Search PubMed⌕ Search

Biomedical subjects

J Chen

Publications and source records attributed to J Chen.

At least 973 records · Page 54Linked to original sources

Formation of malondialdehyde adducts in livers of rats exposed to ethanol: role in ethanol-mediated inhibition of cytochrome c oxidase.

BACKGROUND: Previous studies in our laboratory demonstrated that short-term ethanol consumption by maternal rats increased the hepatic levels of 4-hydroxynonenal (HNE) in both the adult and the fetus. Additionally, HNE inhibited cytochrome c oxidase (COX) by forming adducts with the enzyme subunits. The present study examined modification of COX by another major aldehydic lipid peroxidation product, malondialdehyde (MDA), and its role in COX inhibition by ethanol. METHODS AND RESULTS: It is demonstrated in vitro that MDA inhibits the activity of purified COX while forming adducts with the enzyme. Compared with HNE, MDA is a more potent inhibitor of COX. Overnight incubation at room temperature caused an 80% decrease in COX activity by MDA versus a 67% decrease by HNE. MDA produced marked inhibition of COX activity at physiologically relevant concentrations, e.g., 43% inhibition at 10 microM. Although our previous studies documented that HNE formed adducts primarily with subunit IV of COX via histidine residues, the current report showed that MDA forms adducts with both subunit IV and subunit V via lysine residues. Furthermore, both aldehydes induce carbonyl formation in subunit IV. The in vivo role of MDA in the impairment of COX by ethanol is assessed in both adult and fetal liver after maternal ethanol consumption. CONCLUSIONS: The results showed that: (1) there are significant increases in MDA levels in liver homogenate as well as mitochondria in both adult and fetal livers after ethanol exposure; (2) these MDA levels are in the nanomole/mg protein range, in contrast to picomole/mg protein range of HNE in identical setting; and (3) ethanol-induced production of MDA is accompanied by enhanced formation of MDA adducts with COX. These findings suggest that MDA may play at least as equally an important role as HNE in ethanol-induced inhibition of COX.

Aldehydes↗

Effect of the plant-extract osthole on the relaxation of rabbit corpus cavernosum tissue in vitro.

PURPOSE: We investigated the cavernosal relaxant effect of osthole, a coumarin isolated from Cnidium monnier (L.) Cusson which has been long used in China as a herbal medicine to improve male sexual dysfunction. MATERIALS AND METHODS: Strips of rabbit corpus cavernosum were precontracted with phenylephrine. Corporal relaxation evoked by osthole was then determined in the absence and presence of nitric oxide synthase inhibitor (L-NAME), soluble guanylate cyclase inhibitor (ODQ), cyclooxygenase inhibitor (indomethacin), tetradotoxin, and after endothelium deprivation. RESULTS: Corpus cavernosal strips showed relaxation in response to osthole (0.1 approximately 30 microM) in a dose-dependent manner. These effects were reduced partially but significantly by pretreatment with L-NAME, ODQ and by endothelial disruption. However, they were not affected by indomethacin and tetradotoxin treatment. Osthole pretreatment (from 1 to 30 microM) enhanced the sodium nitroprusside (0.3 microM)-induced relaxation of corpus cavernosum in a dose-dependent manner to a maximum of 3 times the pretreatment level at 30 microM osthole. However, this effect was abolished in the presence of zaprinast. Additionally, a higher concentration of osthole (30 microM) also enhanced forskolin-induced relaxation. CONCLUSION: The data suggested that osthole possesses a relaxant effect on rabbit corpus cavernosal tissues which is attributable to the release of NO from sinusoidal endothelium and to the potentiation of the cGMP and/or cAMP signal mediating relaxation of cavernosal smooth muscle by inhibiting phosphodiesterase.

Animals↗

Does intratympanic gentamicin treatment for Meniere's disease cause complete vestibular ablation?

