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Biomedical subjects

L Cheng

Publications and source records attributed to L Cheng.

At least 181 records · Page 10Linked to original sources
PubMed1999

Effect of terazosin on blood pressure and serum lipids.

In an open multicenter prospective study, the effects of short-term (4 weeks, n = 101) and long-term (6 months, n = 38) terazosin treatment on blood pressure, serum lipids and safety in the patients with mild to moderate essential hypertension were observed. Mean systolic and diastolic blood pressure in sitting position were significantly reduced by 16.4% and 14.0% respectively (P < 0.01) after 4 weeks of terazosin therapy, with the total efficacy rate being 87.1%. During a 6 month therapy, antihypertensive effect of terazosin could be maintained. Total cholesterol (TC) and low density lipoprotein (LDL) cholesterol in serum were significantly decreased P < 0.05-0.01) in patients with hypercholesterolemia (TC > or = 6 mmol/ml) after 4 week terazosin treatment; the levels of TC, LDL and triglyceride were significantly improved in hypertensive patients after 3-6 month terazosin treatment. The improvement of lipid metabolism was related to the dosage of terazosin but not to antihypertensive effects of terazosin. The results suggested that terazosin is effective in decreasing blood pressure and improving lipid metabolism. It may serve as a good antihypertensive agent for hypertensive patients with hypercholesterolemia.

Antihypertensive Agents↗
PubMed1999

Cystic renal cell carcinoma is cured by resection: a study of 24 cases with long-term followup.

PURPOSE: The true incidence and biological behavior of cystic renal cell carcinoma are not known. To our knowledge we present the largest series of patients with cystic renal cell carcinoma with long-term followup. MATERIALS AND METHODS: We reviewed the Mayo Clinic surgical pathology files of renal cell cancer cases with a cystic component resected from 1969 to 1997, and arbitrarily chose 75% tumor involvement by cysts as a cutoff for inclusion in the study. RESULTS: We identified 24 cases of clear cell renal cell carcinoma with 75% or greater involvement by cysts comprising 0.79% of 3,047 renal cell cancer cases resected at our institution between 1969 and 1997. Mean patient age was 62.7 years (range 40 to 83). A total of 11 patients (46%) underwent radical nephrectomy, 4 (17%) simple nephrectomy, 3 (12%) partial nephrectomy and 6 (25%) tumor enucleation. Mean tumor involvement by cysts was 84% (range 75 to 95) and in 11 cases (46%) involvement was 90% or greater. Cancer stage was T1 in 20 patients (83%), T2 in 1 (4.4%) and T3a in 4 (12.5%). Cancers were diploid in all but 1 case. Mean followup was 77.6 months (range 8 to 428, median 51). A total of 22 patients (92%) had no evidence of cancer and 2 died of intercurrent disease. CONCLUSIONS: Our results indicate that cystic renal cell carcinoma is uncommon and usually cured by resection, regardless of size, stage or number of cysts. These patients may benefit from nephron sparing surgery, such as partial nephrectomy.

Adult↗
PubMed1999

Demonstrability of the glycoprotein A-80 in postradiation prostatic carcinoma.

Radiation therapy results in significant morphological changes in prostatic carcinoma, including decreased cancer size, acinar shrinkage and distortion, cytoplasmic vacuolization, and nuclear pyknosis. Benign acini usually display enlarged, atypical cells with hyperchromatic nuclei. These changes confound the evaluation of limited postradiation samples. The glycoprotein A-80 is known to be upregulated in prostatic intraepithelial neoplasia (PIN) and prostatic carcinoma. In this study, we assessed the expression of A-80 in radiation-treated prostatic carcinoma. Paraffin sections from 64 postradiation prostatic carcinomas obtained at salvage prostatectomy were immunostained with a monoclonal antibody to A-80; selected sections were doubly immunostained with antibodies to A-80 and various cytokeratin polypeptides. All cases showed readily detectable and often intense staining in the cytoplasm of cancer cells and in intraluminal material of malignant acini. The extent and intensity of the reactions were independent of cancer size and grade. Strong reactions were seen in preserved and distorted acini, clear cell areas, single cancer cells, and in colloid pools with few or no recognizable cancer cells. PIN was present in 34 cases (53%), of which 27 (79%) stained strongly for A-80; atrophic and hyperplastic acini generally did not stain, irrespective of the degree of cellular atypia. The A-80 glycoprotein appears remarkably durable and is readily demonstrable in postradiation prostatic carcinoma despite profound architectural and cytologic changes. This characteristic may prove useful in evaluating small samples for confirmation of diagnosis and determination of extent of residual or recurrent prostatic carcinoma after radiation therapy.

