Biomedical subjects

C Chow

Publications and source records attributed to C Chow.

At least 37 records · Page 2Linked to original sources

PubMed1999

Paclitaxel chemotherapy after autologous stem-cell transplantation and engraftment of hematopoietic cells transduced with a retrovirus containing the multidrug resistance complementary DNA (MDR1) in metastatic breast cancer patients.

The MDR1 multidrug resistance gene confers resistance to natural-product anticancer drugs including paclitaxel. We conducted a clinical gene therapy study to determine whether retroviral-mediated transfer of MDR1 in human hematopoietic cells would result in stable engraftment, and possibly expansion, of cells containing this gene after treatment with myelosuppressive doses of paclitaxel. Patients with metastatic breast cancer who achieved a complete or partial remission after standard chemotherapy were eligible for the study. Hematopoietic stem cells (HSCs) were collected by both peripheral blood apheresis and bone marrow harvest after mobilization with a single dose of cyclophosphamide (4 g/m2) and daily filgrastim therapy (10 microg/kg/day). After enrichment for CD34+ cells, one-third of each collection was incubated ex vivo for 72 h with a replication-incompetent retrovirus containing the MDR1 gene (G1MD) in the presence of stem-cell factor, interleukin 3, and interleukin 6. The remaining CD34+ cells were stored without further manipulation. All of the CD34+ cells were reinfused for hematopoietic rescue after conditioning chemotherapy with ifosfamide, carboplatin, and etoposide regimen. After hematopoietic recovery, patients received six cycles of paclitaxel (175 mg/m2 every 3 weeks). Bone marrow and serial peripheral blood samples were obtained and tested for the presence of the MDR1 transgene using a PCR assay. Six patients were enrolled in the study and four patients received infusion of genetically altered cells. The ex vivo transduction efficiency, estimated by the PCR assay, ranged from 0.1 to 0.5%. Three of the four patients demonstrated engraftment of cells containing the MDR1 transgene. The estimated percentage of granulocytes containing the MDR1 transgene ranged from a maximum of 9% of circulating nucleated cells down to the limit of detection of 0.01%. One patient remained positive for the MDR1 transgene throughout all six cycles of paclitaxel therapy, whereas the other 2 patients showed a decrease in the number of cells containing the transgene to undetectable levels. Despite the low level of engraftment of MDR1-marked cells, a correlation was observed between the relative number of granulocytes containing the MDR1 transgene and the granulocyte nadir after paclitaxel therapy. No adverse reactions to the genetic manipulation procedures were detected. Therefore, engraftment of human HSCs transduced with the MDR1 gene can be achieved. However, the overall transduction efficiency and stable engraftment of gene-modified HSCs must be improved before MDR1 gene therapy and in vivo selection with anticancer drugs can be reliably used to protect cancer patients from drug-related myelosuppression.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1998

The fission yeast chromo domain encoding gene chp1(+) is required for chromosome segregation and shows a genetic interaction with alpha-tubulin.

In eukaryotes, the segregation of chromosomes is co-ordinated by the centromere and must proceed accurately if aneuploidy and cell death are to be avoided. The fission yeast centromere is complex, containing highly repetitive regions of DNA showing the characteristics of heterochromatin. Two proteins, Swi6p and Clr4p, that are associated with the fission yeast centromere also contain a chromo (chromatin organisation modifier) domain and are required for centromere function. We have analysed a novel fission yeast gene encoding a putative chromo domain called chp 1(+) (chromo domain protein in Schizosaccharomyces p ombe ). In the absence of Chp1p protein, cells are viable but show chromosome segregation defects such as lagging chromosomes on the spindle during anaphase and high rates of minichromosome loss, phenotypes which are also displayed by swi 6 and clr 4. A fusion protein between green fluorescent protein (GFP) and Chp1p, like Swi6p, is localized to discrete sites within the nucleus. In contrast to Swi6p and Clr4p, Chp1p is not required to repress silent mating-type genes. We demonstrate a genetic interaction between chp 1(+) and alpha-tubulin ( nda 2(+)) and between swi 6(+) and beta-tubulin ( nda 3(+)). Chp1p and Swi6p proteins may be components of the kinetochore which captures and stabilizes the microtubules of the spindle.

Amino Acid Sequence↗

PubMed1998

Selection of local therapy after neoadjuvant chemotherapy in patients with stage IIIA,B breast cancer.

