Bronchoalveolar mastocytosis in farmer's lung is related to the disease activity.

Patients (n = 10) at the acute phase of farmer's lung were investigated with chest roentgenography, lung function tests, and bronchoalveolar lavage (BAL) fluid analysis (n = 9). They had diffuse interstitial lung infiltrates and a reduction of the diffusion capacity. The dominating recovered cell types during BAL were lymphocytes; and in two patients, granulocytes. A prominent increase in mast cell numbers was seen in all patients. After avoidance of contact with moldy plant material for four to ten weeks (n = 7), lung function started to improve; and the BAL cell counts, to decrease. At clinical remission six to 14 months later (n = 7), the chest roentgenogram was normal and the diffusion capacity was slightly subnormal. The BAL numbers of mast cells and lymphocytes had further decreased but still remained increased compared with those in the healthy controls. Parallel to the normalization of the lung function and the recovery of BAL fluid cells, the increased BAL fluid concentrations of hyaluronic acid and procollagen III peptide started to decrease. These potential markers of fibroblast activation were significantly related to the mast cell number, but not to the lymphocyte number. The study has demonstrated that pulmonary mastocytosis is a prominent finding in farmer's lung and is related to the disease activity. The observed relationship between pulmonary mastocytosis and biochemical signs of lung fibroblast activation is further evidence to support the hypothesis of a mast cell interaction with lung connective tissue.

Class 2 aldehyde dehydrogenase. Characterization of the hamster enzyme, sensitive to daidzin and conserved within the family of multiple forms.

Mitochondrial (class 2) hamster aldehyde dehydrogenase has been purified and characterized. Its primary structure has been determined and correlated with the tertiary structure recently established for this class from another species. The protein is found to represent a constant class within a complex family of multiple forms. Variable segments that occur in different species correlate with non-functional segments, in the same manner as in the case of the constant class of alcohol dehydrogenases (class III type) of another protein family, but distinct from the pattern of the corresponding variable enzymes. Hence, in both these protein families, overall variability and segment architectures behave similarly, with at least one 'constant' form in each case, class III in the case of alcohol dehydrogenases, and at least class 2 in the case of aldehyde dehydrogenases.

The risk of malignant tumours in first-degree relatives of men with early onset prostate cancer: a population-based cohort study.

Previous studies have indicated that hereditary prostate cancer is common among men with early onset prostate cancer. The aim of this study was to investigate the incidence of malignant tumours in first-degree relatives of men with early onset prostate cancer. All prostate cancer cases diagnosed before the age of 51 years from 1958 to 1994 were identified in the population-based Swedish Cancer Register. The first-degree relatives of clinical cases were identified through parish data. Their vital status and cancer incidence were studied in the Swedish Cancer Register, the Cause of Death Register and the Census Register. The expected incidence of malignant tumours for the first-degree relatives were calculated using regional cancer register data. Cause-specific standardised incidence ratios (SIR) and 95% confidence intervals (CI) were calculated. The study included 423 first-degree relatives of 89 men with clinical prostate cancer. The first-degree relatives' SIR for malignant tumours was 0.99 (95% CI 0.78-1.23). The SIR for prostate cancer diagnosed at any age was 1.43 (95% CI 0.82-2.33), and 3.37 for first-degree relatives diagnosed before the age of 70 years (95% CI 1.36-6.94). There was no significantly increased risk of any non-prostatic malignant tumour. Only in five of the families did the pedigree show a pattern of hereditary prostate cancer. The first-degree relatives of men with early onset prostate cancer had more than a 3-fold increase in the risk of developing prostate cancer before the age of 70 years, but their total cancer risk was not increased. This study does not support the assumption that dominantly inherited susceptibility is a major cause of early onset prostate cancer.

Familial and hereditary prostate cancer in southern Sweden. A population-based case-control study.

