Biomedical subjects

A Chen

Publications and source records attributed to A Chen.

At least 217 records · Page 12Linked to original sources

PubMed1998

Fas-mediated apoptosis and activation-induced T-cell proliferation are defective in mice lacking FADD/Mort1.

Programmed cell death, or apoptosis, is important in homeostasis of the immune system: for example, non-functional or autoreactive lymphocytes are eliminated through apoptosis. One member of the tumour necrosis factor receptor (TNFR) family, Fas (also known as CD95 or Apo-1), can trigger cell death and is essential for lymphocyte homeostasis. FADD/Mort1 is a Fas-associated protein that is thought to mediate apoptosis by recruiting the protease caspase-8. A dominant-negative mutant of FADD inhibits apoptosis initiated by Fas and other TNFR family members. Other proteins, notably Daxx, also bind Fas and presumably mediate a FADD-independent apoptotic pathway. Here we investigate the role of FADD in vivo by generating FADD-deficient mice. As homozygous mice die in utero, we generated FADD-/- embryonic stem cells and FADD-/- chimaeras in a background devoid of the recombination activating gene RAG-1, which activates rearrangement of the immunoglobulin and T-cell receptor genes. We found that thymocyte subpopulations were apparently normal in newborn chimaeras. Fas-induced apoptosis was completely blocked, indicating that there are no redundant Fas apoptotic pathways. As these mice age, their thymocytes decrease to an undetectable level, although peripheral T cells are present in all older FADD-/- chimaeras. Unexpectedly, activation-induced proliferation is impaired in these FADD-/- T cells, despite production of the cytokine interleukin (IL)-2. These results and the similarities between FADD-/- mice and mice lacking the beta-subunit of the IL-2 receptor suggest that there is an unexpected connection between cell proliferation and apoptosis.

Adaptor Proteins, Signal Transducing↗

PubMed1998

In vivo investigation of blood compatibility of titanium oxide films.

Titanium oxide films were synthesized by ionbeam-enhanced deposition. The films were prepared by depositing titanium atoms and simultaneously bombarding them with Xe+ ions at an energy of 40 keV in an O2 environment. An in vivo investigation, which entailed implanting low-temperature isotropic pyrolytic carbon (LTI carbon) cylinders, widely used to fabricate artificial heart valves, and titanium-oxide-coated LTI carbon cylinders with diameters of 5 mm and thicknesses of 0.5 mm into the ventral aorta of dogs for 14 days, showed that the amount of thrombus on the titanium-oxide-coated LTI carbon was much less than that formed on the surface of LTI carbon alone. Scanning electron microscopy (SEM) was used to observe the morphology of thrombus. On the titanium oxide films no platelet aggregation was found, almost no red blood cells were damaged, and almost no fibrin was found on the surface. However, all three characteristics were found on the surface of LTI carbon alone, proving that the blood compatibility of titanium oxide films is better than that of LTI carbon and titanium-oxide-coated LTI carbon.

Animals↗

PubMed1998

A cell-based potency assay for insulin-like growth factor-I.

The authors developed a cell-based bioassay for determining the potency of recombinant human insulin-like growth factor I (IGF-I) using HU-3 human megakaryoblastic cell line. Cell proliferation was measured using the alamarBlue fluorescence method. The addition of IGF-I resulted in a dose-dependent growth response after 48 hours under serum-free conditions. The effective range was 0.1-25 ng/ml with half-maximal response at approximately 2 ng/ml IGF-I. The assay is simple, requiring just three steps, performed in 96-well microtitre plates and is able to detect changes in activity of truncated analogues of IGF-I (such as des-Gly-IGF-I, des-Gly-Pro-IGF-I and des-Gly-Pro-Glu-IGF-I) as well as IGF-I samples that had been subjected to proteolytic or disulfide reduction treatments. This assay is precise, with interassay variability of less than 10% and accurate, with percentage recoveries of nearly 100%. The relative efficacies of other insulin-related peptides in stimulating cell growth of the cell line were examined. IGF-II was 5-fold less potent than IGF-I and insulin had little or no proliferative activity. In addition, the growth-promoting activity correlated well with IGF-I stimulation of glucose consumption in this system. In conclusion, the HU-3 human megakaryoblastic cell line constitutes a simple system for measuring the biological activity of recombinant IGF-I in quality control set-up. The safety, convenience and precision of the assay make it an attractive alternative to radioactive and other colorimetric methods.