BACKGROUND: Stage IIIA,B breast cancer is commonly treated with neoadjuvant chemotherapy because of high objective response rates and improved operability. Criteria for subsequent selection of local therapy--mastectomy, radiotherapy, or both--are not well defined. We adopted a policy of selective local therapy based on rebiopsy of the breast and clinical axillary lymph node status at the time of best response to chemotherapy. METHODS: Between 1980 and 1993, 126 patients with stage IIIA,B breast cancer were treated with neoadjuvant chemotherapy and definitive local therapy. The long-term incidence of locoregional failure (in-breast, chest wall, axilla, supraclavicular, neck), relapse-free survival, and overall survival was determined. RESULTS: The overall clinical objective response rate to chemotherapy was 95.2%. Eighty-three patients underwent mastectomy, with negative margins achieved in 91.6%. Forty-two patients had breast preservation; the overall in-breast recurrence rate was 19.0% (8 of 42 patients). The overall locoregional recurrence rate by site was: chest wall-8.7% (11 of 126 patients), axilla-8.7% (11 of 126 patients), supraclavicular-5.6% (7 of 126 patients), and neck-4.0% (5 of 126 patients). The axillary recurrence rate was 6.6% (5 of 76 patients) for clinically negative axilla treated with radiotherapy only, and 12.0% (6 of 50 patients) for clinically positive axilla treated with surgery only. The overall long-term survival probabilities (6 years) according to stage were: stage IIIA-58.0%, stage IIIB(noninflam)-58.0%, stage IIIB(inflam)-36.0%. CONCLUSIONS: These findings support a selective approach to local therapy in patients with stage IIIA,B breast cancer. This approach provides local control in most patients, and allows for breast preservation and elimination of axillary dissection in selected patients.

Adult↗

PubMed1998

Completing the sequence of the Sulfolobus solfataricus P2 genome.

The Sulfolobus solfataricus P2 genome collaborators are poised to sequence the entire 3-Mbp genome of this crenarchaeote archaeon. About 80% of the genome has been sequenced to date, with the rest of the sequence being assembled fast. In this publication we introduce the genomic sequencing and automated analysis strategy and present intial data derived from the sequence analysis. After an overview of the general sequence features, metabolic pathway studies are explained, using sugar metabolism as an example. The paper closes with an overview of repetitive elements in S. solfataricus.

Base Sequence↗

PubMed1997

Neural-mechanical coupling of breathing in REM sleep.

During rapid-eye-movement (REM) sleep the ventilatory response to airway occlusion is reduced. Possible mechanisms are reduced chemosensitivity, mechanical impairment of the chest wall secondary to the atonia of REM sleep, or phasic REM events that interrupt or fractionate ongoing diaphragm electromyogram (EMG) activity. To differentiate between these possibilities, we studied three chronically instrumented dogs before, during, and after 15-20 s of airway occlusion during non-REM (NREM) and phasic REM sleep. We found that 1) for a given inspiratory time the integrated diaphragm EMG (Di) was similar or reduced in REM sleep relative to NREM sleep; 2) for a given Di in response to airway occlusion and the hyperpnea following occlusion, the mechanical output (flow or pressure) was similar or reduced during REM sleep relative to NREM sleep; 3) for comparable durations of airway occlusion the Di and integrated inspiratory tracheal pressure tended to be smaller and more variable in REM than in NREM sleep, and 4) significant fractionations (caused visible changes in tracheal pressure) of the diaphragm EMG during airway occlusion in REM sleep occurred in approximately 40% of breathing efforts. Thus reduced and/or erratic mechanical output during and after airway occlusion in REM sleep in terms of flow rate, tidal volume, and/or pressure generation is attributable largely to reduced neural activity of the diaphragm, which in turn is likely attributable to REM effects, causing reduced chemosensitivity at the level of the peripheral chemoreceptors or, more likely, at the central integrator. Chest wall distortion secondary to the atonia of REM sleep may contribute to the reduced mechanical output following airway occlusion when ventilatory drive is highest.

Air Pressure↗

PubMed1997

Magnetic resonance imaging of the forearm as a diagnostic aid in patients with sporadic inclusion body myositis.

