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Biomedical subjects

S Lam

Publications and source records attributed to S Lam.

At least 19 recordsLinked to original sources

Evidence of cumulative gene losses with progression of premalignant epithelial lesions to carcinoma of the bronchus.

Human bronchial carcinoma is thought to develop through progressive stages from basal cell hyperplasia to squamous metaplasia, dysplasia, carcinoma in situ, and finally invasive cancer. In this study, we used tissue microdissection to examine loss of heterozygosity of chromosomes 3p21, 5q21, and 9p21 at each stage of the epithelial progression to invasive cancers. Forty-eight premalignant/malignant bronchial sites were biopsied from 13 patients (including 9 subjects without cancer) using fluorescence bronchoscopy. Eighteen sites with moderate/severe dysplasia in 6 patients were subjected to bronchoscopic and molecular follow-up during a 3-month to 2-year period. Seven separate cases of advanced non-small cell bronchial cancers were also analyzed. From the baseline biopsies, the prevalence of 3p and 9p deletions increased significantly from no deletion in the hyperplasia/metaplasia samples (n = 9) to 37 and 31% of the informative cases, respectively, in the dysplasia samples (n = 29), to 100 and 83%, respectively, for the carcinomas in situ (n = 6), and 100% in the invasive cancers (n = 11). Chromosome 5q deletion was significantly more frequent in invasive cancers (70% of the informative cases) as compared to carcinoma in situ (40%), dysplasias (33%), and hyperplasia/metaplasia samples (11%). The number of chromosome alterations also increased significantly from the lowest to the highest grade lesions, showing evidence of accumulation of genetic damage from one group to another. The molecular follow-up analysis showed that the same genomic alteration can persist in a given dysplastic bronchial area for several months or years, and that the persistence or the regression of the molecular abnormality is well correlated with the evolution of the disease on follow-up. Our results suggest that molecular analysis of bronchial biopsies obtained by fluorescence bronchoscopy may be a very useful means to study the natural history of preinvasive bronchial lesions and the outcome of interventions, such as with chemopreventive treatment.

Aged

The challenge of vancomycin-resistant enterococci: a clinical and epidemiologic study.

BACKGROUND: Vancomycin-resistant enterococci have been recovered with increasing frequency from hospitalized patients. Risk factors, mode of nosocomial transmission, extent of colonization in hospitalized patients, and treatment options for these organisms have not been completely delineated. METHODS: We studied 53 patients (group A) with vancomycin-resistant enterococci isolated from various clinical specimens and also surveyed for vancomycin-resistant enterococci in stool specimens submitted for Clostridium difficile toxin assays (group B). Stool specimens submitted for identification of bacterial pathogens and stool specimens from hospital employees were also analyzed for vancomycin-resistant enterococci. RESULTS: Seventy-six isolates of vancomycin-resistant enterococci were recovered in group A. Five of these patients harbored vancomycin-resistant enterococci on admission. Fifty-three of 289 group B stool specimens submitted for C. difficile toxin assays yielded vancomycin-resistant enterococci. Cephalosporins and vancomycin were the most common antimicrobial agents received by both groups of patients. Enterococcus faecium isolates were more resistant than Enterococcus faecalis isolates to antimicrobial agents. All isolates exhibited high-level aminoglycoside resistance and were not beta-lactamase producers. There were at least 15 different molecular clones of E. faecium and three of E. faecalis. Vancomycin-resistant enterococcal bacteremia was associated with a 100% in-hospital mortality rate. CONCLUSIONS: Multidrug-resistant and vancomycin-resistant enterococci have become important nosocomial pathogens that are difficult to treat. Vancomycin-resistant enterococcal bacteremia was associated with a poor prognosis. We found a high rate of colonization in patients with suspected C. difficile toxin colitis. Judicious use of vancomycin and broad-spectrum antibiotics is recommended, and strict infection control measures must be implemented to prevent nosocomial transmission of these organisms.

