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Background and Aim: Partial oculocutaneous albinism and immunodeficiency (OCA-ID) diseases are autosomal recessive syndromes characterized by partial hypopigmentation and recurrent infections. Moreover, some OCA-ID syndromes confer susceptibility to develop a life-threatening hyperinflammatory condition called hemophagocytic lymphohistiocytosis (HLH). We investigated the genetic, clinical and immunological characteristics of 20 OCA patients., Material and Methods: Herein, we present the clinical and immunological characteristics of 20 OCA patients who referred to the Department of Pediatric Immunology, Erciyes University Medical Faculty in Kayseri, Turkey between 2004 and 2014., Results: Of the 20 OCA patients, 7 fulfilled diagnostic criteria for HLH, 9 showed defective functions of CD8 T cells and natural killer cells, and 8 received a definitive molecular diagnosis. Among the patients, we also report a patient diagnosed with two different genetic defects, in TYR and JAK3 genes, causing, respectively, OCA and ID., Conclusion: Our results illustrate the variability of clinical presentations and disease severity in OCA-ID patients, with consequent challenges in diagnosing and treating these patients.

Background: Tuberculosis (TB) has been reported to increase morbidity after kidney transplantation and pose a therapeutic challenge. However, population-based research, specifically focused on the association between kidney transplantation and subsequent pulmonary or extrapulmonary TB, is lacking., Methods: A nationwide population-based study was conducted using Taiwan's National Health Insurance Research Database, which provided claims data belonging to kidney transplant recipients during 1997-2006. Multivariate analysis was used to identify independent risk factors for TB after kidney transplantation. Kaplan-Meier survival analysis was used to assess the outcome of patients with TB., Results: Among 4554 kidney transplant recipients over the 10-year period, 109 (2.4%) patients with newly diagnosed TB were identified: 75 patients with only pulmonary involvement, and 34 with extrapulmonary spread. The incidence of kidney transplant recipients developing TB was 638 per 100,000 person-years. The independent risk factors for post-transplant TB included cyclosporine-based immunosuppressant agents during the first year after kidney transplantation (odds ratio [OR]: 1.98, P = 0.001), hepatitis C infection (OR: 1.79, P = 0.024), and chronic obstructive pulmonary disease (OR: 1.50, P = 0.041). Kidney transplant recipients who developed TB had a lower 5-year survival rate than those who did not (78.6% vs. 93.4%, P = 0.001)., Conclusions: Kidney transplant recipients in Taiwan did have a high risk of TB infection, with high proportion of extrapulmonary spread. Physicians need to be vigilant in surveying for TB in kidney transplantation, especially in high-risk patients., (© 2012 John Wiley & Sons A/S.)

The objective of this study was to compare the effects of risperidone and olanzapine in schizophrenic patients with intolerant extrapyramidal side effects (EPS) on first generation antipsychotics. We conducted an 8-week, rater-blinded, flexible dose study. Seventy patients with schizophrenia, who met the DSM-IV research criteria of having neuroleptic-induced acute dystonia or parkinsonism, were randomly assigned to risperidone or olanzapine group. The primary outcome was a comparison of the incidence of concomitant anticholinergic drugs usage between the groups to manage their acute dystonia and parkinsonism. The average doses of risperidone and olanzapine from baseline to study end point were 1.8-3.5 mg/day and 7.7-11.7 mg/day, respectively. There were no significant differences in demographic data, severity of EPS or psychotic symptoms between the groups at baseline assessment. Patients taking risperidone had significantly higher incidence of using anticholinergic drugs to manage acute dystonia or parkinsonism overall during the study (OR = 5.17, 95%CI = 1.49-17.88, P = 0.013). There was no significant between-group difference in the changing of rating scales of EPS and psychotic symptoms. The results of our study favour olanzapine as a better choice in schizophrenic patients with intolerant EPS. Double-blinded, fixed dose and different ethnical study for EPS-intolerant schizophrenic patients is needed to confirm the results of our study.

Summary: A traditional approach for assessing similarity among N (N > 2) communities is to use multiple pairwise comparisons. However, pairwise similarity indices do not completely characterize multiple-community similarity because the information shared by at least three communities is ignored. We propose a new and intuitive two-stage probabilistic approach, which leads to a general framework to simultaneously compare multiple communities based on abundance data. The approach is specifically used to extend the commonly used Morisita index and NESS (normalized expected species shared) index to the case of N communities. For comparing N communities, a profile of N- 1 indices is proposed to characterize similarity of species composition across communities. Based on sample abundance data, nearly unbiased estimators of the proposed indices and their variances are obtained. These generalized NESS and Morisita indices are applied to comparison of three size classes of plant data (seedling, saplings, and trees) within old-growth and secondary rain forest plots in Costa Rica.

Study Objective: To establish a predictive scoring system and to determine its effectiveness for severe acute respiratory syndrome (SARS) cases confirmed by RT-PCR in patients with fever., Methods: A study was conducted of 484 consecutive patients seen in the emergency department (ED) of our tertiary care center during the SARS outbreak in Taiwan. The scoring system was divided into triage and screening station stages. Data were analysed with multivariable and logistic regression analysis., Results: Of 737 patients who presented to our ED for possible SARS from March to June 2003, we enrolled 484 patients with a temperature >38.0 degrees C (>100.3 degrees F) (age >18 years). Dyspnoea, diarrhoea, travel, close contact, hospital exposure, and household history were identified as predictive indicators in the triage stage. The triage score was the total of six items. With a one-point cutoff value, the sensitivity and specificity were 81.8% (18/22) and 73.6% (340/462). Leukocytosis, thrombocytopenia, lymphopenia, and CXR were identified as predictive indicators in the fever screening stage. Screening station scores (the sum of 10 items) consisted of triage scores, white blood cell count, and CXR. With a three-point cutoff value, the sensitivity and specificity were 95.5% (21/22) and 87.2% (403/462)., Conclusions: Syndromic and traditional surveillance play a role in early identification of SARS in an endemic area. The SARS scoring system described is easily applicable and highly effective in screening patients during outbreaks.