Aged↗
PubMed1999

Does transurethral microwave thermotherapy have a different effect on prostate cancer than on benign or hyperplastic tissue?

OBJECTIVES: Transurethral microwave thermotherapy is useful for the treatment of benign prostatic hyperplasia, but its effect on cancer is not documented. We analyzed the pathologic changes occurring after microwave thermotherapy in whole mount radical prostatectomy specimens from patients with cancer. METHODS: Nine patients scheduled for radical prostatectomy for clinically localized prostate cancer were treated with transurethral microwave thermotherapy (Urologix Targis System). Patients ranged in age from 64 to 72 years (mean 68). Seven patients underwent prostatectomy 4 to 90 hours after thermotherapy, and 2 other patients underwent prostatectomy 12 months after thermotherapy. Whole mount totally embedded prostates were mapped for necrosis and cancer, and the volume of each was measured by the grid method. RESULTS: Pathologic stages were T2a (n = 4), T2b (n = 4), and T3b (n = 1). The prostates from patients who underwent radical prostatectomy within 4 to 90 hours of thermotherapy had a mean prostate weight of 47.4 g (range 19.5 to 70.3). Each consistently showed hemorrhagic necrosis and tissue devitalization without significant inflammation. Necrosis involved contiguous areas of benign epithelium, stroma, and cancer without skip areas. The mean volume of necrosis was 8.8 cc (range 1.4 to 17.8), and the mean percentage of the prostate involved by necrosis was 22% (range 3% to 39%). The necrosis was symmetric around the urethra in 6 of 7 cases. Urethral dilation was observed in 3 patients, and the mean maximum radial distance of necrotic tissue was 1.4 cm (range 0.6 to 1.8). Necrotic change was noted in 80% to 100% of the volume of cancer in 4 cases, 40% to 60% in 2 cases, and 5% in 1 case. The prostates from the 2 patients who underwent radical prostatectomy 12 months after thermotherapy had a mean weight of 88 g (55 and 121 g, respectively). Each showed periurethral fibrosis, nonspecific chronic inflammation, and squamous metaplasia of the urothelium. The mean volume of necrosis remaining was 0.2 cc. The mean percentage of the prostate involved by necrosis 1 year after thermotherapy was less than 1%. There was some reabsorption of dead tissue. The mean maximum radial distance of the necrotic tissue was 0.4 cm (0.2 and 0.7 cm, respectively). The prostatic urethra had viable and partially denuded urothelium in all cases. CONCLUSIONS: Microwave thermotherapy is clinically useful for ablation of benign prostate and cancer contiguous to the urethra, resulting in hemorrhagic necrosis with minimal damage to the urethra. There was no apparent differential morphologic sensitivity of benign prostatic tissue, hyperplastic tissue, or cancer to thermotherapy.

Aged↗
PubMed1999

Treatment changes in prostatic hyperplasia and cancer, including androgen deprivation therapy and radiotherapy.

Substantial and characteristic changes occur in the microscopic appearance and immunophenotype of the hyperplastic prostate and adenocarcinoma following androgen deprivation therapy and radiotherapy. These changes are rarely seen in untreated cancer, and in the authors' opinion, the combinations of features following therapy are sufficiently distinctive to warrant recognition. Pathologists must be aware of these distinct changes because of the reliance placed on nuclear and nucleolar size in the identification of prostate cancer, particularly in small specimens and lymph node metastases.

5-alpha Reductase Inhibitors↗
PubMed1999

Diagnosis and grading of bladder cancer and associated lesions.

Standardized classification and grading of urothelial carcinoma has now been achieved internationally. Uniformity of pathologic reporting should improve the comparability of different studies and therapies and provide more accurate information to urologists in managing patients.

Carcinoma in Situ↗
PubMed1999

Intravitreal pharmacokinetics in rabbits of the foscarnet lipid prodrug: 1-O-octadecyl-sn-glycerol-3-phosphonoformate (ODG-PFA).