Adult

Prevalence of palpebral fissure asymmetry in white persons.

PURPOSE: Because palpebral fissure asymmetry in horizontal gaze is reportedly common in otherwise normal persons, we determined the prevalence of physiologic palpebral fissure asymmetry for primary and horizontal gazes. METHODS: We measured the palpebral fissure height of both eyes of 88 healthy white subjects. Measurements were obtained with high-resolution videography, with the eyes in primary position, in 45-degree right gaze, and in 45-degree left gaze. RESULTS: Of the 88 subjects, 36 (41%) were male and 52 (59%) were female. The ages ranged from 12 to 50 years, with a mean of 32.5 +/- 9.0 years. When a criterion of equal to or greater than 1 mm was used, the prevalence of physiologic palpebral fissure asymmetry was 5.7% (five of 88) in primary gaze, 18.2% (16 of 88) in right gaze, and 14.8% (13 of 88) in left gaze. The largest observed palpebral fissure asymmetry was 2.1 mm. After correcting for any existing fissure asymmetry in primary gaze, two-tailed trivariate analysis of variance showed that the fissure of the adducting eye tended to be wider. The mean increase in the palpebral fissure of the adducting eye was 0.12 mm for right gaze (P = .052) and 0.13 mm for left gaze (P = .034). Additionally, a chi 2 test indicated that the occurrence of wider adducting eye in both right and left gazes was highly significant (P = .0023). CONCLUSIONS: In this sample of white subjects, palpebral fissure height asymmetry increased in horizontal gaze to the right and to the left, which is in part because of a tendency of the adducting eye to widen slightly. In contrast to previous reports, the prevalence of palpebral fissure asymmetry was low, and the abducting eye did not widen significantly.

Adolescent

Diagnostic imaging of the larynx: autofluorescence of laryngeal tumours using the helium-cadmium laser.

The use of tissue autofluorescence for the detection and localization of cancer of the larynx is described. In this pilot study, eight patients with probable carcinoma of the vocal folds underwent laryngoscopy in which the tissue autofluorescence spectra of normal and pathologically confirmed tumour tissue were acquired in vivo. Fluorescence images of the suspect areas were also acquired using the LIFE system (Xillix Technologies Corp.). The results suggest that the autofluorescence properties of laryngeal tissue, under 442 nm illumination, are similar to those of bronchial tissue and that the LIFE system has the potential to increase the accuracy of staging of cancer of the larynx and also to allow earlier diagnosis of tumours and their recurrence.

Carcinoma, Squamous Cell

Bronchial inflammation in occupational asthma due to western red cedar.

Bronchoalveolar lavage cells and bronchial biopsies were obtained from nine patients with red cedar asthma, six atopic asthmatics and six non-atopic, non-asthmatic control subjects. There were similar proportions of neutrophils, mast cells, lymphocytes, and macrophages in BAL samples from all three groups, but eosinophil numbers were elevated in patients with cedar asthma and atopic asthma (3.0 and 2.5% respectively versus 0.5% in control subjects; p < 0.05 for each group). In bronchial mucosal biopsies, mean numbers of T cells were elevated in both asthmatic groups (cedar asthma 9.8 times, and atopic asthma 2.6 times, control values). CD4+ cells accounted for most of the increase in T-cell numbers, while CD8+ cell numbers were elevated in biopsies from a minority of cedar asthma patients. Absolute numbers of CD25+ (IL-2 receptor-bearing) cells were increased in cedar asthma but the proportion of T cells expressing CD25, was similar in all three groups. Activated eosinophils (EG2+) were increased in both asthmatic groups, with mean numbers 2.5 times greater in the cedar asthma biopsies than in atopic asthmatics. Thus both cedar asthma and atopic asthma are associated with increased numbers of T-cells and activated eosinophils in the bronchial mucosa. There was no major histologic difference between atopic asthma and red cedar asthma.

