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Biomedical subjects

T J Huang

Publications and source records attributed to T J Huang.

At least 37 records · Page 2Linked to original sources

Contribution of upregulated airway endothelin-1 expression to airway smooth muscle and epithelial cell DNA synthesis after repeated allergen exposure of sensitized Brown-Norway rats.

Endothelin-1 is a potent bronchoconstrictor peptide with pro-inflammatory and growth-promoting properties. After exposure of sensitized Brown-Norway rats to six repeated ovalbumin exposures, there was an increase in pro-endothelin (ET)-1 messenger RNA compared with saline-exposed control rats 24 h after the final exposure (P < 0.01). ET-1 immunoreactivity was increased sixfold in the bronchial epithelium of the larger conducting airways in the repeated allergen-exposed rats (P < 0.001). After repeated allergen exposure, there were increased rates of DNA synthesis in the airway smooth muscle (ASM) cells (P < 0.001) and epithelial cells (P < 0. 001) compared with saline-exposed controls, as measured by bromodeoxyuridine incorporation. Treatment with a dual endothelin A and B (ET(A+B)) receptor antagonist caused a significant attenuation in both ASM (P < 0.001) and epithelial cell (P < 0.001) bromodeoxyuridine incorporation compared with the allergen-challenged and vehicle-treated group. The dual ET(A+B) antagonist attenuated eosinophil recruitment into the airways (P < 0. 05) but had no significant effect on increased bronchial reactivity to acetylcholine in allergen-exposed rats. Increased levels of ET-1 in the airways may contribute to inflammation and ASM and epithelial cell DNA synthesis after repeated allergen exposure. Such processes may underlie increased proliferation of resident cells leading to airway wall remodeling in asthmatics.

Allergens↗

Minimal-access surgery in managing osteoporotic vertebral fractures with neurological deficits: a preliminary report.

BACKGROUND: Spinal cord compression as a result of osteoporotic vertebral fracture is very rare. Surgical decompression of this recognized complication is indicated when the patient has persistent neurological deficits. Clinically, these patients are usually elderly and in a generally debilitated state. Using formal anterior spinal surgery might significantly violate the patient's respiratory mechanism and increase operative mobidity or mortality. METHODS: From January 1996 to June 1998, the authors used a minimal-access spinal approach to perform 1-stage decompressive corpectomy, interbody fusion, and internal fixation with a Reduction-Fixation titanium spinal plate (Trifix, San Leandro, CA, USA) by thoracoscopic assistance in 8 patients with osteoporotic vertebral fractures from T11 to L1, and neurological deficits. This involved a modified 2-portal technique that required a 2-cm wound in order to initially introduce the thoracoscope, and a minithoracotomy wound (usually 5-6 cm) for surgical manipulation. RESULTS: None of the operations resulted in injury to the great vessels, internal organs, or spinal cord. The average followup period was 30 months (range, 22-50 months). Complications included 1 radiolucent line around a vertebral screw, 1 lateral migration of a vertebral screw with bone graft displacement, 1 transient incisional wound hypesthesia, and 1 iliac donor site pain. In the current patients, the average neurological recovery was 1.1 grades on the Frankel scale. CONCLUSION: The authors advocate that such a minimal-access technique with thoracoscopic assistance presented in the current study is an ideal alternative in treating patients with osteoporotic vertebral fractures and neurological deficits. It can obviate the necessity of dividing the diaphragm in order to facilitate exposure; no patient in the current series required intensive care postoperatively. However, the stability of the vertebral screw purchase in the osteoporotic spine is a matter of concern.

Aged↗

Familial breast cancer in southern Taiwan.