Fabry disease is an X-linked disorder caused by a deficiency of the lysosomal alpha-galactosidase A [EC 3.2.1.22]. The molecular diagnosis of Fabry disease is important for genotype/phenotype correlation, pre-natal or early diagnosis, and detection of carrier status. Although more than 200 genotypes of the alpha-galactosidase A gene have been identified, mutation data on the Chinese population is sparse. We recently identified two unrelated Chinese families with Fabry disease. Mutation analysis was performed by polymerase chain reaction (PCR) sequencing of the seven exons and adjacent introns of the alpha-galactosidase A gene. Two novel mutations were identified: in family I, a C-to-A transversion resulted in an early termination at amino acid 222 (Y222X), while in family II, an A-to-G transition resulted in a substitution of alanine for threonine at amino acid 410 (T410A). Carrier status was identified in all four females in the two families. The genotype Y222X is associated with classic Fabry disease, with unexpectedly rapid deterioration of visual acuity, while T410A is associated with a milder Fabry disease, with ventricular hypertrophy and neuropathic pain., (Copyright Blackwell Munksgaard, 2003)

The purpose of the study was to identify a good abdominal obesity index for insulin resistance in offspring of diabetic patients. A total of 74 non-diabetic subjects (male =36; female =38) were recruited from a diabetic family study. The waist circumference (W), waist-hip ratio (WHR) and conicity index were used as the abdominal obesity indices. The body mass index (BMI) and indices obtained from bioelectric impedance analysis (BIA) (body fat percentage, fat mass and fat mass index) were used as overall obesity indices. Fasting plasma insulin (FPI), homeostasis model assessment for insulin resistance (HOMA-IR) and Matsuda-Defronzo index from oral glucose tolerance test were chosen as the insulin sensitivity indices. We correlated obesity indices with insulin resistance indices with age and family adjusted. W was closely correlated in both sexes of subjects with Matsuda-DeFronzo index (male, r=-0.661,p<0.001; female, r=-0.419,p=0.026), FPI (male, r=0.614,p=0.001; female, r=0.503,p=0.006) and HOMA-IR (male, r=0.609,p=0.001; female, r=0.472,p=0.011). WHR and its log transformation predicted insulin resistance only in males. BMI as an overall obesity index was in good correlation with Matsuda-DeFronzo index (male, r=-0.646,p<0.001; female, r=-0.469,p=0.012), FPI (male, r=0.711,p<0.001; female, r=0.464,p=0.013) and HOMA-IR (male, r=0.708,p<0.001; female, r=0.469,p=0.012). Overall obesity indices from BIA were similar to BMI to predict insulin resistance. In conclusion, W is a good abdominal obesity predictor of insulin resistance in offspring of diabetic patients in Taiwan.

The role of new cytotoxic agents like gemcitabine has not yet been proven in the neoadjuvant settings. We designed a phase II study to test the feasibility of using gemcitabine and cisplatin before local treatment for stage III non-small cell lung cancer patients. Patients received three cycles of induction chemotherapy of gemcitabine (1000 mg m(-2), days 1, 8, 15) and cisplatin (90 mg m(-2), day 15) every 4 weeks before evaluation for operability. Operable patients underwent radical resection. Inoperable patients and patients who had incomplete resection received concurrent chemoradiotherapy with daily low dose cisplatin. All patients who did not progress after local treatment received three more cycles of adjuvant chemotherapy of gemcitabine and cisplatin. Fifty-two patients received induction treatment. Two patients had complete response and 31 patients had partial response (response rate 63.5%) after induction chemotherapy. Thirty-six patients (69%) were operable. Eighteen patients (35%) had their tumours completely resected. Two patients had pathological complete response. Median overall survival was 19.1 months, projected 1-year survival was 66% and 2-year survival was 34%. Three cycles of gemcitabine and cisplatin is effective and can be used as induction treatment before surgery for locally advanced non-small cell lung cancer patients., (Copyright 2002 The Cancer Research Campaign)

Ten cases of tetrahydrobiopterin (BH4) deficiency were identified in 1,337,490 newborns screened in a Chinese population in Taiwan. The high incidence of BH4 deficiency in the Taiwanese population may be explained by a founder effect, since all of the patients revealed 6-pyruvoyltetrahydropterin synthase gene mutations, and grouping N52S and P87S mutations together constituted 88.9% of the disease alleles. BH4 supplementation with restriction of high-protein foods gave control of plasma phenylalanine within normal range, and levodopa itself prevented seizure. However, the average intelligence quotient (IQ) score of these patients was only 76 +/- 14 (56-98). Statistically, the age of starting medication, including 5-hydroxytryptophan (5-HTP), was inversely correlated to IQ scores of these patients. We suggest the combination of BH4, levodopa and 5-HTP as the standard protocol to commence the treatment of BH4 deficiency as early as possible, although prenatal brain damage could have existed.

Acyclovir, a specific and selective inhibitor of the replication of Herpesviridae family, has well-documented efficacy and tolerability in the treatment of herpes zoster. Its limited oral bioavailability and short half-life, however, necessitates frequent dosing. Valaciclovir, the l-valyl ester of acyclovir, could be rapidly converted to acyclovir after oral administration, resulting in a three- to five-fold increase in acyclovir bioavailability compared with oral acyclovir in humans. Valaciclovir allows less frequent dosing and maintains the safety profiles of the parent drug. During the period from October 1996 through May 1998, a randomized, prospective study was performed in the Kaohsiung Veterans General Hospital to compare the safety and efficacy of valaciclovir with acyclovir in the treatment of herpes zoster in Taiwanese patients. Patients presenting with herpes zoster within 72 h after the onset of rash were enrolled and randomized to receive one of the following treatments: 1000 mg valaciclovir three times daily for 7 days or acyclovir 800 mg five times daily for 7 days. Patients were followed up for 29 days beginning with the start of therapy. A total of 57 patients were enrolled and randomized to receive valaciclovir (n = 32) or acyclovir (n = 25). Five patients in the valaciclovir group and three in the acyclovir group did not complete the study. The intent-to-treat analysis (57 patients) showed that valaciclovir significantly accelerated the resolution of herpes zoster-associated pain compared with acyclovir; on day 29, the valaciclovir group was 23% superior to the acyclovir group. There was no clinically significant difference in the nature, frequency or severity of adverse events between these two groups, although one and three adverse events were reported in the acyclovir and valaciclovir group, respectively. Thus, we conclude that in the management of herpes zoster, valaciclovir accelerates the resolution of pain and offers a simpler dosing, and maintains the favorable safety profile of acyclovir.

