Biomedical subjects

C K Shaw

Publications and source records attributed to C K Shaw.

At least 19 recordsLinked to original sources

PubMed2003

Climate, traffic-related air pollutants and allergic rhinitis prevalence in middle-school children in Taiwan.

The prevalence of allergic rhinitis, a common respiratory disorder, may be rapidly increasing. Epidemiological studies, however, indicate little about its association with climatic factors and air pollution. The relationship between traffic-related air pollutants and allergic rhinitis in middle-school students was therefore investigated. In a nationwide survey of middle-school students in Taiwan conducted in 1995/1996, the lifetime prevalence of physician-diagnosed allergic rhinitis and typical symptoms of allergic rhinitis were compared with air-monitoring station data on temperature, relative humidity, sulphur dioxide (SO2), nitrogen oxides (NOx), ozone (O3), carbon monoxide (CO) and particulate matter with a 50% cut-off aerodynamic diameter of 10 microm (PM10). A total of 331,686 nonsmoking children attended schools located within 2 km of 55 stations. Mean (range) annual exposures were: CO 853 (381-1,610) parts per billion (ppb), NOx 35.1 (10.2-72.4) ppb, SO2 7.57 (0.88-21.2) ppb, PM10 69.2 (40.1-116.2) microg x m(-3), O3 21.3 (12.4-34.1) ppb, temperature 22.9 (19.6-25.1) degrees C, and relative humidity 76.2 (64.8-86.2)%. The prevalence of physician-diagnosed allergic rhinitis was 28.6 and 19.5% in males and females, respectively, with prevalence of questionnaire-determined allergic rhinitis 42.4 and 34.0%. After adjustment for age, parental education and history of atopic eczema, physician-diagnosed allergic rhinitis was found to be associated with higher nonsummer (September-May) warmth and traffic-related air pollutants, including CO, NOx and O3. Questionnaire-determined allergic rhinitis correlated only with traffic-related air pollutants. Nonsummer warmth and traffic-related air pollution, probably mediated through exposure to common allergens such as dust mites, are possible risk factors for allergic rhinitis in middle-school-aged children.

Adolescent↗

PubMed2001

Mutation analysis of the human NR4A2 gene, an essential gene for midbrain dopaminergic neurogenesis, in schizophrenic patients.

Recent studies have revealed that an orphan receptor gene of the steroid/thyroid hormone nuclear receptor superfamily, the Nurr1 gene, is essential for the neurogenesis and differentiation of dopaminergic neurons in the midbrain of mice. Transgenic mice lacking the Nurr1 gene soon die after birth and are devoid of dopaminergic neurons in the midbrain. Heterozygous mice survive postnatally without obvious locomotor deficits; however, they have increased vulnerability to dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). In view of the importance of dopamine neurotransmission in brain function, we were interested to know if the human homologous gene of murine Nurr1, the NR4A2 gene, may play a role in the pathogenesis of schizophrenia. We systematically sequenced all the exons of the human NR4A2 gene to search for molecular variants in a cohort of Chinese schizophrenic patients from Taiwan. Two molecular variants were identified: a G-insertion in intron 6 (designated IVS6 + 17 [see text] + 18insG), and a G-deletion in the untranslated exon 1 (designated c.-469delG). The IVS6 + 17 [see text] + 18insG is a polymorphic one; further case control study, however, did not reveal association of this polymorphism with schizophrenia. The c.-469delG is a rare variant found in two unrelated patients among 177 schizophrenic patients, but not in 130 nonpsychotic controls. The result suggests that the c.-469delG and possibly other variants of the NR4A2 gene may be of relevance to the complex factors involved in the pathogenesis of schizophrenia.

DNA↗

PubMed2001

Multilocus linkage analysis of the German asthma data.

We analyzed data from the German Asthma Genetics Group with three methods that utilize pedigree-specific nonparametric linkage scores to facilitate the search for multiple independent and interacting susceptibility loci. The three methods included a conditional analysis, logistic regression, and neural networks. Although there were differences, the three methods identified many of the same susceptibility loci. The most consistent evidence was provided for loci on chromosomes 1, 2, 6, 9, and 15. Both the conditional and the logistic regression analyses suggested an epistatic relationship between loci on chromosomes 2 and 9. The logistic regression analysis further revealed evidence for locus heterogeneity between loci on chromosomes 6 and 15. Finally, the neural network analysis identified a potential locus on chromosome 17 that was not identified in the other analyses.