The purpose of this study is to evaluate whether there are pathobiologic differences and differences in overall rates survival between familial and non-familial breast cancer patients in Taiwan. A retrospective study was performed evaluating 76 familial breast cancer patients in 69 families, which included two BRCA1 related cases and six BRCA2 related cases. Patients were compared with 425 non-familial sporadic cases. Familial breast cancer patients had similar ages and stages as non-familial patients (mean, 46.6 years vs 48.9 years, p = 0.306). However, the familial breast cancer patients with BRCA1 and BRCA2 related cases presented at lower stages (p = 0.034) and younger ages than non-familial patients (mean, 45.1 years vs 48.9 years P = 0.042). The occurrence of infiltrating ductal carcinoma and lobular carcinoma in situ was not significantly different in the two groups. Mucinous carcinoma was represented with 6.7% (4/76) and 1.3% (1/76) medullary carcinoma. The overall grade of familial breast cancer, including BRCA1 and BRCA2 related cases in 8 infiltrating ductal carcinoma, was significantly higher than that of controls. The mean follow up was 4.5 years for familial breast cancers. Five- and 10-year overall survival rates were 69% and 61% for those with a family history, compared with 86% and 64% for those in the control group (p = 0.644). There were no statistically significant differences in disease-free survival rates between the two groups at 5 or 10 years (69% vs 78% in 5 years; 48% vs 58% in 10 years) (p = 0.862). Despite the younger ages and earlier stages at presentation in familial breast cancer patients with BRCA1 and BRCA2 related cases, the familial breast cancer patients had higher grade patholobiologic characteristics, but similar prognoses when compared with sporadic breast cancer patients. Owing to the limited number of familial cases in this study, more cases and longer follow up are needed.

BRCA2 Protein↗

Comparison of appendectomy medical expense and clinical outcome between fee for service and prospective payment system.

Since the introduction of national health insurance on March 1st 1995 in Taiwan, another 9 items (including appendectomy) were introduced into the Taiwan/prospective payment system (T/PPS). The modified T/PPS was based on those complicated appendectomy cases with secondary diagnosis or second operation where a total fee over 37,500 New Taiwan (NT) dollars was paid by National Health Insurance Bureau (NHIB) according to the real cost. The T/PPS was implemented in October 1997 due to the continuously increasing financial burden of medical expenses on the NHIB. The purpose of this study is (1) to compare the length of stay (LOS) and total medical expense of appendectomy of fee for service (FFS) and T/PPS and (2) to compare the clinical outcome of wound healing after discharge of the two systems by telephone interview. Our study investigated 100 consecutive appendectomy cases under FFS payment system and 99 consecutive appendectomy cases under T/PPS. We retrospectively analyzed LOS, operation time, and hospital cost of different items through chart review and computer data. Our results revealed that the LOS and operation time of T/PPS were significantly shorter than those of FFS (both p < 0.01). The total hospital cost, fee for room service, treatment, pharmacy, examination and anesthesia in T/PPS were also significantly less than those in FFS (all p < 0.01, except for anesthesia p < 0.05). There existed positive correlation between total hospital cost and LOS, operation time, fee for room service, treatment, pharmacy, examination and anesthesia both for T/PPS and FFS. To evaluate the clinical outcome of appendectomy between T/PPS and FFS, we interviewed 73 T/PPS cases and 73 FFS cases by telephone and chart review. Our results revealed that there were no significant differences in frequencies of having painful incision, clear incision wound on the day of discharge, and removal of stitches at hospital (p all > 0.05). We concluded that compared to FFS, T/PPS can decrease LOS and total hospital cost of appendectomy, and T/PPS's clinical outcome of appendectomy in T/PPS showed no significant difference from that in FFS.

Adult↗

Inhibition of ozone-induced lung neutrophilia and nuclear factor-kappaB binding activity by vitamin A in rat.

Vitamin A binds to retinoic acid receptors, which in turn may interact with other transcription factors. We determined its effect (2500 and 5000 IU/kg) on nuclear factor-kappaB binding activity in the lung, airway inflammation and bronchial hyperresponsiveness in rats exposed to ozone. Ozone (3 ppm, 3 h) caused neutrophil influx into bronchoalveolar lavage fluid (16.2+/-0.8 x 10(5) cells/ml, p < 0.01) and bronchial hyperresponsiveness (-logPC200ACh = 2.54+/-0.19, p < 0.05, compared to control animals, respectively). Vitamin A inhibited this neutrophilia dose-dependently together with the increased DNA-binding activity of nuclear factor-KB in lung extracts. Vitamin A did not affect bronchial hyperresponsiveness at both doses. Vitamin A inhibits ozone-induced neutrophilic inflammation through a reduction in nuclear factor-kappaB DNA binding activity.

