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Biomedical subjects

O Chan

Publications and source records attributed to O Chan.

At least 37 records · Page 2Linked to original sources

A transforming growth factor beta 1 receptor type II mutation in ulcerative colitis-associated neoplasms.

BACKGROUND & AIMS: Numerous gastrointestinal tumors, notably sporadic and ulcerative colitis (UC)-associated colorectal carcinomas and dysplasias, gastric cancers, and esophageal carcinomas, manifest microsatellite instability. Recently, a transforming growth factor beta 1 type II receptor (TGF-beta 1RII) mutation in a coding microsatellite was described in colorectal carcinomas showing instability. One hundred thirty-eight human neoplasms (61 UC-associated, 35 gastric, 26 esophageal, and 16 sporadic colorectal) were evaluated for this TGF-beta 1RII mutation. METHODS: Whether instability was present at other chromosomal loci in these lesions was determined. In lesions manifesting or lacking instability, the TGF-beta 1RII coding region polydeoxyadenine (poly A) microsatellite tract was polymerase chain reaction amplified with 32P-labeled deoxycytidine triphosphate. Polymerase chain reaction products were electrophoresed on denaturing gels and exposed to radiographic film. RESULTS: Three of 18 UC specimens with instability at other chromosomal loci (17%) showed TGF-beta 1RII poly A tract mutation, including 2 cancers and 1 dysplasia; moreover, 2% of UC specimens without instability (1 of 43) (1 cancer), 81% of unstable sporadic colorectal cancers (13 of 16), and none of the 61 stable or unstable gastric or esophageal cancers contained TGF-beta 1RII mutations. CONCLUSIONS: Mutational inactivation of the poly A microsatellite tract within TGF-beta 1RII occurs early and in a subset of unstable UC neoplasms and commonly in sporadic colorectal cancers but may be rare in unstable gastric and esophageal tumors.

Activin Receptors, Type I↗

Infrequent DPC4 gene mutation in esophageal cancer, gastric cancer and ulcerative colitis-associated neoplasms.

Homozygously Deleted in Pancreatic Cancer 4 (DPC4), a recently identified candidate tumor suppressor gene, was previously shown to be altered in human pancreatic cancers. We examined DPC4 mutation in 30 examples of three other types of gastrointestinal malignancy: 10 esophageal cancers, 10 gastric cancers and 10 colorectal cancers occurring in the preneoplastic condition, ulcerative colitis. The entire coding region of DPC4 (including all 11 exons) was analysed by either direct sequencing of PCR product or the in vitro synthesized protein assay. No coding region mutations of DPC4 were found in any of the samples examined. Our results suggest that inactivation of DPC4 may not be important in the majority of these types of gastrointestinal cancer.

Colitis, Ulcerative↗

Chest trauma.

Trauma is a major cause of morbidity and mortality worldwide. Despite the advent of specialised trauma centres the outcome of patients who sustain major trauma remains disappointing. Plain radiography and more advanced imaging techniques such as ultrasound, computerised tomography (CT) and angiography, have a major role to play in the early decision making and subsequent management of patients who sustain polytrauma. This article discusses the choice of emergency imaging techniques available in chest trauma for clinicians and radiologists; their evaluation and some of the common pitfalls that may lead to errors of interpretation.

Aorta↗

Alterations of transforming growth factor-beta 1 receptor type II occur in ulcerative colitis-associated carcinomas, sporadic colorectal neoplasms, and esophageal carcinomas, but not in gastric neoplasms.

BACKGROUND & AIMS: Gastric cancers, sporadic colorectal cancers, and ulcerative colitis (UC)-associated colorectal carcinomas and dysplasias manifest microsatellite instability (MI); however, esophageal carcinomas rarely exhibit MI. Recently, a transforming growth factor-beta 1 type II receptor (TGF-beta 1RII) mutation in a coding microsatellite was described in primary colorectal carcinomas demonstrating MI. No previous studies of TGF-beta 1RII have addressed mechanisms of inactivation other than MI in human tumors; furthermore, MI-negative tumors have not been examined for TGF-beta 1RII mutation. We evaluated 138 primary human neoplasms for mutation in the poly-A microsatellite tract of TGF-beta 1RII. Additionally, a group of esophageal tumors was evaluated for the expression of TGF-beta 1RII messenger RNA (mRNA). METHODS: First, we determined whether MI was present at other chromosomal loci in these lesions. The poly-deoxyadenine (poly-A) microsatellite tract within the TGF-beta 1RII coding region was then PCR-amplified. In a group of MI-negative esophageal tumors, RT-PCR was performed to determine the expression of TGF-beta 1RII mRNA. RESULTS: Among 17 MI+ UC specimens, 3 (18%) demonstrated TGF-beta 1RII poly-A tract mutation (2 cancers and 1 dysplasia), while 2 (4%) of 44 MI-negative UC specimens (1 dysplasia and 1 tumor), and 13 (81%) of 16 MI+ sporadic colorectal cancers, contained TGF-beta 1RII poly-A mutation. No gastric or esophageal tumors contained TGF-beta 1RII mutation. Among 21 MI-negative esophageal carcinomas. 6 cases (28.5%) had TGF-beta 1RII transcripts that were low or undetectable by RT-PCR. CONCLUSIONS: Mutation within the poly-A microsatellite tract of TGF-beta 1RII occurs early in a subset of UC-neoplasms and commonly in sporadic colorectal cancers, but may be rare in MI+ gastric tumors. Diminished expression of TGF-beta 1RII mRNA in esophageal tumors suggests that mechanisms of inactivation in this gene other than MI play a role in esophageal carcinogenesis.