Adult↗

PubMed2001

HLA-DRB1 antigens in Taiwanese patients with juvenile-onset systemic lupus erythematosus.

OBJECTIVE: This study was done to investigate the frequency of HLA-DRB1 antigens in juvenile-onset systemic lupus erythematosus (SLE) in the Taiwanese population. PATIENTS AND METHODS: Thirty-four Taiwanese patients with juvenile onset SLE and 200 unrelated healthy controls were studied. HLA-DRB1 typing was performed with polymerase chain reaction (PCR) and the sequence-specific oligonucleotide probe (SSO) typing method. RESULT: Among the 14 investigated DRB1 alleles, the frequency of HLA-DRB1*1602 was higher in juvenile onset SLE patients than the controls (15.15% vs 4.50%, odds ratio 3.66, 95% confidence interval 1.15-11.68, Pc = 0.04). Although there were differences in the frequencies of DRB1*0301, DRB1*0803, and DRB1*1501 between patients and controls, the associations were statistically insignificant. CONCLUSION: The frequency of HLA-DRB1*1602 was significantly higher in patients with juvenile onset SLE than in healthy controls. This finding differs from those in the previous studies in Caucasian and Japanese adult onset SLE patients.

Adolescent↗

PubMed2001

A study of the normal temporal healing pattern and the mucociliary transport after endoscopic partial and full-thickness removal of nasal mucosa in sheep.

The aim of this study was to assess the temporal healing process of nasal epithelium after full- thickness and partial thickness mucosal removal in sheep. Healing was assessed by histologically examining serial biopsies of the healing wounds. The histology assessed the regeneration of epithelium and return of cilia. Mucociliary clearance was measured before and after injury. On day 84 post injury partial thickness injuries had 80.7% (SEM = 10.25) normal epithelium and 68.35% (SEM = 19.2) reciliation. Full-thickness wounds had 64.98% (SEM = 19.17) normal epithelium and 32.96% (SEM = 17.46) reciliation. On day 84 the difference for epithelium regeneration was not significant (P > 0.05), but reciliation was significant (P < 0.05). The baseline mucociliary clearance was 0.84 mm per second (SEM = 0.2) and did not differ significantly from either the partial thickness wound transport rate (2.49 mm/s; SEM = 1.02) or the full-thickness transport rate (0.9 mm/s; SEM = 0.37) (paired t-test P > 0.05). The time period (84 days) for evaluation of reciliation was insufficient, as reciliation appeared to be continuing. The healing process took place over a longer time period than what had been previously reported in the literature and this may account for the symptoms seen in the postoperative period in patients after sinus surgery.

Animals↗

PubMed2001

Immunohistochemical localization of deleted-in-colon-cancer (DCC) protein in human epithelial, neural, and neuro-endocrine tissues in paraffin sections with antigen retrieval.

A gene called deleted in colon cancer (DCC) has been identified on a region of chromosome 18, which is deleted in 70% of colorectal cancers. The DCC gene encodes a protein belonging to the immunoglobulin superfamily with similarity to the N-CAM transmembrane proteins, and it is a putative tumor-suppressor gene. Alternative splicing of transcripts of transmembrane proteins, including N-CAM, is know to occur, resulting in different isoforms of the protein. Using a polyclonal antibody against the DCC gene product, we have demonstrated, by antigen retrieval immunostaining, the presence of a DCC protein isoform on the cell surface of goblet cells in the G-I tract, cytoplasm of squamous epithelium in the skin & esophagus and transitional epithelium in the urinary bladder, ductal glandular epithelium of endometrium, endocervix, prostate, gall bladder and breast, cytoplasm of neuron in the cerebral cortex and Purkinje cells in the cerebellum. In addition, we also demonstrated DCC protein expression in neuroendocrine cells including argentaffin cells of the stomach, small intestine, appendix and colon, C cells of thyroid gland, chromaffin cells of the adrenal gland, islets of Langerhans in the pancreas and neurons of the sympathetic ganglion. This restrictive distribution suggests the DCC gene products may be abundant expression in neuroendocrine cells of human tissue.

Animals↗

PubMed2001

Role of urbanization and air pollution in adolescent asthma: a mass screening in Taiwan.

