Cosmetic surgery and the internal morality of medicine.
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Biomedical subjects
Publications and source records attributed to K C Chung.
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We report here that immediate early gene pip92 is expressed during anisomycin-induced cell death in fibroblast NIH3T3 cells. To determine the mechanism by which this occurs and to identify downstream signaling pathways, we investigated the induction of the pip92 promoter. The activation of pip92 by anisomycin is mediated by the activation of MAP kinases, such as JNK and p38 kinase, but not ERK. Deletion analysis of the pip92 promoter indicated that pip92 activation occurs primarily within the region containing a serum response element (SRE). Further analysis of the SRE using a heterologous thymidine kinase promoter showed that both an Ets and CArG-like site are required for anisomycin-induced pip92 expression. Elk1, which binds to the Ets site, was phosphorylated by the JNK- and p38-dependent pathways and the phosphorylation of Elk1-GAL4 fusion proteins by these pathways was sufficient for the transactivation. Overall, this study suggested that different MAPK pathways are involved in the expression of immediate early gene pip92 by growth factors and environmental stresses.
In the mammalian CNS, aspartate and glutamate are major excitatory amino acids, and their receptors are believed to mediate a wide range of physiological and pathological processes, including neurotransmission, plasticity, excitotoxicity, and various forms of neurodegeneration. The immediate early gene pip92 has been identified in serum-stimulated BALB/c 3T3 fibroblasts, activated T lymphocytes treated with cycloheximide, and fibroblast growth factor-stimulated hippocampal cells during neuronal differentiation. In this study we have demonstrated that pip92 is expressed in the mouse brain after a single intraperitoneal injection of NMDA. The distribution of pip92 mRNA levels in the NMDA-treated mouse brain was investigated using in situ RT-PCR. The region-specific activation of pip92 in the CNS was observed 3 h after NMDA injection, and high levels of pip92 mRNA were detected in the hippocampal dentate gyrus and piriform cortex regions. In addition, the activation of pip92 by NMDA was mediated by activation of mitogen-activated protein kinases (MAPKs), such as c-Jun N-terminal kinase (JNK) and p38 kinase, but not extracellular signal-regulated kinase (ERK) in the mouse hippocampus and immortalized rat hippocampal progenitor cells. This study suggests that pip92 is likely to play an important role in neuronal cell death induced by excitotoxic NMDA injury in the CNS.
Although finger replantation has been performed by hand surgeons in the United States for over 30 years the epidemiology of this procedure has not been studied. We used a national sampling database from the Agency for Health Care Policy and Research to summarize descriptive statistics surrounding finger replantation in the United States. This sample contained 304 cases of finger replantation performed in 1996. Mean hospital length of stay was 5.5 days and mean total charges were $20,330. Of the 906 hospitals included in this database, only 136 performed finger replantation during 1996. Of those, 60% performed only one case and 2% performed 10 or more cases. This descriptive analysis provides an examination of the largest sample size to date of finger replantation in the United States. Epidemiologic studies using national databases can provide researchers and policy makers with the analyses needed to examine treatment options and appropriately allocate future health care resources.
Stewart-Treves syndrome (STS) is a rare but aggressive upper extremity lymphangiosarcoma in postmastectomy patients. Unfamiliarity with this disease and the innocuous appearance of the tumor often lead to delayed diagnosis. A comprehensive search of the databases at a single tertiary-care academic institution revealed only 3 cases of STS in the last 63 years. The latency time between breast cancer treatment and diagnosis of STS was 11 to 21 years. Survival after diagnosis of STS ranged from 8 to 15 months. One patient underwent radical surgery. The extensive lymphangiosarcoma in the other 2 patients precluded surgical resection and they underwent chemotherapy. All patients had adjuvant radiation therapy at the time of the original breast cancer resection. This report includes a discussion of the epidemiology, etiology, presentation, treatment, and prognosis of STS.