Biological Assay↗

PubMed1998

Clinical evaluation of atypical glandular cells of undetermined significance on cervical cytology.

OBJECTIVE: To determine the incidence of and identify risk factors for clinically significant diagnoses associated with the diagnosis on Papanicolaou test of atypical glandular cells of undetermined significance. METHODS: A computer search was initiated of diagnoses of atypical glandular cells of undetermined significance at the Massachusetts General Hospital from January 1993 through December 1996. Seventy-three patients with 81 smears were identified that were seen in the Colposcopy Clinic. All cytology was reviewed. A clinically significant lesion was defined as high-grade squamous intraepithelial lesion (SIL) or worse, endocervical glandular atypia or worse, or carcinoma. RESULTS: The rate of diagnoses of atypical glandular cells of undetermined significance was 0.167%. All patients underwent colposcopy, and 88% underwent endocervical curettage. A clinically significant diagnosis was made in 34.2% of patients, including cancer in 8.2%. A concurrent squamous diagnosis carried a risk of clinically significant lesion of 50%, compared with a risk of 25.5% for atypical glandular cells of undetermined significance alone (P = .043). Premenopausal and postmenopausal patients were both at risk for clinically important lesions, but premenopausal patients were more likely to have a high-grade SIL (30.4% versus 7.4%, P = .04). The subtype "suggestive of reactive" was a significant negative predictor of significant lesion (odds ratio = 0.09, 95% confidence interval 0.018, 0.482) in a logistic regression model controlling for age, menopausal status, and concurrent squamous diagnosis. CONCLUSION: Atypical glandular cells of undetermined significance is an important Papanicolaou test diagnosis that needs appropriate and careful evaluation. Further studies are required to clarify areas of risk and to make triage algorithms.

Adult↗

PubMed1998

Different modes of sialyl-Tn expression during malignant transformation of human colonic mucosa.

Monoclonal antibodies TKH2 and B72.3, which react with the mucin-associated sialyl-Tn(STn) antigen, preferentially bind to cancerous but not normal colonic tissues. If O-acetyl groups are removed by saponification of tissues, MAb TKH2 will react with normal colonocytes, whereas MAb B72.3 remains non-reactive. To explain this difference in binding specificity, we tested both MAbs against synthetic constructs of single (monomeric) or clustered (trimeric) STn epitopes by enzyme immunoassay. Both MAb TKH2 and MAb B72.3 reacted with trimeric STn, but MAb TKH2 demonstrated greater binding than MAb B72.3 to monomeric STn. This suggests that normal colonic mucosa expresses monomeric STn epitopes, but that with transformation to malignancy, clustered STn epitopes appear. The appearance of clustered STn epitopes during colonic carcinogenesis represents a novel pattern of carbohydrate antigen expression and implicates alterations at the level of apomucins and/or glycosyltransferases responsible for cluster epitope formation.

Antibodies, Monoclonal↗

PubMed1998

Graded reduction of Pafah1b1 (Lis1) activity results in neuronal migration defects and early embryonic lethality.

Heterozygous mutation or deletion of the beta subunit of platelet-activating factor acetylhydrolase (PAFAH1B1, also known as LIS1) in humans is associated with type I lissencephaly, a severe developmental brain disorder thought to result from abnormal neuronal migration. To further understand the function of PAFAH1B1, we produced three different mutant alleles in mouse Pafah1b1. Homozygous null mice die early in embryogenesis soon after implantation. Mice with one inactive allele display cortical, hippocampal and olfactory bulb disorganization resulting from delayed neuronal migration by a cell-autonomous neuronal pathway. Mice with further reduction of Pafah1b1 activity display more severe brain disorganization as well as cerebellar defects. Our results demonstrate an essential, dosage-sensitive neuronal-specific role for Pafah1b1 in neuronal migration throughout the brain, and an essential role in early embryonic development. The phenotypes observed are distinct from those of other mouse mutants with neuronal migration defects, suggesting that Pafah1b1 participates in a novel pathway for neuronal migration.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

PubMed1998

Mutations in the human alpha-tectorin gene cause autosomal dominant non-syndromic hearing impairment.

