Showing papers by "Taipei Veterans General Hospital published in 2001"

Acquired pulmonary vein stenosis after radiofrequency catheter ablation of paroxysmal atrial fibrillation.

Abstract: PV Stenosis after AF Ablation.Introduction: Elimination of the initiating focus within the pulmonary vein (PV) using radiofrequency (RF) catheter ablation is a new treatment modality for treatment of drug-refractory atrial fibrillation. However, information on the long-term safety of RF ablation within the PV is limited. Methods and Results: In 102 patients with drug-refractory atrial fibrillation and at least one initiating focus from the PV, series transesophageal echocardiography was performed to monitor the effect of RF ablation on the PV. There were 66 foci in the right upper PV and 65 foci in the left upper PV. Within 3 days of ablation, 26 of the ablated right upper PVs (39%) had increased peak Doppler flow velocity (mean 130 ± 28 cm/sec, range 106 to 220), and 15 of the ablated left upper PVs (23%) had increased peak Doppler flow velocity (mean 140 ± 39 cm/sec, range 105 to 219). Seven patients had increased peak Doppler flow velocity in both upper PVs. No factor (including age, sex, site of ablation, number of RF pulses, pulse duration, and temperature) could predict PV stenosis after RF ablation. Three patients with stenosis of both upper PVs experienced mild dyspnea on exertion, but only one had mild increase of pulmonary pressure. There was no significant change of peak and mean flow velocity and of PV diameter in sequential follow-up studies up to 16 (209 ± 94 days) months. Conclusion: Focal PV stenosis is observed frequently after RF catheter ablation applied within the vein, but usually is without clinical significance. However, ablation within multiple PVs might cause pulmonary hypertension and should be considered a limiting factor in this procedure.

Chronic Daily Headache in Taipei, Taiwan: Prevalence, Follow-Up and Outcome Predictors

Abstract: We conducted a two-stage population-based headache survey among subjects aged > or = 15 in Taipei, Taiwan. Subjects with chronic daily headache (CDH) in the past year were identified, interviewed and followed-up. CDH was defined as a headache frequency > 15 days/month, with a duration > 4 h/day. Of the 3377 participants, 108 (3.2%) fulfilled the criteria for CDH, with a higher prevalence in women (4.3%) than men (1.9%). TM was the most common subtype (55%), followed by CTTH (44%). Thirty-four per cent of the CDH subjects overused analgesics. At the 2-year follow-up, 35% of the CDH subjects still had CDH. The significant predictors for persistent CDH at follow-up included: older age ( > or = 40 years) (RR = 2.4), CDH onset after 32 years (RR = 1.8), CDH duration > or = 6 years (RR = 2.0), medication overuse (RR = 1.8), and "daily" headache (RR = 2.1). We found that CDH is not uncommon in the community and its prevalence is similar among different populations. Older subjects and those with medication overuse may have a more protracted course of illness.

Quality of life differs among headache diagnoses: analysis of SF-36 survey in 901 headache patients

Abstract: This paper presents the results of health-related quality of life (HRQoL) in 901 patients consecutively visiting a headache clinic of a national medical center in Taipei, Taiwan. HRQoL was evaluated with the Medical Outcome Study-Short Form (SF-36) and the Hospital Anxiety and Depression Scale (HADS). According to the classification criteria for chronic daily headache (CDH) proposed by Silberstein et al. (Neurology 47 (1996) 871) five hundred and ninety-three (66%) patients had CDH, of whom transformed migraine (TM) was diagnosed in 310, and chronic tension-type headache (CTTH) in 231. One hundred and ninety-three patients had episodic migraine. All SF-36 scale scores significantly correlated with the HADS scores and the intensity and frequency of pain. Compared with the normative data, a pervasive multi-dimensional decline of the SF-36 scores was noted among the headache patients except for the physical functioning scale. The decline was most remarkable in the role limitations of physical and emotional dimensions and in the bodily pain. An increasing impairment of the SF-36 scores was noted from migraine to CTTH to TM. After controlling for the HADS, age, gender, education, and chronic illness by multiple linear regression analyses, the patients with TM had the worst SF-36 profile; whereas, the patients with CTTH and migraine had compatible results. This study is the first to demonstrate that the SF-36 scores differ among headache diagnoses. Psychological distress, as well as the percentages of the types of patients, greatly influenced the SF-36 scores in hospital-based headache samples. Our findings also suggest that improvement in the pain profile as well as psychological well-being can predict a generalized improvement in the SF-36 scales in headache patients.