BACKGROUND AND PURPOSE: The prevalence of asthma in school children in Taiwan is increasing. This study used mass screening among middle school children in Taiwan to determine the prevalence of asthma and related factors. METHODS: Data were collected from parents using a self-reported questionnaire and from children using the International Study of Asthma and Allergies in Childhood (ISAAC) video questionnaire. Six study teams conducted the survey nationwide in 1995-1996, with the assistance of middle school nurses and teachers. RESULTS: Among the 1,018,031 students at 795 middle schools who returned questionnaires, 8.5% had a history of asthma (ranging in prevalence from 4.2% to 13% in 25 areas). The prevalence of asthma was higher in boys than in girls (10.0% vs 7%) and was highest in more urbanized areas (11.2%), followed by moderately urbanized areas (7.4%) and less urbanized and rural areas (6.5%). Controlling for age, family smoking, family incense burning, and parental education level, multivariate logistic regression models indicated that children living in an area with heavy air pollution were more likely to have asthma than those in an area with no or light pollution (odds ratio, OR = 2.01 and 95% confidence interval, CI = 1.94-2.09 based on parental ranking of pollution level, or OR = 1.30 and 95% CI = 1.18-1.42 based on pollution level reported by the Environmental Protection Administration). CONCLUSIONS: Adolescent asthma in Taiwan is most prevalent in the most urbanized areas and decreases in prevalence in less urbanized areas. This study also found that higher parental education level and higher area air pollution were associated with higher adolescent asthma prevalence.

Adolescent↗

PubMed2001

Prediction of bone fracture by bone mineral density in Taiwanese.

BACKGROUND AND PURPOSE: This study evaluated whether lumbar spine bone mineral density (BMDL) and the rate of change of BMDL could predict the risk of bone fracture in Taiwanese. METHODS: In 1989, a baseline survey was carried out in Lin-Kou Township. BMDL was measured using dual photon absorptiometry in 404 healthy volunteers. In 1994/95, a second survey was conducted to reexamine the BMDL and fracture history as well as the risk factors associated with fracture in these subjects. Fractures were classified according to the causes of the injury as severe or mild trauma. RESULTS: Of the 404 original examinees, 381 (79%) participated in the second survey. Twenty-six subjects had experienced a total of 32 fracture incidents during their lifetime and 10 subjects had experienced fracture during the observation period. After adjusting for the effect of body mass index, gender, and age, each standard deviation of decrease in BMDL was found to be associated with a significant 2.38-fold increase in the risk of mild trauma fracture, and a BMDL below the fracture threshold was associated with a 3.93-fold increase of fracture risk. Higher BMDL change rates were found in subjects with a history of fracture. CONCLUSION: This study indicates the importance of maintaining the BMDL above the fracture threshold (1 g/cm2). The strategy for fracture prevention should be directed at prevention of age-related bone loss.

Absorptiometry, Photon↗

PubMed2000

Effectiveness of an organ-sharing program in providing zero HLA-A,B,DR mismatched kidneys for transplantation in Taiwan.

PURPOSE: This study evaluated the effects of organ sharing on the allocation of kidneys from cadaveric donors to uremic patients from National Cheng Kung University Hospital (CKUH) and National Taiwan University Hospital (NTUH) who were waiting for kidney transplantation. METHODS: Standard complement-dependent microcytotoxicity assays were used. Human leukocyte antigen (HLA)-A,B,C typing was performed on nylon-wool-enriched T lymphocytes. HLA-DR typing was performed on either nylon-wool-separated B cells or Dynabeads. Isolation of class II-positive cells was performed with commercial typing trays. RESULTS: Organs were allocated from a total of 88 cadaveric donors to 320 patients treated at CKUH and 179 patients treated at NTUH. Cadaveric kidneys could be allocated with an A,B,DR mismatch to 6.9% of CKUH patients and to 4.7% of NTUH patients. When CKUH and NTUH patients were pooled, the total number of kidneys that could be allocated with 0-A,B,DR mismatch increased to 13.3% (p < 0.004). However, when allocation was assessed using 10,000 potential bone marrow donors instead of the 88 cadaveric donors, kidneys could have been allocated with 0-A,B,DR mismatch to 12% (p = 0.64) of patients. No significant benefit was found when allocation estimates from the 10,000 potential bone marrow donors were compared with those for the 88 cadaveric donors. Use of epitope matching resulted in a 0-A,B cross-reactive epitope group, and a 0-DR mismatch allocation rate of 36.4% in CKUH patients and 31.8% in NTUH patients. This rate increased to 54.6% (p < 0.001) when the patients from these hospitals were pooled. CONCLUSION: The results of this study demonstrate that the pooling of patients among regional transplant centers in Taiwan can significantly enhance the benefits of an organ donation program through better HLA matching.