OBJECTIVE: To determine changes in vestibular function following intratympanic gentamicin (ITG) treatment for Meniere's disease and to correlate changes with the need for further treatment. STUDY DESIGN: Prospective case series. PATIENTS: One hundred and three patients with disabling unilateral Meniere's disease who had failed a minimum of 6 months medical treatment. MAIN OUTCOME MEASURES: Vestibular function was measured by electronystagmography (ENG) caloric testing before and serially following treatment. Caloric responses were classified as normal (excitability difference [ED] < 25%), bithermal response (ED > or = 25%), positive response to ice water only, and absent ice water response. RESULTS: Twenty-one percent of patients had a bithermal caloric response, 62% had an absent ice water response, and 17% had an ice water response only 1 month following treatment. Mean follow-up was 27.3 months (range = 1-106 months). Eighty-four patients had one treatment course only. Fourteen patients required a further course of treatment due to recurrence of vertigo; 38% of these had recovery of caloric function. Significantly more patients with normal caloric function prior to initial treatment required further treatment compared to those with initial reduced caloric function (p < .05). Patients rendered absent ice water responsive were significantly less likely to require further treatment than those with a persistent caloric response (p < .0001). CONCLUSION: An absent ice water response is highly predictive of adequate vertigo control. Regimens of ITG that aim to completely ablate vestibular function are recommended.

Adult↗

Inhibition of TGF-beta-induced apoptosis by ethinyl estradiol in cultured, precision cut rat liver slices and hepatocytes.

Ethinyl estradiol (EE) is a strong promoter of hepatocarcinogenesis in the rat. Treatment with EE and other hepatic promoters induces transient growth stimulation followed by growth inhibition (mitosuppression) in hepatocytes. Previously, we identified several genes whose transcript levels were increased during EE-induced mitosuppression, including transforming growth factor beta (TGF-beta), which inhibits growth and induces apoptosis in hepatocytes. Various hepatic promoters, including phenobarbital and several peroxisomal proliferators, have been shown to inhibit TGF-beta-induced apoptosis in rat hepatocytes. The goal of this study was to investigate whether EE is also an inhibitor of TGF-beta-induced apoptosis in rat hepatocytes. Several approaches to detect apoptosis were used, including the TUNEL assay, detection of high molecular weight DNA fragmentation by field inversion gel electrophoresis and determination of cytosolic cytochrome c levels by western analysis. TGF-beta-induced apoptosis in cultured, precision cut liver slices and hepatocytes of female rats. EE (</=3 microM) completely inhibited TGF-beta-induced apoptosis in these systems in the absence of cytotoxicity. These findings add EE to the list of several hepatic promoters that both induce TGF-beta while simultaneously inhibiting its ability to cause apoptosis.

Animals↗

The effects of recombinant RA538 and antisense c-myc adenovirus on tumor cells and the molecular mechanism concerned.

OBJECTIVE: Compare the biological effects of recombinant RA538 and antisense c-myc adenovirus on human gastric cancer cell line (SGC7901) and explore the molecular mechanism in vitro and in vivo. METHODS: SGC7901 cells were treated with Ad-RA538, Ad-AS c-myc or Ad-LacZ. MTT, DNA ladder, TUNEL and FCM, RT-PCR, Western blot analysis, the tumorigenicity in nude mice and experimental therapy of the nude mice were used. RESULTS: Ad-RA538 and Ad-ASc-myc could strongly inhibit cell growth and induce apoptosis of SGC7901 cells. The growth of the Ad-RA538- and Ad-ASc-myc-infected SGC7901 cells were inhibited by 76.3% and 44.1% respectively. The over expression of RA538 and ASc-myc could down-regulate expression of c-myc, bcl-2 and cyclinD1 gene and up-regulate expression of bax gene, but it could not regulate expression of p53, p16, TGase, and ras gene. The tumorigenicity of Ad-RA538 or Ad-ASc-myc in nude mice showed that three of three mice failed to form tumor, compared with Ad-LacZ and parent SGC7901 cells from 7 to 30 days. Experimental therapy of the nude mice bearing subcutaneous tumor of SGC7901 cells showed that intratumor instillation of Ad-RA538 and Ad-ASc-myc inhibited the growth of the tumors. Ad-RA538- and Ad-ASc-myc-treated tumors were inhibited by 60.7% or 68.9% respectively, compared with the tumor injected with Ad-LacZ and mock. CONCLUSION: The expression of Ad-RA538 and Ad-ASc-myc can inhibit growth and induce apoptosis of gastric cancer cell in vitro and in vivo. RA538 and ASc-myc relate to c-myc, bcl-2, cyclinD1 and bax gene closely and have noticeable biologic effects on gastric cancer cells.

Adenoviridae↗

Genetic heterogeneity of non-specific mental retardation.