PURPOSE: To evaluate the intraocular distribution and metabolism of the lipid prodrug of foscarnet, 1-O-octadecyl-sn-glycerol-3- phosphonoformate (ODG-PFA), following intravitreal administration. METHODS: Twenty rabbits received ODG-[14C]PFA intravitreal injection, yielding 0.632 mM resultant intravitreal concentration. Two animals per group were sacrificed at different intervals post-injection. The drug levels in ocular tissues were determined with counting the radioactivity by Tracor Mark III Liquid Scintillation Counter. Four rabbits were used for analysis of the drug metabolism in vitreous by lipid extraction technique. RESULTS: The drug level in vitreous was 526 microM at day one and 227 microM at the fifth week. The vitreous half life was approximately four to five weeks. The retinal level of the drug was 292 microM at day one, 75 microM at the fifth week and 32 microM at the tenth week, which was still more than ten times higher than the IC90 against HCMV. Lipid extraction analysis showed that, in vivo, both ODG-PFA and PFA were present in vitreous, but in in vitro incubations with vitreous, ODG-PFA conversion to PFA was negligible. CONCLUSION: ODG-PFA possesses a long vitreous half life and sustained high drug level in retina. The vitreous did not metabolize drug but acted as a drug reservoir. Intravitreal liposomal ODG-PFA may be expected to be a long acting potent local therapy for CMV retinitis.

Animals↗
PubMed1999

Intravitreal toxicology and therapeutic efficacy of the carboxymethyl ester of the 1-O-octadecyl-sn-glycerol-3-phosphonoformate (ODG-PFA-O-Me), a novel lipid antiviral prodrug for intraocular drug delivery.

This study was conducted to evaluate the vitreous clarity and intraocular therapeutic index of three preparations ofthe carboxymethyl ester of 1-O-octadecyl-sn-glycerol-3-phosphonoformate (ODG-PFA-O-Me), a long acting lipid derivative of foscarnet with potent anti-CMV activity. Twenty-six New Zealand white rabbits were intravitreally injected with one of three preparations of ODG-PFA-O-Me or control diluent. The vitreous clarity was graded after injection using indirect ophthalmoscopy and fundus photography. Drug intraocular toxicity was evaluated by electroretinography and by post-sacrifice tissue pathology using light and electron microscopy. Intravitreal injection of micellar ODG-PFA-O-Me showed variable local retinal toxicity and vitreal compound aggregates in eyes with the middle and high doses. The intraocular therapeutic index was lower than 465:1. Intravitreal injection of liposomal ODG-PFA-O-Me, either free acid or sodium salt, revealed clear vitreous for the 0.632 and 0.84 mM final intravitreal concentrations. No retinal toxicity was confirmed for the 1.12 mM final intravitreal concentration at the eight week observation following injection. The intraocular therapeutic index was between 585-1037:1. ODG-PFA-O-Me possesses better vitreous compatibility than ODG-PFA. Liposomal ODG-PFA-O-Me can be intravitreally injected with a resulting clear vitreous and high intraocular therapeutic index. Liposomal ODG-PFA-O-Me could be a long acting nontoxic intravitreous injectable drug for CMV retinitis.

Animals↗
PubMed1999

An international study on the acceptability of a once-a-month pill.

Totals of 450 women attending family planning clinics in Hong Kong, Shanghai and Edinburgh, and 468 in Cape Town, completed a questionnaire designed to seek their views on a contraceptive pill which would be taken only once each month. At least two-thirds of the women in all centres liked the idea of a once-a-month pill. In Hong Kong, Cape Town and Edinburgh, women preferred a pill which inhibited ovulation to one which inhibited implantation, while in all centres a pill which worked after implantation (early menstrual inducer) was considered unacceptable by over half the women. A pill which was taken after a missed menstrual period was considered preferable in all centres, perhaps because it would not be used every month but rather only if pregnancy had occurred. No demographic characteristics, contraceptive experiences or beliefs were consistently correlated with attitudes towards a once-a-month pill, except that women who would not consider having an abortion were more likely to dislike a method that either prevented, or worked after, implantation. A once-a-month pill is now technically possible, although the major drawback is the need to determine when it should be taken. It is reassuring that many women from a variety of different cultures and with widely different experiences, would find this an attractive approach to contraception.