HLA-A Antigens↗

PubMed2000

The DCC protein expression in breast carcinoma.

Inactivation of the gene "deleted in colon cancer" (DCC) on chromosome 18 is known to be associated with the tumorigenesis and metastasis of colorectal cancer. In the present study, we investigated the expression of DCC, P53 and HER-2/neu product in surgical specimens from 79 patients with invasive breast cancer by immunohistochemistry staining and found the expression of DCC to be decreased in 42 tumors (52%). Overexpression of HER-2/neu and P53 was detected in 29 (36.8%) and 26 (32.9%) of this 79 breast cancer specimens, respectively. To evaluate the outcomes of the 79 breast cancer patients, we followed up the patients during the period from May 1990 to August 1998. The average length of follow-up was 52 months (ranging from 4 to 94 months). Patients with tumors having a combination of DCC-negative and HER-2/neu overexpression showed a marginal influence on survival time of breast cancer (P = 0.06). However, patients with tumors having a combination of DCC-negative and P53 overexpression showed no influence of these on survival time of breast cancer (P = 0.36). These findings suggest that a decreased DCC expression and HER-2/neu overexpression may influence the prognosis of breast cancer.

Breast Neoplasms↗

PubMed1999

Distribution of HLA gene and haplotype frequencies in Taiwan: a comparative study among Min-nan, Hakka, Aborigines and Mainland Chinese.

A total of 8,497 blood samples were typed for HLA-A, B, DR and DQ. Of these, 7,137 Min-nan, 714 Hakka, 535 Mainland Chinese (152 from North China, 211 from Middle China, and 172 from South China) and 111 Aborigines were randomly selected from Tzu Chi Taiwan Marrow Donor Registry (TCTMDR). Differences in HLA gene and antigen frequencies have been observed between various ethnic groups of the Chinese population in Taiwan. The phylogenic tree shows Taiwan Aborigines and Javanese cluster together; Min-nan shares a common cluster with Hakka, Southern Hans and Thai; and Northern Hans shares a cluster with Middle Hans. The separation between Northern/Middle and Southern Chinese Hans support the idea that Northern and Southern Chinese have different genetic background. Aborigines appeared to be quite distinct in the distribution of a majority of the class I and class II antigens. High frequency of HLA-A24 (60.4%) and relatively restricted HLA polymorphisms are noted in Aborigines. The HLA haplotypes with high frequency in Aborigines included A24-B60-DRB1*04, A24-B60-DRB1*14, A24-B48-DRB1*04, and A24-B48-DRB1*14, which are different from the other ethnic groups. Although the phylogenic tree separates Aborigines and Han Chinese populations, 4 out of 20 most common HLA-A, -B, and -DR haplotypes presented in both Aborigines and Han Chinese may reflect an ancient common origin or intermixture between early settlers of Han Chinese and Taiwan Aborigines. The results in this study are essentially a summary of the observed gene/haplotype frequencies and differences among various ethnic groups in Taiwan.

Asian People↗

PubMed1999

Marrow donor registry and bone marrow transplantation from unrelated donors in Taiwan: initial experience of the Tzu Chi Taiwan Marrow Donor Registry (TCTMDR).

To evaluate the outcomes of unrelated bone marrow transplantation facilitated by TCTMDR, we focused on 48 marrow transplants performed in Taiwan during the period May 1994 to June 1997. Follow-up of these 48 cases was made up to 30 May 1998. The average length of follow-up was 328 days (range 7-1385 days). All the donor/recipient pairs were HLA-A, B and DR matched and were divided into two risk groups based on diagnosis and stage of disease. There were 24 standard risk and 24 high risk patients. Engraftment occurred in 40 patients (83.3%). Acute and chronic GVHD was observed in 80% of evaluable patients and accounts for 41% of deaths. The second leading cause of death was infection, accounting for 35% of deaths. The overall probability of survival for the 48 patients after BMT over 2 years was 33.3% (95% CI 19.67-46.32%). The probability of survival for standard risk and high risk groups was 54% and 8%, respectively. In multivariate analysis, patients who were younger, in the standard risk group, or with a shorter search interval showed a higher survival probability.

