PubMed HealthSearch

Biomedical subjects

E C Jones

Publications and source records attributed to E C Jones.

At least 19 recordsLinked to original sources

Biochemical and pathological effects of 8 months of neoadjuvant androgen withdrawal therapy before radical prostatectomy in patients with clinically confined prostate cancer.

PURPOSE: A prospective, nonrandomized trial was initiated to determine the duration of neoadjuvant therapy required for prostate specific antigen (PSA) to reach its nadir, evaluate the ability of an ultrasensitive assay to measure decreases in PSA less than 0.2 microgram./l., and characterize the effects of 8 months of neoadjuvant therapy on pathological stage, positive margin rates, proliferation and tumor marker immuno-staining. MATERIALS AND METHODS: We evaluated 50 patients with clinically localized prostate cancer treated by 8 months of reversible androgen ablation before radical prostatectomy. Serum PSA and testosterone levels were measured monthly. RESULTS: Serum PSA decreased by 84% after 1 month and by a further 52% between 3 and 8 months. Using an ultrasensitive assay, serum PSA decreased to undetectable levels (less than 0.1 microgram./l.) or reached its nadir in 22% of the cases after 3 months, 42% after 5 months and 84% after 8 months. Overall, the positive margin rate was 4%. Of the cases 68% were organ-confined and 24% were specimen-confined. The positive margin rate was not increased after reevaluation with cytokeratin, PSA and prostatic acid phosphatase immuno-staining but of 4 cases initially staged as P0 on hematoxylin and eosin evaluation 2 had microscopic foci of cancer with prostatic acid phosphatase staining. Immuno-staining with the proliferation markers proliferation cell nuclear antigen and Ki-67 showed decreased staining in surgical specimens relative to pretreatment needle biopsy specimens, which suggests that outgrowth of androgen independent clones does not develop during prolonged neoadjuvant therapy. CONCLUSIONS: Eight months of neoadjuvant androgen withdrawal therapy results in low positive margin rates and PSA nadir levels. The initial rapid decrease in PSA results from cessation of androgen regulated PSA synthesis and apoptosis, while the ongoing slower decrease reflects decreasing tumor volume.

Androgen Antagonists

The differential diagnosis of prostatic carcinoma. Its distinction from premalignant and pseudocarcinomatous lesions of the prostate gland.

Prostate gland specimens account for a significant percentage of diagnostically challenging cases in surgical pathology practice. The understanding of prostate pathology has progressed, and the differential diagnosis of prostatic carcinoma has expanded to include possible premalignant lesions and several recently described pseudocarcinomatous lesions. The authors discuss the histopathology of prostatic intraepithelial neoplasia and atypical adenomatous hyperplasia, review the evidence for their role as premalignant lesions, and discuss the criteria that allow for their distinction from prostatic adenocarcinoma. Pseudocarcinomatous lesions that must be recognized when assessing prostatic tissue include sclerosing adenosis, cribriform hyperplasia, mesonephric hyperplasia, and basal cell hyperplasia. The pathologic features and diagnostic challenges of these and other pseudocarcinomatous lesions are reviewed.

Adenocarcinoma

Renal oncocytoma and granular renal cell carcinoma. A comparative clinicopathologic and DNA flow cytometric study.

Twenty-three renal oncocytomas and 18 granular renal cell carcinomas (GRCC) were comparatively studied clinicopathologically and by DNA flow cytometry to delineate their differences. Of the patients with renal oncocytomas, 15 were men and 8 were women, and their ages ranged from 42 to 81 years (mean, 64 years). The gross appearance of renal oncocytomas was characteristically homogeneous tan-brown, with variable scarring, without areas of large hemorrhage, and with no apparent necrosis. Twenty-two renal oncocytomas were confined within the kidney (Robson stage I) and one tumor extended into the renal vein (stage IIIa). Twenty-two renal oncocytomas, including the stage IIIa tumor, manifested diploid DNA content and only one neoplasm showed a feature suggestive of near-diploid DNA aneuploidy. Of the 17 patients with renal oncocytomas who had adequate follow-up, none developed metastasis or died of disease. Of the patients with GRCC, 13 were men and 5 were women, and their ages ranged from 30 to 73 years (mean, 53 years). The gross appearance of GRCC was variegated, yellow to tan, and punctuated with geographic areas of necrosis. Eleven patients with GRCC were stage I, 4 were stage II, 2 were stage IIIa, and 1 patient had metastases at initial examination (stage IV). Seven GRCCs were DNA diploid, one was DNA tetraploid, and 10 tumors were DNA aneuploid. Twelve patients were alive with no evidence of disease (12 to 36 months; median, 26 months). All patients with DNA diploid neoplasm pursued benign clinical courses. One patient was alive with metastatic disease and two patients developed metastases and died of their disease; all three patients had DNA aneuploid tumors. Two patients died of other causes and one patient was lost to follow-up. Our data indicate that renal oncocytoma is a distinct clinicopathologic disease with characteristic gross, histologic, DNA flow cytometric, and biologic features that are different from GRCC.