Aims: To determine whether diabetic autonomic neuropathy is an important factor contributing to mortality in Type 2 diabetes mellitus., Methods: Between 1989 and 1993, 431 men and 181 women with Type 2 diabetes were given diabetic autonomic neuropathy cardiovascular reflex (CVR) tests. These subjects were followed for the subsequent 5--9 years to assess mortality rates., Results: The prevalence rate of abnormal CVR tests was 46.1% in patients with the history of diabetes less than 5 years and up to 69.4% when the history of diabetes exceeded 20 years. During the follow-up period from 1 January 1989 to 31 December 1997 (mean 7.7 years), a total of 135 participants died. The 8-year survival rate for patients with abnormal CVR tests was 63.6% in males and 76.4% in females, compared with 80.9 and 93.3% for patients with normal CVR tests. The results were grouped as: group 1, normal CVR tests without postural hypotension (PHT); group 2, normal CVR tests with PHT; group 3, abnormal CVR tests without PHT; and group 4, abnormal CVR tests with PHT. The 8-year survival rate was 85.4% in group 1, 80.9% in group 2, 74.5% in group 3 and 61.1% in group 4., Conclusion: Type 2 diabetic patients with abnormal CVR tests may have increased mortality, and those combined with postural hypotension have higher mortality than those without. Abnormal CVR tests may be important predictors of mortality in Type 2 diabetes mellitus.

To evaluate the tolerability of insulin suppression test (IST) using octreotide instead of somatostatin, we compared the steady-state plasma glucose (SSPG) values and the safety during and after the test in 17 normal volunteers. The subject received IST twice (with somatostatin or with octreotide) in random order. During the test, all subjects were infused with regular insulin and glucose simultaneously for 180 min. In addition, either somatostatin or octreotide was infused intravenously over the same period of time. Plasma glucose, insulin and C-peptide were measured. The subject response to the test was recorded during and one day after the test by a structured questionnaire. The SSPG and the steady-state plasma insulin (SSPI) values reached during IST were similar, irrespective of the use of somatostatin or octreotide. There was a positive correlation between the SSPG values obtained from both methods (r = 0.67, P = 0.003). However, the mean intra-individual coefficient of variation is 17.9% for SSPG. The SSPG levels, no matter from which method, correlated positively with the 2-h insulin after oral glucose challenge. Most adverse events (especially gastrointestinal discomfort) occurred after the test, and increased much more after using octreotide than somatostatin (P = 0.002 by chi 2 test). In conclusion, the SSPG values measured by IST using octreotide or somatostatin are similar in normal healthy subjects. Yet, the octreotide method has more adverse events after the test.

Objective: To investigate neurourologic involvement in injuries to the thoracolumbar vertebra junction with magnetic resonance imaging (MRI) and electrophysiologic and urodynamic measurements and to characterize the neurogenic mechanisms of voiding dysfunctions., Design: Baseline comparisons among 3 anatomic groups before neural repair., Setting: Tertiary care center., Patients: Thirty-five T11 to L2 spinal cord injury patients consecutively admitted to a rehabilitation unit. Eight patients (Group 1) had above-conus lesions without denervation and polyphasic waves revealed in the anal sphincter electromyography; 13 patients (Group 2) had conal and/or above-conus lesions and anal sphincter electromyographic abnormalities; and 14 patients (Group 3) had below-conus lesions and anal sphincter electromyographic abnormalities., Main Outcome Measures: Comparison of features identified on pudendal nerve terminal motor latency, urethral pressure profiles, and multichannel voiding pressure-flow study., Results: The pudendal nerve terminal motor latency in Group 3, showing a significantly higher abnormal ratio (100%; p =.011, Fisher's exact test), indicated that cauda equina lesions might be the cause. Urodynamic data from Group 3 showed a significant decrease in maximal urethral closure pressure (48 +/- 17cm H2O, p =.0022, analysis of variance [ANOVA], repeated measure) and an increase in bladder capacity (429 +/- 194mL, p =.037, ANOVA, repeated measure). There were no significant changes in the other groups., Conclusion: Neurourologic abnormalities are less predictable with injuries to thoracolumbar junction, except in patients with cauda equina lesions.

A molecule with two immunoglobulin (Ig) domains cloned from Leishmania mexicana amazonensis was characterized to have a sequence homology to the Ig domains of an ICAM-like molecule telencephalin, cloned from the brain of mammals, as well as to the variable domains of human immunoglobulin lambda light chain. The molecule therefore appears to be an ICAM-like molecule as well as a member of the immunoglobulin superfamily. We thus named it ICAM-L for Leishmania ICAM. The gene was coamplified with the ribonucleotide reductase M(2) subunit gene responsible for hydroxyurea resistance from hydroxyurea (Hu)-resistant Leishmania variants. As expected, an increase of the ICAM-L protein as well as an increase of the specific ICAM-L transcript of 2.1 kb was detected in the Hu-resistant variants with increasing doses of the drug used for resistance selection. Structurally, ICAM-L is more similar to the secretory adhesive molecules, such as 1Bgp and the link protein of the immunoglobulin superfamily, in that it lacks a transmembrane region and a GPI anchor sequence. Although ICAM-L was mainly localized in the nucleus of the parasite by confocal microscopy, however, detailed studies by electron microscopy and FACS analysis indicated that the protein was also localized on the surface of the parasite. The surface localization of the protein was furthered strengthened by the observations that anti-ICAM-L or ICAM-L itself can significantly block the binding of the parasite to macrophages. The blocking of the attachment of parasite to macrophages may indicate that ICAM-L functions as an intercellular adhesive molecule.