Acetylcholine↗

Benefits of endorectal ultrasound for management of smooth-muscle tumor of the rectum: report of three cases.

Smooth-muscle tumor of the rectum is rare, and the therapeutic strategy is still controversial. Endorectal ultrasound was used to evaluate three patients with smooth-muscle tumor of the rectum. Endorectal ultrasound demonstrated a homogenous hypoechoic tumor without invasion to the perirectal tissue in two patients. The tumor was 5 cm in diameter in one patient and 4 cm in diameter in the other patient, and they were excised locally. Their histologic types were leiomyoma and leiomyosarcoma. The third patient had a recurrent leiomyosarcoma. Proctosigmoidoscopy found a linear lesion with ulcerated mucosa on the rectal wall. Endorectal ultrasound observed a hypoechoic solid tumor of 3.5 cm x 1 cm, which involved the mucosal, submucosal, and muscle layers of the rectal wall. Disruption of the first hypoechoic layer was identified. Abdominoperineal resection was performed. Endorectal ultrasound follow-up revealed no evidence of recurrence in any of these patients. Endorectal ultrasound can help to define the extent of disease and may be a useful adjunct in deciding about the appropriate surgical procedure in these diseases.

Adult↗

Molecular characterization of germline mutations in the BRCA1 and BRCA2 genes from breast cancer families in Taiwan.

A total of 18 families with multiple cases of breast cancer were identified from southern Taiwan, and 5 of these families were found to carry cancer-associated germline mutations in the BRCA1 and BRCA2 genes. One novel cryptic splicing mutation of the BRCA1 gene, found in two unrelated families, was shown to be a deletion of 10 bp near the branch site in intron 7. This mutation causes an insertion of 59 nucleotides derived from intron 7 and results in a frameshift, leading to premature translational termination of BRCA1 mRNA in exon 8. Deletions of 2670delC, 3073delT and 6696-7delTC in the BRCA2 gene were found in three other breast cancer families. All three deletions are predicted to generate frameshifts and to result in the premature termination of BRCA2 protein translation. Several genetic polymorphisms in both BRCA1 and BRCA2 genes were also detected in this investigation.

Adult↗

Video-assisted thoracoscopic surgery to the upper thoracic spine.

BACKGROUND: The standard open technique for exposure of the upper thoracic spine, T1-T4, usually requires a difficult thoracotomy. From November 1, 1995 to June 30, 1997, eight patients underwent video-assisted thoracoscopic spinal surgery in our institute to treat their upper thoracic spinal lesions endoscopically. METHODS: A new approach, the so-called "extended manipulating channel method," was used in this series that allows the combined use of video-assisted thoracoscopy and conventional spinal instruments to enter the chest cavity freely for the procedures. Patients' ages ranged from 44 to 89 years (average, 60 years). Definitive diagnoses included two pyogenic spondylitis and six spinal metastases. Five patients presented initially with myelopathy. RESULTS: There were no deaths or neurologic injuries associated with this technique. The mean surgical time was 3.1 h. The mean duration of chest tube retention was 3.3 days. The mean total blood loss was 1,038 ml, and two patients had a blood loss of more than 2,000 ml owing to bleeding from epidural veins or raw osseous surfaces. Complications included one superficial wound infection and one subcutaneous emphysema that resolved spontaneously. In this series, there was no need of conversion to open thoracotomy for the patients. CONCLUSIONS: The thoracoscopy-assisted spinal technique using the extended manipulating channels, usually 2.5-3.5 cm, allows variable instrument angulations for manipulation. The mean surgical time (3.1 h) was considered no longer than for an open technique for the equivalent anterior procedure. Such an approach can achieve less procedure-related trauma and has proved to be a good alternative to other treatment modalities.

