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Biomedical subjects

D A Lynch

Publications and source records attributed to D A Lynch.

At least 19 recordsLinked to original sources
PubMed1996

Ascorbic acid and total vitamin C concentrations in plasma, gastric juice, and gastrointestinal mucosa: effects of gastritis and oral supplementation.

Epidemiological evidence suggests that high dietary ascorbic acid reduces gastric cancer risk. It may do this by either reducing N-nitroso compound formation in gastric juice, or by scavenging reactive oxygen species in gastric mucosa. The aim of this study was to discover if potential ascorbic acid protection might be increased by supplementation. Thirty two patients were supplemented with ascorbic acid, 500 mg twice daily for two weeks. Gastric juice, plasma, and upper gastrointestinal biopsy ascorbate concentrations were measured and compared with values in 48 unsupplemented patients. It was found that ascorbic acid and total vitamin C concentrations were considerably higher in biopsy specimens from oesophagus, body, antrum, duodenum, and rectum, compared with values in plasma or gastric juice. Plasma and mucosal concentrations were unaffected by the presence of chronic gastritis but gastric juice concentrations were substantially lower in patients with chronic gastritis than in patients with normal histological assessment (p < 0.01). Patients receiving ascorbic acid supplements had higher ascorbic acid concentrations in plasma (p < 0.001), gastric juice (p < 0.001), and at all biopsy sites in the upper gastrointestinal tract (p < 0.05). Gastric juice ascorbic acid and total vitamin C concentrations in gastritic patients, however, were still less after supplementation than in normal subjects (p < 0.01). These data suggest that high ascorbic acid intake could reduce gastric cancer risk, but its protective effect might be greater if gastritis is treated (for example, by Helicobacter pylori eradication).

Adult↗
PubMed1996

Diffuse panbronchiolitis in the United States.

Diffuse panbronchiolitis (DPB), an important cause of progressive obstructive lung disease in the Far East, represents a distinctive sinobronchial syndrome with typical radiologic and histologic features. We have identified DPB in five citizens of the United States, three with histologic confirmation, who have never traveled to the Far East. There were four men and one woman, whose ages ranged from 46 to 75 yr at the time of diagnosis. All had a prior history of chronic sinusitis and presented with cough, dyspnea, and sputum production. Three were never smokers and two were current smokers. Pulmonary function testing revealed severe airflow limitation (the FEV1 ranging from 22% to 56% of predicted), and overdistention. All patients had high-resolution computed tomographic (HRCT) scans indicating centrilobular nodules with adjoining thickened and dilated bronchioles. In the three patients in whom open lung biopsy was performed, there was bronchiolocentric infiltration of lymphocytes, plasma cells, and foamy macrophages. Three patients remain alive and are being treated with chronic macrolide therapy. The clinical, radiographic, and histologic features of these patients closely resemble those described in Japanese patients. DPB must be considered in the differential diagnosis of sinopulmonary syndromes, bronchiolitis, and cryptic cases of obstructive lung disease among United States citizens, since therapy now offers an improved prognosis.

Aged↗
PubMed1996

Quantitative CT predicts the severity of physiologic dysfunction in patients with lymphangioleiomyomatosis.

