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Biomedical subjects

D Y Lin

Publications and source records attributed to D Y Lin.

At least 19 recordsLinked to original sources

Genomic basis of developmental defects of enamel and sex-specific effects.

We conducted a multi-ancestry genome-wide association study (GWAS) of developmental defects of enamel (DDE) in the primary dentition among 6,061 U.S. preschool-aged children (3-5 years). We investigated four DDE phenotypes (demarcated opacities, diffuse opacities, hypoplastic defects, and a combined DDE trait) leveraging main-effect models, joint gene-sex interaction testing (2df), and sex-stratified analyses. SNP-based heritability for the combined DDE trait was estimated at 20%, with concordance analyses robustly supporting a genetic etiology. We identified 39 unique genome-wide significant loci (P<5&#xd7;10 ), with five surpassing a study-wide Bonferroni-corrected statistical significance criterion (P<1.25&#xd7;10 9), including Y RNA and ALDH1A1. The main-effect GWAS identified 20 loci, including HBS1L and MYB, genes regulating hematopoiesis with plausible roles in amelogenesis. Joint test and sex-stratified analyses revealed 19 additional loci, including ALDH1A1, TENM2, and DLGAP2, demonstrating sex-specific heterogeneity. Nineteen loci exhibited sex-specific differences after Bonferroni correction (P<2x10-3), including genes involved in retinoic acid signaling (ALDH1A1), odontogenesis (TENM2), and neurodevelopment (DLGAP2, CDH10). Pathway enrichment highlighted ectodermal and synapse organization networks, suggesting shared etiological mechanisms between DDE and systemic conditions like neurofibromatosis and autism spectrum disorder. Notably, no locus generalized in an external GWAS of permanent dentition DDE, underscoring fundamental biological differences in the genetic architectures governing primary versus permanent enamel formation. Crucially, a comprehensive cross-trait pleiotropy lookup against early childhood caries (ECC) revealed no shared genetic architecture, supporting the notion that the established clinical and epidemiological association between DDE and ECC is likely driven by structural defects increasing caries lesion susceptibility rather than genetic pleiotropy. By integrating gene-sex interaction testing, this study offers novel insights into the complex, sexually dimorphic genetic etiology of DDE and augments the biological evidence base that can support the development of precision pediatric dentistry.

developmental defects of enamel

GOFCOX: a computer program for the goodness-of-fit analysis of the Cox proportional hazards model.

GOFCOX is a user-friendly FORTRAN program for assessing the adequacy of the Cox proportional hazards model. The underlying methodology is based on the comparison of the maximum partial likelihood estimator and a weighted parameter estimator. The latter is the root to an estimation equation that assigns varying weights to the individual contributions to the partial likelihood score function. The weighted and unweighted parameter estimators have the same expectation under the Cox model, but tend to differ when the model is inappropriate. The GOFCOX program computes a rich class of weighted parameter estimators and corresponding goodness-of-fit test statistics. The program runs on both mainframe computers and microcomputers. The running time is minimal even for large data sets. A simple example is provided to illustrate the features of the program.

Computers, Mainframe

The prevalence of hepatitis C virus antibodies in patients treated with continuous ambulatory peritoneal dialysis.

OBJECTIVE: To assess the prevalence of anti-HCV (hepatitis C virus antibodies) in continuous ambulatory peritoneal dialysis (CAPD) patients and staff members. DESIGN: Fifty-nine serum samples were collected and tested by an enzyme immunoassay for anti-HCV. Records and past history of blood transfusion and hemodialysis were reviewed. Results were analyzed using the Fisher's exact test. SETTING: A medical college-operated teaching hospital. PARTICIPANTS: Fifty-two patients and 7 staff members from the Chang Gung Memorial Hospital CAPD unit were studied. RESULTS: Anti-HCV prevalence in patients and staff were 15.4% and 0%. A history of maintenance hemodialysis was associated with a higher prevalence of anti-HCV (33.3% versus 5.9% without hemodialysis, p = 0.015). The prevalence of anti-HCV did not increase with longer CAPD duration. Among those with an episode of hepatitis, higher prevalence of anti-HCV was observed (57.1% versus 8.9% without hepatitis, p = 0.0073). CONCLUSION: HCV is an important agent of hepatitis in CAPD patients. The risk of HCV infection among CAPD staff members is negligible. CAPD offers better control of HCV infection among patients with end-stage renal failure.

Blood Transfusion

Retrograde jejunogastric intussusception caused by a jejunal polyp.

