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Biomedical subjects

J D Schmidt

Publications and source records attributed to J D Schmidt.

At least 19 recordsLinked to original sources

Transepithelial leak in Barrett's esophagus.

Using orally administered sucrose as a probe of gastrointestinal permeability, this study focused on determining whether Barrett's metaplasia exhibits a paracellular transepithelial leak to small nonelectrolytes. Subjects in five separate classes (nonendoscoped, asymptomatic controls; endoscoped, asymptomatic controls; gastroesophageal reflux disease without mucosal complications; grossly visible esophagitis; and Barrett's esophagus) consumed a sucrose solution at bedtime and collected all overnight urine. Urine volume was measured and sucrose concentration was determined by high-performance liquid chromatography. Patients with Barrett's were observed to exhibit a transepithelial leak to sucrose whose mean value was threefold greater than that seen in healthy control subjects or patients with reflux but without any mucosal defect. A parallel study of claudin tight junction proteins in endoscopy biopsy samples showed that whereas Barrett's metaplasia contains dramatically more claudin-2 and claudin-3 than is found in normal esophageal mucosa, it is markedly lower in claudins 1 and 5, indicating very different tight junction barriers.

Amylases↗

Ileal conduit perforation-iatrogenic injury and conservative management.

The ileal conduit was popularized by Bricker in the 1950s. Since then, surveillance of the upper urinary tract has been accomplished with intravenous urography, ultrasonography, or loopography. Loopography is used as an imaging modality at our institution because of its safety and avoidance of intravenous contrast. We report the first case of an iatrogenic rupture of an ileal conduit during loopography.

Abdominal Pain↗

Cytotoxic T cell immunity against telomerase reverse transcriptase in humans.

Telomerase is a ribonucleoprotein enzyme which has been linked to malignant transformation in human cells. Telomerase activity is increased in the vast majority of human tumors, making its gene product the first molecule common to all human tumors. The generation of endogenously processed telomerase peptides bound to Class I MHC molecules could therefore target cytotoxic T lymphocytes (CTL) to tumors of different origins. This could advance vaccine therapy against cancer provided that precursor CTL recognizing telomerase peptides in normal adults and cancer patients can be expanded through immunization. We demonstrate here that the majority of normal individuals and patients with prostate cancer immunized in vitro against two HLA-A2.1 restricted peptides from telomerase reverse transcriptase (hTRT) develop hTRT-specific CTL. This suggests the existence of precursor CTL for hTRT in the repertoire of normal individuals and in cancer patients. Most importantly, the CTL of cancer patients specifically lysed a variety of HLA-A2(+) cancer cell lines, demonstrating immunological recognition of endogenously processed hTRT peptides. Moreover, in vivo immunization of HLA-A2.1 transgenic mice generated a specific CTL response against both hTRT peptides. Based on the induction of CTL responses in vitro and in vivo, and the susceptibility to lysis of tumor cells of various origins by hTRT CTL, we suggest that hTRT could serve as a universal cancer vaccine for humans.

Adult↗

Proliferative actinic keratosis: three representative cases.

OBJECTIVE: This article describes a new subtype of actinic keratosis that exhibits proliferative characteristics both histologically and clinically. We describe three representative cases occuring in the presence of infiltrative squamous cell carcinoma (SCC) and/or basal cell carcinoma (BCC). METHODS: Histories of each lesion in the three cases discussed were obtained. The lesions were removed by Mohs micrographic surgery. Permanent sections, stained with hematoxylin and eosin, were examined and studied under light microscopy. RESULTS: All three lesions had failed conventional treatment with liquid nitrogen and/or 5-fluorouracil (5-FU). Histologic examination of the lesions revealed sheets of dysplastic cells growing along the basal layer of the epidermis and migrating down hair follicles and sweat ducts. An associated infiltrative SCC and/or BCC was found in each case. CONCLUSIONS: Proliferative actinic keratosis is resistant to standard therapies because of deep migration of abnormal cells along hair follicles and sweat ducts. It has a strong propensity to develop infiltrative SCC and may occur concomitantly with BCC.