Because weakness of finger flexors and atrophy of the forearms are frequent findings in inclusion body myositis (IBM) patients, we examined the forearm muscles by MRI to determine if involvement of the distal musculature has a characteristic diagnostic pattern. We performed MRI of the forearms in 21 randomly selected patients with histologically confirmed IBM and in 9 patients with other, age-matched, neuromuscular diseases who served as controls. In addition, we analyzed axial images of 10 individual forearm muscles blindly without knowledge of the clinical status or diagnosis of the patients. T1-weighted MR images showed marbled brightness of the flexor digitorum profundus (FDP) in 20 of 21 IBM patients, of the flexor carpi ulnaris in 7, the flexor digitorum superficialis (FDS) in 6, the flexor carpi radialis in 4, the supinator in 3, and the brachioradialis in 1. The extensors were normal. The abnormalities of the FDP correlated with the severity but not the duration of the disease and in some patients preceded overt clinical signs of FDP weakness. In contrast, the FDS was spared even late in the disease. We conclude that selective involvement of the FDP may occur early in the course of IBM and can be easily demonstrated by MRI in up to 95% of patients. Because selective FDP involvement appears to be a very frequent and characteristic finding in patients with IBM, MRI of the forearm is a useful noninvasive test in supporting the diagnosis of sporadic IBM.

Adult↗

PubMed1996

Preliminary results for positron emission mammography: real-time functional breast imaging in a conventional mammography gantry.

In order to optimally integrate radiotracer breast imaging within the breast clinic, anatomy and pathology should be easily correlated with functional nuclear medicine breast images. As a first step in the development of a hybrid functional/anatomic breast imaging platform with biopsy capability, a conventional X-ray mammography gantry was modified to image the compressed breast with positron emitters. Phantom studies with the positron emission mammography (PEM) device showed that a 1-cc hot spot could be detected within 5 min. A preliminary clinical trial demonstrated in vivo visualization of primary breast cancer within 4 min. For sites where positron-emitting radionuclides are available, PEM promises to achieve low-cost directed functional examination of breast abnormalities, with the potential for achieving X-ray correlation and image-guided biopsy.

Breast↗

PubMed1996

Phase I/II study of 72-hour infusional paclitaxel and doxorubicin with granulocyte colony-stimulating factor in patients with metastatic breast cancer.

PURPOSE: We conducted a phase I/II trial of concurrently administered 72-hour infusional paclitaxel and doxorubicin in combination with granulocyte colony-stimulating factor (G-CSF) in patients with previously untreated metastatic breast cancer and bidimensionally measurable disease. PATIENTS AND METHODS: We defined the maximum-tolerated dose (MTD) of concurrent paclitaxel and doxorubicin administration and then studied potential pharmacokinetic interactions between the two drugs. Forty-two patients who had not received prior chemotherapy for metastatic breast cancer received 296 total cycles of paclitaxel and doxorubicin with G-CSF. RESULTS: The MTD was determined to be paclitaxel 180 mg/m2 and doxorubicin 60 mg/m2 each by 72-hour infusion with G-CSF. Diarrhea was the dose-limiting toxicity (DLT) of this combination, with three of three patients developing abdominal computed tomographic (CT) scan evidence of typhlitis (cecal thickening) at the dose level above the MTD. All patients developed grade 4 neutropenia (absolute neutrophil count [ANC] < 500 microL), generally less than 5 days in duration. This combination was generally safely administered at dose levels at or below the MTD. The overall response rate was 72% (28 of 39 patients; 95% confidence interval [CI], 55% to 85%), with 8% complete responses (CRs) (three of 39; 95% CI, 2% to 21%) and a median response duration of 9 months. The median overall survival time for all patients is 23 months, with a median follow-up duration of 28 months. Pharmacokinetic studies showed that administration of paclitaxel and doxorubicin together by 72-hour infusion did not affect the steady-state concentrations of either drug. CONCLUSION: Concurrent 72-hour infusional paclitaxel and doxorubicin can be administered safely, but is associated with significant toxicity. The overall response rate of this combination in untreated metastatic breast cancer patients is similar to that achieved with other doxorubicin-based combination regimens. The modest complete response rate achieved suggests that this schedule of paclitaxel and doxorubicin administration does not produce significant additive or synergistic cytotoxicity against breast cancer.

Adult↗

PubMed1996

Functional results in oral cavity reconstruction using reinnervated versus nonreinnervated free fasciocutaneous grafts.