Adult↗

Complications in thoracoscopic spinal surgery: a study of 90 consecutive patients.

BACKGROUND: The literature contains few reports on negative outcomes after thoracoscopic spinal surgery. METHODS: From November 1995 to February 1998, 90 patients underwent minimally invasive spinal surgery by thoracoscopic assistance as treatment for their anterior spinal lesions. The diagnoses included 41 spinal metastases, 13 cases of scoliosis, 12 burst fractures, 10 cases of tuberculous spondylitis, 8 cases of pyogenic spondylitis, 2 thoracic disc herniations, 2 cases of ankylosing spondylitis with discitis, 1 osteoporotic compression fracture, and 1 case of thoracolumbar kyphosis. The procedures included biopsy only (3 patients); thoracic discectomy (3 patients); multilevel anterior releases, discectomy, and fusion (14 patients); corpectomy for decompression (6 patients); corpectomy and interbody fusion (32) patients; and internal instrumentation (28 patients). RESULTS: A total of 30 complications were noted in 22 patients (24.4%). Two fatal complications occurred, resulting from massive blood transfusion in one case and postoperative pneumonia in another. Other nonfatal complications included four cases of transient intercostal neuralgia, three superficial wound infections, three cases of pharyngeal pain, two cases of lung atelectasis, two cases of residual pneumothorax, two cases of subcutaneous emphysema, one inadvertent pericardial penetration due to adhesion, one chylothorax that resolved after conservative management, one vertebral screw malposition, and one graft dislodgement that needed late revision surgery. Three patients required ventilatory support for longer than 72 hours. Five patients with spinal metastases had an estimated intraoperative blood loss of more than 2,000 ml. No injury to the internal organs or spinal cord was observed. There were four conversions to open procedures due to two cases of severe pleural adhesions and two poorly tolerated one-lung ventilation. At the latest follow-up, nine patients had died as a result of cancer dissemination. CONCLUSIONS: (a) Well-selected patients and attention to details are essential to optimizing surgical results. (b) A refined technique for less invasive tumor surgery has been developed. (c) Surgeons had better experience with the standard anterior spinal approach and showed no hesitation in converting to an open procedure when necessary. A procedure failure does not mean a treatment failure.

Adolescent↗

Differential regulation of cytokine expression after allergen exposure of sensitized rats by cyclosporin A and corticosteroids: relationship to bronchial hyperresponsiveness.

BACKGROUND: Cyclosporin A and dexamethasone exhibit different effects on allergic airway eosinophilia and bronchial hyperresponsiveness (BHR). OBJECTIVE: We determined whether these were related to alteration of cytokine expression, particularly with regard to the profile of Th1- versus Th2-derived cytokines. METHODS: Brown-Norway rats sensitized with ovalbumin were administered cyclosporine or dexamethasone before ovalbumin aerosol challenge. Bronchial responsiveness was measured 18 to 24 hours after aerosol exposure. Airway cellular influx was determined by bronchoalveolar lavage and tissue immunohistochemistry. The expression of Th1 and Th2 cytokine messenger RNA (mRNA) was analyzed by reverse transcriptase-PCR. RESULTS: Ovalbumin exposure induced significant BHR, with increases in eosinophils, lymphocytes, and neutrophils in bronchoalveolar lavage fluid and an increase in eosinophils, CD2(+) and CD8(+), but not CD4(+) T cells, in the airway submucosa. IL-2, IFN-gamma, IL-4, and IL-5 mRNA expression in the lungs of sensitized ovalbumin-exposed rats was increased (P <.05) compared with controls. Cyclosporin A had no significant effect on BHR and neutrophil accumulation but reduced the number of bronchoalveolar lavage eosinophils (P <.002), airway submucosal eosinophils, and CD4(+) and CD8(+) T cells (P <.02). It also suppressed the induced mRNA expression of IL-2, IL-4, IL-5, and IFN-gamma. By contrast, the inflammatory cell influx and mRNA expression for IL-2, IL-4, and IL-5, as well as BHR, were suppressed by dexamethasone. However, an increase in IL-10 and IFN-gamma mRNA expression was found. CONCLUSION: The differential activities of cyclosporin A and dexamethasone on inflammatory cell influx, particularly neutrophils, or cytokine expression such as IL-10 and IFN-gamma may underlie their contrasting effects on BHR.