Adult

Nonequivalent requirements for PS1 and PS2 integrin at cell attachments in Drosophila: genetic analysis of the alpha PS1 integrin subunit.

We report on the generation and phenotype of mutant alleles of multiple edematous wings (mew), the gene encoding the alpha PS1 subunit of the PS1 integrin of Drosophila. None of the six alleles examined makes detectable protein, and one allele results from a chromosome break near the middle of the translated sequence, so we are confident that we have described the null phenotype. In contrast to if (alpha PS2) and mys (beta PS) mutants, most mutant mew embryos hatch, to die as larvae. Mutant mew embryos display abnormal gut morphogenesis but, unlike mys or if embryos, there is no evidence of defects in the somatic muscles. Thus, the complementary distributions of PS1 (alpha PS1 beta PS) and PS2 (alpha PS2 beta PS) integrin on tendon cells and muscle, respectively, do not reflect equivalent requirements at the myotendinous junction. Dorsal herniation, characteristic of the mys lethal phenotype, is not observed in mew or in mew if embryos. Clonal analysis experiments indicate that eye morphogenesis is disrupted in mew clones, but if clones in the eye are relatively normal in morphology. Adult wings display blisters around large dorsal but not ventral mew clones. In contrast to dorsal mys clones, small mew patches do not necessarily display morphogenetic abnormalities. Thus, another integrin in addition to PS1 appears to function on the dorsal wing surface.

Alleles

Malignancy-associated changes in bronchial epithelial cells in biopsy specimens.

A total of 152 normal bronchial biopsy sections--63 from normal subjects, 42 from patients with dysplasia, 28 from patients with early or advanced lung cancer with squamous and nonsquamous histopathology, and 19 from resected lung cancer patients--were examined for the presence of malignancy-associated changes (MACs). A standard, white light bronchoscope examination and a multispectral fluorescence bronchoscope examination were performed on every subject to determine the status of the bronchial epithelial tissue. Any suspect areas were biopsied to determine the status of the area and to establish the highest grade of abnormality in the patient. In addition, for every subject, a bronchoscopically normal area of the bronchus in the opposite lung or another lobe was biopsied. The specimens were confirmed to be normal by conventional histopathologic criteria using hematoxylin and eosin stain. Sections of biopsies were stained using a DNA stoichiometric stain, and approximately 250 images of visually normal epithelial cell nuclei from each of the biopsies were collected, as were approximately 40 images of leukocyte cell nuclei. For each of these images > 60 nuclear features were calculated that quantified the size, shape and DNA volume of the nuclei as well as DNA spatial organization in the nuclei. The features were then used to train an automated classifier to recognize normal epithelial cell nuclei from normal subjects and normal-appearing epithelial cell nuclei (MAC cell nuclei) from lung cancer patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Biopsy

Use of high-resolution cytometry in predicting the biologic behavior of T1 adenocarcinoma of the lung.

Touch preparations from 60 cases of T1 adenocarcinoma were analyzed using a high-resolution, automated image cytometer. These cases were divided according to pathologic stage: stage I, 31; stage II, 3; stage III, 19; and stage IV, 7. For each nucleus 57 features were analyzed, and using a linear combination of three texture features describing the DNA distribution in the cell nucleus (TARL, ODMAX and FAREA1), aggressive cancer cells belonging to stage III/IV could be identified. The best discrimination between the stages was achieved when the frequency of aggressive cancer cells was 48%; the correct classification rate was 77%. Using this criterion, 22 of 27 patients (81%) who died of cancer within five years after surgery were correctly predicted. These results suggest that high-resolution cytometry may be of value in predicting the biologic behavior of adenocarcinoma cases, especially in stage I/II.

Adenocarcinoma

Peripherally inserted central catheters in an acute-care hospital.