Abortifacient Agents↗
PubMed1999

A randomized double-blind placebo-controlled study to assess the effect of oral contraceptive pills on the outcome of medical abortion with mifepristone and misoprostol.

This was a randomized double-blind placebo-controlled trial to determine the effect of oral contraceptive (OC) pills taken immediately after medical abortion on the duration of bleeding and complete abortion rate. Two hundred women in the first 49 days of pregnancy were given 200 mg mifepristone orally followed by 400 microg misoprostol vaginally 48 h later. One day later, they were randomized to receive either OC pills (30 microg of ethinyl oestradiol and 0.15 mg of levonorgestrel per tablet) or placebo for 21 days. The complete abortion rates were 98% in the OC group and 99% in the placebo group. The median duration of bleeding was similar: 17 (range: 5-57) days in the OC group and 16 (range: 6-55) days in the placebo group. In the OC group there was a small but significant fall in the haemoglobin concentration by 14 days (5.3 g/dl) after administration of mifepristone. The incidence of side-effects was similar in the two groups. We conclude that the use of OC pills does not decrease the duration of bleeding after medical abortion nor does it affect the abortion rate.

Abortifacient Agents, Steroidal↗
PubMed1999

Natural history of urothelial dysplasia of the bladder.

Urothelial dysplasia is the putative precursor of urothelial carcinoma in situ (CIS) and invasive urothelial carcinoma of the urinary tract. Urothelial dysplasia is frequently identified in patients with urothelial CIS and cancer. However, very little is known about the clinical presentation and natural history of urothelial dysplasia in the absence of urothelial CIS or invasive cancer. The authors studied 36 patients with isolated urothelial dysplasia at the Mayo Clinic between 1969 and 1984. None of these patients had previous or concurrent urothelial CIS or invasive cancer, and none received treatment for dysplasia. The histopathologic features of urothelial dysplasia were examined, and long-term clinical follow-up was obtained. Progression was defined as the development of urothelial CIS or carcinoma. The male-to-female ratio was 2.6:1, and the mean patient age at the time of diagnosis was 60 years (range 25-79). Urothelial dysplasia has a predilection for the posterior wall. Eleven patients had urinary irritative symptoms, 10 had hematuria, 3 had both irritative symptoms and hematuria, and 12 were found to have dysplasia incidentally. The mean follow-up was 8.2 years (range 0.1-25.5). Seven (19%) of 36 patients developed biopsy-proven progression, including 4 with CIS and 3 with invasive cancer, and 1 of them died of bladder cancer. The intervals from diagnosis to progression ranged from 6 months to 8 years (mean 2.5 years). One of the remaining 29 patients had positive cytologic results 2.5 years after the initial diagnosis of dysplasia. The authors conclude that urothelial dysplasia is a significant risk for the development of CIS and invasive urothelial carcinoma, and patients with urothelial dysplasia should be followed up closely.

Adult↗
PubMed1999

Villous adenoma of the urinary tract: a report of 23 cases, including 8 with coexistent adenocarcinoma.

Villous adenoma originating in the urinary tract is uncommon. We present the first study of a large number of cases of villous adenoma of the urinary tract with clinical follow-up. Our series consisted of 15 patients with isolated villous adenoma and 8 patients with coexistent adenocarcinoma. The tumors occurred in elderly patients and had a predilection for the urachus, dome, and trigone of the urinary bladder. The typical clinical presentation was hematuria and irritative symptoms, and endoscopic examination usually identified a tumor growth. There was no gender predominance. Light microscopic examination showed morphologic similarity to colonic villous adenoma in all cases. Each tumor was composed of pointed or blunt finger-like processes lined by pseudostratified columnar epithelium. The epithelial cells displayed nuclear stratification, nuclear crowding, nuclear hyperchromasia, and occasional prominent nucleoli and mitotic figures. There was intense carcinoembryonic antigen immunoreactivity on the luminal surfaces (89%). Most cases (78%) contained cytoplasmic acid mucin, demonstrated by Alcian blue periodic acid-Schiff stain. Cytokeratin 20 was positive in all cases, cytokeratin 7 was positive in 56% of cases, and epithelial membrane antigen was positive in 22% of cases. Recurrence or invasive adenocarcinoma did not develop in any patient with isolated villous adenoma during a mean follow-up of 9.9 years. Lung metastasis developed in one patient with coexistent adenocarcinoma and multiple recurrences in another (mean follow-up, 3 years). We conclude that the prognosis is excellent in patients with isolated villous adenoma, and complete surgical resection is curative. Patients with coexistent adenocarcinoma may experience recurrence or distant metastasis, and more aggressive treatment may be indicated.