OBJECTIVE: To explore genetic patterns of non-specific mental retardation (NSMR). METHODS: Using segregation analysis, Finney method and Falconer method, the authors studied 157 pedigrees with NSMR selected in a population survey in Shandong province. RESULTS: Ux U multiplex families may accept the autosomal recessive inheritance, Ux U total families is the autosomal recessive inheritance while it may be the multifactorial inheritance with major-gene effect, the frequency of sporadic cases is approximately 46%; Ux A mating families may keep the incomplete penetrance in autosomal dominant inheritance. CONCLUSION: The genetic pattern of NSMR has the genetic heterogeneity.

Female↗

Detection of mosaic chromosome 21 aneuploidy in vivo with CB-FISH method.

OBJECTIVE: To explore the mechanism by which the ratio of mosaic diploid cells in vivo increased in trisomy 21 cases. METHODS: Fluorescence in situ hybridization (FISH) with pericentric DNA probes specific to human chromosome 21 to the binucleated cells cytokinesis- blocked by cytochalasin-B(CB), namely, CB-FISH method. RESULTS: The mean frequency of diploid cells (1.69%+/-1.07%) was significantly higher than that of tetrasomy 21 cells(0.042%+/-0.064%)(P=0.000) in 12 trisomy 21 cases aged 0-9 years (mean 4 years) in vivo; whereas the incidence of spontaneous monosomy 21 cells (0. 265%+/-0.13%) was close to the frequency of trisomy 21 cells (0. 225%+/-0.184%) in 20 control individuals aged 0-10 years (mean 5 years). The frequency of cells undergone chromosome 21 nondisjunction was 0.822%+/-0.554% in cultured trisomy 21 cells, which was significantly higher than that in the cultured diploid cells (0.369%+/-0.25%). However, the rates of cells with chromosome 21 loss in the two cultured cell lines (0.01%+/-0.03% vs 0.043%+/-0.049%) were not significantly different. In both cultured cell lines, chromosome 21 nondisjunction occurred more frequently than loss. CONCLUSION: The increased frequency of diploidies in trisomy 21 cases may result from the accumulation of diploid cells originating from malsegregation of chromosome 21 in trisomic cells rather than the increase of chromosome 21 loss.

Aneuploidy↗

Synergistic effect of Bcl-2 and BAG-1 on the prevention of photoreceptor cell death.

PURPOSE: Ectopic expression of Bcl-2 in photoreceptors of mice with retinal degenerative disease slows progression of the disease. BAG-1 has previously been shown to augment the inhibitory effect of Bcl-2 on programmed cell death in cultured cell systems. This study was designed to determine whether the coexpression of BAG-1 and Bcl-2 in the photoreceptors of mice with an autosomal dominant form of retinitis pigmentosa (RP) would enhance the protective effect provided by Bcl-2 alone. METHODS: An expression vector using the 5' regulatory region of the murine opsin gene was used to target the expression of BAG-1 specifically to photoreceptor cells of mice. The BAG-1 transgenic mice were crossed to Bcl-2 transgenics to obtain animals that coexpress the two transgenes in photoreceptor cells. BAG-1/Bcl-2 animals were then crossed to an RP mouse model (a transgenic line overexpressing the S334ter rhodopsin mutant) to assess the effect of coexpression of BAG-1 and Bcl-2 on retinal degeneration. Morphologic analysis was performed on retinas isolated at various times after birth to monitor disease progression. RESULTS: High levels of BAG-1 expression resulted in retinal degeneration that was not prevented by Bcl-2 expression. However, coexpression of appropriate levels of BAG-1 and Bcl-2 was found to have a profound inhibitory effect on retinal degeneration caused by overexpression of a mutant rhodopsin transgene. Whereas expression of Bcl-2 alone was previously found to delay degeneration of the retina from 2 weeks to approximately 4 weeks of age, coexpression of BAG-1 and Bcl-2 inhibited photoreceptor cell death for as long as 7 to 9 weeks. CONCLUSIONS: The synergistic effect against photoreceptor cell death produced by the coexpression of Bcl-2 and BAG-1 indicates that these proteins can function in concert to prevent cell death. At the correct dosage, coexpression of Bcl-2 and BAG-1 may serve as a potential means to treat retinal degenerative diseases.