The purpose of this study was to evaluate outcomes following microvascular toe to thumb transfer in a cohort study using the Michigan Hand Outcomes Questionnaire, the 36-item Short-Form Health Survey, the Lower Limb Function Questionnaire, and standardized hand function tests. Twenty-one patients who had unilateral, isolated thumb amputations at the metacarpophalangeal joints were studied: 16 patients had toe transfer and 5 patients did not have reconstruction. The mean follow-up period was 7.2 years (range, 3-13 years). Toe transfer patients showed statistically significantly better overall hand function (effect size = 1.4), ADL (effect size = 3.4), work performance (effect size = 2.1), aesthetics (effect size = 1.9), and satisfaction (effect size = 1.1). Functional testing showed that strength and dexterity of the toe transfer hands were comparable to the opposite normal hands. Foot donor site morbidity was minimal. No significant difference was found in the mean Lower Limb Function Questionnaire scores between the toe transfer patients (1.4) and the amputation patients who did not undergo reconstruction (1.6). The results of our study showed that patients with toe transfer have better hand function than patients with thumb amputations at the level of the metacarpophalangeal joints.
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Maternal cigarette smoking during pregnancy as a risk factor for having a child with cleft lip/palate has been suggested by several epidemiologic studies. However, most of these studies contained small sample sizes, and a clear association between these two factors could not be established. The U.S. Natality database from 1996 and a case-control study design were used to investigate the association between maternal smoking during pregnancy and having a child with cleft lip/palate. The records of 3,891,494 live births from the 1996 U.S. Natality database were extracted to obtain cleft lip/palate cases and random controls. The National Center for Health Statistics collects maternal and newborn demographic and medical data from the birth certificates of all 50 states. New York (excluding New York City), California, Indiana, and South Dakota did not collect smoking data, and the data from these states were excluded from the analysis. A total of 2207 live births with cleft lip/palate cases were identified, and 4414 controls (1:2 ratio) were randomly selected (using the SAS program) from live births with no congenital defects. Odds ratios and 95 percent confidence intervals were determined from logistic regression models, adjusting for confounding variables, including maternal demographic and medical risk factors. A significant association was found between any amount of maternal cigarette use during pregnancy and having a child with cleft lip/palate [unadjusted odds ratio 1.55 (1.36, 1.76), p < 0.001]. Univariate analysis showed that maternal education level, age, race, and maternal medical conditions (diabetes and pregnancy-associated hypertension) were potential confounders. After adjusting for these confounders, the odds ratio remained significant [Mantel-Haenszel odds ratio 1.34 (1.16, 1.54), p < 0.001]. To determine the dose response of cigarette smoking during pregnancy, the cigarette consumption per day was divided into four groups: none, 1 to 10, 11 to 20, and 21 or more. A dose-response relationship was found when comparing each smoking category with the no smoking reference group: 1.50 (1.28, 1.76), 1.55 (1.23, 1.95), and 1.78 (1.22, 2.59), respectively. This means that increased cigarette smoking during pregnancy resulted in increased odds of having a child with cleft lip/palate. This is the largest study to date to test the association between maternal cigarette smoking during pregnancy and having a newborn with cleft lip/palate. The significant trend in the dose-response relationship strongly suggests the association of smoking tobacco and this common congenital deformity. These results emphasize the public health risks associated with smoking during pregnancy. To prevent this devastating craniofacial anomaly, educational initiatives should be considered that will alert expectant mothers to the association between smoking during pregnancy and the occurrence of cleft lip/palate.
OBJECTIVE: To investigate the effectiveness of Swanson silastic metacarpophalangeal joint arthroplasty (SMPA) in improving hand function for patients with rheumatoid arthritis. METHODS: A systematic overview of all published series in the literature on SMPA from 1966 to 1999. RESULTS: Research design deficiencies were quite prevalent in the literature on SMPA. However, SMPA was effective in correcting ulnar drift and in improving the arc of motion of the fingers. Health related quality of life was improved in the domains of hand function, pain, activities of daily living, aesthetics, and satisfaction. CONCLUSION: SMPA appeared to be an effective procedure in correcting rheumatoid hand deformities. Future research must establish objective, quantifiable measures of hand function improvement by using standardized hand function tests and validated hand outcome questionnaires.