Adenocarcinoma↗
PubMed1999

Prevalence and distribution of prostatic intraepithelial neoplasia in salvage radical prostatectomy specimens after radiation therapy.

High-grade prostatic intraepithelial neoplasia (PIN) is the most likely precursor of prostate cancer. The effect of radiation therapy (RT) on the prevalence of PIN is uncertain. We studied 86 patients who underwent salvage radical prostatectomy after irradiation failure at the Mayo Clinic. The prevalence, volume, multicentricity, spatial proximity to cancer, and architectural patterns of PIN were evaluated. High-grade PIN was identified in 53 (62%) of 86 prostatectomy specimens. Multiple architectural patterns were usually observed, including tufting in 87%, micropapillary in 66%, cribriform in 38%, and flat in 17%. The mean volume of PIN was 0.12 cm3 (range, 0.05-1.20 cm3). PIN was usually multicentric (70%), with a mean number of PIN foci of 2.5 (range, 1-10). Ninety-four percent of PIN foci were located within 2 mm of invasive cancer. There was no correlation between PIN and pathologic stage, surgical margin, tumor size, DNA ploidy, post-RT Gleason score, time interval from RT to biopsy-proven recurrence, postoperative prostate-specific antigen level, distant metastasis-free survival, or cancer-specific survival. Our examination of salvage radical prostatectomy specimens indicated that the prevalence and extent of PIN appeared to be reduced after RT compared to published studies of prostatectomies without prior RT.

Aged↗
PubMed1999

Diagnosis of prostate cancer in needle biopsies after radiation therapy.

Interpretation of postirradiation needle biopsies is a major diagnostic challenge for the pathologist because of substantial radiation-induced changes in benign and malignant prostatic tissue. Reports that have systematically evaluated the histopathologic findings in postirradiation needle biopsies are limited. In this study, we evaluated 46 histologic features in 29 postirradiation needle biopsy specimens from 29 patients. All patients had recurrent cancer on needle biopsies after external beam radiation, and all subsequently underwent salvage radical prostatectomy and bilateral pelvic lymphadenectomy. Patient age ranged from 57 to 78 years (mean, 61 years). The interval from radiation therapy to biopsy ranged from 1.0 to 17 years (mean, 3.9 years). Histologic features that were helpful in the diagnosis of cancer after radiation therapy included infiltrative growth, perineural invasion, intraluminal crystalloids, blue mucin secretions, the absence of corpora amylacea, and the presence of coexistent high-grade prostatic intraepithelial neoplasia. Benign glands usually showed nuclear enlargement (86%) and prominent nucleoli (50%), and therefore, these cytologic features alone were not reliable for the diagnosis of cancer after irradiation. Postirradiation needle biopsies underestimated the prostatectomy Gleason grade in 35% of cases and overestimated it in 14% of cases; these results were similar to published reports from patients not receiving radiation therapy. There was a major discrepancy in degree of radiation effect between radical prostatectomy and biopsies. Moderate or severe radiation effect on cancer was present in 48% of needle biopsy specimens, whereas 94% of radical prostatectomy specimens had no or minimal radiation effect on cancer when the areas with the least amount of radiation effect were chosen for quantification. These findings indicate that quantification of radiation effect in needle biopsy specimens was inaccurate and potentially misleading. Conversely, Gleason grade in postirradiation needle biopsy specimens appeared to provide useful predictive information and should be reported.

Adenocarcinoma↗
PubMed1999

Treatment of herpes retinitis in an animal model with a sustained delivery antiviral drug, liposomal 1-O-octadecyl-SN-glycerol-3-phosphonoformate.