Animals↗

[Ultrastructure study of hepatocellular carcinoma treated by diamminedichloroplatinum].

OBJECTIVE: To study the changes of the ultrastructure of hepatocellular carcinoma (HCC) after being treated by diamminedichloroplatinum. METHODS: The changes of morphological feature of HCC treated by diamminedichloroplatinum were observed with transmission electron microscope. RESULTS: The cells lost its specialized cell surface elements such as microvilli and cell-cell junctions. The nucleus chromatin condensed and segregated. The cytoplasm was hollow. The ribosomes on the endoplasmic reticulum reduced or lacked. The glycogen granules reduced. The mitochondria vacuolalized or produced flocculi, and the apoptotic bodies could be found. CONCLUSION: The changes of the ultrastructure of HCC treated by diamminedichloroplatinum correspond with the procedure of programmed cell death. Apoptosis of HCC cells can be induced by diamminedichloroplatinum.

Adult↗

Are recent cohorts healthier than their predecessors?

OBJECTIVES: This article examines changes in the health status of Canadian adults between 1978/79 and 1996/97. DATA SOURCES: Data are from the the Canadian Vital Statistics Data Base, the 1991 General Social Survey, the 1978/79 Canada Health Survey (CHS), and the 1996/97 National Population Health Survey (NPHS). ANALYTICAL TECHNIQUES: Age-specific mortality rates are presented for 1978 and 1996. The cumulative incidence of heart disease is shown for 1991. Cross-sectional comparisons of prevalence rates for selected chronic conditions, activity limitation, disability days, smoking and overweight are shown for 1978/79 and 1996/97. Multiple logistic regression models were used to test differences in odds ratios for the chronic conditions and for activity limitation between the CHS and the NPHS. SUDAAN, which accounts for the complex survey design, was used to estimate standard errors of the prevalence and of the coefficients in the logistic model. MAIN RESULTS: Lower mortality rates and lower prevalence of heart disease, high blood pressure, arthritis and activity limitation suggest that recent cohorts are healthier than previous cohorts. When the age effect was controlled along with education and income, the odds of having these conditions were generally lower for each successive cohort, and lower in the mid-1990s than in the late 1970s. However, the odds of having diabetes were higher in 1996/97 than in 1978/79, and higher among more recent cohorts than among earlier cohorts.

Adult↗

[Studies on fermentation conditions for the accumulation of poly-beta-hydroxybutyrate in Alcaligenes eutrophus].

The results of the cultivation of Alcaligenes eutrophus showed that nitrogen limitation or exhaustion could stimulate the substantial accumulation of PHB. But the exhaustion of nitrogen source in PHB formation period would result in the rapid drop of PHB synthetic rate. Oxygen limitation could also stimulate the formation of PHB, but the content of PHB in the cell was much less than that in case of nitrogen controlled conditions. Obvious influences were observed on PHB fermentation when ammonia water feeding was stopped at different cell growth phases, and better results could be obtained when it was performed at 20 g/L to 30 g/L of residual biomass. Cell dry weight, PHB content and PHB concentration reached 61.9 g/L, 80.5% and 49.0 g/L, respectively under desired conditions.

Cell Division↗

[Transcriptional expression of apoptosis suppression gene bcl-2 in non-small cell lung carcinoma].

OBJECTIVE: To investigate the role of Bcl-2 gene in oncogenesis and progression of non-small cell lung carcinoma(NSCLC). METHODS: The mRNA expressions of Bcl-2 gene in a series of 137 pulmonary tissues collected at various sites and with different properties were studied with Northern hybridization and non-radioactive digoxigenin labeling and detection system. RESULTS: According to the observations on benign lesions, non-cancer tissues distant from tumour, para-tumour tissues and cancer tissues, there was a tendency of mRNA expression increasing of Bcl-2 gene. Among them, Bcl-2 mRNA expression in lung cancer tissues was significantly increased, compared with that in benign lesions and tissues distant from tumour (P<0.01). The Bcl-2 mRNA expression in lymph node with cancer metastasis was significantly higher than that in lymph node without cancer metastasis(P<0.05). The Bcl-2 mRNA expression was relative to cell differentiation of the cancer, but not to the histological classification. CONCLUSION: Over expression of Bcl-2 gene might be involved in the oncogenesis and metastasis of NSCLC.