Colitis, Ulcerative↗

Adenomatous polyposis coli gene mutations in ulcerative colitis-associated dysplasias and cancers versus sporadic colon neoplasms.

Adenomatous polyposis coli (APC) gene mutations occur in most sporadic colonic adenomas and carcinomas. Precursor lesions of ulcerative colitis (UC)-associated colon carcinomas, although morphologically similar to sporadic adenomas, may be biologically distinct from them and are, in fact, managed differently. Since sporadic adenomas may also occur in UC, a method of discriminating between these forms of neoplasia could have clinical utility. We examined 33 patients with UC-associated dysplasias and cancers and 23 sporadic colon neoplasms in a side-by-side comparison for APC mutations. Codons 686-1693, containing 64% of all reported APC mutations (the mutation cluster region), were screened for truncating mutations using an in vitro synthesized protein assay. Two of thirty-three patients (6%) with UC-associated dysplasias and cancers had a total of three truncating APC mutations, all in frank carcinomas, while 17 of 23 (74%) with sporadic colonic neoplasms had mutations. DNA sequencing confirmed two mutations in codon 1460, replacing arginine with a stop codon, as well as one 2-base pair deletion, resulting in a frameshift and a stop at codon 1477. One specimen contained one each of these APC mutations. This apparent contrast in mutation rates at the mutation cluster region of APC is consistent with other biological characteristics separating sporadic colon neoplasms from UC-associated dysplasias and cancers. These data raise the possibility that nonadenomatous UC dysplasias may arise by a molecular pathway distinct from that prevailing in sporadic colon carcinogenesis, and they suggest a molecular assay to discriminate between sporadic adenomas and dysplasias occurring in UC.

Base Sequence↗

Preliminary observations on the changing roles of malaria vectors in southern Belize.

A survey for larval and adult Anopheles mosquitoes was conducted in Toledo District of southern Belize during August-September 1992. We surveyed for larvae in 145 habitats and conducted paired indoor-outdoor collections of adult mosquitoes landing on humans at 6 houses. In 1940-41, Kumm and Ram reported Anopheles darlingi females to be the most common Anopheles mosquitoes inside houses and reported no specimens of Anopheles vestitipennis in southern Belize. In our 1992 survey we found no An. darlingi mosquitoes either as adults or larvae. More An. vestitipennis females were captured indoors than outdoors, whereas most Anopheles albimanus and Anopheles apicimacula females were captured outdoors. All 3 species were represented occasionally in 145 collections of larvae from diverse habitats. Anopheles vestitipennis now appears to be a potentially important vector of malaria during the wet season in Toledo District.

Animals↗

Case report: widespread tuberculosis in sickle cell disease.

We report a case of a patient with sickle cell disease who presented with mesenteric nodes and pulmonary TB and who subsequently relapsed on triple therapy and presented with disseminated tuberculous osteomyelitis and cervical lymphadenopathy. We emphasize the difficulty of establishing the diagnosis at all stages of presentation.

Adolescent↗

Misinterpretation of the upper parathyroid adenoma on thallium-201/technetium-99m subtraction scintigraphy.

Pre-operative thallium-technetium subtraction scintigraphy of 50 patients with primary hyperparathyroidism, which was subsequently proven on histology to be due to an adenoma, was compared with operative findings. Six scans were negative and seven uninterpretable. Of the remaining 37 patients, 34 had correct scan prediction of the anatomical locations of the adenomas. On examination of the origins of the adenomas, all six scintigraphic predictions of upper adenomas corresponded to tumours arising from the upper gland found at operation. Of the 25 lower predictions, there was one false positive and 16 were correct, i.e. of lower gland origin, but eight were found to originate from the upper gland. This misinterpretation is though to be due to the prolapse of an adenoma arising from the upper gland towards the lower pole of the thyroid, thereby mimicking a lower lesion on the scan.

Adenoma↗

The incidence of popliteal aneurysms in patients with arteriomegaly.