Aged↗

New indications for radical prostatectomy.

PURPOSE: Radical prostatectomy is considered the gold standard for treatment of localized prostate cancer, either as primary or salvage therapy. Recently with the advent of increased organ transplantation, use of prostatic specific antigen for cancer detection and cryoablation as an alternative treatment, more men with prostate cancer can be considered for radical surgery. We review these new indications. MATERIALS AND METHODS: Clinically localized untreated prostate cancers were identified in 3 men being considered for cardiac or lung transplantation (group 1), and 4 men originally treated with transperineal cryoablation had local relapse (group 2). All 7 men underwent radical prostatectomy. RESULTS: Organ confined cancer (pT2C) was found in all 3 patients in group 1. All 3 men underwent successful cardiac or lung transplantation 1 to 12 months after radical prostatectomy, and they are disease-free at short-term followup. Of the group 2 patients 2 had organ confined disease (pT2b and c) and 2 had extensive extraprostatic disease (pT3cN1 and pT3cN0). Only 2 patients remain disease-free and do not require adjuvant endocrine therapy. Major perioperative complications of rectotomy and total incontinence occurred only in group 2 patients. CONCLUSIONS: Patients being considered for heart and lung transplantation need to be free of concurrent malignancy because of immunosuppressive therapy. Radical prostatectomy can achieve this goal in select patients. Cases of failed cryoablation can be salvaged with radical prostatectomy but with less chance of success and with greater risk of complications.

Aged↗

Elevated stress protein in transitional cells exposed to urine from interstitial cystitis patients.

BACKGROUND: It has been hypothesized that urine from interstitial cystitis (IC) patients may contain one or more toxic factors not present in "normal" urine. Bladder tissues exposed to these toxic factors could have elevated stress proteins. If this assumption is correct, stress protein levels could be a useful marker for identifying patients at risk for developing this syndrome. METHODS: To experimentally investigate this possibility, a sensitive assay (ELISA) was used to measure levels of the 72 kDa stress protein in urothelial target cells after in vitro exposure to urine from IC patients. RESULTS: We observed a modest 12% increase in 72 kDa stress protein in cells treated with urine from IC patients compared to cells exposed to normal urine (1.12 compared to 0.99 ng/microg extracted protein; P < 0.05). In addition, it was possible to demonstrate the 72 kDa stress protein in histologic sections obtained from mucosal biopsies of IC patients. Stress protein was located primarily in the surface urothelial cells of the mucosa. CONCLUSIONS: These results seem to indicate that stress protein could play an important protective role at this particular site. They further suggest that IC urine is more toxic than normal urine and, in contact with underlying urothelial and deeper bladder tissue, may upregulate genes involved in stress protein responses. This may be an important concept in the etiology of IC.

Biomarkers↗

Cryoablation for carcinoma of the prostate.

Percutaneous transperineal cryoablation of the prostate is now available in the armamentarium for treatment of prostate cancer. Technical advances in real-time transrectal imaging of the prostate and improvements in cryosurgical equipment have brought this modality into the limelight of available prostate cancer management. Cryosurgery can be offered to many patients with prostate cancer. However, the main indications for its use include primary treatment for localized disease, salvage therapy after failure of traditional methods, and relief of local symptoms. A historical background, description of the technique, and clinical experience at several medical centers including the University of California San Diego, Allegheny General Hospital, University of Texas M.D. Anderson Cancer Center, and Crittenton Hospital, are presented.

Biopsy↗

Evaluation of adjuvant estramustine phosphate, cyclophosphamide, and observation only for node-positive patients following radical prostatectomy and definitive irradiation. Investigators of the National Prostate Cancer Project.