Adenoma

The frequency and significance of small (less than or equal to 15 mm) hepatic lesions detected by CT.

The purpose of our study was to determine the frequency of detection of small hepatic lesions (less than or equal to 15 mm) in outpatients who had abdominal CT and to assess the significance of these lesions in the presence or absence of known malignant tumors. Contrast-enhanced abdominal CT scans in 1454 patients were reviewed. In 254 patients (17%), hepatic lesions 15 mm or smaller were detected. In 51% of these patients, lesions were judged benign on the basis of other imaging studies, biopsy results, or stability for at least 6 months as shown by CT. Lesions were judged malignant on the basis of progression seen on radiologic studies or biopsy in 22%. The other 27% of the patients had lesions that could not be classified. The majority of patients with small hepatic lesions (82%) were known to have a malignant tumor; in 51% of these patients, lesions were diagnosed as benign. No patient without a known malignant tumor had a small hepatic lesion that was determined to be malignant. Multiple small lesions were more likely to represent malignant disease than were single small lesions. We conclude that small hepatic lesions are common (seen in 17% of our patients), and that there is a high probability that hepatic lesions smaller than 15 mm are benign, even in patients known to have an extrahepatic malignant tumor.

Humans

Cytomegalovirus epididymitis following renal transplantation.

Cytomegalovirus infection is an important cause of morbidity and mortality in immunocompromised individuals. The disease is usually systemic in expression although localized infection can occur, particularly in the lung, liver, retina and gastrointestinal tract. We report a case of cytomegalovirus epididymitis with limited systemic manifestations occurring 2 months after renal transplantation in a patient immunosuppressed with azathioprine, prednisone and cyclosporine. Diagnosis was confirmed by observation of typical cytopathic changes in epididymal cells. Clinical resolution occurred with epididymo-orchiectomy and 9-(1,3-dihydroxy-2-proproxymethyl)guanine therapy. To our knowledge this presentation has not been described previously in the transplant literature and it is extremely rare in other forms of inherited or acquired immune deficiency.

Antiviral Agents

Sclerosing adenosis of the prostate gland. A clinicopathological and immunohistochemical study of 11 cases.

Eleven cases of sclerosing adenosis of the prostate gland, a recently reported uncommon pseudoneoplastic lesion with characteristic histological, histochemical, and immunohistochemical features, are described. The well-circumscribed cellular lesions were composed of variably sized and shaped, often compressed, glands and small clusters of epithelial cells embedded in a cellular, often myxoid stroma. Mild cytologic atypia was occasionally present, and one case had moderate cytologic atypia. A distinct basement membrane often surrounded the glands and clusters. Luminal acid mucin was typically present. Keratin-positive basal cells were present in the glands and as spindle cells in the stroma. The basal cells were also immunoreactive for S-100 and muscle-specific actin, suggesting myoepithelial differentiation. Clinical follow-up has shown no evidence of prostatic carcinoma. The available evidence suggests that sclerosing adenosis of the prostate gland is a benign lesion with distinctive features that should enable it to be distinguished from prostatic adenocarcinoma.

Adenocarcinoma

Hepatic dynamic sequential CT: section enhancement profiles with a bolus of ionic and nonionic contrast agents.

The enhancement characteristics in different portions of the liver during dynamic sequential bolus computed tomography (CT) with iodinated contrast material (DSBCT) were prospectively evaluated in 75 patients by using iothalamate meglumine, iopamidol, and iohexol (25 patients received each agent). After baseline noncontrast CT was performed, DSBCT was performed with a 180-mL intravenous bolus administered at 2 mL/sec. Scanning was started 25 seconds after the bolus was initiated, by using a 3-second scan time and rapid cephalocaudal table incrementation, yielding contiguous 8-mm-thick sections at a rate of nine sections per minute. On postcontrast images, peak enhancement was 115% for iopamidol and 117% for iohexol, both of which were superior to iothalamate meglumine at 95% (P less than .05). After peaking, enhancement then decreased for all three contrast agents, although the decline was more precipitous for iothalamate meglumine. Enhancement on the more caudal sections with both iopamidol and iohexol was superior to that with iothalamate meglumine (P less than .05). The data suggest that the enhancement characteristics for the two nonionic agents may be more optimal for detection of focal hepatic lesions than the ionic agent.