The tectorial membrane is an extracellular matrix of the inner ear that contacts the stereocilia bundles of specialized sensory hair cells. Sound induces movement of these hair cells relative to the tectorial membrane, deflects the stereocilia, and leads to fluctuations in hair-cell membrane potential, transducing sound into electrical signals. Alpha-tectorin is one of the major non-collagenous components of the tectorial membrane. Recently, the gene encoding mouse alpha-tectorin (Tecta) was mapped to a region of mouse chromosome 9, which shows evolutionary conservation with human chromosome 11q (ref. 3), where linkage was found in two families, one Belgian (DFNA12; ref. 4) and the other, Austrian (DFNA8; unpublished data), with autosomal dominant non-syndromic hearing impairment. We determined the complete sequence and the intron-exon structure of the human TECTA gene. In both families, mutation analysis revealed missense mutations which replace conserved amino-acid residues within the zona pellucida domain of TECTA. These findings indicate that mutations in TECTA are responsible for hearing impairment in these families, and implicate a new type of protein in the pathogenesis of hearing impairment.

Alternative Splicing↗

PubMed1998

Administration of dexamethasone induces proteinuria of glomerular origin in mice.

The administration of glucocorticoids has been reported to exacerbate proteinuria in a few patients with glomerulonephritis. This effect has not been well recognized, and the pathogenetic mechanism responsible for this phenomenon remains to be clarified. In this study, we observed that a high daily oral dose (0.5 mg/kg body weight) of dexamethasone was capable of inducing overt proteinuria in mice, beginning on day 5 and persisting for a 19-day duration. One fourth of mice also intermittently presented with slight hematuria beginning on day 12. Renal lesions in the dexamethasone-treated mice, which were killed on day 23, were characterized by mild mesangial expansion, segmental or global hyalinosis/sclerosis in deep cortical glomeruli, and focal tubular changes. No glomerular inflammatory cell infiltration or proliferative lesion was noted in any of the mice. Ultrastructural features of glomeruli included mesangial widening characterized by either an increase of mesangial matrix, dilated mesangial channels filled with slightly electron-dense material or mesangial lysis-like appearance showing intracytoplasmic microcysts filled with electron-lucent material, and evidence to support injury of endothelial cells, erythrocytes, and podocytes. An immunofluorescence study revealed enhanced glomerular deposition of IgG, IgA, IgM, and fibrinogen (P < 0.001, compared with normal control mice), but no glomerular C3 deposition was identified in any of the dexamethasone-treated mice. Charge analysis showed no impairment in anionic property of glomerular tufts in the dexamethasone-treated mice. In addition, the dexamethasone-induced proteinuria was greatly attenuated by treatment with a low molecular weight heparin, although it was not reduced by an angiotensin-converting enzyme inhibitor. Data from these experiments suggest that a large dose of glucocorticoids is potentially nephrotoxic. Alteration of a size-dependent permeability may predominantly contribute to the dexamethasone-induced proteinuria. However, the effect of glomerular hyperfiltration may be only partially involved in the pathogenesis of this dexamethasone-induced glomerulopathy in mice.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1998

Characterization of mouse ubiquitin-like SMT3A and SMT3B cDNAs and gene/pseudogenes.