Salvianolic acid B attenuates VCAM-1 and ICAM-1 expression in TNF-alpha-treated human aortic endothelial cells.

Abstract: Attachment to, and migration of leukocytes into the vessel wall is an early event in atherogenesis. Expression of cell adhesion molecules by the arterial endothelium may play a major role in atherosclerosis. It has been suggested that antioxidants inhibit the expression of adhesion molecules and may thus attenuate the processes leading to atherosclerosis. In the present study, the effects of a potent water-soluble antioxidant, salvianolic acid B (Sal B), and an aqueous ethanolic extract (SME), both derived from a Chinese herb, Salvia miltiorrhiza, on the expression of endothelial-leukocyte adhesion molecules by tumor necrosis factor-alpha (TNF-alpha)-treated human aortic endothelial cells (HAECs) were investigated. When pretreated with SME (50 and 100 microg/ml), the TNF-alpha-induced expression of vascular adhesion molecule-1 (VCAM-1) was notably attenuated (77.2 +/- 3.2% and 80.0 +/- 2.2%, respectively); and with Sal B (1, 2.5, 5, 10, and 20 microg/ml), 84.5 +/- 1.9%, 78.8 +/- 1.2%, 58.9 +/- 0.4%, 58.7 +/- 0.9%, and 57.4 +/- 0.3%, respectively. Dose-dependent lowering of expression of intercellular cell adhesion molecule-1 (ICAM-1) was also seen with SME or Sal B. In contrast, the expression of endothelial cell selectin (E-selectin) was not affected. SME (50 microg/ml) or Sal B (5 microg/ml) significantly reduced the binding of the human monocytic cell line, U937, to TNF-alpha-stimulated HAECs (45.7 +/- 2.5% and 55.8 +/- 1.2%, respectively). SME or Sal B significantly inhibited TNF-alpha-induced activation of nuclear factor kappa B (NF-kappaB) in HAECs (0.36- and 0.48-fold, respectively). These results demonstrate that SME and Sal B have anti-inflammatory properties and may explain their anti-atherosclerotic properties. This new mechanism of action of Sal B and SME, in addition to their previously reported inhibition of LDL, may help explain their efficacy in the treatment of atherosclerosis.

Pulmonary vein dilation in patients with atrial fibrillation: detection by magnetic resonance imaging.

Abstract: Pulmonary Vein Dilation in AF. Introduction: The positive relationship between left atrial (LA) size and atrial fibrillation (AF) is well recognized; however, there is little information on the association of pulmonary vein (PV) diameter and AF. The purpose of this study was to investigate by magnetic resonance angiography the change of PV and LA size in patients with no history of AF, patients with paroxysmal AF (PAF), and patients with chronic AF (CAF). Methods and Results: The study included 47 patients. Group I included 15 patients with normal sinus rhythm and no history of documented AF. Group II included 24 patients with drug-refractory PAF who underwent electrophysiologic study and radiofrequency ablation of PV foci. Group III included 8 patients with CAF who were converted to sinus rhythm by external electrical cardioversion. Age and concomitant heart diseases were similar among the three groups. We measured the diameter of each PV at its junction with the LA in addition to LA dimensions by gadolinium-enhanced magnetic resonance angiography with three-dimensional reconstruction. Significant dilation of both superior PVs (P < 0.01) and transverse diameter of LA (P < 0.01) was seen in the three groups. There were no significant changes of both inferior PVs, corrected PV (PV/LA) diameter, or longitudinal diameter of LA among the three groups. Only 28% patients showed arrhythmogenic foci from the largest PV. Conclusion: Significant dilation of both superior PVs with simultaneous LA enlargement was demonstrated in PAF and CAF patients. Although PV size cannot predict AF firing, the anatomic and geometric differences may participate in perpetuation of AF.