Recent advances in free-tissue transfer have given the otolaryngologist--head and neck surgeon a number of reliable options for reconstruction of the oral cavity following ablative procedures. One recent modification has been the transfer of free reinnervated fasciocutaneous grafts in the hope of enhancing oral rehabilitation following surgery. To assess the efficacy of this modification, a protocol was established to retrospectively evaluate patients that received either reinnervated or non-reinnervated free-tissue transfers. Factors including site, surgical resection, type of tissue transfer, and follow-up period were controlled. Evaluation of free-graft sensory return and quality of life was carried out through physical examination and patient interview. Speech assessment was carried out using standardized tests of intelligibility administered by a speech pathologist. Swallowing assessment was carried out with videocinefluoroscopic and scintigraphic techniques, and the oropharyngeal swallow efficiency was calculated. Sensory return in the reinnervate free grafts was superior; however, there was not statistical difference between groups in the speech and swallowing tests. Quality of life was judged to be good in both groups. Sensory return and functional outcome in intraoral reconstruction after tumour ablation was reviewed and discussed

Adult↗

PubMed1996

Sleep-induced breathing instability. University of Wisconsin-Madison Sleep and respiration Research Group.

We present a view of the neuromechanical regulation of breathing and causes of breathing instability during sleep. First, we would expect transient increases in upper airway resistance to be a major cause of transient hypopnea. This occurs in sleep because a hypotonic upper airway is more susceptible to narrowing and because the immediate excitatory increase in respiratory motor output in response to increased loads is absent in non-REM sleep. Secondly, sleep predisposes to an increased occurrence of ventilatory "overshoots", in part because abruptly changing sleep states cause transient changes in upper airway resistance and in the gain of the respiratory controller. Following these ventilatory overshoots, breathing stability will be maintained if excitatory short-term potentiation is the prevailing influence. On the other hand, apnea and hypopnea will occur if inhibitory mechanisms dominate following the ventilatory overshoot. These inhibitory mechanisms include: a) hypocapnia-if transient, will inhibit carotid chemoreceptors and cause hypopnea, but if prolonged will inhibit medullary chemoreceptors and cause apnea; b) a persistent inhibitory effect from lung stretch; c) baroreceptor stimulation, from a transient rise in systemic blood pressure immediately following termination of apnea or hypopnea may partially suppress the accompanying hyperpnea; d) depression of central respiratory motor output via prolonged brain hypoxia. Once apneas are initiated, reinitiation of inspiration is delayed even though excitatory stimuli have risen well above their apneic thresholds, and these prolonged apneas are commonly accompanied by tonic EMG activation of expiratory muscles of the chest wall and upper airway.

Adult↗

PubMed1996

In vitro activity of cefoperazone-sulbactam: Singapore experience.

In vitro activity of commonly used antimicrobial agents against consecutively isolated 521 strains of Gram negative bacilli causing serious infections in the National University Hospital, Singapore were tested in parallel with cefoperazone-sulbactam combination. With the combination complete resistance of 2% and intermediate resistance of 5% were noted among the 521 strains tested. Resistance to imipenem was low (5%) but resistance against other antimicrobial agents varied from 12% (amikacin) to 80% (ampicillin). In vitro data demonstrated a possible future role for cefoperazone-sulbactam in the treatment of sepsis caused by Gram negative bacilli in our hospital.

Anti-Bacterial Agents↗

PubMed1995

A phase I study of sequential versus concurrent interleukin-3 and granulocyte-macrophage colony-stimulating factor in advanced breast cancer patients treated with FLAC (5-fluorouracil, leucovorin, doxorubicin, cyclophosphamide) chemotherapy.