Adult

DNA content in prostatic adenocarcinoma. A flow cytometry study of the predictive value of aneuploidy for tumor volume, percentage Gleason grade 4 and 5, and lymph node metastases.

DNA content of prostatic adenocarcinoma was determined by flow cytometry on formalin-fixed, paraffin-embedded tissue from 57 radical prostatectomies. This was done to define the relationship of aneuploidy to prostatic adenocarcinoma grade, volume, and pathologic stage and to examine its utility in candidates for surgical treatment. Aneuploidy was found in 26 (46%) cases. With one exception, all of the aneuploid cases were found in tumors larger than 4 cc. The percentage of aneuploid cases increased with advancing pathologic stage, and it was highest in those cases with lymph node metastases. This percentage was also higher among more poorly differentiated tumors. However, diploid tumors were also found among these groups, and the relationship between aneuploidy versus pathologic stage and grade did not achieve statistical significance. Except for a 91% specificity for tumor volume greater than 4 cc, the sensitivity and specificity of DNA content analysis to predict these groups was low (50% to 72%). It is concluded that aneuploidy is a later event linked to tumor progression, but it is not a requirement for progression to occur. The overlap in aneuploid and diploid tumor behavior precludes the use of DNA content analysis as an independent predictor to direct preoperative treatment of prostatic carcinoma.

Adenocarcinoma

Resection margin status in radical retropubic prostatectomy specimens: relationship to type of operation, tumor size, tumor grade and local tumor extension.

Since the introduction of the nerve-sparing radical retropubic prostatectomy, there has been a steady increase in the number of prostatic cancer cases treated operatively and concern with the frequency of positive resection margins has developed. To identify factors that determine resection margin status the hospital charts of 199 radical retropubic prostatectomy patients from 1980 to 1987 were reviewed, as well as slides from 52 patients in 1987. Of the 199 patients 92 (46%) had positive resection margins; there was no difference in the frequency between the nerve-sparing and standard procedures. The 1987 slide review showed a positive resection margin frequency of 58%. The presence and extent of positive resection margins were directly related to tumor size. The positive resection margin frequency also increased with poorly differentiated carcinoma, capsular penetration and seminal vesicle involvement. Determination of these risk factors identifies patients at greatest risk for positive resection margins.

Adenocarcinoma

Palpable prostatic nodules: comparison of US and digital guidance for fine-needle aspiration biopsy.

This study was undertaken to evaluate the use of transrectal sonographically guided fine-needle aspiration biopsy and to compare sonographic with digital guidance for biopsy. In 62 patients in whom prostatic carcinoma was suspected at digital rectal examination, fine-needle aspiration biopsies were performed transperineally under sonographic guidance and transrectally under digital guidance. These patients had 89 nodules, 73 of which were sampled with both techniques. Malignant cells were obtained under digital guidance in 17 of 73 nodules (23%) and under sonographic guidance in 16 (22%). An additional seven nodules, which were not seen sonographically, were sampled under digital guidance and proved to be negative. In nine other nodules that were nonpalpable and evident only with sonography, malignant cells were obtained under sonographic guidance in three. These findings indicate that sonographic guidance for fine-needle aspiration biopsy is as good as digital guidance for palpable lesions.

Adult

Pharmacokinetics and pharmacodynamics of codeine in end-stage renal disease.

The pharmacokinetics and pharmacodynamics of codeine and its metabolites codeine glucuronide, morphine, and morphine glucuronide were assessed after the administration of a single 60 mg oral dose of codeine sulfate and a single 60 mg intravenous dose of codeine phosphate in six healthy volunteers and six patients on chronic hemodialysis. Plasma and urine drug and metabolite concentrations were determined by sensitive and specific RIA procedures. Pharmacodynamics were assessed by pupillometry and vital sign determinations. Codeine elimination half-life and mean residence time were increased significantly in the hemodialysis group (18.69 +/- 9.03 hours and 12.77 +/- 7.09 hours, mean +/- SD, respectively) compared with the healthy volunteer group (4.04 +/- 0.60 hours and 3.90 +/- 0.52 hours, respectively). The total body clearance and volume of distribution of codeine were not significantly different between groups. Peak concentrations, times to peak concentrations, and AUCs for the three metabolites were also not significantly different between the groups, in part as a result of significant interpatient variability in the hemodialysis group. Examination of pupillometry and vital sign data did not reveal clinically significant differences in pharmacodynamics between the groups. Adjustment of dosage regimen may be required in some patients with uremia receiving multiple-dose codeine therapy.

Adult

Essential thrombocythemia in pregnancy.