Cefuroxime-impregnated cement at primary total knee arthroplasty in diabetes mellitus: A PROSPECTIVE, RANDOMISED STUDY

Abstract: We have performed a prospective single-blinded randomised study to evaluate the role of antibiotic-impregnated cement in the prevention of deep infection at primary total knee arthroplasty (TKA) in patients with diabetes mellitus. We studied prospectively 78 arthroplasties performed for osteoarthritis in such patients. They were randomly separated into two groups. In group 1 (41 knees), cefuroxime-impregnated cement was used while in group 2 (37 knees) cefuroxime was not added to the cement. The preoperative, intraoperative and postoperative management was the same for both groups. The mean follow-up was 50 months (26 to 88). There were no cases of deep infection in group 1, but five (13.5%) occurred in group 2 (p = 0.021). We conclude that cefuroxime-impregnated cement is effective in the prevention of deep infection at primary TKA in patients with diabetes mellitus.

A left-lateralized network for reading Chinese words: A 3 T fMRI study

Abstract: fMRI was used to investigate brain organization for reading in Chinese. Subjects were shown two-character Chinese words. A control task was used to eliminate the non-linguistic visual and motor confounds. Results show that naming of Chinese logographs is characterized by left-lateralized neuronal networks for the processing of orthographic, phonological, and semantic attributes. The orchestration of the middle frontal cortex, superior temporal cortex, superior parietal cortex, basal temporal area and extrastriate cortices of the left hemisphere may manifest the particularity of the central representation of simple word naming in Chinese.

Spinocerebellar ataxia type 2 presenting as familial levodopa-responsive parkinsonism.

Abstract: A genetic analysis identified 2 patients, approximately one-tenth of our patients with familial parkinsonism, who had expanded trinucleotide repeats in SCA2 genes. The reduction of 18F-dopa distribution in both the putamen and caudate nuclei confirmed that the nigrostriatal dopaminergic system was involved in parkinsonian patients with SCA2 mutation.

Thymoma is associated with an increased risk of second malignancy

Abstract: BACKGROUND An association between thymoma and second malignancy has been suggested but has not been validated. Whether the relation is due to treatment or to other thymoma-associated conditions is unclear. METHODS The authors studied 192 consecutive patients with thymoma and compared the incidence of second malignancies with those of 206 patients who underwent thymectomy for nonthymomatous conditions and 1426 patients with nasopharyngeal carcinoma (NPC). Detailed clinicopathologic features of thymoma patients with second malignancies were described. RESULTS Additional malignancies were detected in 15 of 192 patients (8%) during their clinical courses. The risk for those patients was significantly greater compared with the risk for patients with nonthymomatous conditions (adjusted odds ratio [OR], 3.81; 95% confidential intervals [95%CI], 1.05–13.81; P = 0.042) and patients with NPC (adjusted OR, 4.89; 95%CI, 2.26–10.53; P < 0.0001) after adjustment for age, gender, length of follow-up, myasthenia gravis, and radiation therapy. The occurrence of second malignancies did not correlate with histologic type or stage of thymoma, radiation therapy, or myasthenia gravis. CONCLUSIONS Thymoma is associated with an increased risk of second malignancy. The association cannot be attributed to the effect of thymectomy or radiation therapy. Patients with thymoma, even if it is benign, should be followed regularly to facilitate the early detection of other malignancies. Cancer 2001;92:2406–11. © 2001 American Cancer Society.

Quantitative assessment of retinal thickness in diabetic patients with and without clinically significant macular edema using optical coherence tomography

Abstract: PURPOSE: To assess patients with diabetic macular edema quantitatively using optical coherence tomography (OCT). METHODS: OCT was performed in 14 eyes with diabetic retinopathy and ophthalmoscopic evidence of clinically significant macular edema (CSME) and in 19 diabetic eyes without CSME. Retinal thickness was computed from the tomograms at fovea and other 36 locations throughout the macula. RESULTS: The mean +/- standard deviation foveal thickness was 255.6 +/- 138.9 microm in eyes with CSME, and 174.6 +/- 38.2 microm in eyes without CSME (p = 0.051). Within 2000 microm of the center of the macula, eyes with CSME had significantly thicker retina in the inferior quadrant than those without CSME (p < 0.01). The foveal thickness was correlated with logMAR visual acuity (gamma = 0.68, p < 0.01). OCT identified sponge-like retinal swelling and/or cystoid macular edema in 11 (58%) eyes without CSME, and in 12 (86%) eyes with CSME. CONCLUSIONS: Criteria of CSME seem to be insufficient in really identifying macular edema. OCT may be more sensitive than a clinical examination in assessing diabetic macular edema and is a quantitative tool for documenting changes in macular thickening.