BACKGROUND: Peripherally inserted central catheterization is a relatively new approach for intravenous therapy in acute-care hospitals. Few studies are available on peripherally inserted central catheters (PICCs) used in adult patients in an acute-care setting. We examine the natural history and outcome of PICC use in our hospital. METHODS: A retrospective review was undertaken of all hospitalized patients who had PICCs inserted in an acute-care, metropolitan teaching hospital for any reason from July 1991 through July 1992. Patients who had PICCs inserted, used, and then removed in the same hospitalization were evaluated. RESULTS: A total of 135 PICCs were inserted in 114 patients. Six PICCs (4.4%) were inserted in intensive care unit settings and 129 (95.6%) in general medical or surgical service. The mean duration catheters were in place before removal was 14.1 days. Sixty-three catheters (46.7%) were removed following completion of therapy. The rate of PICC-related infection was 2.2% (three catheters). The occlusion rate was higher for 20-gauge catheters (18.4%) than for 18-gauge catheters (8.2%) (P = .08). When the rate of complications was compared as a function of catheter use (total parenteral nutrition vs any other use), there was no statistically significant difference (P = .12). Overall complications related to catheter insertion and removal were uncommon. CONCLUSIONS: Based on our study, we conclude that the PICC provides a reasonable and safe alternative to other centrally placed venous devices. In addition, the convenience of maintaining a PICC compared with peripheral intravenous access makes this an attractive method for in-hospital use.

Adult

Lysosomal enzyme activities in conjunctival tissues of patients with keratoconus.

OBJECTIVE: To examine the lysosomal enzyme activities in the conjunctival tissues of patients with keratoconus. METHODS: Tissues collected from 11 patients with keratoconus, eight patients with senile cataract, three patients with Fuchs' corneal dystrophy, and 11 normal control subjects were processed for histochemical staining for two lysosomal hydrolases, acid esterase and acid phosphatase. RESULTS: The epithelium of all conjunctival specimens stained positively for the two enzymes. The staining in the conjunctival tissues of patients with keratoconus was more prominent than that seen in specimens from either normal control subjects or patients with other diseases. CONCLUSION: Our results suggest that the conjunctival epithelium may be altered in keratoconus. Elevation of lysosomal enzyme levels has been demonstrated in the epithelium of corneas with keratoconus, implicating a role of this layer in the disease. The conjunctival abnormality seems to corroborate the corneal epithelial theory. It also adds one dimension to the pathogenesis of keratoconus.

Acetylesterase

Response to thymectomy in Chinese patients with myasthenia gravis.

Myasthenia gravis was diagnosed in 48 patients between 1985 and 1991 in this Chinese community. Thymectomy was performed on 36 patients and the mean postoperative follow-up period was 49 months. Significant improvement was seen in 72% of the thymectomised patients, with 33% achieving complete remission. Patients with mild generalised myasthenia at presentation or those found to have thymic hyperplasia had the best prognosis. Patients with more severe symptoms or those with an underlying thymoma also responded favourably. Only patients with ocular myasthenia or those with a normal or atrophic thymus gland had no more than an even chance of gaining significant improvement. Although previous reports suggested a high prevalence of ocular myasthenia and of thymoma among Chinese myasthenic patients, the present study has found no evidence that they respond differently to thymectomy than their Western counterparts.

Adolescent

Community-acquired soft-tissue infections caused by Flavimonas oryzihabitans.

Flavimonas oryzihabitans has rarely been implicated in human infections. Previously reported cases of infections caused by this bacterium were nosocomially acquired. We report two cases of community-acquired soft-tissue infections due to F. oryzihabitans. It remains unclear how the patients were exposed to the organism.

Abscess

Reduction of macular oedema by acetazolamide in patients with chronic iridocyclitis: a randomised prospective crossover study.