A 32-year-old women with essential thrombocythemia and a history of bleeding completed a full-term pregnancy. During pregnancy, the platelet count declined markedly to near-normal levels, but returned to prepregnancy levels within two weeks after delivery. The clinical course was uneventful, except for two brief episodes of vaginal bleeding during the second trimester. Possible etiologic mechanisms for pregnancy-related reduction of platelet levels in thrombocythemia include increased platelet consumption or down-regulation of platelet production by a placental or fetal factor.

Adult

Fine-needle aspiration cytology of neoplastic cysts of the pancreas.

Herein is reported the cytologic features of four cases of cystic neoplasms of the pancreas as seen in fine-needle aspirates. Cytologically, the cases fall into two distinct groups: mucinous cystic neoplasm and serous cystadenoma. The aspirates from the mucinous cystic neoplasms characteristically showed columnar mucus-secreting epithelial cells, some of which were arranged in a papilloglandular pattern, with abundant mucous material in the background. The aspirates from the serous cystadenoma yielded small sheets of cuboidal cells with small nuclei and clear cytoplasm, without a background of mucous material. This cytologic division corresponds closely to the histologic classification proposed by Compagno and Oertel and hence is of prognostic and therapeutic value. The diagnostic challenges confronted by the cytopathologist are (1) to differentiate neoplastic cysts from the inflammatory pseudocysts; (2) to differentiate neoplastic epithelium from the normal epithelium of the bowel and pancreatic ducts; and (3) to differentiate mucinous cystic neoplasms from serous cystadenomas.

Adult

Pharmacokinetics of codeine after single- and multiple-oral-dose administration to normal volunteers.

The pharmacokinetics of codeine, codeine glucuronide, morphine, and morphine glucuronide were assessed after single- (60 mg) and multiple-dose (60 mg every six hours for nine doses) oral administration of codeine sulfate to six normal volunteers. Multiple blood and urine samples were collected after administration of the single- and last multiple-oral doses. Drug concentrations were analyzed using radioimmunoassay techniques. No significant alterations in codeine pharmacokinetics were noted after multiple-dose oral administration. However, accumulation of morphine during multiple dosing was significant (AUC24 = 102 +/- 33 ng/mL/hr after single dose versus 212 +/- 118 ng/mL/hr after the last multiple dose). Peak concentration and AUC24 data for morphine glucuronide indicated that significant accumulation of this compound occurs upon multiple-dose administration. These data indicate that morphine and morphine glucuronide serum concentrations are significantly increased during chronic oral codeine therapy and suggest that morphine, and perhaps morphine glucuronide, contribute significantly to the analgesic activity of chronic oral codeine therapy.

Adult

Comparative disposition of codeine and pholcodine in man after single oral doses.

Four healthy male subjects received single oral doses of 15, 30 and 60 mg of codeine and pholcodine according to a balanced cross-over design with an interval of 7 days between the six treatments. Blood samples were collected for 8 h after each drug administration. In phase 2 of the study six different male volunteers received single oral doses of 60 mg of codeine and pholcodine with a 14 day interval between successive drug treatments. Blood was sampled for 12 h after codeine and 121 h after pholcodine administration. Plasma concentrations of free (unconjugated) and total (unconjugated plus conjugated) codeine, pholcodine and morphine were determined by radioimmunoassay and selected pharmacokinetic parameters were derived from these data. Pharmacokinetics of both drugs were independent of dose. Codeine was absorbed and eliminated relatively rapidly [elimination t1/2 = 2.3 +/- 0.4 h (mean +/- s.d.)]. While codeine kinetics were adequately described by a one-compartment open model with first-order absorption, a two-compartment model was required to describe pholcodine elimination from plasma (t1/2,z = 37.0 +/- 4.2 h). Plasma concentrations of conjugated codeine were much greater than those of the unconjugated alkaloid. By contrast, pholcodine appeared to undergo little conjugation. Biotransformation of codeine to morphine was evident in all subjects, although the extent of this metabolic conversion varied considerably between subjects. Morphine was not detectable in the plasma of any subject after pholcodine administration.

Administration, Oral

Diagnostic value of bone marrow examination in isolated thrombocytopenia.

Bone marrow examination often is performed to assess isolated thrombocytopenia. A three-year retrospective study demonstrates that bone marrow aspiration in isolated thrombocytopenia predictably shows megakaryocytic thrombocytopenia. Little additional information is obtained by bone marrow examination that cannot be determined by noninvasive tests. In this series, the Jamshidi biopsy did not add significant information to that obtained from the aspirate. The authors conclude that bone marrow examination is not necessary in patients with isolated thrombocytopenia. In acute care hospital patients, the cause of the thrombocytopenia usually is apparent from the clinical history, and bone marrow examination is necessary infrequently.

Adolescent