PURPOSE: To assess quantitative high-resolution CT (quantitative CT) as a diagnostic and prognostic tool in pulmonary lymphangioleiomyomatosis. METHODS: Spirometry, lung volumes, diffusing capacity, exercise physiology, and expiratory high-resolution CT (HRCT) examinations were performed on a cohort of ten patients with the diagnosis of lymphangioleiomyomatosis (LAM) referred to a tertiary care center. HRCT examinations were also done on ten normal control subjects. A thresholding technique was used to quantitatively assess the amount of abnormal cystic parenchyma present on each of the two images obtained for each subject with LAM and for each normal control subject. This numeric index of cystic parenchyma, the quantitative CT index, was then examined (1) as a diagnostic measure to distinguish the subjects with LAM from the normal control subjects and (2) as a prognostic measure to assess disease severity in the subjects with LAM. Linear regression of the quantitative CT index against physiologic indexes of pulmonary function and exercise performance was analyzed to determine the relationship between this radiologic assessment of disease severity and functional impairment. RESULTS: The quantitative CT index was significantly greater for the LAM patients, 37.2 +/- 6.9 (SEM), compared with the control group, 0.8 +/- 0.2 (p = 0.0001). Linear regression analysis demonstrated significant linear correlation between the quantitative CT index and measures of airflow (FEV1, r = -0.90, p = 0.0005), air trapping (residual volume, r = 0.70, p = 0.02), diffusing capacity (diffusing capacity for carbon monoxide, r = -0.76, p = 0.01), gas exchange (alveolar to arterial oxygen gradient) at rest, r = 0.69, p = 0.007, and at maximum exercise, r = 0.79, p = 0.007) and exercise performance (maximum workload, r = -0.84, p = 0.002), and oxygen utilization (oxygen utilization at maximum exercise, r = -0.76, p = 0.01). CONCLUSION: Quantitative CT techniques can distinguish subjects with LAM from normal controls. Further, the quantitative CT index correlates well with physiologic measurements of airflow, lung volumes, diffusing capacity, and exercise performance and, thus, may provide a useful measure of disease severity.

Adult↗
PubMed1995

Cell proliferation in Helicobacter pylori associated gastritis and the effect of eradication therapy.

Helicobacter pylori causes chronic (type B) gastritis. The 'intestinal' form of gastric cancer arises against a background of chronic gastritis, and prospective epidemiological studies have shown that H pylori is a major risk factor for this. An increase in mucosal cell proliferation increases the likelihood of a neoplastic clone of epithelial cells emerging where there is chronic epithelial cell injury associated with H pylori gastritis. In vitro bromodeoxyuridine labelling of endoscopic antral biopsy specimens was used to measure mucosal cell proliferation in H pylori associated gastritis before and after therapy for H pylori triple infection. Cell proliferation was increased in H pylori associated gastritis patients compared with normal controls and patients with H pylori negative chronic gastritis (p = 0.0001; Tukey's Studentised range). There was no difference in antral epithelial cell proliferation between duodenal ulcer and non-ulcer subjects infected with H pylori (p = 0.62; Student's t test). Antral mucosal cell proliferation fell four weeks after completing triple therapy, irrespective of whether or not H pylori had been eradicated (p = 0.0001). At retesting six to 18 months later (mean = 12 months), however, those in whom H pylori had not been successfully eradicated showed increased mucosal proliferation compared with both H pylori negative subjects at a similar follow up interval and all cases (whether H pylori positive or negative) four weeks after completion of triple therapy (p = 0.024). These findings suggest that H pylori infection causes increased gastric cell proliferation and in this way may play a part in gastric carcinogenesis.

Adult↗
PubMed1995

Cell proliferation in the gastric corpus in Helicobacter pylori associated gastritis and after gastric resection.

Patients who have undergone gastric resection are at higher risk of developing gastric carcinoma than normal subjects, and bile reflux is believed to play a role in carcinogenesis. An increase in mucosal cell proliferation increases the likelihood of a neoplastic clone of epithelial cells emerging, particularly where there is chronic epithelial injury associated with bile reflux. Helicobacter pylori is considered a major risk factor for gastric cancer in the intact stomach. It has been shown previously that antral cell proliferation is increased in H pylori gastritis and falls to normal levels after eradication of the organism. Little is known of corpus cell proliferation in H pylori gastritis or after gastric resection. Using in vitro bromodeoxyuridine labelling of endoscopic biopsy specimens we have found that corpus cell proliferation is increased in H pylori gastritis. Cell proliferation was greater in corpus biopsy specimens of resected stomachs than in H pylori gastritis. Subgroup analysis of patients who had undergone gastric resection indicated that those positive for H pylori had higher levels of cell proliferation than those negative for the organism. These findings provide further evidence that H pylori and bile have a role in gastric carcinogenesis and suggest that their presence has a synergistic effect on gastric epithelial cell proliferation.

