PDC) exhibits biphasic kinetics with 52 +/- 11% of the PDC reacting with k1 = (1.0 +/- 0.3) x 10(-2) s-1 and 48 +/- 12% of the PDC reacting with k2 = (1.1 +/- 0.6) x 10(-1) s-1 when TDP (KTDP = 0.5 +/- 0.2 mM) is added to apo-PDC equilibrated with saturating Mg2+. PDC reconstitution exhibits first-order kinetics with k1 = (1.6 +/- 0.5) x 10(-2) s-1 upon addition of Mg2+ (KMg2+ = 0.2 +/- 0.1 mM) to apo-PDC equilibrated with saturating TDP. Biphasic kinetics for the PDC isozymes provides evidence that apo-PDC reconstitution with TDP and Mg2+ involves two pathways, TDP binding followed by Mg2+ (k1) or Mg2+ binding followed by TDP (k2). This is supported by a change in reconstitution pathway with the order of cofactor addition and is inconsistent with a single pathway involving ordered binding of the metal ion followed by TDP. The presence of pyruvamide has no significant effect on the rate constants for apo-PDC reconstitution and favors the k2 pathway; pyruvate decreases the value of k2 < or = 3-fold and has no effect on the value of k1.(ABSTRACT TRUNCATED AT 250 WORDS)

Isoenzymes

Determination of indwelling ureteral stent patency: comparison of standard contrast and nuclear cystography, and lasix renography.

OBJECTIVE: Because of the difficulty in determining patency of Double-J ureteral catheters, a study was devised at Madigan Army Medical Center to determine the best method to demonstrate stented ureteral patency. METHODS: Forty-two patients requiring Double-J ureteral stenting for various clinical reasons were the study group. Outpatients underwent contrast retrograde cystography, nuclear cystography, and diuretic renography every four to six weeks during the stent duration or just prior to stent removal if the stents were indwelling for less than four weeks. In addition, four weeks after stent removal diuretic renography alone was done to evaluate for possible delayed obstructive effect of the ureteral stenting. RESULTS: A total of 53 stents and 42 patients were evaluated. Seventy-seven sets of studies were obtained. In only four instances did all three imaging methods agree on the obstruction. In the remaining 73 sets of data, at least one imaging technique indicated stented ureteral patency. The contrast retrograde cystogram was positive for reflux 52 times (71%). Nuclear cystography showed patency 54 times (74%) and an unobstructed diuretic renogram was obtained 59 times (81%). In addition, five of the six diuretic renograms accomplished with patients in the supine position only and which showed obstruction were repeated with patients in the upright position, and they showed unobstructed function. The overall sensitivity for diuretic renography was 89 percent when the diuretic renogram was done with patients in the supine and upright positions. CONCLUSIONS: Diuretic renography is the most sensitive test for detecting stented ureteral patency. This test needs to be performed with patients in both the supine and upright positions.

Adult

Perineal xanthogranulomatous pseudotumor due to intermittent catheterization: a liposarcoma mimic. Case report.

A large perineal fatty tissue mass shown to be an encapsulated xanthogranulomatous reaction was found in a spinal cord injured man whose neuropathic bladder was for a long time being managed by clean intermittent catheterization, but who had chronic urinary tract infection. He was also known to be a chronic alcoholic. We would say that an alcohol numbed sensorium and multiple catheterizations led to recurrent small urethral perforations which in the setting of chronic bacteriuria promoted the unusual inflammatory mass. Appreciating the increasing use of clean intermittent catheterization for the spinal cord injured, we suspect that similar cases of 'xanthogranulomatous pseudotumors' will be found, and therefore we describe this most unusual clinical presentation.

Granuloma

Replacement of nephrostomy tube using ureteroscopes.

Replacement of a percutaneous nephrostomy tube can be a difficult task. The often time-consuming procedure involves replacement of a guide wire blindly or under fluoroscopic control, or by using ultrasound after decompression of hydronephrosis. A rigid 8.5F ureteroscope was used successfully to replace nephrostomy tubes in 3 patients with obstructive uropathy secondary to prostate carcinoma and in 1 with an ileoureteral anastomotic leak following radical cystectomy.

Aged

Prostate-specific antigen and digital rectal examination in long-term follow-up of stage A1 prostatic carcinoma.

Twenty-six individuals with Stage A1 carcinoma of the prostate (less than or equal to 5%, Gleason score less than or equal to 4) diagnosed from 1969 to 1980 were evaluated with digital rectal examination (DRE) and prostate-specific antigen (PSA). This unique cohort, sixty-one to eight-two years of age (median 72 years), had a mean interval from diagnosis of thirteen years (median 12.5 years). Abnormal findings on DRE were found in 6 individuals, whereas only one elevated PSA was detected. Ninety-six percent of the PSA levels were less than 3.0 ng/mL and nearly 60 percent of the group had 1.0 ng/mL or less. These levels compare favorably with healthy control subjects under forty years of age and with the limited data available for PSA in healthy men over seventy years of age (87% and 26%, respectively). While biopsy showed persistent or recurrent carcinoma in 2 of 5 individuals, further evaluation disclosed only localized disease. Though the PSA provided little additional information to DRE in the individual patient, it appears from an overview of this group that a low level of PSA in Stage A1 prostatic carcinoma may be associated with long-term survival.