Acute Disease↗

PubMed1999

Genetic association study of a polymorphic CAG repeats array of calcium-activated potassium channel (KCNN3) gene and schizophrenia among the Chinese population from Taiwan.

Chandy et al suggested that a novel human neuronal small conductance, calcium-activated potassium channel gene, KCNN3, might be a candidate for schizophrenia. The KCNN3 cDNA sequences contain two stretches of CAG trinucleotide repeats encoding two separate polyglutamine segments near the N-terminus of this channel protein. The second CAG repeat was found to be highly polymorphic in the Caucasian population from both Europe and USA. Upon comparing the allelic frequency distribution between schizophrenic patients and ethnically matched controls, a significant excess of longer CAG repeats in schizophrenic patients was observed. A similar result was obtained in a recent replication study by Bowen et al, performed in Caucasians from UK or Eire. These results suggest an association between the longer CAG repeat allele of the KCNN3 gene and schizophrenia susceptibility. To verify if similar results can be observed in the Chinese population, we carried out a case-control study to compare the allelic frequency distribution of the CAG repeat of the KCNN3 gene between 92 Chinese schizophrenic patients and 100 normal controls from Taiwan. No significant difference of the allelic frequency distribution of the second CAG repeats was detected between the two groups (Wilcoxon Rank Sum test, P = 0.664). In addition, no over-representation of CAG repeats longer than the mode (19 repeats) was found in the patients' group (Fisher's exact test, P = 0.739). Thus, our data do not support that the second polymorphic CAG repeat of the KCNN3 gene may have an association with schizophrenia in our population.

Alleles↗

PubMed1999

High seroprevalence of Borna virus infection in schizophrenic patients, family members and mental health workers in Taiwan.

Borna disease virus (BDV), a negative-strand RNA virus, has been reported to be associated with severe psychiatric disorders. The association is mainly based on the findings that patients with schizophrenia and depression have a higher seroprevalence rate of BDV-specific antibodies than controls. In addition, psychiatric patients were also found to have a higher detection rate of BDV transcripts in their blood than controls. By using an improved Western blot analysis, we first demonstrated that Chinese schizophrenic patients from Taiwan also have a higher seroprevalence of BDV-specific antibodies than controls (12.1% vs 2.9%, P< 0.001), providing support to the positive association between BDV and psychiatric disorders in our population. Because of the contagious nature of viral infection, we further examined patients' family members and mental health workers, who have close contact with patients. We found that both groups also have a higher seroprevalence of BDV-specific antibodies, 12.1% and 9.8%, respectively, than controls. This finding provides some evidence for a possible human-to-human transmission of Borna disease virus. Our finding needs further independent verification from other research groups and the clinical relevance of this preliminary observation deserves further study.

Adult↗

PubMed1999

Detection of Borna disease virus RNA from peripheral blood cells in schizophrenic patients and mental health workers.

Accumulating evidence suggests that Borna disease virus (BDV), a neurotropic, negative-stranded RNA virus, might be associated with certain human mental disorders. Several research groups reported that psychiatric patients had a significantly higher prevalence of BDV serum antibodies than normal controls. In addition, a significantly higher presence of BDV RNA from peripheral blood cells was identified in mental patients than in controls. In our previous study, we first identified the presence of BDV serum antibodies in a cohort of Chinese schizophrenic patients from Taiwan, and we also demonstrated a significantly higher seroprevalence of BDV antibodies among schizophrenic patients than in non-psychiatric controls. Prompted by the positive seroepidemiological result, we set out to investigate the detection of BDV RNA from the peripheral blood cells of our schizophrenic patients. By using the reverse transcription-polymerase chain reaction (RT-PCR) method, 10 out of 74 Chinese schizophrenic patients from Taiwan were found to have BDV RNA in their blood cells, whereas only one out of 69 controls was positive. The BDV RNA detection rate among schizophrenic patients was significantly higher than that in controls (14% vs 1.4%, P < 0.01). Furthermore, we studied the BDV RNA detection rate among mental health workers, and seven out of 45 mental health workers were found to have positive results. The prevalence rate was significantly higher than that in normal controls (15% vs 1.4%, P < 0.001), which lends further support to our previous finding that mental health workers have a significantly higher presence of BDV serum antibodies. In summary, our data support the finding that BDV infection might be a contributory factor to the pathogenesis of schizophrenia in the Chinese population.