Mouse SMT3A and SMT3B cDNAs encoding ubiquitin-like proteins of 110 and 95 amino acids, respectively, were isolated and sequenced. The sequence of the first 92 amino acids (ending with the conserved Gly-Gly) of mouse SMT3A exhibited two differences at amino acid no. 38 and 76 in comparison with that of human SMT3A. The C-terminal 18 amino acid sequence of mouse SMT3A was completely different from the C-terminal 11 amino acid sequence of human SMT3A. Mouse and human SMT3B were identical for a sequence of 95 amino acids. Mouse SMT3A genomic DNAs were amplified by polymerase-chain-reaction and sequenced. The nucleotide sequence of a PCR-amplified SMT3A genomic DNA fragment was found to be identical to that of SMT3A cDNA, indicating the absence of intron(s) in its protein coding region. Another genomic DNA fragment of 1,531 nucleotides, containing 7% differences from that of cDNA, is unable to encode a functional protein, and thus, it is a SMT3A processed pseudogene. Three mouse SMT3B processed pseudogenes were cloned and sequenced. The genuine mouse SMT3B gene has not yet been isolated. Mouse SMT3A transcript of 1.8 kb was predominantly expressed in most tissues, while SMT3B transcript of 1.0 kb was abundantly present in all tissues analyzed. A family of ubiquitin-like proteins was recently discovered. One distinguishing feature of ubiquitin and ubiquitin-like proteins is the capacity to conjugate with other proteins post-translationally. The ubiquitin-like proteins are cleaved endoproteolytically after a diglycine sequence, corresponding to the C-terminal Gly75-Gly76 of ubiquitin. The cleavage activates the molecule for conjugation. The yeast SMT3 gene was originally identified as a suppressor of mutations in MIF2 gene, which encodes an essential protein binding to the A+T-rich CDEII region of centromere DNA (1). Studies using temperature-sensitive mutants showed that the loss of yeast Mif2 protein function results in chromosome missegregation, mitotic delay, and aberrant microtubule morphologies (2). The yeast Mif2 protein shares at least two regions of similarity with mammalian centromere protein CENP-C, an integral component of active kinetochores (3, 4). Human SMT3A cDNA was identified from the genome sequencing project of chromosome 21 (5). We have cloned human SMT3B (formerly designated as HSMT3) cDNA (6). Human SMT3C protein was independently isolated by several groups and denoted as SUMO-1 (7), GMP1 (8), PICI (9), UBL1 (10), sentrin (11). SUMO-1/GMP1 was found to be covalently linked to the Ran GTPase-activating protein RanGAP1, and attachment of SUMO-1 targets the otherwise cytosolic RanGAP1 to the nuclear pore complex. The modified form of RanGAP1 also appeared to associate with the mitotic spindle apparatus during mitosis (7, 8). PIC1 was shown to interact with the PML component of nuclear multiprotein complex that is disrupted in acute promyelocytic leukemia (9). UBL1 was found to associate with human RAD51/RAD52 proteins involved in DNA recombination and DNA double-strand break repair (10). Sentrin was shown to interact with Fas/APO-1 or the TNF receptor 1 death domain, and the overexpression of sentrin provided protection against both anti-Fas/APO-1 and TNF-induced cell death (11). Here we report the characterization of mouse SMT3A and SMT3B cDNAs, gene/pseudogenes, and mRNA expression.

Amino Acid Sequence↗

PubMed1998

Premorbid prevalence of ADHD and development of secondary ADHD after closed head injury.

OBJECTIVE: To determine premorbid prevalence of attention-deficit hyperactivity disorder (ADHD) in children with moderate and severe closed head injury (CHI), to determine incidence of ADHD 1 year after injury, and to characterize children who develop ADHD by demographic, neuropsychiatric, and outcome variables. METHOD: Ninety-nine children who had severe and moderate CHI were followed up for 1 year. Premorbid and 1-year postinjury psychiatric status were ascertained by parent and child structured interviews and questionnaires measuring affective lability, aggression, apathy, and social judgment. RESULTS: Premorbid prevalence of ADHD was 0.20, significantly higher than in a reference population (0.045). Fifteen of the remaining 80 children (0.19) developed full ADHD criteria (except for age of onset) by the end of the first year. Children who developed secondary ADHD (S-ADHD) had significantly greater premorbid psychosocial adversity, posttraumatic affective lability and aggression, posttraumatic psychiatric comorbidity, and overall disability than children who did not develop S-ADHD. CONCLUSIONS: There is an excess prevalence of premorbid ADHD among children who present with moderate and severe CHI. Children with high psychosocial adversity are more likely to develop S-ADHD after CHI. S-ADHD has criteria in common with personality change due to CHI, a deficit in behavioral inhibition being the major overlapping feature.