Adult↗
PubMed1995

Helicobacter pylori infection and dental care.

Sixty two patients (mean age 45.6 years) were assessed for oral hygiene and periodontal disease by dental examination before endoscopy. Information about oral care, smoking, and dentures was obtained and samples of dental plaque collected. The presence of Helicobacter pylori in plaque as sought by culture and polymerase chain reaction (PCR), and gastric antral biopsy specimens were taken for histological examination. Although H pylori was detected in the antral specimens of 34 patients (54%) all of the cultures of dental plaque were negative, and PCR was only positive from the dentures of one patient. Smokers had poor oral hygiene, visited their dentist less often, and brushed their teeth less frequently. There was no correlation of H pylori gastritis with either dental hygiene or periodontal disease. These results suggest that dental plaque or dentures are not an important reservoir for H pylori and are probably not a significant factor in transmission of the organism. The conflicting results in published works may be caused by differences in sample collection, culture techniques, or oral contamination from gastric juice as a result of gastro-oesophageal reflux at the time of endoscopy.

Adult↗
PubMed1995

Lymphocytic gastritis and associated small bowel disease: a diffuse lymphocytic gastroenteropathy?

AIM: To investigate the natural history of lymphocytic gastritis (LG) and its relation to Helicobacter pylori infection and to coeliac disease using serology, duodenal biopsy and a small intestinal permeability test. METHOD: Twenty two patients diagnosed as having LG between 1984 and 1994 were investigated by upper gastrointestinal endoscopy at which gastric and duodenal biopsy specimens were taken for histological assessment and immunohistology. Serum was collected for measurement of anti-H pylori, anti-gliadin and anti-endomysial antibodies. A lactulose/mannitol absorption test was performed within one week of endoscopy. Control groups were studied by histology, serology and permeability tests. RESULTS: Three patients had been recently diagnosed as having LG while 15 still had the condition after a mean of 13.9 (range two to 38) months. LG involved the antrum alone in three patients, antrum and body in seven, body alone in six, and gastric remnant in two. Gastroduodenal intraepithelial lymphocytes (IELs) were T cells and predominantly of T suppressor (CD8) type. Duodenal IELs were increased compared to age/sex matched controls with chronic gastritis. Four patients had duodenal villous atrophy. Four patients no longer had LG after a mean of 29.3 (10-70) months but had increased gastroduodenal IELs. H pylori was present in four (22%) of 18 patients with LG but H pylori serology was positive in 11 (61%) of 18. There was no difference in seropositivity when compared with age/sex matched controls with dyspepsia. Eleven of 20 patients with LG tested had abnormal lactulose/mannitol absorption (v none of 22 controls with chronic gastritis). Four patients with LG, all with villous atrophy, were seropositive for IgA endomysial antibody. CONCLUSIONS: The persistence of LG with time, the association with increased duodenal IELs and abnormal small intestinal permeability suggests LG may be a manifestation of a diffuse lymphocytic gastroenteropathy related to sensitivity to gluten or some other agent.

Adult↗
PubMed1995

How common are renal angiomyolipomas in patients with pulmonary lymphangiomyomatosis?