Allergens↗

Involvement of cysteinyl leukotrienes in airway smooth muscle cell DNA synthesis after repeated allergen exposure in sensitized Brown Norway rats.

Airway smooth muscle thickening is a characteristic feature of airway wall remodelling in chronic asthma. We have investigated the role of the leukotrienes in airway smooth muscle (ASM) and epithelial cell DNA synthesis and ASM thickening following repeated allergen exposure in Brown Norway rats sensitized to ovalbumin. There was a 3 fold increase in ASM cell DNA synthesis, as measured by percentage bromodeoxyuridine (BrdU) incorporation, in repeatedly ovalbumin-exposed (4.1%, 3.6-4.6; mean, 95% c.i.) compared to chronically saline-exposed rats (1.3%, 0.6-2.1; P<0.001). Treatment with a 5-lipoxygenase enzyme inhibitor (SB 210661, 10 mg kg(-1), p.o.) and a specific cysteinyl leukotriene (CysLT1) receptor antagonist, pranlukast (SB 205312, 30 mg kg(-1), p.o.), both attenuated ASM cell DNA synthesis. Treatment with a specific leukotriene B4 (BLT) receptor antagonist (SB 201146, 15 mg kg(-1), p.o.) had no effect. There was also a significant, 2 fold increase in the number of epithelial cells incorporating BrdU per unit length of basement membrane after repeated allergen exposure. This response was not inhibited by treatment with SB 210661, pranlukast or SB 201146. A significant increase in ASM thickness was identified following repeated allergen exposure and this response was attenuated significantly by SB 210661, pranlukast and SB 201146. Rats exposed to chronic allergen exhibited bronchial hyperresponsiveness to acetylcholine and had significant eosinophil recruitment into the lungs. Treatment with SB 210661, pranlukast or SB 201146 significantly attenuated eosinophil recruitment into the lungs, whilst having no significant effect on airway hyperresponsiveness. These data indicate that the cysteinyl leukotrienes are important mediators in allergen-induced ASM cell DNA synthesis in rats, while both LTB4 and cysteinyl leukotrienes contribute to ASM thickening and eosinophil recruitment following repeated allergen exposure.

Acetylcholine↗

Effect of CD8+ T-cell depletion on bronchial hyper-responsiveness and inflammation in sensitized and allergen-exposed Brown-Norway rats.

We examined the role of CD8+ T cells in a Brown-Norway rat model of asthma, using a monoclonal antibody to deplete CD8+ T cells. Ovalbumin (OA)-sensitized animals were given anti-CD8 antibody (0.5 mg/rat) intravenously 1 week prior to exposure to 1% OA aerosol and were studied 18-24 hr after aerosol exposure. Following administration of anti-CD8 antibody, CD8+ cells were reduced to <1% of total lymphocytes in whole blood and in spleen. In sensitized animals, OA exposure induced bronchial hyper-responsiveness (BHR), accumulation of eosinophils, lymphocytes and neutrophils in bronchoalveolar lavage (BAL) fluid, and also an increase in tissue eosinophils and CD2+, CD4+ and CD8+ T cells in airways. Anti-CD8 antibody caused a further increase in allergen-induced BHR (P<0.03, compared with sham-treated animals), together with a significant increase in eosinophil number in BAL fluid (P<0.05). While CD2+ and CD4+ T cells in airways were not affected by anti-CD8 treatment, the level of CD8+ T cells was significantly reduced in sensitized, saline-exposed animals (P<0.04, compared with sham-treated rats), and sensitized and OA-challenged rats (P<0.002, compared with sham-treated rats). Using reverse transcription-polymerase chain reaction, an increase of T helper (Th)2 cytokine [interleukin (IL)-4 and IL-5], and also of Th1 cytokine [interferon-gamma (IFN-gamma) and IL-2], mRNA in the lung of sensitized and OA-exposed animals was found; after CD8+ T-cell depletion, Th1 cytokine expression was significantly reduced (P<0.02), while Th2 cytokine expression was unchanged. CD8+ T cells have a protective role in allergen-induced BHR and eosinophilic inflammation, probably through activation of the Th1 cytokine response.