Adolescent↗

PubMed1998

Persistent transforming growth factor-beta 1 expression may predict peritoneal fibrosis in CAPD patients with frequent peritonitis occurrence.

The efficiency of continuous ambulatory peritoneal dialysis depends on the permeability of the peritoneal membrane. Peritoneal fibrosis (PF) causes loss of the dialytic function. Several studies have indicated that PF is closely related to the proliferation of peritoneal fibroblasts and the deposition of extracellular matrix. Transforming growth factor-beta 1 (TGF-beta1) plays a major role in stimulating extracellular matrix deposition. Frequent peritonitis occurrence may cause persistent TGF-beta1 mRNA expression. In an attempt to search for a factor related to PF, we designed a longitudinal study to measure TGF-beta1 levels in dialysate and TGF-beta1 mRNA expression in peritoneal mononuclear cells from peritoneal dialysate before onset, once a week during peritonitis, and after peritonitis in high and low peritonitis occurrence (HPO and LPO) patients. Fifteen patients with a LPO rate and 5 patients with a HPO rate were followed up longitudinally. Meanwhile, TGF-beta1 levels and TGF-beta1 mRNA expression were augmented in peritoneal dialysate effluents before, during, and after the episodes of peritonitis. The peritoneal permeability was evaluated by the peritoneal equilibration test. The results revealed that in the LPO group, TGF-beta1 and TGF-beta1 mRNA were detectable at early stages of peritonitis, but the levels decreased rapidly and were undetectable 2 weeks after peritonitis. On the other hand, in the HPO group, TGF-beta1 and TGF-beta1 mRNA persisted for a long time. We could detect TGF-beta1 and TGF-beta1 mRNA in dialysate effluents and peritoneal mononuclear cells even 2, 3, and 4 weeks after episodes of peritonitis. When compared with that of first or second episode of peritonitis, the peritoneal function evaluated with the peritoneal equilibration test was found to obviously deteriorate during the third episode of peritonitis. These findings were confirmed by an in situ hybridization technique to evaluate the relationship between TGF-beta1 mRNA expression and PF from biopsied peritoneal specimens. These findings suggest that the high TGF-beta1 levels in the dialysate are related to an increased expression of TGF-beta1 in the peritoneum. Thus, the persistent TGF-beta1 expression in the peritoneum may serve as a useful parameter in predicting PF in continuous ambulatory peritoneal dialysis patients with frequent peritonitis occurrence.

Adolescent↗

PubMed1998

Involvement of immunopathogenic mechanisms in a spontaneously occurring glomerulopathy in mice.

Mice have been found to be susceptible to spontaneous renal localization of immune deposits. However, the significance of these immune deposits is still debated. We investigated the immunopathogenesis of a naturally occurring glomerulopathy associated with progressive proteinuria and glomerulosclerosis in 75 BALB/c mice. The mice were divided into five groups of 15 and killed at the age of 1, 3, 6, 12, or 18 months for laboratory and renal pathologic studies. These mice showed persistently increasing serum levels of immune complexes, a marked increase of glomerular immune deposits which were capable of fixing C3, and interstitial infiltration of lymphocytes and plasma cells, followed by the occurrence of proteinuria, mesangiopathy, and glomerulosclerosis. Our findings suggest that an immune system mediated process occurred in the kidneys of the mice tested.

Animals↗

PubMed1998

Experimental focal segmental glomerulosclerosis in mice.