Pulmonary lymphangiomyomatosis has been associated with renal angiomyolipoma in case reports, but the prevalence of this association has not been well documented. The objective of this study was to determine the frequency of renal angiomyolipoma in a series of subjects with pulmonary lymphangiomyomatosis. Eighteen consecutive patients with pulmonary lymphangiomyomatosis were seen at a single institution between 1989 and 1994. Of these, one patient was excluded because she did not have an abdominal computed tomographic (CT) scan. We found eight out of 17 (47%) patients with pulmonary lymphangiomyomatosis to have renal angiomyolipomas. These were found either at surgery or on abdominal CT scanning. Thus, renal angiomyolipomas occur commonly in association with pulmonary lymphangiomyomatosis. Consequently, the early detection of renal angiomyolipoma by abdominal CT may be important, because lesions with dimensions larger than 4 cm may present an increased risk for complications related to tumor growth or hemorrhage. Serial follow-up by ultrasonography or CT scanning is important in identifying and monitoring high-risk patients. Prophylactic treatment (partial or total nephrectomy) may be considered for patients with tumors that show significant growth or other complications, such as hemorrhage.

Adult↗
PubMed1995

CT for asbestosis: value and limitations.

CT is more sensitive than clinical evaluation for the detection of asbestosis but is inevitably less sensitive and less specific than pathologic evaluation. For the asbestos-exposed individual, CT is useful for the evaluation of suspected lung masses, particularly rounded atelectasis [15], for identifying pleural plaques, and for confirming unequivocal asbestosis (grade 2 or grade 3 [8]). CT also will identify and quantify emphysema as a cause of physiologic impairment. Because clinicians commonly use CT to resolve clinical uncertainties, radiologists often feel pressured to categorize disease as unequivocally present or absent. Gamsu et al. [8] show that the borderline between normal and abnormal is not always sharply defined. In the absence of pathologic proof, the diagnosis of asbestosis must be based on a thoughtful evaluation of the likelihood of asbestosis by use of all available clinical, physiologic, and radiologic information. The scoring systems used by Gamsu et al. [8] offer a practical approach to defining the likelihood of asbestosis based on CT appearances.

Asbestosis↗
PubMed1995

Can CT distinguish hypersensitivity pneumonitis from idiopathic pulmonary fibrosis?

OBJECTIVE: The clinical management of patients with idiopathic pulmonary fibrosis differs markedly from that of patients with hypersensitivity pneumonitis. However, the two diseases often cannot be differentiated on clinical grounds. The purpose of this study was to establish whether CT can be used to make the distinction. MATERIALS AND METHODS: Thirty-six patients with idiopathic pulmonary fibrosis and 27 patients with hypersensitivity pneumonitis were studied. All diagnoses were confirmed or supported by open lung biopsy. Three of the patients with idiopathic pulmonary fibrosis had desquamative interstitial pneumonia, and the remainder had usual interstitial pneumonia. In 19 of the 27 patients with hypersensitivity pneumonitis, the disease was chronic (symptoms lasting more than 1 year), while eight had acute or subacute symptoms. Two radiologists, who had not previously seen any of the cases and were blinded to the diagnosis, reviewed the CT images by consensus. The extent and distribution of CT features (including ground-glass attenuation, honeycombing, and micronodules) were recorded. In each case, a CT diagnosis was made, and the level of diagnostic confidence was recorded. RESULTS: A CT diagnosis was made with a high level of confidence in 39 (62%) of 63 patients. In these patients, the CT diagnosis was correct in 35 cases (90%): 23 of 26 patients with a CT diagnosis of idiopathic pulmonary fibrosis and 12 of 13 patients with a CT diagnosis of hypersensitivity pneumonitis. In the three patients with desquamative interstitial pneumonia, the CT diagnoses were probable hypersensitivity pneumonitis in two cases and definite hypersensitivity pneumonitis in one case. Of the 19 patients with chronic hypersensitivity pneumonitis, only seven had a definite diagnosis of hypersensitivity pneumonitis based on CT findings; three had a definite diagnosis of idiopathic pulmonary fibrosis. The patients with idiopathic pulmonary fibrosis and usual interstitial pneumonia were more likely to have honeycombing and peripheral or lower lung zone predominance of disease, and less likely to have micronodules, than were patients with chronic hypersensitivity pneumonitis. The patients with idiopathic pulmonary fibrosis and desquamative interstitial pneumonia had widespread ground-glass opacity indistinguishable from some cases of acute or subacute hypersensitivity pneumonitis. CONCLUSION: Our results show that CT can be used to distinguish idiopathic pulmonary fibrosis from hypersensitivity pneumonitis in most but not all cases. Desquamative interstitial pneumonia cannot reliably be distinguished from acute or subacute hypersensitivity pneumonitis. Chronic hypersensitivity pneumonitis may have findings identical to those of usual interstitial pneumonia. Lung biopsy should still be considered the gold standard for diagnosis of interstitial lung disease.