Pyrrolidine dithiocarbamate (PDTC) suppresses NF-kappaB activity and exhibits cytotoxic effects in bovine cerebral endothelial cells (BCECs), and we have previously reported that these PDTC effects were accompanied by an increase in intracellular zinc levels. To further explore the role of zinc in the modulation of NF-kappaB activation, we studied the effect of pyrithione, a zinc ionophore, on NF-kappaB activation in BCECs. Pyrithione inhibited NF-kappaB activity in a time- and dose-dependent manner. Ca-EDTA, but not Zn-EDTA, prevented pyrithione inhibition of NF-kappaB activity. Pyrithione increased the intracellular zinc level within 15 min. This effect was also abolished by Ca-EDTA, but not by Zn-EDTA. The potency of pyrithione on NF-kappaB inhibition and zinc influx was approximately one order of magnitude more potent than PDTC. These findings establish the regulatory role of intracellular zinc levels on NF-kappaB activity in BCECs.
Nitric oxide (NO) is a signaling molecule that mediates several physiological processes in a range of cell and tissue types. Here we investigated the effect of serum deprivation in the absence or presence of phorbol 12-myristate 1 3-acetate (PMA) or tumor necrosis factor-alpha (TNFalpha) on cell viability, NO formation, inducible NO synthase (iNOS) induction, and activation of mitogen-activated protein kinase in neuronal PC12 cells. Within 24 h of serum deprivation, apoptosis occurred in up to 65-70% of the cells, and significant levels of NO were generated. When PMA was added in serum-free medium, NO formation and cell death were decreased. In contrast, addition of TNFalpha in serum-free medium increased the levels of NO formation and apoptosis compared with those in serum-deprived cells. We have demonstrated that differential generation of NO levels by PMA or TNFalpha under conditions of serum deprivation is mediated by the same pattern of iNOS induction. NO formation via iNOS induction resulted in the activation of c-Jun N-terminal kinase (JNK) but not extracellular signal-regulated kinase. From this study it is suggested that the differential formation of cytotoxic NO by serum deprivation plus PMA or TNFalpha is primarily mediated by the induction of iNOS enzymes in neuronal PC12 cells and that its action is mediated by the activation of JNK.
A carpal tunnel release was performed on a patient with recurrent carpal tunnel syndrome and asymptomatic hyperuricaemia with no prior history of gouty arthritis. Intraoperatively, the patient was found to have tenosynovitis without crystals or tophaceous deposits in the carpal tunnel. Postoperatively, the patient developed an acutely inflamed hand, which responded dramatically to anti-gout medications. We report this patient as an initial attack of gout after a carpal tunnel release.
We investigated the effect of a new PAF antagonist pinusolide, isolated from the leaves of Biota orientalis, on PAF-induced [3H]serotinin release from rabbit platelets, hypotension and vascular permeability. Pinusolide (IC50, about 5 x 10(-6) M) inhibited specifically [3H]serotinin release from rabbit platelets when stimulated with PAF (5 x 10(-8) M), but showed no effect when induced by ADP, collagen, and thrombin. It also inhibited PAF-induced hypotension in a dose-dependent manner in rats with no effect on the hypotension induced by acetylcholine, histamine and serotonin. The inhibitory effect of pinusolide on the PAF-induced vascular permeability is less specific than the induced hypotension. These results suggest that pinusolide may prove of therapeutic value in the treatment of hypotension and a molecular design of pinusolide analogues may provide the possibility of a new PAF specific antagonists.
The relationship between walking-track measurements and maximum force generation in reinnervated rat hindlimb muscles was assessed. A rat model was designed to result in a broad range of recoveries of both muscle force and walking-track measurements after unilateral sciatic nerve injury and reconstruction. Three months following sciatic nerve injury, maximal force in the extensor digitorum longus (EDL) muscle ranged from 1325 to 3666 mN, and maximal specific forces ranged from 137.5 to 359.4 kNm(-2). In the same animals, functional intermediate toe spread factor (FIS) ranged from -0.03 to -0.78. Neither the correlation coefficient between EDL muscle maximal force and FIS (r = 0.4) nor that between EDL maximal specific force and FIS (r = -0.2) were statistically significant. The lack of correlation between muscle maximal force values and walking-track measurements suggests that these neuromuscular tests are assessing different factors.