IL‐17 expression as a possible predictive parameter for subclinical renal allograft rejection

Abstract: In the present study we have tried to establish the role of IL-17 in subclinical renal allograft rejection. In this animal model, renal grafts from BN (RT1n) were transplanted heterotopically into LEW (RT1l) rats. As controls, LEW grafts were transplanted into LEW rats. The histopathological examination demonstrated that the changes in the allograft kidney on day 2 were similar to those ranked as borderline changes according to the Banff classification scale. On day 2, the serum level of blood urea nitrogen (BUN) and creatinine were the same as on day 1. The examination of allograft cytokines mRNA showed that IL-17 mRNA expressed earlier on the second postoperative day, peaked at day 5, and then declined, becoming almost undetectable at day 9, when most rats died. IL-17 antigen was also proven, by histochemical staining, to be expressed early, however we could not find the same early appearance on other Th1/Th2 cytokines. In human renal biopsy samples, the IL-17 antigen could be found scattered around in the borderline changed rejected renal allografts without evidence of a serum creatinine increase, but was undetectable both in normal controls and in renal transplant tissue without signs of rejection. IL-17 mRNA was detected in the mononuclear cells of the urinary sediment of patients suffering from borderline subclinical rejection. From the above results we can hypothesize that IL-17 could serve as a predictive parameter for borderline subclinical renal allograft rejection in the future.

Thermal symmetry of skin temperature: normative data of normal subjects in Taiwan.

Abstract: BACKGROUND The aims of this study were (a) to establish normative data of thermal symmetry (left vs. right) in normal subjects; (b) to compare the skin temperature in various regions between young and old people in Taiwan and between male and female. METHODS The skin surface of 57 healthy volunteers (aged 24 to 80 yr) was divided into 25 areas and measured by an infrared thermography (Avionics TVS-2000, Japan). The average temperatures of these 25 regions were compared: (a) left vs. right side, (b) young ( 60 yr, n = 20), and (c) male vs. female. Student's t-test was used to assess means between both groups. RESULTS The neck carried the highest skin temperature (31.9 degrees C +/- 0.6; mean +/- SD) of the body in comparison with the toes that had the lowest one (27.5 degrees C +/- 2.0). The side-to-side temperature differences were subtle, which did not exceed 0.5 degrees C. The average skin temperature of elderly was slightly lower than that of young subjects in 11 out of 25 areas (p < 0.05), especially the distal parts of extremities. Elderly female had lower skin temperature in various truncal areas as compared with their counterpart. However, the skin temperature was higher in the distal extremity (p < 0.05). CONCLUSIONS The thermoregulatory system is substantially symmetrical. The result of this study offered valuable normative database on skin thermal symmetry in normal population of Taiwan, and may be useful as a diagnostic aid in patients with various states of disorders associated with autonomic dysfunctions.

Comparative genomic hybridization of esophageal squamous cell carcinoma: correlations between chromosomal aberrations and disease progression/prognosis.

Abstract: BACKGROUND Esophageal carcinoma is a major cause of cancer-related deaths among males in Taiwan. However, to date, the genetic alterations that accompany this lethal disease are not understood. METHODS Chromosomal aberrations of 46 samples of esophageal squamous cell carcinoma (EC-SCC) were analyzed by comparative genomic hybridization (CGH), and their correlations with pathologic staging and prognosis were analyzed statistically. RESULTS In total, 321 gains and 252 losses were found in 46 tumor samples; thus, the average gains and losses per patient were 6.98 and 5.47, respectively. Frequent gain abnormalities were found on chromosome arms 1q, 2q, 3q, 5p, 7p, 7q, 8q, 11q, 12p, 12q, 14q, 17q, 20q, and Xq. Frequent deletions were found on chromosome arms 1p, 3p, 4p, 5q, 8p, 9p, 9q, 11q, 13q, 16p, 17p, 18q, 19p, and 19q. It was found that deletions of 4p and 13q12–q14 and gain of 5p were significantly correlated with pathologic staging. Losses of 8p22-pter and 9p also were found more frequently in patients with advanced disease. Gain of 8q24-qter was seen more frequently in patients with Grade 3 tumors. A univariate analysis found that pathologic staging; gains of 5p and 7q; and deletions of 4p, 9p, and 11q were significant prognostic factors. However, pathologic staging became the only significant factor in a multivariate analysis. CONCLUSIONS CGH not only revealed novel chromosomal aberrations in EC-SCC, but also found possible genotypic changes associated with disease progression. Despite all of the possible associations of chromosomal aberrations with disease progression, the most important prognostic factor for patients with EC-SCC was pathologic staging. Cancer 2001;92:2769–77. © 2001 American Cancer Society.