Acetylcholine↗

Inhibitory effects of endogenous and exogenous interferon-gamma on bronchial hyperresponsiveness, allergic inflammation and T-helper 2 cytokines in Brown-Norway rats.

Interferon-gamma (IFN-gamma) is an important cytokine involved in the regulation of allergen-induced immune responses. We examined the role of IFN-gamma in a Brown-Norway rat model of bronchial hyperresponsiveness (BHR) and airway eosinophilia, and its effects on the mRNA expression of T helper type 1 (Th1)/Th2 cytokine. Ovalbumin (OA)-sensitized animals were given either exogenous IFN-gamma (105 U/rat over 3 days, intraperitoneally) or anti-IFN-gamma blocking antibody (DB-1 0.3 mg/rat, intravenously) prior to exposure to OA aerosol and were studied 18-24 hr later. In sensitized animals, OA induced significant BHR, accumulation of eosinophils, T lymphocytes and neutrophils in bronchoalveolar lavage (BAL) fluid, and also increased eosinophils and CD8+ T cells in the airways. Exogenous IFN-gamma attenuated allergen-induced BHR (P<0.02, compared with sham-treated animals) together with a significant reduction in eosinophil and neutrophil numbers in BAL fluid (P<0. 005), and eosinophils and CD8+ T cells in airways (P<0.05). By contrast, anti-IFN-gamma antibody increased airway CD4+ T cells and BHR. Using reverse transcriptase-polymerase chain reaction, significant increases in Th2 [interleukin-4 (IL-4), IL-5 and IL-10], and IFN-gamma cytokine mRNA were found in the lungs of sensitized and OA-exposed animals, while exogenous IFN-gamma significantly suppressed IL-4, IL-5 and IL-10 mRNA expression, and anti-IFN-gamma antibody increased IL-4 and IL-5 mRNA expression. These results indicate that Th1 effects, such as those mediated by IFN-gamma, play a down-regulatory role to suppress the Th2 responses associated with allergen-induced BHR and eosinophilic inflammation.

Analysis of Variance↗

Contribution of bradykinin B(1) and B(2) receptors in allergen-induced bronchial hyperresponsiveness.

Bradykinin (BK) is a peptide mediator generated at sites of inflammation and its effects are mediated through constitutively expressed B(2) receptor or through induction of B(1) receptors. We examined the role of these receptors in bronchial hyperresponsiveness (BHR). Brown-Norway rats sensitized with ovalbumin (OA) and Al(OH)(3) intraperitoneally, were exposed 3 wk later to either saline or OA aerosol. B(1) receptor antagonist desArg(10)[Hoe140] (200 nmol/kg or 1 micromol/kg, intraperitoneally) or B(2) receptor antagonist Hoe140 (200 nmol/kg, intraperitoneally) was administered 30 min before allergen exposure. Hoe140 had no effect on OA-induced BHR to acetylcholine (ACh) and bronchoalveolar lavage fluid (BALF) cellular profiles, but inhibited bronchoconstriction to BK (p < 0.04). At both doses, desArg(10)[Hoe140] dose-dependently inhibited allergen-induced BHR to ACh (p < 0.01), but had no effect on bronchoconstriction to BK or baseline ACh responsiveness. The inflammatory cells in BALF were not affected apart from reduced lymphocyte numbers at the highest dose. B(1) receptor mRNA expression measured by Northern analysis was increased after allergen exposure in sensitized lungs, with a peak at 2 to 6 h after exposure, whereas B(2) receptor mRNA expression remained unchanged. Newly induced BK B(1) receptors may be involved in allergen-induced BHR to ACh, whereas constitutive B(2) receptors mediate BK-induced bronchoconstriction.