A 70-year-old male presented with epigastric pain, vomiting and upper gastrointestinal bleeding 11 years after a subtotal gastrectomy. Retrograde jejunogastric intussusception was diagnosed by endoscopy and barium meal study and finally confirmed by laparotomy. After reduction of the intussusception, a small polyp was found at 20 cm distal to the anastoma, which served as the leading point of intussusception. The pathophysiology and clinical manifestations of this disease were reviewed.

Aged

Gastric adenocarcinoma simulating benign gastric ulcer.

The pathologic features and prognosis of patient in whom gastric cancer simulates at endoscopy as a benign gastric ulcer has been poorly characterized. We performed a retrospective study with particular reference to the long term prognosis on 191 patients treated for gastric adenocarcinoma over the period 1980-1986. In 176 of these 191 patients (92.2%), the endoscopic findings suggested cancers, while in the remaining 15 patients (7.8%), the endoscopic appearance suggested benign ulcer. Comparing gastric cancers masquerading as benign gastric ulcers with those appeared malignant endoscopically, the former had higher resectability rate (100% vs 77.3%), higher incidence of early gastric cancer (73.3% vs 6.25%), less poorly differentiated carcinoma (33.3% vs 65.4%), less lymph node metastasis (13% vs 69.5%) and a higher five-year survival rate (86.6% vs 24.8%) (p less than 0.05 in all). Our study indicated that gastric adenocarcinomas simulated benign gastric ulcers at endoscopy are mostly early gastric cancers that carry a much better prognosis.

Adenocarcinoma

A prospective randomized controlled trial of sandostatin and vasopressin in the management of acute bleeding esophageal varices.

To study the hemostatic effect of Sandostatin, a long-acting analogue of somatostatin, in acute variceal bleeding, a prospective randomized controlled trial comparing it with Vasopressin was conducted in 41 cirrhotic patients with esophageal variceal bleeding. Initial hemostasis was achieved within 6 hours in 75% of patients treated with Sandostatin and in 61.9% treated with Vasopressin. Recurrent bleed developed in 20% of patients in Sandostatin group and 46.2% in Vasopressin group following initial hemostasis. Complete control of bleeding for 24 hours was attained in 60% of the Sandostatin group and in 33.3% of the Vasopressin group. There was no statistically significant difference in both the rate of initial hemostasis and complete bleeding control. Hospital mortality was also similar in both groups. However, transfusion requirements were less (P less than 0.05) and side effects tended to be milder in patients treated with Sandostatin. In conclusion, Sandostatin is at least as effective as Vasopressin in the treatment of acute variceal bleeding, and carries less severe complications than Vasopressin does.

Adult

Hepatitis C virus infection in patients with chronic liver diseases in an endemic area for hepatitis B virus infection.

Taiwan is an endemic area for hepatitis B virus (HBV) infection, which is responsible for up to 80% of chronic liver diseases there. In contrast to an HBV carrier rate of 15-20% in the general population, only 1% of its population are seropositive for anti-HCV. To evaluate the role of HCV infection in chronic liver diseases in Taiwan, serum anti-HCV was studied using an enzyme immunoassay in 123 "healthy" administration staff of the hospital, 724 hepatitis B surface antigen (HBsAg)-positive and 157 HBsAg-negative patients with chronic liver disease. The prevalence of anti-HCV was 0.8% in the hospital staff, 24.3% in HBsAg-positive and 80.9% in HBsAg-negative patients with chronic liver diseases. Anti-HCV was positive in 10 (9.6%) of 104 HBsAg-positive and 31 (77.5%) of 40 HBsAg-negative patients with inactive chronic hepatitis; 94 (27.2%) of 346 HBsAg-positive and 53 (85.5%) of 62 HBsAg-negative patients with active chronic hepatitis; 49 (26.1%) of 181 HBsAg-positive and 33 (86.8%) of 38 HBsAg-negative patients with cirrhosis; 23 (26.7%) pf 86 HBsAg-positive and 10 (58.8%) of 17 HBsAg-negative patients with hepatocellular carcinoma. In HCV infected HBsAg-positive patients, the optical density was usually lower, and anti-HCV became negative in 27% on follow-up. HCV infection tends to occur more frequently in older, HBeAg-negative and anti-HD-positive patients with chronic HBV infection. It is concluded that HCV not only is the major agent for non-B chronic liver diseases but also plays a significant role in HBsAg-positive chronic liver diseases in Taiwan.

Chronic Disease

Is preoperative ultrasound cancer survey necessary in patients with normal liver function tests?