Aged

Renal leiomyosarcoma: plea for aggressive therapy.

We report a case of renal leiomyosarcoma arising from the renal pelvis with immunohistochemical confirmation of the diagnosis. Treatment was extirpative surgery for both primary and metastatic lung lesions as well as adjunctive radiation and chemotherapy. This patient remains disease-free twelve months following treatment.

Adult

Digitally-directed transrectal biopsy using Biopty gun versus transrectal needle aspiration: comparison of diagnostic yield and comfort.

A technique for digitally-directed core biopsy using the Biopty device and prospective comparison of accuracy and comfort, using this technique simultaneously with transrectal needle aspiration, are presented. To better estimate the true prevalence of carcinoma in the study population, a repeat combined procedure was performed on all subjects who did not have carcinoma confirmed on the initial core biopsies. All procedures were done by one investigator and all pathology reviewed by one senior pathologist. A total of 180 combined procedures were performed on 100 consecutive patients with palpably abnormal prostates; 30 carcinomas were detected. Digitally-directed Biopty biopsy yielded a sensitivity rate of 87 percent compared with 57 percent for needle aspiration (p less than 0.05). Using a numerical comfort scale, the Biopty device was also rated less painful than needle aspiration (p = 0.0001). The morbidity of the combined procedure was minimal, with a minor complication rate of 2.2 percent. No infections occurred.

Aged

Eosinophilic ureteritis associated with eosinophilic cholangitis: a case report.

Eosinophilic infiltrate of the urinary tract is rare. We report on a patient with eosinophilic cholangitis who later had eosinophilic ureteritis. This case emphasizes the potential serious nature of eosinophilic ureteritis, which often presents with complete ureteral obstruction. The literature pertaining to eosinophilic ureteritis and eosinophilic biliary disease is reviewed.

Bile Ducts

Use of resectoscope for colon cancer.

Urologic endoscopic resectoscopes greatly simplify electrofulguration and resection of rectal tumors. The most important advantage is the enhanced visibility that allows determination of the depth of resection and good hemostasis. The indications for this procedure are otherwise-poor surgical candidates, palliation, excision of locally aggressive tumors such as villous adenomas, and bowel diversion prior to definitive therapy. Bleeding, peritoneal perforation requiring colostomy, and postoperative infection have all been reported, but the complication rate appears to be acceptable. Further clinical studies are necessary to determine if, indeed, this can be considered a curative procedure. Finally, because the practicing urologist is intimately aware of the technical aspects of the urologic resectoscope, he will probably be called on to perform, and should be aware of, this procedure.

Adenocarcinoma

Elective cholecystectomy during major urological surgery.

A total of 6 patients underwent a major urological operation with simultaneous elective cholecystectomy for cholelithiasis. All patients did well with no morbidity or increased hospital stay attributable to the biliary operation. Numerous articles in the vascular, general and gynecological surgery literature advocate concomitant cholecystectomy when gallstones are present. The complications of nonoperated biliary calculous disease, including postoperative cholecystitis, are well known. A concomitant operation could reduce over-all risks and costs to the patient and health care system.

Adult

Acute urinary retention associated with prostatic carcinoma.

We describe the prospective evaluation of 90 patients seen at 2 medical centers who presented with acute urinary retention. All patients had a pre-retention history obtained, as well as careful prostate examination, perineal prostate biopsy and followup treatment or monitoring. Prostate cancer was found in 12 of the 90 patients (13.3 per cent), while 1 had metastatic leukemia to the prostate. Of the 90 patients 69 (76.7 per cent) had a palpably benign prostate and 2 malignancies (2.9 per cent) were diagnosed, while 11 malignancies occurred in 21 patients (52.4 per cent) with a suspicious examination. A total of 46 patients (51.1 per cent) underwent further prostate resection and no malignancy was found in any of these specimens: 43 underwent transurethral resection (24.9 gm. average), while 3 underwent open prostatectomy (97 gm. average). Other etiologies of acute retention included benign hyperplasia, other underlying illness, medical procedures, medications, prostatitis and prostatic infarction. Among the 44 patients who did not undergo prostatectomy 13 had treatment of the diagnosed cancer, 9 had resolution of retention and symptoms without intervention, 9 remained catheterized due to severe medical problems, 8 were treated for prostatitis, 2 had discontinuation of sympathomimetic drugs and 1 each underwent urethrotomy, bladder neck incision and resolution of prostatic infarction. In contrast to the older literature in which approximately 25 per cent of the patients presenting with acute urinary retention had prostate cancer, our data suggest a lower incidence. Prostatic biopsy for patients who present with acute urinary retention and a benign examination does not appear to be justified.

Acute Disease

Suprarenal occurrence of an adenomatoid tumor.

Adenomatoid tumors are rare, benign mesotheliomas that usually are associated with genito-urinary tract. The suprarenal occurrence of this tumor is uncommon. We present such a case and review the origin of the adenomatoid tumor.

Adult

Traumatic hematocele: association with rupture of the testicle.

Ten patients with hematoceles associated with blunt trauma have been seen during the last 4 years. In 80 per cent of the cases the hematocele was caused by rupture of the testicle. Prompt early exploration, adequate débridement, primary repair of the tunical laceration and Penrose drainage resulted in a salvage rate of 75 per cent.

Hematocele