Acetylcholine↗

alpha4 integrin-dependent eotaxin induction of bronchial hyperresponsiveness and eosinophil migration in interleukin-5 transgenic mice.

We investigated the roles of eosinophil infiltration and activation induced by the eosinophil-selective chemokine eotaxin, and of the expression of eosinophil alpha4 and beta2 integrins in causing bronchial hyperresponsiveness (BHR) in interleukin (IL)-5 CBA/Ca transgenic mice. These mice did not show BHR, despite the presence of some eosinophils in the lungs. Intratracheal mouse recombinant eotaxin (3 micrograms) did not induce BHR in wild-type mice. In IL-5 transgenic mice, eotaxin (3 and 5 micrograms) increased responsiveness at 24 h and increased eosinophils in bronchoalveolar lavage (BAL) fluid by 9.4- and 14-fold by 24 h, respectively, together with augmentation of eosinophil peroxidase activity and eosinophil infiltration in the airway submucosa. Using flow cytometry, the expression of alpha4, CD11b, and CD18 was upregulated in BAL, but not in blood, eosinophils. A rat anti-alpha4 antibody inhibited eotaxin-induced BHR and eosinophil migration and activation, but an anti-CD11b antibody had no significant effects on BHR. A combination of both antibodies was more effective. IL-5 and eotaxin synergize in the induction of BHR and airway eosinophilia, effects that are dependent on the induction of eosinophil alpha4 integrin. Expression of BHR depends on the recruitment and activation of eosinophils.

Animals↗

Secure placement of continuous ambulatory peritoneal dialysis catheters under laparoscopic assistance.

Laparoscopic surgical procedures were performed in 18 patients with end-stage renal disease for the placement of a Tenckhoff peritoneal dialysis catheter. Among them, 6 patients had received previous lower abdominal surgical treatment and 3 patients underwent laparoscopic rescue of dysfunctional Tenckhoff catheters. The operating time was between 40 and 80 minutes (median, 50 minutes). After a median follow-up period of 11 months, the short-term results revealed that no significant morbidity was associated with this procedure, and all catheters except two functioned well postoperatively. One of the catheters was not functional because of the patient's death, and the other one was removed because of persistent peritonitis. Laparoscopic secure placement of continuous ambulatory peritoneal dialysis catheters appears to be a simple, safe, and viable procedure, even in patients with previous lower-abdominal operations. The same technique can be used to rescue dysfunctional catheters that are displaced or obstructed by adhesion and omental wrapping, thus increasing catheter longevity.

Adult↗

The oxidoreductase, biliverdin reductase, is induced in human renal carcinoma--pH and cofactor-specific increase in activity.