The objectives of this study were to investigate the effect of family history on prostate cancer risk, to estimate the incidence of hereditary prostate cancer in southern Sweden and to assess the reliability of self-reported family history of prostate cancer. The study included consecutive prostate cancer patients and age-matched control subjects from a geographically defined population. The controls consisted of 1 male patient with malignant melanoma or non-Hodgkin's lymphoma and 1 male from the community per prostate cancer case. Family history was assessed with questionnaires, and diagnoses of fathers and brothers of cases were validated by the Southern Swedish Regional Tumour Registry. Among fathers and brothers whose names and birth dates were available, 56 (92%) of the 61 reported prostate cancer diagnoses were verified. Fifteen per cent of 356 cases and 5.0% of 712 controls reported at least 1 case of prostate cancer among their brothers or fathers, giving a relative risk of 3.2 (95% confidence interval 2.1-5.1). The relative risk increased with decreasing age at diagnosis of the patient. Based on the pedigree, 3.1% of the 356 patients were classified as having hereditary prostate cancer. This proportion was significantly higher among patients diagnosed before the age of 60 years (7.1%) than among older patients (2.2%). We conclude that there is a substantially increased risk of prostate cancer for sons and brothers of prostate cancer patients. The risk increases with decreasing age at diagnosis of the patient as an effect of a higher prevalence of hereditary prostate among early onset cases. Furthermore, we found self-reported family history of prostate cancer to be a valid estimate of the true incidence of prostate cancer in fathers and brothers of men with prostate cancer.

Risk perception, screening practice and interest in genetic testing among unaffected men in families with hereditary prostate cancer.

Approximately 5-10% of prostate cancer cases are caused by dominantly inherited susceptibility to the disease. Although advances have been made in research concerning the genetic mechanisms of hereditary prostate cancer, little is known about the psychological consequences for men at high risk of developing the disease. The aims of the present study were to examine risk perception, interest in genetic investigations, cancer-specific worry, and screening practice among unaffected men, aged 40-72 years old, with a pedigree consistent with hereditary prostate cancer and an estimated lifetime risk of prostate cancer of 35-45%. A questionnaire was sent by mail to 120 subjects, of whom 110 responded. Most of the men (n = 90, 82%) worried about having an inherited susceptibility to prostate cancer, and 34 (31%) claimed that worry about prostate cancer affected their daily life (3 (3%) fairly much, 31 (28%) slightly). As many as 40% of the study subjects perceived their lifetime risk of prostate cancer as 67% or more. Perceived high risk was associated with symptoms of depression and with cancer worry affecting daily living. Two-thirds of the men aged 50 years old or more were regularly screened for prostate cancer. Subjects with high levels of cancer-specific stress, as measured by the avoidance subscale of the Impact of Event Scale, were less likely to opt for screening. Almost all of the men (94%) were interested in presymptomatic genetic testing (84 (76%) "definitely yes" and 20 (18%) "probably yes"). We conclude that hereditary susceptibility to prostate cancer has significant psychological consequences although it rarely causes psychiatric morbidity. The present study underlines the importance of giving thorough, repeated information to men at high risk of prostate cancer.

Hemodynamic effects of flexible fiberoptic bronchoscopy performed under topical anesthesia.

Central hemodynamics and blood gases were measured continuously during flexible fiberoptic bronchoscopy performed under topical anesthesia in ten patients with restrictive lung disease. The procedure induced marked hemodynamic changes, which were maximal and similar in magnitude, during passage through the larynx and during suctioning. Mean arterial pressure increased by 30 percent, heart rate by 43 percent, cardiac index by 28 percent and mean pulmonary arteriolar occlusion pressure by 86 percent compared with pre-bronchoscopic control values. A slight fall in arterial oxygen tension was measured during bronchial suctioning and in the post-bronchoscopic period. Rate pressure product reached its highest value during bronchial suctioning at which time three of the ten patients developed ST-T-segment changes, implying that myocardial oxygen demand might have exceeded supply. It is suggested that the major mechanism behind the hemodynamic changes is a reflex sympathetic discharge caused by mechanical irritation of larynx and bronchi.

Tracheobronchopathia osteochondroplastica. A clinical bronchoscopic and spirometric study.

Tracheobronchopathia osteochondroplastica (TO) is a rare disease, although it probably occurs more frequently than expected. During an eight-year period, nine patients with TO were found among 2,180 performed bronchoscopies. There were four women and five men, with a mean age of 60 years. Cough, expectoration, dyspnea, hemoptysis, and recurrent airway infections were common, and most of the patients had had symptoms for more than ten years. Bronchoscopy revealed multiple yellow-white, hard, papilla-like formations reaching from the trachea to the segmental bronchi. Microscopy of biopsy specimens from the macroscopically altered mucosa showed osteocartilaginous tissue typical for TO in all patients. In eight of the patients spirometry showed an obstructive pattern.