In 1978 the National Prostate Cancer Project launched two protocols evaluating adjuvant therapy following surgery (Protocol 900) or irradiation (Protocol 1,000) for clinically localized prostate cancer. All patients underwent staging pelvic lymphadenectomy. Following definitive treatment, patients were randomized to either cyclophosphamide 1 gram/m2-IV every 3 weeks for 2 years, estramustine phosphate 600 mg/m2-po daily for up to 2 years, or to observation only. Patient accession closed in 1985 and includes 184 to Protocol 900 (170 evaluable) and 253 to Protocol 1,000 (233 evaluable). Lymph node involvement was identified in 198 patients (49% of total), 29% in Protocol 900, 63% in Protocol 1,000. Median progression-free survival (PFS) for patients with nodal involvement in Protocol 1,000 receiving estramustine phosphate adjuvant was longer (37.3 mo) compared to cyclophosphamide (30.9 mo) and to no treatment (20.9 mo). Median PFS for patients with limited nodal disease in Protocol 1,000 was longer (39.9 mo), regardless of adjuvant, compared to extensive nodal disease (20.7 mo). However for patients with extensive nodal involvement, those receiving adjuvant estramustine phosphate experienced a significantly longer median PFS (32.8 mo) compared to adjuvant cyclophosphamide (22.7 mo) and no adjuvant (12.9 mo). We conclude that adjuvant estramustine phosphate is of benefit in prostate cancer patients with extensive pelvic node involvement receiving irradiation as definitive treatment.

Antineoplastic Agents, Alkylating↗

Adjuvant therapy for clinical localized prostate cancer treated with surgery or irradiation.

OBJECTIVE: Because of efficacy demonstrated with chemotherapy in patients with metastatic disease, the National Prostate Cancer Project in 1978 initiated two protocols evaluating adjuvant therapy following surgery (Protocol 900) and irradiation (Protocol 1000) for patients with localized disease at high risk for relapse. METHODS: All patients underwent staging pelvic lymph node dissection. Following definitive treatment, patients were randomized to either cyclophosphamide 1 g/m2 intravenously every 3 weeks for 2 years, estramustine phosphate 600 mg/m2 orally daily for 2 years or to observation only. Accession closed in 1985 and included 184 patients in Protocol 900 (170 evaluable) and 253 in Protocol 1000 (233 evaluable). RESULTS: Nodal involvement was identified in 198 patients (49% of total): 29% in Protocol 900 and 63% in protocol 1000. Median progression-free survival (PFS) and survival have been greater for patients in Protocol 900 regardless of adjuvant, reflecting their lower pathologic stage. Median PFS is significantly greater for patients in Protocol 1000 receiving estramustine (52.2 months) compared to cyclophosphamide (35.0 months). Median PFS for patients with nodal involvement in Protocol 1000 receiving estramustine is increased (43.5 months) compared to no treatment (21.5 months). Patients with limited nodal involvement in Protocol 1000 have a longer median PFS (45.6 months) compared to patients with extensive disease (23.6 months). But in the latter group patients receiving estramustine experienced a significantly longer median PFS (43.5 months) compared to cyclophosphamide (29.1 months) or no adjuvant (13.5 months). Increased PFS with estramustine adjuvant was also noted in stage C patients (only Protocol 900) and in those with high-grade (grade 3) tumors (both protocols). CONCLUSIONS: With now over 10 years mean follow-up for this series of patients, we conclude that adjuvant estramustine is beneficial for prostate cancer patients receiving definitive irradiation. This benefit is particularly noted in those patients with extensive nodal involvement (N+, D-1).

Adenocarcinoma↗

Transrectal ultrasound-guided transperineal cryoablation in the treatment of prostate carcinoma: preliminary results.

PURPOSE: We studied ultrasound-guided percutaneous cryoablation for treatment of prostate carcinoma. MATERIALS AND METHODS: Our series includes 83 individuals who underwent transrectal ultrasound-guided transperineal percutaneous cryoablation of the prostate. Prostate specific antigen levels, biopsy results and complications were assessed at 3 months. RESULTS: Of 61 biopsies 8 (13.1%) were positive for carcinoma (half showed stage D disease). Of patients with stages T1 to T3 cancer 92.6% were free of disease at 3 months. Prostate specific antigen levels were significantly decreased by an average of 1.90 ng./ml. (p < 0.05). Major complications were infrequent, including bladder perforation in 1 patient, urethral strictures in 3, bladder outlet obstruction in 2 and partial incontinence in 2. Impotence was frequent but transient. CONCLUSIONS: Transrectal ultrasound-guided transperineal percutaneous cryoablation of the prostate produces few major complications and appears at 3 months to be effective in eradicating local prostate tumors. Longer followup is required to test the original hypothesis.