Life-threatening hypersensitivity pneumonitis induced by docetaxel (taxotere).

Abstract: 4 patients with advanced non-small-cell lung cancer (NSCLC) treated with docetaxel developed life-threatening pneumonitis requiring mechanical ventilation. Docetaxel (30–60 mg m−2, according to a different protocol) was infused within one hour with standard premedications. One patient's pneumonitis occurred 5 days after the first dose of docetaxel, and that of the other 3 between the 2nd and 6th cycles. Based on the clinical course, radiological findings of an interstitial pneumonitis, and exclusion of other possible resultant causes, including metastatic cancer, radiation pulmonary injury, infection, or connective tissue disease, hypersensitivity pneumonitis was diagnosed. The patients were treated with hydrocortisone at 1200 mg per day or methylprednisolone at 240 mg per day. Although 3 of the 4 had a partial improvement in lung oxygenation, all patients’ conditions of hypersensitivity pneumonitis persisted and were complicated by other events, such as hospital-acquired infection and tension pneumothorax. The presence of this unusual hypersensitivity pneumonitis, which was so severe as to be life-threatening and refractory to high-dose corticosteroid therapy, should be taken into account during docetaxel treatment. © 2001 Cancer Research Campaign

Acetylcholinesterase Inhibition and the Extrapyramidal Syndrome: A Review of the Neurotoxicity of Organophosphate

Abstract: Organophosphate poisonings are not uncommon, and are the leading cause of death in suicide patients in Taiwan Acute cholinergic crisis caused by the inhibition of synaptic acetylcholinesterase is the major manifestation of organophosphate poisoning and may cause death within minutes Delayed neurotoxicities include intermediate syndrome and delayed polyneuropathy have also been described However, these symptoms may not characterize the complete picture of organophosphate poisoning Among the 633 patients ever admitted to our hospital with organophosphate poisoning, three patients were found exhibiting impermanent neuromuscular dysfunction, including blepharoclonus, oculogyric crisis, intermittent dystonia, rigidity, and tremor, with two of them developing mask face, dyskinesia and akathisia later, following acute cholinergic crisis The symptoms appeared within 4 days with the duration ranging from 25 days to 2 months Other causes of the extrapyramidal syndrome noted on these patients have been excluded, and we consider the extrapyramidal syndrome a possible neurotoxic manifestation of organophosphate poisoning, which is transient, needs no treatment, and may be missed because of the critical condition, in a minority of patients The mechanism remains to be identified, but may be related to the impediment of the function of acetylcholinesterase to modify nigrostriatal dopaminergic system, which is independent of hydrolyzing acetylcholine More detailed observation for organophosphate poisoned patients and more studies for the biological functions of acetylcholinesterase including the influence on the nigrostriatal dopaminergic system are needed

Human papillomavirus type 18 in colorectal cancer.

Abstract: Human papillomaviruses (HPVs) have been recognized as the etiological agent of warts, and they may also be associated with many cancers. HPV-18 is very common both in genital papillomas and in large bowel cancer. The relation between HPV-18 infection and natural course of colorectal cancer has not been fully defined. In this study, normal mucosa and colorectal cancer tissue were evaluated for the presence of HPV gene to determine whether or not HPV was involved in the development of colon neoplasm. The DNA extracted from colon tissue was screened for HPV by polymerase chain reaction (PCR) to amplify the viral gene fragment. These PCR products were digested with restriction enzyme, and Southern blotting was then performed to confirm the existence of HPV-18. The nucleotide sequence related to HPV-18 DNA was detected in 53% (10/19) of the normal mucosa specimens and in 84% (16/19) of the colorectal cancer specimens. The correlation between cancer samples and positive rate of HPV-PCR was statistically significant by chi-square test (p < 0.01). These data indicate that HPV-18 can infect the normal mucosa of the colon, and that this infection may be a risk factor for the development of colorectal cancer. The presence of HPV-18 DNA in patients with colorectal cancer suggests that the pathogenesis of colorectal cancer includes viral involvement.