Alveolitis, Extrinsic Allergic↗
PubMed1995

Helicobacter pylori, gastric cancer and gastric epithelial kinetics: a review.

AIM: To review the evidence that Helicobacter pylori promotes gastric carcinogenesis, with particular reference to gastric epithelial proliferation. MATERIALS AND METHODS: Gastric epithelial kinetics were reviewed and a series of studies of gastric mucosal proliferation in H. pylori-associated gastritis were performed in the intact and postsurgical stomach. In vitro bromodeoxyuridine labelling was performed on endoscopic antral biopsies from subjects with a normal gastric mucosa, with H. pylori-negative gastritis and with H. pylori-positive gastritis. The effect of eradication therapy was assessed. Corpus biopsies from the intact stomach were also examined and compared to body-type biopsies from the postsurgical stomach. RESULTS: Cell proliferation was increased in patients with H. pylori-positive gastritis and returned to normal levels following eradication therapy. The presence of H. pylori in the postsurgical stomach had a synergistic effect on gastric epithelial proliferation. CONCLUSIONS: H. pylori may promote gastric carcinogenesis by increasing epithelial proliferation. H. pylori and bile appear to have a synergistic effect on gastric cell proliferation.

Animals↗
PubMed1994

Patient and staff exposure to glutaraldehyde from KeyMed Auto-Disinfector endoscope washing machine.

Activated glutaraldehyde (2%) is the recommended agent for disinfection of endoscopic equipment. Exposure to the disinfectant is associated with side-effects and guidelines have been set to avoid these complications. Endoscope washing machines are used to provide automated high level disinfection of endoscopes as well as reduce exposure to the irritant aldehyde. We report a design fault in an endoscope washing machine which results in patients and staff being exposed to activated glutaraldehyde. The Auto-Disinfector (KeyMed) comprises a washing chamber supplied by three separate reservoirs (detergent, disinfectant, and rinse water) via a common channel. After the first cycle endoscopes are processed using previously used detergent and rinse water. Rinse water glutaraldehyde concentrations were measured in four machines during routine endoscopy lists on at least two occasions and showed a progressive rise in glutaraldehyde concentration up to 0.1% after two to six cycles. This results in staff being exposed to glutaraldehyde present on the processed instrument and the disinfectant being pumped from the internal channels of the endoscope into direct contact with the gastrointestinal mucosa during endoscopy at concentrations of 200-1000 ppm. The present atmospheric limit for glutaraldehyde is 0.2 ppm. Skin and mucosal irritation occur at concentrations of 0.3 ppm and severe synovitis in experimental animals at 100 pm. Tongue swelling and bloody diarrhoea with characteristic mucosal histological changes have been reported in patients exposed to activated glutaraldehyde on inadequately rinsed equipment. To reduce this problem the rinse water should be changed after every cycle and the endoscope should be dried thoroughly before use.

Disinfection↗
PubMed1994

Comparison of labelling by bromodeoxyuridine, MIB-1, and proliferating cell nuclear antigen in gastric mucosal biopsy specimens.