Adult↗

PubMed1999

Heterogeneity of HLA-DR2 haplotypes in Caucasoid Americans, African Americans, Chinese Americans, Native Americans and Xiamen Chinese.

HLA-DR, -DQ specificities were determined by PCR amplification with SSOP in 4560 individuals: Caucasoid Americans (CA), African Americans (AA), Chinese Americans (ChA), Native Americans (NA) and Xiamen Chinese (XC). DR2 subtypes were compared amongst the five ethnic populations. The DRB1*1501-DRB5*0101 haplotype was found to be the most frequent in all populations except African Americans, in which DRB1*1503-DRB5*0101 was the predominant haplotype, accounting for 65% of DR2 subtypes. In contrast to Caucasoid Americans, the DRB1*1602 is strongly associated with the DRB5*0101 allele in Chinese populations. The presence of DRB5*0203 and DRB1*1602-DRB5*0101 haplotypes in Chinese populations, especially in Xiamen Chinese, suggests that various DR2 haplotypes may be generated via multiple gene conversion events together with point mutations and reciprocal recombination. The strong DR and DQ associations are found in DRB1*1501/DQB1*0602 (66.22%) for CA, DRB1*1503/DQB1*0602 (56.58%) for AA, DRB1*1501/DQB1*0602 (30.20%) and DRB1*1602/DQB1*0502 (15.76%) for ChA, DRB1* 1501/DQB1*0602 (41.55%) and DRB1*1602/DQB1*0301 (40.25%) for NA, and DRB1*1501/DQB1*0602 (30.26%) and DRB1*1602/DQB1*0502 (25.81%) for XC.

Alleles↗

PubMed1999

Systematic mutation analysis of the catechol O-methyltransferase gene as a candidate gene for schizophrenia.

OBJECTIVE: Catechol O-methyltransferase (COMT) is involved in the degradation of catecholamine neurotransmitters. Recent linkage studies of schizophrenia and molecular studies of velocardiofacial syndrome suggest that the COMT gene might be a candidate gene for schizophrenia. METHOD: The authors systematically searched for mutations and microdeletion of the COMT gene in 177 Chinese schizophrenic patients from Taiwan; 99 comparison subjects were also studied. RESULTS: Five molecular variants were identified: c.186C > T at exon 3, c.408C > G at exon 4, c.472G > A at exon 4, c.597G > A at exon 5, and c.821-827insC at the 3' untranslated region. However, no differences in the genotype and haplotype frequencies of these molecular variants between the schizophrenic and comparison subjects were detected. Furthermore, no microdeletion was identified among the patients. CONCLUSIONS: These data suggest that the COMT gene does not play a major role in the pathogenesis of schizophrenia, and the genotypic overlap between schizophrenia and velocardiofacial syndrome was rare in this cohort.

Catechol O-Methyltransferase↗

PubMed1999

Gender differences in the presentation of adult obstructive hypertrophic cardiomyopathy with resting gradient: a study of 122 patients.

The present study investigated gender differences among adult patients with obstructive hypertrophic cardiomyopathy (OHCM) and resting gradient. Using outflow gradients >10 mmHg and the presence of asymmetrical septal hypertrophy of the left ventricle as inclusion criteria, 122 patients were identified among patients referred for echocardiographic examinations between May 1990 and October 1996. Clinical, echocardiographical and follow-up data were compared between male and female patients. The female patients were significantly older than male patients (mean age +/-SD 66.7+/-10.5 vs 54.8+/-12.5 years). The female patients had a smaller interventricular septal wall thickness, less frequent systolic anterior movement of the mitral valve, more frequent association with hypertension, and less frequent association with ischemic heart disease (IHD) and giant T wave inversion. In this study population, adult female patients presented with OHCM 12 years later than males. Whether this represents female patients' reluctance to seek medical attention early, a different disease process that affects predominantly elderly females, or a gender-specific end organ response to aging, hypertension, IHD and other processes, or the protective effects of estrogen remains to be determined.

Adolescent↗