Cumulative thrombocytopenia is a dose-limiting toxicity of dose-intensive chemotherapy for advanced breast cancer. In this phase I study, we have studied the hematologic toxicity associated with sequential interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF; molgramostim) administration after multiple cycles of FLAC (5-fluorouracil, leucovorin, doxorubicin, cyclophosphamide) chemotherapy compared with that after concurrent cytokine administration or to each cytokine administered alone. Ninety-three patients with advanced breast cancer were treated with five cycles of FLAC chemotherapy and either IL-3 alone, GM-CSF alone, sequential IL-3 and GM-CSF administered by schedule A (5 days of IL-3 followed by 10 days of GM-CSF) or schedule B (9 days of IL-3 followed by 6 days of GM-CSF), or concurrent administration of IL-3 and GM-CSF for 15 days. Cohorts of patients were treated with one of four dose levels of IL-3 (1,2.5, 5, and 10 micrograms/kg) administered subcutaneously for each schedule of cytokine administration. The GM-CSF dose in all schedules was 5 micrograms/kg/day. Sequential IL-3 and GM-CSF (schedule B) was associated with higher platelet nadirs, shorter durations of platelet counts less than 50,000/microL, and the need for fewer platelet transfusions over five cycles of FLAC chemotherapy compared with concurrent cytokines, sequential IL-3 and GM-CSF schedule A, and GM-CSF alone. Concurrent IL-3 and GM-CSF was associated with unexpected platelet toxicity. The duration of granulocytopenia after FLAC chemotherapy was significantly worse with IL-3 alone compared with each of the GM-CSF-containing cytokine regimens. Although no cycle 1 maximum tolerated dose for IL-3 was defined in this study, 5 micrograms/kg was well tolerated over multiple cycles of therapy and is recommended for future studies. The data from this phase I study suggest that sequential IL-3 and GM-CSF with IL-3 administered for 9 days before beginning GM-CSF may be superior to shorter durations of IL-3 administered sequentially with GM-CSF, to concurrent IL-3 and GM-CSF, and to either colony-stimulating factor alone in ameliorating the cumulative hematologic toxicity associated with multiple cycles of FLAC chemotherapy. Additional studies of sequential IL-3 and GM-CSF are warranted.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1995

Bacteria, viruses, yeasts and protozoans associated with diarrheal disease in Singapore.

Labile toxin producing enterotoxic E. coli (ETEC) were the commonest pathogen isolated from diarrheal stools of hospitalized children (21%) and adults (26%) in Singapore. Salmonellas ranked a close second in children (19%). Other bacterial pathogens were isolated from less than 5% of subjects. Blastocystis hominis was detected in 4.3% of diarrheal stools when a simple sedimentation technique was used. Cryptosporidium was not detected at all. An analysis of yeast counts in smears of diarrheal and non-diarrheal stools suggested they were etiologically associated with at least 6% of diarrhea in children and 19% in adults. Testing for rotaviruses by Latex agglutination and for adenovirus by electronmicroscopy showed an association with 6 per cent and 3 per cent diarrhea respectively. The study highlighted a need for: case control studies on ETEC and B. hominis; studies on the epidemiology of diarrhea by yeasts; establishing the true incidence of adenovirus diarrhea; studies on the prevalence and seasonality of rotavirus infection in Singapore.

Adenovirus Infections, Human↗

PubMed1995

Antimicrobial resistance problem in a university hospital.

In a study conducted in 1991 in the National University Hospital, Singapore, the susceptibilities of a total of 2156 recent clinical isolates were tested against 25 antimicrobial drugs. The organisms were those isolated from routine specimens received in the microbiology laboratory. About 40% Staphylococcus aureus isolations in the hospital were resistant to methicillin. A high incidence of the resistance was noted among Staphylococcus aureus and coagulase negative staphylococci to antistaphylococcal drugs. Acinetobacter sp. and Klebsiella sp. are becoming major threats with regard to antimicrobial treatment as they are multi-drug resistant. Pseudomonas aeruginosa did not show a resistance problem except to pefloxacin (74%). Ampicillin resistance of Acinetobacter sp. (93%) was reduced to 71% by ampicillin/clavulanic acid and to 7% by ampicillin/sulbactam. With regards to the urinary isolates higher rates of resistance were noticed with Pseudomonas aeruginosa to antipseudomonas drugs and for co-trimoxazole with other Gram negative organisms, compared to non-urinary isolates.

Acinetobacter↗

PubMed1995

Differences in diaphragm fiber types in SIDS infants.

The diaphragm is a vital respiratory muscle in the sleeping infant. Any changes in diaphragm fiber type number or size could represent either a primary developmental delay or a secondary reaction to increased workload, and could give a clue as to the pathogenesis of sudden infant death syndrome (SIDS). We therefore quantitated by point counting on ATPase histochemistry the numbers and areas of type 1 and 2 fibers in the diaphragm, external intercostal and psoas muscles of 37 SIDS and 20 control infants. The amount of slow, fast and fetal myosin in the diaphragm and psoas muscles was measured by electrophoresis to check the ATPase quantitation. There were fewer type 1 fibers in SIDS (median 30.0%) compared with control (median 40.0%) infants (p < 0.02), whereas the diameter of type 1 fibers in SIDS (median 33.9 microns) was larger than in control (median 30.3 microns) infants (p < 0.007). The total cross-sectional area occupied by type 1 and 2 fibers was similar in both groups. No changes were found in the external intercostal or psoas. The amount of slow and fast myosins correlated well with type 1 and type 2 fibers, respectively. The finding of fewer type 1 (fatigue-resistant) fibers of large diameter in SIDS diaphragms suggests that differences in muscle fiber types may predispose these infants to diaphragm fatigue and respiratory failure.