Objective: To estimate the incidence of and risks for bleeding and thromboembolic events after warfarin anticoagulation. We also explored the dosage and international normalized ratio (INR) among Chinese patients during long-term warfarin therapy., Methods: The population in this retrospective study consisted of inpatients of the only medical center for northern Taipei City, whose initial course of warfarin therapy continued for more than four weeks. Enrollment began in June 1995 and ended in February 1996. Follow-up was completed in March 1998. Relevant data were collected by chart review. The rate of events was calculated using the Kaplan-Meier method, and risk factors were identified by the Cox proportional hazard model., Results: During the study period, 226 patients were identified. The total follow-up time was 248.7 patient-years. Sixty-one patients (27.0%) received anticoagulation for mechanical prosthetic valve, but their duration of therapy accounted for 48.6% of the total patient-years of follow-up. The starting dosage (mean +/- SD) was 3.4+/-1.4 mg/d (range 1.3-10); the maintenance dosage was 3.1+/-1.2 mg/d (range 1.2-7.7). There were 1060 dosing adjustments and 3398 INR measurements collected for these patients. The independent determinants of maintenance dosage were age, body weight, and indication of mechanical prosthetic valve. The INR was 1.9+/-0.5 (range 1.0-3.7). The cumulative probabilities for hemorrhage at 12, 24, and 34 months were 24.5%, 32.3%, and 38.4%, respectively. The corresponding figures for thromboembolism were 8.5%, 10.7%, and 10.7%, respectively. Three hemorrhages were fatal. After adjusting for other patient characteristics, increasing age was the only independent risk factor identified for bleeding., Conclusions: Antithrombotic efficacy seemed to be maintained, although the mean INR was 1.9. Even so, the substantial incidence of bleeding, especially fatal bleeding, remains a concern. Low-intensity anticoagulation might be needed for Chinese patients during long-term warfarin therapy.

Background: Ophthalmic data, while different among individuals, are usually similar between fellow eyes of the same individual. This study was designed to illustrate alternative approaches to account for the correlation between fellow eyes. This is important for making inferences using data from both eyes., Methods: With the use of a real data set from a population-based study, we described the distribution of intraocular pressure (IOP) by estimating the mean and standard deviation (SD) and evaluated the potential risk factors of higher IOP based on the regression method. The units of observation studied were of both eyes, right eye only, left eye only, the eyes with higher IOP and the mean value of both eyes. Furthermore, the generalized estimating equation (GEE) method was used to account for the correlation between fellow eyes in the regression analysis. Results and inferences from the different approaches were compared., Results: The analysis included all the eyes, providing the largest sample size and unbiased estimates of the mean and SDs. There were some discrepancies among different approaches in the regression analysis. The GEE method simultaneously evaluated the effects of both eyes, and increased precision and enhanced inferences., Conclusions: Inconsistent results among different ophthalmic studies result from variations in not only study design and courses but also statistical methods. Making the best use of appropriate statistical techniques, which account for between eye correlation, provides valid statistical inferences.

Background and Purpose: In animal studies, ethambutol (EMB) has been shown to be toxic to cone pedicles and to cause their degeneration in the retinas of fish. The purpose of this study was to determine whether EMB is toxic to retinas in humans., Methods: Twenty-seven patients with EMB-induced optic neuropathy and 20 normal control subjects were included in this study. The following details were recorded: age, sex, and systemic condition of the patients, daily dosage of EMB, duration of EMB treatment, visual function at the time of electrophysiologic investigation, time from the onset of blurred vision to the discontinuation of EMB treatment (symptom duration), and time from termination of EMB treatment until electrophysiologic investigation., Results: The electroretinograms were normal in 25 patients. Twelve patients had normal electro-oculogram (EOG) findings in both eyes and the remaining 15 patients had abnormal EOG findings in at least one eye. Ten eyes showed supranormal EOG (light/dark (L/D)) ratios of more than 2.33, and 13 eyes had decreased L/D ratios (< 1.65). The symptom duration was shorter in the supranormal EOG group., Conclusions: The results suggest that a supranormal EOG may be indicative of an early toxic state during EMB therapy and that EMB may cause dysfunction of the retinal pigment epithelium.

Background: Ovarian cancer is a well-known disease with a poor prognosis. Due to the relatively small number of cases in Taiwan, the outcome and prognostic factors of patients with primary epithelial ovarian carcinoma are unknown., Methods: We retrospectively studied patients with proven surgical and pathologic (Federation Internationale de Gynecologie et d'Obstetrique) FIGO IIIC primary epithelial ovarian carcinoma. All patients underwent standard staging surgery, including washing cytology, total abdominal hysterectomy, bilateral salpingo-oophorectomy, retroperitoneal lymphadenectomy, infracolic omentectomy and excisional biopsy of all suspicious lesions followed by adjuvant chemotherapy with four to 12 courses of cyclophosphamide, epirubicin and cisplatin (CEP) or cyclophosphamide, adriamycin and cisplatin (CAP) intravenously, every three weeks. To avoid the coeffects of chemotherapy and surgical procedures upon the outcome, patients who received paclitaxel-based regimens or underwent incomplete surgery were excluded. Ninety-eight patients from 1990 to 1996 were identified., Results: The mean follow-up time was 28.7 months, ranging from 5.4 months to 105.9 months. The cumulative five-year disease-free survival rate for all patients was 31.6%. Optimal debulking surgery was completed in 41.8% of patients, which contributed to long-term patient survival (54% vs 16%, p < 0.0001), compared to patients without optimal debulking surgery. Optimal debulking surgery was the only statistically significant independent prognostic factor for five-year disease-free survival using multivariate analysis., Conclusions: To improve survival of patients with FIGO stage IIIC epithelial ovarian carcinoma, optimal debulking surgery should be performed as the initial form of surgical intervention.