Reversal of central sleep apnea with oxygen.

OBJECTIVE: To examine the effect of oxygen on apneas and sleep quality in patients with frequent central apneas during sleep. DESIGN/SUBJECTS: Prospective intervention study of 20 consecutive patients with predominant central apnea identified from 570 patients referred for suspected sleep apnea syndrome. Sixteen patients had congestive heart failure and seven of them had a previous stroke. Three of the remaining four patients without heart failure had experienced a previous stroke, and one was being treated with morphine. SETTING: The Department of Pulmonary Medicine at Umeå (Sweden) University Hospital. INTERVENTIONS: The patients were investigated for one night receiving nasal oxygen and one night without it. MEASUREMENTS: Overnight polysomnography with transcutaneous PCO2 and arterial blood gases. RESULTS: Central apneas occurred during Cheyne-Stokes respiration in 18 of 20 patients and two patients had idiopathic central apneas. Without oxygen, the median number of all central apneas and hypopneas was 33.5 (range, 8.0 to 52.0) per hour of sleep. These episodes decreased to 5.0 (range, 0.0 to 31.0)(p < 0.01) during oxygen therapy. In 17 of 20 patients, the frequency of central apneas was reduced by more than 50%. Central apneas were reduced by oxygen irrespective of the presence or absence of heart failure or Cheyne-Stokes respiration. The arousal frequency was reduced during oxygen treatment. Daytime sleepiness, difficulty falling asleep, snoring, and self-scored awakenings were reduced in seven patients who were given nocturnal oxygen at home. Obstructive and mixed apneas were unaffected by oxygen. CONCLUSIONS: Oxygen effectively reduces central sleep apnea in eucapnic patients.

The effect of a mandibular advancement device on apneas and sleep in patients with obstructive sleep apnea.

OBJECTIVE: To evaluate the effects of a mandibular advancement device on apneas and sleep in mild, moderate, and severe obstructive sleep apnea. DESIGN: Prospective study. SUBJECTS: Forty-four of 47 patients included. INTERVENTION: Individually adjusted mandibular advancement devices. MEASUREMENTS: Polysomnographic sleep recordings for 1 night without the device and 1 night with it, with a median of 1 day and no changes in weight, medication, or sleep position between the recordings. RESULTS: The device reduced the median obstructive apnea-hypopnea index from 11 (range, 7 to 19) to 5 (range, 0 to 17) (p<0.001) in 21 patients with mild sleep apnea, from 27 (range, 20 to 38) to 7 (range, 1 to 19) (p<0.001) in 15 patients with moderate sleep apnea, and from 53 (range, 44 to 66) to 14 (range, 2 to 32) (p<0.05) in 8 patients with severe sleep apnea. The arousal index decreased and the sleep stage patterns improved in all severity groups. Twenty-eight of 44 patients were successfully treated with an obstructive apnea-hypopnea index of below 10 and a subjective reduction in snoring. Nine of 16 patients with treatment failure still reported a reduction in snoring. The success rate correlated inversely to the disease severity (r=-0.41; p<0.01). CONCLUSIONS: A mandibular advancement device reduces apneas and improves sleep quality in patients with obstructive sleep apnea, especially in those with mild and moderate disease. A follow-up sleep recording during treatment is necessary because of the risk of silent obstructive apneas without subjective snoring with the device.

Indirect and direct gas exchange at maximum exercise in beryllium sensitization and disease.

STUDY OBJECTIVES: To determine whether pulse oximetry accurately estimates arterial blood gas measurements during exercise in the assessment of chronic beryllium disease (CBD) and beryllium sensitization (BeS). DESIGN: Participants underwent maximal exercise physiology testing in a clinical-practice setting. Oxygen saturation in the blood was measured through an indwelling arterial line and by pulse oximetry. SETTING: All exercise physiology tests were performed in the pulmonary physiology unit of the National Jewish Medical and Research Center (NJMRC) between December 1985 and November 1998. PATIENTS: We analyzed the exercise physiology data for 168 individuals who were referred to NJMRC for evaluation of possible CBD and underwent exercise testing. On evaluation, they subsequently received diagnoses of either CBD or BeS. RESULTS: In BeS subjects, the percentage of oxygen saturation as measured by pulse oximetry (SpO(2)) often underestimated the percentage of arterial oxygen saturation (SaO(2)) (mean [+/- SD] underestimation, 0.88 +/- 4.6%) at maximum exercise and showed no significant correlation (r = -0.13; p = 0.3). The use of SpO(2) misclassified 14.9% of BeS subjects as having abnormal gas exchange levels (< 90%) that were normal by arterial blood gas measurement. In contrast, SpO(2) and SaO(2) values correlated at maximum exercise in CBD subjects (r = 0.55 [corrected]; p = 0.0001) without exhibiting SpO(2) underestimation of SaO(2), and misclassification occurred in only 5.9%. CONCLUSIONS: These data suggest that pulse oximetry cannot be used reliably to distinguish between CBD and BeS and, thus, is not an adequate substitute for arterial blood gas analysis with exercise.