Although outcome measurement in medical care has traditionally included various aspects of clinical and functional status, patient satisfaction is another important metric in the assessment of health care quality. Determining which factors contribute most to patient satisfaction can assist health care providers in improving care. In an era of diminishing resources, satisfaction ratings can further aid third-party payers in determining who provides those services. The authors used the ordinal logistic regression method to develop a predictive model for patient satisfaction in an outpatient plastic surgery clinic. Consecutive patients who attended a university outpatient plastic surgery clinic were asked to complete the Visit Specific Patient Satisfaction Questionnaire (VSQ) after their clinic visit. Type of clinic (e.g., hand clinic, aesthetic clinic, breast clinic) and demographic variables like age, gender, race, and education were added to the questionnaire to control for possible confounding effects. The authors constructed an ordinal logistic regression model using the overall visit response as the dependent variable and the eight other response categories as independent variables. A total of 345 patients completed the VSQ, which takes each patient less than 2 minutes to complete. The patient response rate was more than 95%. Statistically significant predictors included (1) personal manner of physician (odds ratio [OR], 18.0; p = 0.0002), (2) time spent with physician (OR, 4.7; p = 0.0099), (3) length of time to get an appointment (OR, 4.6; p = 0.0055), and (4) explanation of what was done (OR, 3.9; p = 0.0263). There was no statistically significant association between overall satisfaction scores and the following factors: (1) length of wait in the clinic (OR, 2.7; p = 0.0747), (2) getting through to the clinic by phone (OR, 0.71; p = 0.5439), (3) convenience of the clinic's location (OR, 2.3; p = 0.1368), and (4) technical skills of the physician (OR, 1.0; p = 0.9974). The predictive model was adjusted for possible confounding due to the type of clinic and demographic variables. In this study the most important predictors of patient satisfaction were those related to efficient clinic operation (scheduling of appointments and clinic waiting time) and the quality of the patient-physician interaction. Clinic facilities (like clinic location and ease of phone contact) were not significant predictors. Because patients often have difficulty assessing the technical skills of physicians, this variable was not a significant predictor. To improve patient satisfaction in plastic surgery outpatient clinics, efforts and resources should be directed toward expedient and empathic delivery of care.
The authors describe an uncommon case of flexor tenosynovitis caused by Mycobacterium terrae, an atypical mycobacterium generally considered nonpathogenic in humans. A prolonged delay in diagnosis and various ineffective therapies led to synovial biopsy and culture. After confirming the diagnosis of M. terrae, appropriate antimycobacterial chemotherapy resolved the synovitis. For chronic tenosynovitis without a clear etiology, limited synovectomy and culture are essential in establishing a diagnosis and in initiating treatment for this atypical mycobacterial infection.
Responsiveness is an important property of an outcomes questionnaire. It can be defined as the ability of an instrument to capture important changes in a patient's health status over time. The authors previously designed the Michigan Hand Outcomes Questionnaire (MHQ), a hand-specific outcomes instrument that contains six distinct scales: (1) overall hand function, (2) activities of daily living, (3) pain, (4) work performance, (5) aesthetics, and (6) patient satisfaction with hand function. In the first study, the authors demonstrated that the MHQ is a reliable and valid instrument for the hand. The purpose of this second study is to assess the responsiveness, or sensitivity, of the MHQ to clinical change in patient status. A total of 187 consecutive patients with chronic hand disorders completed a baseline MHQ prior to receiving treatment at a university plastic surgery clinic. Approximately 6 to 18 months after completing the first questionnaire, patients were sent a follow-up MHQ by mail. The second questionnaire was identical to the first, with the exception of one additional question added to each of the six MHQ scales. This additional question asked patients to rate the change in their hands since completing the last questionnaire using a seven-point response scale. Spearman's correlation coefficient was used to correlate the responses from patients' self-assessment questions with the actual score change (after score - before score). The response rate for the second administration was 49% (92 questionnaires returned)-a fairly good rate of return for mail surveys. There were no significant differences in gender, race, education, and income between responders and nonresponders. When patients' self-assessment of change was correlated with the change in the six scale scores over time, all six correlations were statistically significant, with p < 0.05. The correlations ranged from 0.25 for the aesthetics scale to 0.43 for the pain scale. The MHQ was responsive using patients' self-assessment of their clinical change. Future studies will evaluate the responsiveness of the MHQ compared with objective physiological measures such as grip strength, range of motion, and the Jebson-Taylor test. Additionally, research is underway to assess the responsiveness of the MHQ for specific procedures, including metacarpophalangeal arthroplasties for rheumatoid arthritis and microvascular toe-to-hand reconstructions.
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