Thirty patients with cystoid macular oedema secondary to chronic iridocyclitis were enrolled in a two period, prospective, randomised, double masked, crossover study that compared sustained release acetazolamide (500 mg twice a day) with a placebo to measure the effects on the reduction of cystoid macular oedema and improvement of visual acuity. All patients were treated for 1 month with either acetazolamide or placebo, received no treatment for 1 month, and were then treated for 1 month with the other medication. Statistically significant improvement in visual acuity was seen at 14 and 28 days in the treated patients. No improvement was seen when patients received placebo. Improved visual acuity was not associated with race or sex. However, younger patients (under age 55 years) were more likely to benefit from treatment. Results of vitreous fluorophotometry, obtained at baseline and 4 weeks, demonstrated an improvement in posterior vitreous penetration ratios and mid vitreous penetration ratios after treatment with acetazolamide but not with placebo.

Acetazolamide

Persistent asthma after repeated exposure to high concentrations of gases in pulpmills.

This is a clinicopathologic study of three subjects with irritant-induced asthma. They were pulpmill workers who had a history of multiple "gassing" episodes that occurred over a period of years. Persistent symptoms of asthma and nonspecific bronchial hyperresponsiveness and/or variable airflow obstruction occurred after at least one episode of "gassing," resulting in symptoms severe enough to require emergency room treatment. One of the three subjects had normal spirometry values before he entered the pulpmill. Bronchial biopsy done on these subjects showed changes compatible with asthma, including thickened basement membrane in two and cellular infiltration with activated eosinophils and mononuclear cells in all three. The results of immunohistology of bronchial mucosal biopsy of these subjects were compared with those of patients with allergic asthma and patients with Western red cedar-induced asthma. Subjects with irritant-induced asthma had a greater density of activated eosinophils and fewer T-lymphocytes, suggesting that cell-mediated immune mechanisms are not involved in the pathogenesis of this condition.

Adult

Photodynamic therapy of lung cancer.

Photodynamic therapy (PDT) has been used investigationally for the treatment of lung cancer since 1980. Following systemic administration of a photosensitizing agent such as porfimer sodium (Photofrin; manufactured by Lederle Parenterals, Carolina, Puerto Rico, under license from Quadra Logic Technologies, Inc, Vancouver, British Columbia, Canada), specialized optical delivery systems are engaged to deliver light of a specific wavelength (630 nm for porfimer sodium) to neoplastic tissue. A promising use of PDT appears to be treatment of early stage lung carcinoma. Phase I-II clinical trials by Hayata's group in Japan showed that for superficial early lung cancer less than 1 cm in surface diameter, complete eradication can be achieved in approximately 90% of cases. Additional phase II-III clinical trials have demonstrated an average of 90% complete response rates for superficial tumors less than 1 cm in diameter. Preoperative PDT may be useful for larger neoplasms to reduce tumor burden and potentially lessen the degree of surgery required. At the British Columbia Cancer Agency, 22 patients with 30 radiologically occult cancers were treated with PDT. In contrast to Hayata's studies, most of these patients had rather extensive tumor burden. Thirty percent of the tumors involved two or more bronchi, and more than half of them were greater than 1 cm in surface diameter. Twenty-three percent of the cases were bronchial stump recurrences. In the group of patients with bronchial stump recurrence, although a complete response was obtained with PDT initially, local recurrences occurred in 75% of cases. These results suggest that recurrent tumor in the bronchial stump should not be treated with PDT because of difficulty in delivering light endobronchially to distal tissues. Photodynamic therapy may have a role in the palliation of advanced, inoperable, obstructive bronchial tumors. Phytodynamic therapy in combination with external radiotherapy may produce better local control than external radiotherapy alone in patients with obstructive bronchial cancers. Photodynamic therapy and conventional Nd:YAG laser therapy appear to be equally effective in relieving intraluminal obstruction by tumor. An advantage of PDT for this purpose is longer time to treatment failure; a disadvantage is photosensitization that usually occurs for up to 4 weeks after treatment. In summary, PDT is a promising curative treatment for patients with small early bronchial cancers.

Airway Obstruction