PURPOSE: To evaluate the clinical treatment efficacy of a long-lasting intravitreous injectable anti-cytomegalovirus (CMV) liposomal drug, 1-O-octadecyl-sn-glycerol-3-phosphonoformate (ODG-PFA). METHODS: Sixty-four pigmented rabbits were used for evaluation of the potency and duration of action of ODG-PFA after intravitreal injection using a herpes simplex virus (HSV)-1 retinitis model. For the potency evaluation, liposomal ODG-PFA was injected into rabbit vitreous at the same time that HSV-1 virus was inoculated onto the retina (simultaneous treatment). For the duration evaluation, ODG-PFA was injected days or weeks before inoculation (pretreatment). Retinitis was clinically graded by indirect ophthalmoscopy, and the retinitis scores were compared across the treatment and control groups. RESULTS: Simultaneous treatment study revealed that ODG-PFA was much more potent than its parent compound, foscarnet (P = 0.0027). Pretreatment study indicated that ODG-PFA possesses a much longer antiviral effect (at least 2 weeks) than foscarnet after a single intravitreal injection. CONCLUSION: Liposomal ODG-PFA is a potent long-lasting intravitreal injectable antiviral compound that may be an ideal alternative for treatment of CMV retinitis in patients with acquired immunodeficiency syndrome.

Animals↗
PubMed1999

Cell cycle regulation of DNA replication initiator factor Dbf4p.

The precise duplication of eukaryotic genetic material takes place once and only once per cell cycle and is dependent on the completion of the previous mitosis. Two evolutionarily conserved kinases, the cyclin B (Clb)/cyclin-dependent kinase (Cdk/Cdc28p) and Cdc7p along with its interacting factor Dbf4p, are required late in G1 to initiate DNA replication. We have determined that the levels of Dbf4p are cell cycle regulated. Dbf4p levels increase as cells begin S phase and remain high through late mitosis, after which they decline dramatically as cells begin the next cell cycle. We report that Dbf4p levels are sensitive to mutations in key components of the anaphase-promoting complex (APC). In addition, Dbf4p is modified in response to DNA damage, and this modification is dependent upon the DNA damage response pathway. We had previously shown that Dbf4p interacts with the M phase polo-like kinase Cdc5p, a key regulator of the APC late in mitosis. These results further link the actions of the initiator protein, Dbf4p, to the completion of mitosis and suggest possible roles for Dbf4p during progression through mitosis.

Aldehyde Oxidoreductases↗
PubMed1999

Differential microvascular response to disuse in rat hindlimb skeletal muscles.

The aim of the study was to address discrepant findings in the literature regarding coupling between decreased functional demand during disuse and reduced capillarity. We previously reported [K. Tyml, O. Mathieu-Costello, and E. Noble. Microvasc. Res. 49: 17-32, 1995] that severe disuse of rat extensor digitorum longus (EDL) muscle caused by a 2-wk application of tetrodotoxin (TTX) on the sciatic nerve is not accompanied by capillary loss. Using the same animal model, the present study examined whether this absence of coupling could be explained in terms of 1) too short a duration of disuse and 2) muscle-specific response to disuse. Fischer 344 rats were exposed to either no treatment (control) or to 2- or 8-wk TTX applications. Fiber size, capillary density per fiber cross-sectional area, and capillary-to-fiber (C/F) ratio were determined by morphometry in the EDL muscle (control, 2- and 8-wk groups) and in the superficial portion of medial gastrocnemius (Gas) muscle (control, 2 wk). In both muscles, microvascular blood flow was evaluated by intravital microscopy [red blood cell velocity in capillaries (V(RBC))] and by laser Doppler flowmetry (LDF). Regardless of duration of TTX application or muscle type, TTX-induced disuse resulted in a significant reduction of fiber area (44-71%). However, capillary density increased in EDL muscle (both at 2 and 8 wk) but not in Gas muscle. C/F ratio decreased in EDL muscle at 8 wk (18%) and in Gas muscle (39%). This indicates that the effect on capillarity depended on duration of disuse and on muscle type. V(RBC) and LDF signal were significantly larger in EDL than in Gas muscle. Analysis of change in capillarity vs. V(RBC) suggested that the outcome of disuse may be modulated by blood flow. We conclude that the duration of skeletal muscle disuse per se does not dictate capillary loss, and we hypothesize that discrepant findings of coupling between functional demand and capillarity could be due to the presence/absence of flow-related angiogenesis superimposed on the capillary removal process during disuse.

Animals↗