Abdominal ultrasound examination is so easy that it may be overused. To reduce medical costs, we investigated whether preoperative ultrasonic abdominal survey was necessary for oncologic patients with normal liver function tests. We used the ultrasound diagnosis as the final standard to test the value of liver function tests for the prediction of liver metastases. Five hundred forty-four patients with various primary malignancies were referred for preoperative ultrasonic survey of the abdomen. The results showed that for a single test, serum albumin was most sensitive (87.2%) but least specific (29.4%), and serum bilirubin was least sensitive (13.0%) but most specific (97.2%), for the prediction of liver metastases. For a combination of five tests or more, the sensitivity was 95.9% and the specificity 29.5%. In patients with normal liver function tests, liver metastases were detected by ultrasound in two of 106 (1.9%) patients. One hundred of 544 (18.4%) patients having major abnormalities that may influence clinical management were also detected during the ultrasound examination. We conclude that ultrasound is convenient, cheap, and without side effects. It can provide additional information affecting patient management, even in the presence of normal liver function tests.

Aged

Prevalence of antibodies to hepatitis C virus in the hemodialysis unit.

An enzyme immunoassay was used to detect antibodies to hepatitis C virus (anti-HCV) in 261 patients and 69 staff members of a hemodialysis unit. The prevalence of anti-HCV was 46.7% in patients and 2.9% in staff members (p less than 0.001). The prevalence of anti-HCV increased significantly with increasing duration of hemodialysis (p less than 0.001), but was not related to age, sex, history of blood transfusion, status of hepatitis B or hepatitis A virus infection, or serum ALT. Patients with hepatitis episode increased with increasing duration of hemodialysis and showed a significantly higher prevalence of anti-HCV than those without (63.1 vs. 34.7%, p less than 0.001). The prevalence of anti-HCV in patients with hepatitis also increased with increasing duration of hemodialysis (p = 0.05). Thus, HCV appears to be the major cause of hepatitis in hemodialysis patients. Besides strict infection control measures, further studies are needed to determine the mode of HCV infection and its prevention in the hemodialysis unit.

Female

Noise-induced hearing loss in iron-deficient rats.

The role of iron deficiency in noise-induced hearing loss (NIHL) was evaluated in 64 rats of four different experimental groups. Iron-deficient rats (ID-rats) and normal rats (N-rats) were simultaneously exposed to a steady state white noise (20-10,000 Hz) at 110 dB SPL for 30 min. Unexposed ID- and N-rats served as controls. In N-rats the temporary threshold shifts (TTS) would have completely disappeared if the animals were allowed to survive for 72 h. No permanent threshold shift (PTS) was seen in any of the N-rats. The ultrastructural correlates in N-rats are stereocilia disarray and mitochondria swelling in outer hair cells (OHCs). The TTS in ID-rats were larger than those in the N-rats, and most ID-rats with larger threshold shifts showed varying degrees of PTSs at 11 days post-exposure. The ultrastructural correlates of NIHL in ID-rats are obvious pathology of the stereocilia, such as segmental coalescence of stereocilia of many continuous OHCs and fusion of the tips of stereocilia of OHCs, and a significant reduction of mitochondria as well as slight degeneration of nucleus in the OHCs. It is concluded that iron deficiency can provide a pathological basis for NIHL.

Anemia, Hypochromic

Exact statistical inference for group sequential trials.

This paper considers clinical trials comparing two treatments with dichotomous responses where the data are examined periodically for early evidence of treatment difference. The existing group sequential methods for such trials are based on the large-sample normal approximation to the joint distribution of the estimators of treatment difference over interim analyses. We demonstrate through extensive numerical studies that, for small and even moderate-sized trials, these approximate procedures may lead to tests with supranominal size (mainly when unpooled estimators of variance are used) and confidence intervals with under-nominal coverage probability. We then study exact methods for group sequential testing, repeated interval estimation, and interval estimation following sequential testing. The new procedures can accommodate any treatment allocation rules. An example using real data is provided.

Biometry

Repeated confidence intervals for a scale change in a sequential survival study.

This note considers the problem of comparing the survival distributions of two treatment groups in a clinical trial where the treatment difference is measured in terms of a time-scale change. Patients enter the study sequentially and may be subject to random loss to follow-up. The survival data are reviewed periodically for early evidence of the treatment difference. An approach to constructing repeated confidence intervals for the scale-change parameter is described. These intervals provide useful information about the magnitude of the treatment difference in interim analyses. An example taken from an AIDS clinical trial is given.

Biometry

MULCOX: a computer program for the Cox regression analysis of multiple failure time variables.