Background/purpose: Angiogenesis plays an integral role in wound healing and tissue remodeling. The authors hypothesized that inhibition of angiogenesis would reduce intraabdominal adhesion formation., Methods: In 98 C57BL6/J mice, a 2-cm midline laparotomy was performed and a 5 mm2 SILASTIC (Dow Corning, Midland, MI) patch fixed to the right side of the peritoneum. Mice were injected with normal saline (n = 54) or TNP-470, an inhibitor of angiogenesis (n = 44; 30 mg/kg every other day over 6 days before surgery until 10 days after surgery). Animals were killed on postoperative days 10, 15, 35, and 55. Adhesions to the SILASTIC (Dow Corning) patch were scored based on their extent, type, and tenacity. Angiogenesis was quantified digitally as the area of vascularized peritoneum over the patch., Results: At day 10, when TNP-470 was stopped, the percentage of vascularized peritoneum over the patch was less in treatment animals than in controls (P = .004). At day 35, the patch in treatment animals was completely covered by vascularized peritoneum, similar to controls. Adhesions in TNP-470 animals were reduced at day 10 compared with controls (P<.05) and remained reduced off treatment at day 55., Conclusions: Angiogenesis appears to play an important role in the development of intraabdominal adhesions, because the extent of early neovascularization correlates with adhesion formation. Perioperative treatment with TNP-470, a potent endothelial cell inhibitor, reduced vessel ingrowth over the patch and was associated with a sustained reduction in adhesion formation.

Carnitine (beta-hydroxy-gamma-trimethylaminobutyric acid) is involved in the transport of long-chain fatty acids into the mitochondrial matrix and removal of potentially toxic acylcarnitine esters. Carnitine transport defect is a very rare metabolic disease. A 7-month-old female infant was found to have consciousness disturbance, hyperammonemia, hepatomegaly and elevated transaminases. Both the concentrations of free carnitine and acylcarnitines in her blood were very low. The diagnosis of carnitine transport defect was confirmed by assays of carnitine uptake and transport in skin fibroblasts. She responded dramatically to carnitine therapy, and there was no hyperammonemia attack for more than 3 years. Her cardiac function also remained normal.

Glycogen storage disease type Ia (GSD Ia) is caused by a deficiency of glucose-6-phosphatase (G6Pase) activity. Eighteen GSD Ia families were studied for G6Pase gene mutations. Thirty-two mutations were found in 36 GSD Ia chromosomes: 16 were 727 G-->T (44.44%); 13 were R83H (327 G-->T; 36.11%); 1 was 341delG; 1 was 933insAA; and 1 was 793 G-->T. The 727 G-->T and R83H mutations together accounted for 80.56% (29/36) of the GSD Ia chromosomes. These two mutations were easily examined by polymerase chain reaction-based methods, and the prenatal diagnosis of a non-affected fetus was successfully made. The 727 G-->T mutation is the predominant mutation in Japanese GSD Ia patients, but is rarely seen in Western counties. The 727 G-->T mutation is also the most prevalent mutation in Taiwan Chinese, although the incidence is not as high as in Japan.

Purpose: To determine the retrobulbar hemodynamics in glaucoma patients with different degrees of optic nerve damage., Methods: Color Doppler imaging was performed in 52 patients with controlled primary open angle glaucoma (POAG) and in 25 control subjects. Glaucomatous eyes were divided into early and late groups based on the perimetry findings. Peak systolic velocity (PSV), end diastolic velocity (EDV), and resistive index of the central retinal artery (CRA) and posterior ciliary arteries (PCA) were evaluated., Results: Early glaucoma showed significantly decreased PSV in nasal PCA when compared with the normal. Late glaucoma showed significantly decreased PSV and EDV in the CRA and nasal PCA, and significantly decreased PSV in temporal PCA as compared with the control and early glaucoma. The resistive index of the CRA also increased significantly in late glaucoma., Conclusion: Eyes with advanced glaucomatous optic neuropathy were associated with more marked alterations in retrobulbar circulation than eyes with less nerve damage.

We raised a specific antiserum against the recombinant M2 subunit protein of ribonucleotide reductase of Leishmania mexicana amazonensis in rabbit. This antiserum was used to study the expression and cellular location of the M2 protein in wildtype as well as hydroxyurea-resistant variants (HuR) of the parasite. The protein increased with increasing dose of the drug used for selection of resistance. The increase in protein level was accompanied by an increase in the copy numbers of mRNA of the M2 gene in the variants. In contrast to mammalian cells, the M2 protein of Leishmania is located in the nucleus rather than in the cytoplasm. The number of cells expressing M2 protein is also different in mammalian cells versus Leishmania. In mammalian cells, expression of M2 protein is a strictly S-phase-correlated event and in exponentially growing cells only approximately 50% of the cells are in S-phase and only these cells synthesize M2 protein. In L. m. amazonensis, however, almost all exponentially growing cells are positive for M2 protein. This makes it unlikely that M2 protein expression in Leishmania is S-phase dependent. In view of these findings, a fresh look in the future into the regulatory mechanisms of synthesis and the site of action of RNR in L. m. amazonensis is warranted.

Fragile X syndrome is an important disease of hereditary mental retardation. Its prevalence in the Chinese population is not clear. We amplified FMR1 CGG repeats from male newborns' blood spots. Approximately 45% of the males had 28 CGG repeats and another 19% had 29 repeats. Besides this major peak, there was a second peak at 34 and 35 repeats. From the 1000 males studied, 3 were found to have repeat numbers in the high borderline range (each with 50, 52 and 53 repeats). This result provides a low but significant risk of fragile X syndrome in the Chinese population.

Objective: We had previously reported a reasonable categorization of the number of positive lymph nodes (LN: 0, 1-4, 5-8, and > 8) as a prognostic indicator. This study was an extension, to see which factors correlated with number of positive lymph nodes., Methods: A total of 533 patients with gastric adenocarcinoma, who underwent curative surgery between January 1988 and December 1995, were entered into this study. Patients were divided into four groups according to metastatic LN number (0, 1-4, 5-8, and > 8). Their survival and clinicopathological factors were analyzed., Results: A total of 16,457 LNs, with an average of 30.9 per specimen, were removed, of which 1686 (10.2%) showed metastases. The 5-yr cumulative survival rate decreased as the number of metastatic LNs increased, ie., 91.3% for LN 0; 67.4% for LN 1-4; 37.2 for LN 5-8, and 14.1% for LN > 8. Multivariate analyses showed that depth of cancer invasion (odds ratio: 2.4), gross appearance (odds ratio: 1.9), size (odds ratio: 1.9), and location (odds ratio: 1.4) of tumor were four independent factors correlated with the number of metastatic LNs. Number of metastatic LNs increased with advanced Japanese nodal stage and UICC-TNM stage., Conclusions: Depth of tumor invasion, and gross appearance, size, and location of tumor were four pathological factors independently correlated with number of metastatic LNs in gastric cancer.