Although a lot of animal models of proteinuria have been established, proposals for the mechanisms of proteinuria are still controversial. In this work, during an 18-day trial, mice injected with a single dose of adriamycin (AD) rapidly showed combined glomerular albuminuria and immunoglobulinuria, progressively elevated levels of nitrite/nitrate in urine, hypercholesterolemia, abnormal renal function, segmentally or globally glomerular hyalinosis/sclerosis associated with tubular atrophy, enhanced glomerular deposition of immunoglobulins and fibrinogen, augmented expression of matrix components in the whole glomerular tuft, and loss of glomerular negative charge property. These laboratory and pathological features are comparatively similar to those of human focal segmental glomerulosclerosis in the advanced state. Juxtamedullary glomeruli appear to be more susceptible to the AD-related nephrotoxicity than those in the superficial renal cortex. A change in size-dependent glomerular permselectivity may precede a charge-dependent defect in glomeruli in this mouse model of proteinuria. Data in this study confirm the hypothesis of glomerular hyperfiltration involved in the pathogenesis of this chronic glomerulopathy associated with proteinuria in mice. In addition, nitric oxide may play a crucial role in the progression of the chronic glomerulopathy model.

Animals↗

PubMed1998

Anti-idiotype antibody directly interferes with glomerular IgA immune complex deposition.

Data from both animal and clinical studies suggest that anti-idiotype antibodies deposited in glomeruli may be involved in the pathogenesis of glomerulonephritis. This study was conducted to examine the role of a hybridoma-AB1-2-derived IgG anti-T15 idiotype (IgG anti-T15) in the immunopathogenesis of a short-term experimental IgA nephropathy. BALB/c mice (12/group) were administered intravenously with: (1) an equal mass (1 mg) of T15-hybridoma-derived IgA antiphosphorylcholine (PC) and PC-conjugated bovine serum albumin (BSA-PC) antigen; (2) 1 mg of IgA anti-PC, 1 mg of BSA-PC antigen, and 3 mg of IgG anti-T15, or (3) 1 mg of BSA-PC antigen alone. The mice were sacrificed 6 h after the injection. A 6-hour clearance study was performed. The initial phase of elimination of BSA-PC antigen in mice receiving IgA anti-PC/BSA-PC/IgG anti-T15 or those receiving the antigen alone was significantly faster than that in those receiving IgA anti-PC/BSA-PC (p < 0.001). There was no significant difference in the elimination rate of BSA-PC antigen between mice receiving IgA anti-PC/BSA-PC/IgG anti-T15 and those receiving BSA-PC antigen alone. The late phases of elimination of the BSA-PC antigen in mice receiving IgA anti-PC/BSA-PC/IgG anti-T15 showed somewhat similar to those of BSA-PC antigen in mice receiving IgA anti-PC/BSA-PC. Moreover, mice injected with IgA anti-PC/BSA-PC/IgG anti-T15 showed a significantly less glomerular BSA-PC antigen deposition than those injected with IgA anti-PC/BSA-PC (positive control), as demonstrated by light microscopy, autoradiography, and immunohistochemistry (each p < 0.001). It is inferred that the injected IgG anti-T15 could react with the IgA anti-PC in vivo, directly interfering with immune complex formation by the IgA anti-PC and BSA-PC antigen, thereby resulting in diminished glomerular deposition of the BSA-PC antigen. These findings suggest that an anti-idiotype antibody may be protective in the immunopathogenesis of IgA nephropathy, because of its inhibitory effect on glomerular trapping of an antigen.

Animals↗

PubMed1998

Molecular identification and analysis of a novel human corticotropin-releasing factor (CRF) receptor: the CRF2gamma receptor.

We report the discovery of a new CRF2 receptor splice isoform found in human brain, which we have termed the CRF2gamma receptor. The CRF2gamma cDNA encodes for a 397-amino acid receptor that has an amino terminus with no significant homology to the already reported alpha- and beta-termini. When expressed in 293-EBNA (Epstein-Barr nuclear antigen) cells, the CRF2gamma receptor responds in a dose-dependent manner to CRF and related peptides with a rank order of potency of urocortin > or = sauvagine>urotensin>r/h CRF, with EC50 values more similar to CRF2alpha than CRF2beta. Equilibrium saturation isotherm analysis with radiolabeled sauvagine reveals a two site/state model for binding to CRF2gamma with a 60 pM Kd high-affinity site and a 5 nM Kd low-affinity site. Analysis of CRF2gamma RNA expression in human brain demonstrates expression in septum and hippocampus, with weaker but detectable expression in amygdala, nucleus accumbens, midbrain, and frontal cortex.