PURPOSE: Biliverdin reductase is an oxidoreductase unique among all enzymes characterized to date in having dual pH/dual cofactor requirement - NADH and NADPH at 6.7 and 8.7, respectively. The protein shows extensive microheterogeneity that is caused by post-translational modification. The reductase converts the heme degradation product, biliverdin, to bilirubin. Bilirubin has been shown to inhibit responses of human lymphocytes, including phytohemagglutinin-induced proliferation, interleukin-2 production, and antibody dependent and independent cell mediated cytotoxicity. In addition to acting as an antioxidant, it inhibits protein phosphorylation and activity of enzymes such as protein kinase C and NADPH oxidase. This research was to evaluate whether renal cell carcinoma differs from normal tissue in regard to the expression and activity of the reductase. MATERIALS AND METHODS: Kidney tissue with or without visible renal carcinoma and normal kidney tissue from a brain dead patient were frozen at -80C shortly after removal. Ten microm. tissue sections were used for immunostaining of biliverdin reductase, pooled isolated tumors and surrounding tissue that did not contain visible tumor were used for Northern blot analysis of mRNA and Western blot analysis of protein. Enzyme activity was also measured in these preparations at pH 6.7 with NADH, and at pH 8.7 with NADPH. Ten additional formalin fixed specimens of renal cell carcinoma were also used for immunostaining. RESULTS: There was a striking increase in the reductase protein levels, as visualized by immunostaining in tumor tissue cells. The increase was also evident by Western blotting, and involved in increased transcription of biliverdin reductase as suggested by Northern blot analysis. The protein would also be detected in the infiltrating monocytes, macrophages, T cells and neutrophils as well as in circulating lymphocytes. The enzyme activity was nearly doubled in the tumor tissue, but selectively with NADH as the cofactor. CONCLUSION: Increases in biliverdin reductase expression and activity only with NADH is found in renal cell carcinoma. The net effects of this change are uncertain at present but several pathways, which could be affected by the reductase, may alter local physiology. Biliverdin reductase as a zinc metalloprotein may directly interact with other regulatory proteins, generation of increased bilirubin may alter immune function and increased enzyme activity may deplete NADH with contrasting consequence of blocking free radical formation and depleting cellular ATP. To the benefit of the host, the latter could culminate in tumor cell death.

Carcinoma, Renal Cell↗

Biochemical markers for assessment of bone metastases in patients with breast cancer.

Breast cancer commonly metastasizes to bones, producing both osteolytic and osteoblastic deposits. Different markers for quantitative determination of bone turnover have been developed to evaluate bone metastases of breast cancer. The urinary deoxypyridinoline (Dpd), a crosslink product of collagen molecules found in bone and excreted in urine during bone degradation, and bone specific alkaline phosphatase (B-ALP), an isoenzyme localized in the membrane of osteoblasts and released in circulation during bone formation, were recently described as a group of markers of bone turnover in metastatic cancer. The urinary Dpd/creatinine (Cre) ratios and the serum B-ALP activity were determined in the samples from 148 patients who suffered from breast cancer (BC patients) with or without bone metastases, and 42 healthy women. For comparison, other biochemical markers, e.g. carcinoembryonic antigen (CEA), CA15-3, tissue polypeptide antigen (TPA), tissue polypeptide specific antigen (TPSA), and total alkaline phosphatase (T-ALP) in these samples were also evaluated. The results showed that there was a significant difference in urinary Dpd/Cre ratio between the control group and the patients with breast cancer (BC group) (mean +/- S.D., 5.69 +/- 1.26 vs. 8.19 +/- 3.95 nM/mM, P < 0.05). However, there was no significant difference between their B-ALP activities in the two groups. In addition, the BC patients with bone metastases showed elevated urinary Dpd/Cre ratios and B-ALP activities and ratios of (Dpd/Cre)/B-ALP in compare with BC patients without bone metastases (P < 0.05). Meanwhile, the urinary Dpd/Cre ratios (10.50 +/- 5.04 nmol/mmol) in the advanced stage of BC patients were higher than those in an early stage (7.45 +/- 3.23 nmol/mmol) (P < 0.05), but their serum B-ALP activities increased only in stage IV (P < 0.05). The urinary Dpd/Cre ratios also increased progressively according to the degree of bone metastases (P < 0.05), but their serum B-ALP activities only increased in severe bone metastases (P < 0.05). The results showed that the increase of a bone osteolytic activity took place earlier than that of a bone osteoblastic activity in the metastatic BC patients. In compare with other conventional markers, the best diagnostic efficiency of biochemical markers, analyzed by step wise discriminate analysis, was provided by CEA followed by Dpd/Cre ratio, CA15-3, TPA, TPSA, B-ALP and T-ALP. We conclude that showed the urinary Dpd/Cre ratio was a useful tumor marker to evaluate breast cancer with bone metastases.

Adult↗