Accumulation of mitochondrial DNA deletions in human oral tissues — effects of betel quid chewing and oral cancer

Abstract: Accumulation of mitochondrial DNA (mtDNA) mutations in human tissues has been associated with intrinsic aging and environmental insult. Recently, mtDNA mutations have been detected in various tumors, including head and neck tumors. However, the factors affecting the occurrence and accumulation of mtDNA deletions in tumor tissues are poorly understood. In Taiwan, betel quid chewing is a major risk factor for oral cancer. Using polymerase chain reaction (PCR) techniques, we examined large-scale deletions of mtDNA in 53 pairs of tumor and non-tumor oral tissues from the patients with or without betel quid chewing history. The results revealed that irrespective of the history of betel quid chewing, the incidences of the 4977bp deletion and other deletions of mtDNA were lower in the tumor portion as compared with the non-tumor portion. The average proportions of the 4977bp deleted mtDNA in the tumor tissues of the betel quid chewers and non-betel quid chewers were 13- and 5-fold, respectively, lower than those in the corresponding non-tumor tissues. Moreover, the average proportion of 4977bp deleted mtDNA was significantly higher (P<0.05) in the non-tumor oral tissues of the patients with betel quid chewing history than that of the patients without the history of betel quid chewing. These results suggest that betel quid chewing may increase mtDNA mutation in human oral tissues and that accumulation of mtDNA deletions and subsequent cytoplasmic segregation of these mutations during cell division could be an important contributor to the early phase of oral carcinogenesis.

Persistent migrainous visual phenomena might be responsive to lamotrigine

Abstract: Two patients with migraine reported having experienced persistent auralike visual phenomena for months to years. All laboratory investigations were normal except for occipital hypoperfusion on the brain single photon emission computed tomography. After lamotrigine treatment for 2 weeks, they both had a resolution of the visual symptoms. Persistent migrainous visual phenomena are potentially benign and probably a status of spontaneous aura.

Visual impairment in a Taiwanese population: Prevalence, causes, and socioeconomic factors

Abstract: PURPOSE We sought to estimate the prevalence of visual impairment among an elderly population in urban Taiwan, determine the causes of visual impairment, and gain information about certain socioeconomic factors associated with visual impairment.METHODS A population-based survey of ocular diseases in residents aged 50 years or older was conducted in Peitou Precinct, Taipei, Taiwan. All participants underwent a comprehensive ophthalmic examination, including visual acuity measurement, using standardized protocols. Demographic data, marital status, employment status, and educational level were gathered through an interview.RESULTS A total of 2034 participants completed the visual acuity measurements. The prevalence of visual impairment (defined as best-corrected visual acuity in the better eye <6/18) among this population was 2.75% (95% confidence intervals: 2.04%–3.46%). Three major causes of visual impairment were cataract (30.4%), high myopic macular degeneration (25.0%), and age-related macular d...

A silent mutation induces exon skipping in the phenylalanine hydroxylase gene in phenylketonuria.

Abstract: An A-->T substitution in cDNA nucleotide 1197 (c.1197A/T) of the human phenylalanine hydroxylase (PAH) gene has been regarded as a silent mutation, because both the wild-type (GUA) and the mutant (GUU) alleles encode a valine residue at codon 399 (V399 V). The nucleotide c.1197 is located at the 3'-end of exon 11at position -3 of the exon-intron junction. To explore whether the substitution exerts any effects on the processing of the PAH mRNA, illegitimate PAH transcripts from lymphoblast cultures of a phenylketonuria (PKU) patient heterozygous for c.1197A/T were analyzed by the polymerase chain reaction following reverse-transcription (RT-PCR). mRNAs with an exon 11 deletion were revealed. Furthermore, by using an R408 W mutation in the paternal allele as a marker, sequence analysis of the RT-PCR products indicates that virtually all PAH transcripts from the maternal allele with the c. 1197A/T substitution do not contain exon 11. To address whether this substitution is the main determinant for exon skipping, PAH minigenes with or without the substitution were constructed and transfected to a human hepatoma cell line. Analysis of the transcription products by S1 nuclease mapping clearly indicated that such exon 11 skipping was directly associated with the c.1197A/T substitution. Thus, this study demonstrates that the c.1197A/T substitution in the PAH gene is not just a neutral polymorphism but a mutation that induces post-transcriptional skipping of exon 11 leading to a PKU phenotype.