Background: The data of histopathological factors affecting prognosis of patients with FIGO Stage IIB squamous cell carcinomas of the cervix are rarely known. The purpose of this study was to evaluate the histopathological factors rendering therapeutic failure in patients with FIGO Stage IIB., Methods: Survival and prognostic factors were analyzed in 83 patients with FIGO stage IIB squamous cell carcinoma of the cervix treated with radical hysterectomy and retroperitoneal lymphadenectomy between 1980 and 1989. The relapse-free and overall survival rate was 61.4%., Results: Univariate analysis demonstrated that the degree of lymphoreticular cells infiltrating the cervix, lymph node metastases, barrel shape of the cervix, lymph-vascular space invasion, more than three lymph nodes involved, and bulky tumor size (i.e. tumor size larger than 4 cm) were of prognostic significance in disease-free survival. However, pronounced lymphoreticular cells infiltrating the cervical cancer was the only independent factor to disease-free survival in patients with FIGO stage IIB squamous cell carcinoma treated with radical hysterectomy and retroperitoneal lymph node dissection using multivariate analysis., Conclusions: We concluded that the immune function of the host might play a crucial role in the process of anti-neoplasm even if local advanced carcinoma of the cervix is noted. Individual therapies may very well have limited efficacy based on the patient's tumor or the inherent host response. How to strengthen the power of the host's immune system may offer another thinking process to treat such a subgroup of patients. More studies are required.

The mucopolysaccharidoses are a group of inherited disorders of lysosomal storage of glycosaminoglycans. Among them, mucopolysaccharidosis (MPS) type II (Hunter's syndrome), caused by a deficiency in iduronate sulfatase, is the only one inherited in an X-linked recessive manner. We describe 12 Hunter's syndrome patients and seven carriers, with precise analysis of glycosaminoglycan content in urine and iduronate sulfatase activity in cultured fibroblasts and plasma. Their ages at the time of diagnosis ranged from 1 year 10 months to 11 years (mean 4.3 yr). The delay in diagnosis was from 1 month to 5 years (mean 2.1 yr) after the initial presentation. The most frequent initial complaints of the patients were delayed developmental milestones (75%) and speech (67%), although all patients were found to have coarsening of facial features at diagnosis. The difficulties in disease recognition allowed disease recurrence in four of the 11 families. Prompt clinical suspicion and referral will be important in genetic counseling for MPS type II and its management, if definitive therapy becomes available.

Sixty-five ankle arthrograms of the patients who underwent surgical reconstruction for their chronic ankle instability from 1987 to 1995 were studied retrospectively by comparing their operative findings. There were 15 cases (23.1%) with definite positive arthrographic findings. In the remaining 50 cases (76.9%), the arthrograms showed a "tear-drop" extravasation of dye beneath the fibular tip which we called "suspectable positive". Of these all but one, which had normal ligament, proved to correspond to the operative finding. As there was only one false positive finding among our surgical cases with both the "definite" and "suspectable" positive arthrograms, we concluded that ankle arthrography is relatively reliable and may be worth doing even in chronic cases if only for reference. Even when other diagnostic methods are negative, arthrography might help surgeons make surgical decisions in clinical symptomatic cases.

The human N-formyl peptide receptor (FPR) is a member of the family of leukocyte, G protein-coupled, chemoattractant receptors. To determine the role(s) of receptor phosphorylation in FPR processing and formylmethionylleucylphenylalanine (fMLF)-mediated chemotaxis, we utilized U937 cells expressing the recombinant wild type receptor and a mutant form of the FPR. This mutant, which lacks all of the serine and threonine residues in the C terminus of the receptor, DeltaST, has recently been shown to produce a receptor capable of fMLF binding and G protein activation but was demonstrated not to undergo fMLF-dependent phosphorylation or desensitization of the calcium mobilization response upon repeated exposure to agonist (Prossnitz, E. R. (1997) J. Biol. Chem. 272, 15213-15219). In this report, we examined the role of receptor phosphorylation in FPR internalization and leukocyte chemotaxis. Whereas the wild type receptor was rapidly internalized upon stimulation, the phosphorylation-deficient mutant was not, remaining entirely on the cell surface. In addition, contrary to the hypothesis that receptor processing and recycling are required for chemotaxis, we found no defect in the ability of the mutant FPR to migrate up a concentration gradient of fMLF. These results indicate that phosphorylation of the FPR is a necessary step in receptor internalization but that receptor phosphorylation, desensitization, and internalization are not required for chemotaxis.

A mixture of 5 porphyrins were separated by capillary electrophoresis. A UV-VIS detector was used to detect the separated components. Separation was performed in 2 types of capillaries, i.e. fused-silica and ethylene vinyl acetate copolymer (EVA) plastic capillaries. The concentration limit of detection (CLOD), mass limit of detection (MLOD), and relative standard deviations (RSD) of migration time and area were investigated. LOD was comparable to that of epi-fluorescence detection. LOD was lower when separation was performed in EVA capillary compared to fused-silica capillary. RSD of migration times of the porphyrins when separated in fused-silica capillary ranges between 0.5 to 1.6% and in EVA capillary ranges between 0.3 to 1.2%. Area RSD in fused-silica capillary ranges between 7 to 20% and in EVA capillary ranges between 4.7 to 12.3%. Urine spiked with porphyrins was also analysed by CE using fused-silica and EVA capillaries. Analysis of urine sample spiked with porphyrins showed that stacking effect of porphyrins was observable only in fused-silica and not in EVA capillary. This led to similar LOD in fused-silica capillary to those for EVA capillary.