AIMS: To compare proliferating cell nuclear antigen (PCNA) and MIB-1 with bromodeoxyuridine (BrdU) pulse labelling, a specific marker of cell proliferation, in endoscopic gastric biopsy specimens. METHODS: Twenty four biopsy specimens were obtained from 12 patients: 10 antral and eight body specimens were suitable. Each specimen was routinely processed and stained with haematoxylin and eosin. A modified Giemsa stain was used to detect the presence of Helicobacter pylori. Sections of the specimens were labelled with BrdU, MIB-1, and PC10. Gastric mucosa specimens were divided into three zones. The numbers of positively staining nuclei for 500 epithelial cell nuclei were counted in each zone and expressed as a percentage. RESULTS: The proportion of PCNA positive cells (range 0-90%) was much greater in all specimens (10 antrum, eight body). BrdU positive cells were virtually all confined to zone 2 (0-17% cells in this zone were positive) (zone 1 = surface and gastric pit, zone 2 = isthmus, zone 3 = gland base), while PCNA positive cells were present in all three zones (1 = 23-90%, 2 = 43-90%, 3 = 0-74%). Spearman's rank coefficient correlation of 0.57 confirmed that the percentage of positively staining cells varied in the same direction for both PCNA and BrdU (p < 0.001). PCNA, however, was overexpressed in all zones of the gastric epithelium compared with BrdU. In 38 biopsy specimens from 19 patients, of which 14 antrum and 11 body were suitable, the proportion of MIB-1 positive cells (0-59%) was greater than BrdU in most. As with BrdU labelling, the MIB-1 positive cells were confined to zone 2 (zone 1 = 1-11%); zone 2 = 21-59%; zone 3 = 0-13%) and the coefficient correlation for MIB-1 and BrdU was 0.63 (p < 0.001). CONCLUSIONS: MIB-1 accurately reflects the S-phase fraction in gastric mucosa, determined by BrdU labelling in conventionally processed gastric biopsy material. Caution is needed in the interpretation of PCNA labelling detected by PC10, which should not be accepted uncritically as a marker of cell proliferation in paraffin wax embedded material.

Antibodies, Monoclonal↗
PubMed1994

Beryllium disease: assessment with CT.

PURPOSE: To describe the thin-section computed tomographic (CT) features of beryllium disease and compare the sensitivities of thin-section CT and chest radiography. MATERIALS AND METHODS: In 28 patients with biopsy-proved beryllium disease and 12 healthy control subjects, radiographs were scored with an international classification system. Thin-section CT scans were scored for 11 parenchymal, airway, pleural, and mediastinal findings. RESULTS: Thin-section CT revealed at least one abnormality in 25 patients (89%); chest radiography, in 15 patients (54%). After the finding of bronchial wall thickening attributable to tobacco smoking was excluded, CT scans in 21 (75%) of 28 patients were abnormal because of beryllium disease. The most common CT abnormalities were parenchymal nodules (n = 16) and septal lines (n = 14). With use of CT, abnormalities were detected in 10 (77%) of 13 patients with normal radiographs. CONCLUSION: Thin-section CT was more sensitive than chest radiography in detection of beryllium disease, but the diagnosis was missed in up to 25% of cases with histologic proof.

Berylliosis↗
PubMed1994

Bronchiolitis obliterans: the lone manifestation of rheumatoid arthritis?

The patient was a 62 year old man, who suddenly developed obstructive lung disease without a readily definable cause. He had a remarkable family history of deforming rheumatoid arthritis, and a serum rheumatoid factor of 1:1,256, but with no evidence of active rheumatological disease. Clinical, physiological and radiologic features suggested bronchiolitis obliterans, and this was confirmed by open lung biopsy. Immune staining of tissue revealed immunoglobulin M (IgM) as well as rare immunoglobulin (IgG) containing plasma cells in a peribronchiolar location. Because of these findings, we suggest that this case represents bronchiolitis obliterans secondary to a rheumatoid process. This case is unusual since it appeared in a man and is the first and, so far, the only manifestation of rheumatoid arthritis. Prior studies indicate that the bronchiolitis obliterans of rheumatoid arthritis occurs primarily in women and only in ongoing cases.

Arthritis, Rheumatoid↗