Diaphragm↗

PubMed1995

Genital Group B Streptococcus carriage in the antenatal period: its role in prom and preterm labour.

Of 326 high vaginal swabs taken during the antenatal period, Group B Streptococcus (GBS) was isolated from the birth canal in 46 women, giving a carrier rate of 14.1%, which is within the often quoted range of between 5% - 25% in different parts of the world. Carriage rates were similar at different gestations. In a subgroup of 34 women, 2 swabs taken at least 5 weeks apart yielded results which were discordant in over one fifth of the time. This knowledge of the natural history of GBS carriage questions the practice of treating asymptomatic carriers of GBS in the antenatal period to prevent transmission of GBS to the neonate. The group of women with positive swabs in the antenatal period did not have a significantly higher incidence of preterm labour and/or prelabour rupture of membranes (PROM) compared with the group of women with negative swabs. Routine screening of the antenatal population for GBS carrier status prior to 32 weeks gestation may not identify women at high risk of PROM or preterm labour.

Adult↗

PubMed1994

Listeriosis--a review of eighty-four cases.

OBJECTIVE: To review the epidemiology, risk factors for acquisition, clinical features and outcomes of Listeria monocytogenes infection in Sydney. DESIGN: A retrospective study over the period 1983-1992 at four university teaching hospitals in Sydney. Cases were identified from microbiology laboratory records of the isolation of L. monocytogenes from sterile sites. RESULTS: Eighty-four cases were reviewed, with 72 patients (86%) having a predisposing underlying condition, including 13 perinatal patients (15%). Septicaemia (56%) and central nervous system disease (41%) were the major clinical presentations. Nineteen patients (23%) had hospital-associated infection. A mortality of 21% (18 patients) was directly attributable to L. monocytogenes infection, with another 10% (nine patients) dying of their underlying disease during admission. The 84 cases represented 80% of all L. monocytogenes cases occurring in Sydney during the study period. CONCLUSIONS: Listeriosis is predominantly a disease of the elderly or of immunosuppressed individuals, pregnant women and neonates. The presentation and outcome in these groups are similar to those reported in other Western countries. A significant feature of this study was the number of cases occurring in already hospitalised patients, suggesting that L. monocytogenes may be an important hospital-associated pathogen in immunocompromised patients.

Adult↗

PubMed1994

The HLA association with Graves' disease is sex-specific in Hong Kong Chinese subjects.

OBJECTIVE: Graves' disease is associated with different HLA genes in Caucasians and the Chinese, in whom the HLA associations may be stronger in males than females. Common HLA-associated susceptibility in both races may occur at the HLA-DQ loci. The aims of this study were to examine the HLA-A, B, DR and DQ associations with Graves' disease in a Hong Kong Chinese population and to determine whether the HLA associations differ between the sexes and between subjects with and without thyrotoxic periodic paralysis. DESIGN: HLA-A, B and DR types were determined by serological typing and DQA1 and DQB1 alleles by oligonucleotide probing of the respective enzymatically amplified gene. PATIENTS: Ninety-seven Chinese patients with Graves' disease (31 males with, 35 males without and 31 females without thyrotoxic periodic paralysis) and 105 racially matched healthy controls. MEASUREMENTS: Frequencies of HLA types/alleles at each locus were compared between patients and controls and between the Graves' subgroups using the chi 2-test. RESULTS: HLA-B46, DR9 and DQB1*0303 were associated with Graves' disease in males only; these associations were weaker in males with thyrotoxic periodic paralysis. DR12, DQA1*0401 and DQB1*0301 were protective, regardless of sex or the presence of thyrotoxic periodic paralysis. The positive HLA associations in the Hong Kong Chinese were distinct from those in Caucasians whereas the protective haplotype was similar to that described in Caucasians. CONCLUSIONS: These findings call in question the role of HLA genes in disease susceptibility but suggest a role for HLA in protection from Graves' disease.

Adult↗