MULCOX is a user-friendly FORTRAN program for the analysis of regression effects when individual study subjects may experience multiple events or failures. Each marginal distribution of the multivariate failure time variable is formulated by a Cox proportional hazards model. The maximum partial likelihood estimators of the regression parameters in these marginal models are approximately jointly normal. The MULCOX program estimates the marginal models as well as the joint covariance matrix. In addition, it implements several multivariate inference procedures. The program runs on both mainframe computers and microcomputers. The running time is quite acceptable even for large samples. A simple example is provided to illustrate the features of the program.

Mathematical Computing

Ultrasonographic difficulties and pitfalls in diagnosing primary carcinoma of the gallbladder.

In order to more specifically define gallbladder carcinoma with real-time ultrasonography, a retrospective study was performed involving 29 sonographically false-negative and 22 sonographically false-positive cases of gallbladder carcinoma. Among the false negative cases, 18 (62.1%) were diagnosed as gallbladder stone only, 6 cases (20.7%) were incorrectly diagnosed as either acute or chronic cholecystitis, 2 cases (6.9%) were diagnosed as bile sludge, 2 cases (6.9%) were diagnosed as polyps, and 1 case (3.4%) was diagnosed as liver tumor. In false-positive cases, 8 (31.8%) were erroneously diagnosed as liver tumor. In false-positive cases, 7 (31.8%) were erroneously diagnosed as a mass projecting from the gallbladder wall but were pathologically proven to be polyps (4 cases) or bile sludge (3 cases); 8 cases (36.4%) were incorrectly diagnosed due to irregular thickening of the gallbladder wall but histology revealed them to be acute (3 cases) or chronic (5 cases) cholecystitis. Seven cases (31.8%) had a solid mass in porta hepatis, indicating gallbladder carcinoma; of these, 2 cases were lumps of bile sludge and 5 cases were acute cholecystitis with empyema. The differentiation of gallbladder carcinoma from cholecystitis (acute or chronic), polyps, and bile sludge is sometimes very difficult. With an understanding of the sonographic pitfalls and difficulties in the diagnosis of gallbladder carcinoma, a more specific diagnosis may be made.

Carcinoma

Natural course after the development of cirrhosis in patients with chronic type B hepatitis: a prospective study.

To examine the early stage of the natural course of liver cirrhosis, a prospective follow-up study was conducted in a series of 76 patients with recent development of cirrhosis during the course of chronic type B hepatitis. During a mean follow-up period of 34.4 months, 45 episodes of acute exacerbation were recorded; the majority of the episodes occurred within 2 years after entry. The calculated annual incidence of acute exacerbation was significantly higher in patients seropositive for hepatitis B e antigen (HBeAg) and/or hepatitis B virus (HBV)-DNA (25.9%) than in those without these markers (11.9%). Three-fourths of the acute exacerbations were attributable to the reactivation of HBV. Spontaneous HBeAg seroconversion to anti-HBe also occurred in the early phase, but less than 30% of the events were preceded by acute exacerbation. Late hepatitis B surface antigen clearance occurred in two patients. Hepatic decompensation, esophageal variceal bleeding and hepatocellular carcinoma developed relatively late in the course of the disease with a calculated annual incidence of 2.3%, 2.3% and 2.8%, respectively. Seven patients (9.2%) died of hepatic failure or variceal bleeding, usually more than 3 years after entry. The estimated 5-year survival rate was 80%. The results suggest that the natural events of chronic HBV infection, including exacerbation, seroconversion and its sequelae could occur after the development of cirrhosis. In addition, these events might be responsible for the clinicopathological changes and the outcomes of these cirrhotic patients.

Adult

Resolution of liver abscesses: comparison of pyogenic and amebic liver abscesses.

To examine the resolution of liver abscesses, a prospective ultrasonographic follow-up study was conducted in 51 patients, each with a solitary abscess (26 pyogenic and 25 amebic) which had been treated successfully by non-surgical measures. The rate of complete abscess resolution for each of the initial 6 months was 0%, 5%, 10%, 23%, 30%, and 30% in the amebic group; and 20%, 54%, 77%, 89%, 94%, and 94% in the pyogenic group. The absorption volume of the pyogenic group in the first month was also greater than that of the amebic group (3.0 +/- 5.0 ml/day vs. 1.1 +/- 0.8 ml/day, P less than 0.05). The resolution ratio of pyogenic and amebic liver abscesses in the first month was 74% +/- 38% and 36% +/- 23%, respectively. In 3 patients in the amebic group, the abscess was still detectable 2 years after treatment. These results suggest that pyogenic liver abscesses resolve more rapidly than amebic abscesses. These findings should be considered in the differential diagnosis of asymptomatic space-taking lesion in the liver.

Actuarial Analysis