Sixty-five patients with arteriomegaly were investigated by arteriography or digital subtraction angiography, and ultrasound or computed tomography to exclude popliteal aneurysms. In 36 (55%) patients popliteal aneurysms were demonstrated. In view of this high incidence and the known serious complications of popliteal aneurysms, we suggest that all patients with angiographic evidence of arteriomegaly should be further investigated by ultrasound or computed tomography.

Adult↗

The incidence and sites of medial thigh communicating veins: a phlebographic study.

One hundred saphenograms in 65 patients were reviewed to assess the number and distribution of communicating veins on the medial aspect of the thigh. Sixty-one per cent of the legs had one or more communicating veins in the middle third of the thigh (Hunter's canal), 27% were in the lower third and 1% in the upper third. Eleven per cent of the legs investigated had no evidence of communicating veins. The number of communicating veins ranged from none to three. Because of the range in the number and position of the communicating veins, which are potential sites of venous incompetence, their phelebographic demonstration by varicography is recommended in legs with recurrent varicose veins.

Adult↗

A double-blind clinical study comparing the safety, tolerance and efficacy of ioversol and iohexol in intravenous urography.

A double-blind trial in 80 patients showed no significant difference in the efficacy, tolerance and safety for intravenous urography between the new contrast medium Ioversol (Optiray Mallinckrodt Inc.) and the well established medium Iohexol (Omnipaque, Nycomed [UK] Ltd). Minor transient rises in AST/ALT were noted in approximately 10% of each group which were regarded as clinically insignificant. Both media were well tolerated with no significant side-effects.

Adult↗

A comparison of the effects of spatial separation on apparent motion in the auditory and visual modalities.

In the present investigation, the effects of spatial separation on the interstimulus onset intervals (ISOIs) that produce auditory and visual apparent motion were compared. In Experiment 1, subjects were tested on auditory apparent motion. They listened to 50-msec broadband noise pulses that were presented through two speakers separated by one of six different values between 0 degrees and 160 degrees. On each trial, the sounds were temporally separated by 1 of 12 ISOIs from 0 to 500 msec. The subjects were instructed to categorize their perception of the sounds as "single," "simultaneous," "continuous motion," "broken motion," or "succession." They also indicated the proper temporal sequence of each sound pair. In Experiments 2 and 3, subjects were tested on visual apparent motion. Experiment 2 included a range of spatial separations from 6 degrees to 80 degrees; Experiment 3 included separations from .5 degrees to 10 degrees. The same ISOIs were used as in Experiment 1. When the separations were equal, the ISOIs at which auditory apparent motion was perceived were smaller than the values that produced the same experience in vision. Spatial separation affected only visual apparent motion. For separations less than 2 degrees, the ISOIs that produced visual continuous motion were nearly equal to those which produced auditory continuous motion. For larger separations, the ISOIs that produced visual apparent motion increased.

Adult↗

Cerebrovascular disease and antiphospholipid antibodies in systemic lupus erythematosus, lupus-like disease, and the primary antiphospholipid syndrome.

PURPOSE AND PATIENTS AND METHODS: Antiphospholipid antibodies, lupus anticoagulant antibodies to cardiolipin, and a false-positive result on testing for syphilis have been linked to thrombotic vascular occlusions, particularly in patients with systemic lupus erythematosus (SLE) or lupus-like disease, i.e., patients not fulfilling four American Rheumatism Association criteria for the classification of SLE. The clinical and serologic features of 35 patients with cerebrovascular disease (strokes/transient ischemic attacks) who demonstrated antibodies to phospholipids are presented. Complete histories were obtained from all 35 patients, and all underwent routine physical examinations, radiography, electrocardiography, computed tomographic brain scanning, and immunologic studies. Psychometric tests were performed in nine patients. RESULTS: The strokes were often multiple and were followed by multi-infarct dementia in nine patients. Of particular interest were 10 patients in whom the presence of antiphospholipid antibodies was the major and often the sole immunologic disturbance present. Several of these patients were antinuclear antibody-negative, and the antinuclear antibodies, when present, were usually of a low titer (1:40 to 1:160). These patients conform to a group classified as having a primary antiphospholipid syndrome. CONCLUSION: Antiphospholipid antibodies are strongly associated with cerebrovascular occlusions in patients with SLE as well as in those with lupus-like disease and the primary antiphospholipid syndrome. All patients with any of these conditions who present with vascular events should be screened for these antibodies, as their occurrence may have a bearing on future therapy.

Adult↗

Lateral thigh varicose veins: a phlebographic study.

The phlebographic findings in nine patients with primary varicose veins on the lateral aspect of the thigh are described. These were shown by varicography to connect primarily with the deep femoral vein via communicating veins: the symptoms were either cosmetic or mild aching in the thigh. Surgical treatment, if indicated, consists of subfascial ligation or sclerosis of the varices, or flush ligation of the incompetent communicating veins at their connections with the deep femoral vein.

Adult↗