Carcinoma, Non-Small-Cell Lung↗

ATPase and GTPase activities copurifying with GTP-binding proteins in E. coli.

Intrinsic GTPase activity of GTP-binding proteins plays the vital role in regulating the downstream activation pathway. We examined the GTP and ATP hydrolyzing (NTPase) abilities of various bacterial and human GTP-binding proteins under different metabolic conditions. Two metabolic components, acetate and 3-phosphoglyceric acid (3-PG), have shown significant stimulatory action on NTPase activity of G-protein preparations. Acetyl phosphate and 2,3-bisphosphoglyceric acid (2,3-BPG) blocked these stimulations. From gel filtration analyses, we have determined two fractions containing metabolite-inducible NTPase activities which are independent of GTP-binding protein enzymatic actions. Therefore, one should be cautious when NTPase activity is examined in a buffer containing acetate often used for NTPase assay.

Acetates↗

Crystal structure and mutagenic analysis of the inhibitor-of-apoptosis protein survivin.

The coupling of apoptosis (programmed cell death) to the cell division cycle is essential for homeostasis and genomic integrity. Here, we report the crystal structure of survivin, an inhibitor of apoptosis, which has been implicated in both control of cell death and regulation of cell division. In addition to a conserved N-terminal Zn finger baculovirus IAP repeat, survivin forms a dimer through a symmetric interaction with an intermolecularly bound Zn atom located along the molecular dyad axis. The interaction of the dimer-related C-terminal alpha helices forms an extended surface of approximately 70 A in length. Mutagenesis analysis revealed that survivin dimerization and an extended negatively charged surface surrounding Asp-71 are required to counteract apoptosis and preserve ploidy. These findings may provide a structural basis for a dual role of survivin in inhibition of apoptosis and regulation of cell division.

Amino Acid Motifs↗

[Effect of nutritional conditions on the fermentative production of pyruvic acid by Torulopsis glabrata].

The effects of some nutritional conditions, such as peptone concentration, feeding glucose as well as oxygen supply manner and ratio of C/N in batch culture, on the fermentative production of pyruvic acid by Torulopsis glabrata WSH-IP12 were investigated. In shaking-flask culture: (1) peptone of more than 20 g/L inhibited the accumulation of pyruvic acid; (2) production of pyruvic acid was increased from 23.5 g/L to 30.2 g/L by simply feeding glucose. In 5 L jar-fermentor batch culture: (1) high level of dissolved oxygen and (2) increasing the concentration of glucose and peptone proportionally with constant C/N ratio(26:1) improved the production of pyruvic acid. It was also found that, glucose consumption and pyruvic acid production almost stopped under the condition of nitrogen difficiency while recovered by adding peptone and (NH4)2SO4. By using ammonia water instead of potassium hydroxide for the control of pH, the cells kept stronger ability for synthesizing pyruvic acid within the whole process, 57.3 g/L pyruvic acid with the yield of 0.498 g/g was achieved at 55 h of fermentation.

Candida↗

Analysis of genotype frequencies and interlocus association for the PM, DQA1, and D1S80 loci in four populations.

Allele frequencies of the LDLR, HBGG, GYPA, D7S8, GC, DQA1, and D1S80 loci are presented and genotypes are analyzed for each of four ethnic groups: African Americans (n = 200), US Caucasians (n = 200), US Hispanics (n = 200), and Japanese (n = 89). Hardy-Weinberg genotypic proportions were observed in all but two of the 28 population-locus tests undertaken. Those two instances are attributable to type I statistical error. Gametic equilibrium among loci is an assumption invoked for application of the product rule to utilize the discriminatory power from two or more loci simultaneously. Two statistical methods, a genotype matching statistic and log-linear modeling, were used to evaluate gametic disequilibrium. The match statistic, comparing observed to expected likelihood of genotypic identity for seven loci among pairs of individuals within the database, revealed only one statistically significant deviation among 20 tests. As expected, the probability of match was generally lowest in the test on all ethnic groups combined, indicating that allele frequencies differ among ethnic groups for some of the loci. This was confirmed with the statistic theta to measure ethnic stratification, in which about 0.10 of the genetic variation is apportioned among the four ethnic groups for four of the structural loci (LDLR, HBGG, GC, and DQA1), while for GYPA, D7S8, and D1S80, variation is more uniformly distributed among ethnic groups. Log-linear modeling was also applied to the five PM loci. The most parsimonious log-linear model included only three higher order terms: the two-way interactions of three of the PM loci with ethnic group. These three instances (LDLR, HBGG, and GC) indicated differences in allele frequencies between ethnic groups. No two or higher way interaction (disequilibrium) was observed among loci. In summary, the assumptions of Hardy-Weinberg and gametic equilibrium that facilitate the use of the five PM loci, DQA1 and D1S80 in forensic applications are consistent with the allele and genotype frequencies observed in these populations.