Adult↗

Primary yolk sac tumor of the prostate in a patient with Klinefelter's syndrome.

Primary yolk sac (endodermal sinus) tumor of the prostate is extremely rare with only 2 cases reported in the literature. We describe a case of primary yolk sac tumor of the prostate in a man with Klinefelter's syndrome. Treatment included 4 courses of combination chemotherapy followed by retroperitoneal lymph node dissection, cystoprostatectomy and ileal conduit urinary diversion. We review the association of Klinefelter's syndrome with extragonadal germ cell tumor along with the management of this rare disease.

Adult↗

Treatment of interstitial cystitis with intravesical heparin.

OBJECTIVE: To control the symptoms of interstitial cystitis with chronic self-administered intravesical heparin and determine whether the drug's continued use can sustain remission. PATIENTS AND METHODS: A total of 48 patients were selected to undergo intravesical heparin therapy, 10,000 units in 10 ml sterile water, three times per week for 3 months. For patients who attained a good clinical remission, therapy was available for up to a further 9 months. RESULTS: At 3 months 27 of 48 patients (56%) attained good clinical remissions. All were offered continuous therapy and 23 elected for an additional 3 months. Twenty of the 23 continued in remission. Sixteen of these patients elected to have a further 6 months of therapy (12 months total) and 15 of 16 remained in remission. CONCLUSION: In over half of the patients studied, intravesical heparin controls the symptoms of interstitial cystitis with continued improvement even after one year of therapy.

Administration, Intravesical↗

Adjuvant therapy for localized prostate cancer.

BACKGROUND: In 1978, the National Prostatic Cancer Project launched two protocols evaluating adjuvant therapy after surgery (Protocol 900) or irradiation (Protocol 1000) for clinically localized prostate cancer. All patients underwent staging pelvic lymphadenectomy. METHODS: After definitive treatment, the patients were randomized either to receive cyclophosphamide 1 g/m2 intravenously every 3 weeks for 2 years or estramustine phosphate 600 mg/m2 orally daily for up to 2 years or to undergo observation only. Patient accession closed in 1985 and includes 184 patients in Protocol 900 (170 evaluable) and 253 in Protocol 1000 (233 evaluable). RESULTS: Lymph node involvement was identified in 198 patients (49% of total), 29% in Protocol 900 and 63% in Protocol 1000. The median progression-free survival (PFS) and survival were greater for patients in Protocol 900 compared with 1000, regardless of the adjuvant therapy. This reflected the greater proportion of patients with lower pathologic stage disease in the surgically treated group. The median PFS was significantly greater for all patients in Protocol 1000 receiving estramustine phosphate adjuvant (48.2 months) compared with patients randomized to receive cyclophosphamide (35.6 months). The median PFS for patients with nodal involvement in Protocol 1000 who received estramustine phosphate adjuvant was prolonged significantly (37.3 months) compared with no treatment (20.9 months). The median PFS for patients with limited nodal disease in Protocol 1000 was longer (39.9 months), regardless of the adjuvant therapy, compared with those with extensive nodal disease (20.7 months). However, in the latter patient group, those receiving adjuvant estramustine phosphate had a significantly longer median PFS (32.8 months) compared with those receiving adjuvant cyclophosphamide (22.7 months) or no adjuvant therapy (12.9 months). CONCLUSION: Adjuvant estramustine phosphate was beneficial in patients with prostate cancer and pelvic node involvement who received irradiation as definitive treatment.

Chemotherapy, Adjuvant↗