Amino Acid Sequence↗

PubMed1998

Intraoperative brachytherapy following thoracoscopic wedge resection of stage I lung cancer.

STUDY OBJECTIVES: Local recurrence is high when sublobar resection is chosen as primary management of stage I non-small cell lung carcinoma. Postoperative external-beam radiotherapy may reduce this local recurrence problem. A technique of intraoperative brachyradiotherapy following thoracoscopic wedge resection is described as an alternative to adjuvant external-beam radiotherapy for high-risk patients who are not candidates for pulmonary lobectomy. PATIENTS: Fourteen patients with significant impairment in cardiopulmonary function having small peripheral solitary pulmonary nodules underwent video-assisted thoracoscopic (VATS) wedge resection and were found to have non-small cell cancer. Surgical margins were pathologically clear and mediastinal nodes were benign-stage I (T1NO). INTERVENTIONS: A custom polyglyconate mesh (Vicryl) containing 125I seeds was applied to pulmonary resection margins following wedge resection of peripheral lung cancers. A total dose of 100 to 120 Gy at 1 cm was applied to the target area. RESULTS: All patients had histologically clear surgical margins. Postoperative dosimetry confirmed adequate resection margin coverage. There was neither operative mortality nor morbidity related to the VATS wedge resection or the brachytherapy implants. Implants did not migrate, and there were no cases of significant radiation pneumonitis or local recurrence at mean follow-up of 7 months (range, 2 to 12 months). CONCLUSIONS: Intraoperative brachytherapy appears to be a safe and efficient alternative to external-beam radiation therapy when adjuvant radiotherapy is considered following therapeutic wedge resection of stage I (T1NO) lung cancers. The impact on local recurrence, disease-free interval, and survival will require additional follow-up.

Brachytherapy↗

PubMed1998

Comparison of biodegradable and metallic tension-band fixation for patella fractures. 38 patients followed for 2 years.

We compared the outcome of patella fractures fixed by biodegradable tension-band (B) with self-reinforced polyglycolide or self-reinforced poly-L-lactide plugs and polyester ligaments or by metallic tension-band (M) with Kirschner wires and metallic cerclage wire in a randomized study. 38 fractures (18 with B and 20 with M) were treated. The follow-up time was 24 (14-32) months. The fractures healed in all patients after a medium of 8 weeks. In the B group, the clinical outcome was good in 13, fair in 4, and poor in 1 patient. In the M group, the corresponding figures were 15, 3 and 2. There were no clinical or radiographic differences between the two methods. Patella fractures can be treated, successfully using biodegradable tension-band fixation with no need for a second operation to remove the implants after bone union.

Absorption↗

PubMed1998

[Clinical study of gentamycin-loaded chitosan drug delivery system].

An clinical and pharmacokinetic study for a drug delivery system (DDS) of gentamycin-loaded chitosan bar were carried out with the purpose to evaluate its efficacy and giving further data for its clinical applications. Eighteen cases of chronic osteomyelitis were treated by surgical necrectomy with implantation of gentamycin-load chitosan bar in the prepared bone cavity. After operation, the concentration of gentamycin in serum and wound drainage fluid were examined at different times and blood urea nitrogen (BUN) and serum creatinine (Cr) as well. The clinical results were evaluated by the conditions of wound healing and clinical and roentgenographic manifestations. The results showed that the serum gentamycin concentration reached its peak level (0.86 microgram/ml) at 24 hours after operation and lasted for 4 days. No increase in the concentrations of BUN and Cr were observed after implantation. The gentamycin concentration in wound drainage fluid was several hundred times higher than the minimum inhibitory concentration (MIC) for staphylococcus aureus. All of the 18 cases were followed up for 24.8 months (in an range of 6-34 months) 16 patients received initial cure and without any recurrence. So, it could be concluded that the gentamycin-loaded chitosan DDS was a simple and effective method for the treatment of chronic osteomylitis without the necessity to carry out a second operation to remove the drug carrier, and it was sound to popularize its clinical application.

Administration, Topical↗