Asian People↗

DeltaFosB-induced cataract.

PURPOSE: The objective of this study was to investigate a possible relationship between posterior subcapsular cataract (PSC) formation and expression of the transcription factor DeltaFosB. METHODS: Western blot analysis was performed on bitransgenic NSE-tTA, TetOp-DeltaFosB, and single-transgenic NSE-tTA control mice to determine the pattern of DeltaFosB expression within the eye. Light and scanning electron microscopy and biochemical analyses were also performed. RESULTS: In mice expressing DeltaFosB, cataract developed that initially appeared to be posterior subcapsular and gradually matured to involve the entire lens. The enlarged posterior ends of developing secondary fibers curved away from the visual axis to form an elevated opaque posterior plaque. As a result, posterior suture formation did not occur. At a later time, the attenuated posterior capsule overlying the plaque ruptured and the lens nucleus subluxated into the vitreous. Retinal damage was also observed but only from postnatal day 65, a time when extensive lens degeneration had already occurred. DeltaFosB expression was observed well before the detection of morphologic change in both the lens and the retina. Within the lens, DeltaFosB expression was found in both the epithelium and fibers. The development of cataracts was a direct consequence of DeltaFosB expression and was not due to the disruption of an endogenous gene by transgene integration since cataracts could be prevented by silencing expression of DeltaFosB by feeding bitransgenic animals doxycycline (Dox). Moreover, cataracts were observed in bitransgenic mice derived from two independent TetOp-DeltaFosB founder lines but not in single NSE-tTA transgenic controls. Cataractogenesis was not a consequence of abnormal development, because mice conceived and raised on Dox to prevent expression of DeltaFosB also were subject to formation of PSC when expression of DeltaFosB was turned on in adult animals by removing Dox. Examination of biochemical parameters indicated that the earliest change observed was the disruption of calcium homeostasis with a significant increase in Ca(2+) influx, followed by a gradual but marked decrease in protein content. Significant changes in certain metabolic parameters and protein composition were also observed. CONCLUSIONS: The DeltaFosB-induced cataract in which the major morphologic early event was the disruption of normal posterior fiber formation, may be a good model for PSC. By identifying DeltaFosB-regulated target genes, it should be possible to achieve a better understanding of the molecular mechanisms through which PSC is formed.

Animals↗

Metastatic renal cell carcinoma of bone: indications and technique of surgical intervention.

PURPOSE: We describe the efficacy of surgical excision of metastatic renal cell carcinoma of bone for achieving local tumor control, pain control and functional outcome with emphasis on the indications and techniques of surgical intervention as well as oncological outcome. MATERIALS AND METHODS: Between 1980 and 1997 we performed surgery on 45 patients (56 lesions) with metastatic renal cell carcinoma of bone. Indications for surgery were solitary bone metastasis, intractable pain, or impending or present pathological fracture. Surgery involved wide excision in 29 cases, marginal excision with adjunctive liquid nitrogen in 25 and amputation in 2. RESULTS: None of the patients had significant bleeding intraoperatively. Mean hospital stay was 9.8 days, during which there was no flap necrosis, deep wound infection, nerve palsy or thromboembolic complication. Postoperatively pain was significantly relieved in 91% of patients, while 89% achieved a good to excellent functional outcome, and 94% with metastatic lesions of the pelvic girdle and lower extremities were ambulatory. Local recurrence developed in only 4 of the 56 lesions (7.1%), including 3 after marginal resection. Survival was more than 2 years in 22 patients (49%) and more than 3 in 17 (38%). CONCLUSIONS: Surgical excision is safe and reliable for restoring mechanical bone stability, relieving pain and providing good function in most patients with metastatic renal cell carcinoma who meet the criteria for surgical intervention. Relatively prolonged survival in these cases justifies considering surgical intervention when feasible.

Adult↗