From 1986 to 1993, 49 cases of untreated or poorly treated ankle fractures who received salvage surgery were followed up for an average of 36.4 months. The patients included 31 males & 18 females with an average age of 41.6y/o and the time interval from initial injury to reconstructive surgery average due 17.6 months. They were classified and treated according to their grade of reduction and degree of arthrosis. The surgical methods included arthrotomy & joint debridement, revised open reduction, lower tibial osteotomy and ankle arthrodesis, depending on different individual conditions. After surgery, all cases had symptomatic relief and functional improvement with an average score increased from 26.3 preoperatively to 86.8 at follow up. The goals of ankle fractures is as articular fractures, they are treated by surgical anatomic reduction with rigid fixation as early as possible in order to provide good functional results. Nevertheless they are varied in neglected ankle fractures according to their individual conditions: open reductions were performed on cases with no or little arthritic change even though arthrosis might occur later because, if necessary, future conversion to osteotomy or arthrodesis would be easier. As for late cases with advanced arthritis, ankle arthrodesis were done by compressive arthrodesis with necessary bone graft to secure fusion in an optimal position.

Purpose: To determine the effect of spontaneously elevated intraocular pressure (IOP) on the ocular circulation, and evaluate the result of IOP-lowering procedures in terms of haemodynamics., Methods: Colour Doppler imaging (CDI) was employed to determine the peak systolic velocity (PSV), end-diastolic velocity (EDV) and time average maximal velocity (TAMV), as well as the Pourcelot ratio (PR) and pulsatility index (PI), of the central retinal artery (CRA), posterior ciliary arteries (PCA) and ophthalmic artery. Various CDI parameters of the eyes with elevated IOP were compared with those of the clinically healthy fellow eyes and the control eyes, separately. Also, data from CDI of glaucoma eyes obtained during the period of elevated IOP and then following IOP-lowering procedures were compared, deliberately avoiding the influence of glaucoma medications., Results: Eyes (n = 12) with elevated IOP showed significantly decreased flow velocities of the CRA and significantly increased PR and PI of the nasal and temporal PCA, compared with the fellow and control eyes, respectively. Following IOP-lowering procedures, the PR and PI of the nasal PCA decreased significantly., Conclusion: Spontaneously elevated IOP may induce haemodynamic changes in the CRA and PCA, but no significant change is identified in the ophthalmic artery. Flow velocities tend to decrease while the resistance indices tend to increase with elevated IOP. Such haemodynamic changes may reverse following normalisation of IOP.

Objective: To investigate the roles of the second and third thoracic spinal segments in the preganglionic sympathetic innervation of the hand, and to compare skin temperature changes between thenar and other parts of palm before, during, and after endoscopic thoracic sympathectomy., Design: Twelve patients, four women and eight men, with severe palmar hyperhydrosis underwent endoscopic thoracic sympathectomy. The T3 segment was identified and dissected first, followed by T2 segment extirpation. Skin temperature changes of the hand were assessed by thermograph and thermometer simultaneously before, during, and after sympathectomy. Sympathetic skin responses were undertaken 1 day preoperatively and followed up 6 months postoperatively., Setting: An electrophysiological laboratory and operating room in a national medical center., Subjects: Twelve patients who sustained a profound degree of palmar hyperhydrosis., Interventions: Skin temperature differences of the hands were measured by infrared thermograph and thermometer before, during, and after endoscopic thoracic sympathectomy., Main Outcome Measures: Group's average temperature differences, and sympathetic skin response (all or none response)., Results: The T2 spinal segment is thought to be the main source of sympathetic outflow to the sweat glands of the hand. The group's average temperature changes were significantly higher at the 2nd through 5th fingers' tips than at the thenar after completion of T2 extirpation (p < .005)., Conclusions: Intraoperative monitoring of palmar skin temperature, as judiciously measured by infrared thermograph, yields useful information about the locations of the sympathetic segments and confirmation of their entire ablation by endoscopic thoracic sympathectomy.

Background: Aged people are considered prone to gram-negative bacteremia and septic shock. This relationship was tested in murine endotoxin shock., Methods: Balb/c mice of various ages (1.4-13.4 months) were intraperitoneally injected with lipopolysaccharide (LPS), and rates of survival were observed. The production of TNF-alpha in vivo induced by LPS was measured., Results: The survival rates were the smallest in the oldest and youngest groups. Production of TNF-alpha attained a maximum at 2 h after LPS injection and was smaller in the oldest group; it had a reciprocal relationship to survival rates in each group except the youngest group., Conclusion: Old and young mice had smaller rates of survival and greater production of TNF-alpha following endotoxin shock induced by LPS.

The rise in the incidence of lung cancer has been associated with shifts in histologic distribution. A study was conducted to investigate changes in the cell type distribution in lung cancer in relation to age, sex, and smoking history, based on a retrospective analysis of 10,910 proven cases of lung cancer at the Veterans General Hospital-Taipei during the period from 1970 to 1993. The diagnosis in each case was substantiated by histologic samples from the original tumor site in the lung. Detailed smoking histories were obtained by personal interview at the time of the first admission. Adenocarcinoma (38.3%) was the most common type of lung cancer, followed by squamous cell carcinoma (37.1%) and small cell carcinoma (12.2%). Over the study period, the incidence of squamous cell carcinoma decreased from 46.4% to 36.2% in men (P < 0.005), adenocarcinoma increased from 30% to 36% in men (P = 0.001) and 50.7% to 64.8% in women (P = 0.008), and small cell carcinoma increased from 7% to 14% in men but showed no significant change in women. Adenocarcinoma exhibited a marked increase in both men and women, and surpassed squamous cell carcinoma as the most frequent type of lung cancer. Lung cancer among younger men, and among non-smoking older men and women, was more often adenocarcinoma. Small cell carcinoma showed a significant increase among males, differing from the trend for squamous cell carcinoma in men, though both are strongly associated with smoking. These findings suggest factors other then cigarette smoking could influence the development and distribution of lung cancer.

1. To determine the effectiveness of ongoing immediate concurrent feedback (ICF) in minimizing 'inappropriate' sultamicillin or co-amoxiclav prescribing via the parenteral route (i.e. when the oral route was accessible and not contraindicated), a prospective controlled audit was carried out on hospital inpatients over a 20 month period. 2. After an education programme to promote oral rather than unnecessary intravenous (i.v.) use of sultamicillin, co-amoxiclav and certain other drugs, an ongoing ICF strategy was instituted. 3. ICF entailed issue of memos on the following day to prescribers of i.v. sultamicillin or co-amoxiclav for inpatients in whom this route was deemed 'inappropriate', by a specially trained nurse using strict objective criteria. The memos recommended oral prescribing (particularly of co-amoxiclav, currently the less expensive alternative). 4. After starting ICF, there were consistent, clinically and statistically significant reductions in the monthly proportions of (i) admissions prescribed i.v. sultamicillin or co-amoxiclav (38% P < 0.001), (ii) those in whom the route was 'inappropriate' (75%, P < 0.001), and (iii) corresponding ratios of i.v./oral usage and expenditure, oral sultamicillin/co-amoxiclav usage and expenditure, as well as total and per admission expenditure on i.v. forms (> or = 43%, P < 0.01). 5. For i.v. cefuroxime (for which there was no ICF) and its oral counterpart cefuroxime-axetil, there were no comparable changes in usage or expenditure. 6. This simple, ongoing ICF strategy was effective and well accepted; estimated net monthly savings being HK$26-30,000.

An A + T-rich repeated DNA sequence cloned from maxicircle DNA of Leishmania mexicana amazonensis was found to be conserved in the maxicircles of human-infective Leishmania species but totally absent from non-human-infective ones. Differences in the pattern of distribution of this repeated sequence in the maxicircles of each human-infective Leishmania species potentially allow the development of a sensitive probe to differentiate among these species.

One hundred and fifty-six patients with neck lesions were selected into this retrospective study between January, 1989 and December, 1990. All the patients visited OPD with the chief complaint of neck mass without other apparent symptoms and signs after initial work-up. They can be divided into 5 types according to the pathological reports: type a) metastatic lesion, type b) malignant lymphoma, type c) TB lymphadenitis, type d) miscellaneous benign lesion, and type e) inadequate specimen. They represent 24.4%, 12.8%, 9.6%, 52.6%, and 0.6% of the patients respectively. Type a) and type b) were classified as group of malignancy and the other three types were group of benignancy. Chi-square test and t-test were then used to evaluate the significant level of difference in each semiological factor between both groups. Several parameters were found to reach significant level, including tumor fixation, age of the patients, tenderness, location and size of the tumor, and history of cancer. Stepwise logistic regression was utilized to obtain a regression equation to predict the probability of malignancy in OPD patients with neck masses. The accuracy rate of prediction is 83.3%, if the cutpoint value is 0.5. A clinician can therefore avoid untimely excisional biopsy and delay in treatment planning.

A rapid method for the detection of hog cholera virus (HCV) in infected tissues, using polymerase chain reaction (PCR) was developed. Total RNA isolated from HCV-infected tissues was reverse transcribed with AMV reverse transcriptase and the resulting complementary DNA was amplified by Taq DNA polymerase in the presence of two HCV-specific primers. The amplified DNA fragment was detected by agarose gel electrophoresis. The sensitivity of this method was at 10(4) TCID50 of HCV. The sensitivity increased approximately 1000-fold when the DNA was reamplified with a set of nested primers. DNA sequencing analysis of the PCR products revealed that the HCV sequence amplified from a local field isolate was highly homologous to the HCV Alfort strain. This method may be useful for pathological and epidemiological studies of HCV in pigs.

Angular and rotational profile of the lower limbs of 2,630 normal Chinese children from newborn to age 12 years were compiled using tibiofemoral angle, intercondylar, intermalleolar distance, medial and lateral rotation of the hip, and thigh-foot angle. Children with clinical tibiofemoral angles, intercondylar or intermalleolar distances tended to be bowlegged at birth, maximally knock-kneed at age 3 and to have normal lower limbs by age 8. Medial hip rotation increased steadily from birth to a maximum of 56 degrees at age 9, and lateral hip rotation decreased from birth to a minimum of 30 degrees at age 9. Significant differences between Chinese children and children of other races were highlighted.

The association between hepatic tumours and oestrogen and progestogen therapy is well established. The risk of developing primary hepatocellular carcinoma (PHC) is small. In Africa and Asia where hepatitis B virus (HBV) infections are common, the development of PHC is also high. The presence of Hepatitis B core antibody indicates previous exposure to HBV and carries a risk of developing PHC by more than 34 times of non-infected normal. A Chinese female 29 years who had been on oral oestrogen and progestogen contraceptives continuously for 8 years developed PHC. She had no known illness due to HBV but was found to have concomitantly positive Hepatitis B core antibody in her sera. The presence of this HB core antibody and the long term consumption of oestrogen/progesterone derivatives may have been responsible for the early presentation of PHC in this patient. It is the first report in this country of PHC developing in a pill consumer since the introduction of oral contraceptives a decade ago In view of the prevalence of Hepatitis B in the region, this case finding warrants further study to determine whether (a) there is a higher frequency in pill consumers (b) an earlier age of presentation of hepatic malignancy. Meanwhile, it may be prudent to recommend alternative methods of birth control in individuals known to have been previously exposed to HBV infection, clinically or otherwise.

Thyrotoxicosis occurring in conjunction with myasthenia gravis is rare. The usual treatment consists of medical control of the thyrotoxicosis, then thymectomy and later subtotal thyroidectomy. The case reported here concerns a 19-year-old girl who had surgical treatment for both lesions on the same occasion. With proper medical preparation, modern anaesthesia and respiratory care, the surgical treatment of both lesions can be accomplished in one stage.

A case of relapsing polychondritis in a 30-year-old Chinese male is reported. The patient showed the following features: dyspnoea; hoarseness of voice; cauliflower deformity of the right ear; upper tracheal stenosis; swelling of the lower part of the sternum; pain in the costal cartilages. Airway obstruction as a presenting feature (as in this case) is unusual. The aetiology, clinical features and management of relapsing polychondritis are briefly discussed.