Hyaluronic acid (hyaluronan) in BAL fluid distinguishes farmers with allergic alveolitis from farmers with asymptomatic alveolitis.

Pulmonary function measurements, bronchoalveolar lavage (BAL), and analyses of precipitating antibodies in blood were performed in 12 farmers wtih no symptoms from the airways and 12 farmers who were admitted to the hospital due to acute symptoms of alveolitis (all nonsmokers). In addition, a bronchial methacholine provocation test was performed in the asymptomatic farmers. In 11 of the 12 symptomatic farmers but in none of the asymptomatic farmers, precipitating antibodies against one or more of the microorganisms which usually occur in a farmer's environment were found. In the farmers with symptomatic alveolitis, a restrictive impairment of pulmonary function was found, while pulmonary function was normal in all asymptomatic farmers. Findings in the BAL fluid showed increased concentrations of total cells, lymphocytes, and neutrophils and elevated levels of albumin, fibronectin, and angiotensin-converting enzyme in asymptomatic farmers compared with our own reference group. The same analyses in BAL fluid from the symptomatic farmers revealed a further increase in all parameters compared with the asymptomatic farmers. The BAL fluid from asymptomatic farmers had normal levels of hyaluronic acid (hyaluronan) and procollagen 3 N-terminal peptide, while these levels were significantly increased in the symptomatic group. We conclude that inflammation in the alveolar space and signs of activation of alveolar macrophages are present in farmers regardless of respiratory symptoms, although these findings are more pronounced in the presence of symptoms of acute alveolitis; however, the findings of impaired pulmonary function and the occurrence of precipitins and elevated levels of hyaluronic acid and procollagen 3 N-terminal peptide in BAL fluid were exclusively found in the farmers with airways symptoms. We postulate the hyaluronic acid, due to its pronounced ability to immobilize water, may be of importance in the development of the pulmonary function impairment observed in farmer's lung disease.

Intestinal parasitism in the United States: update on a continuing problem.

To document patterns of intestinal parasitism in the United States, we analyzed results of 216,275 stool specimens examined by the state diagnostic laboratories in 1987; parasites were found in 20.0%. Percentages were highest for protozoans: Giardia lamblia (7.2%), Entamoeba coli and Endolimax nana (4.2% each), Blastocystis hominis (2.6%), and Entamoeba histolytica (0.9%). The most commonly identified helminths were nematodes: hookworm (1.5%), Trichuris trichiura (1.2%), and Ascaris lumbricoides (0.8%). Identifications of G. lamblia increased broadly from the 4.0% average found in 1979, with 40 states reporting increases and seven reporting decreases. Seasonally, Giardia identifications increased in the summer and fall, especially in the Midwest. Nine states reported hookworms in more than 2% of specimens; none were states with indigenous transmission. We analyzed similar, but abbreviated, data for 1991; parasites were found in 19.7% of the 178,786 specimens and Giardia was found in 5.6%. States reporting percentages of Giardia identification in the highest quartile for both 1987 and 1991 were located in the Midwest or in the Northwest. Cryptosporidium was identified in both the 1987 and 1991 surveys; it had not been identified in a previous survey. For each year, Cryptosporidium was reported from 25 states across the country (for both years in 17 states). We conclude that intestinal parasitism should not be overlooked as a cause of gastrointestinal illness in the United States and that the prevalence of Giardia may be increasing.

Constitutive heterochromatin C-band polymorphism in prostatic cancer.

The size of the heterochromatin C-bands on chromosomes has been reported to be associated with some, but by no means all, human malignancies. No studies along these lines have been performed in prostatic cancer. We therefore investigated the size, incidence of inversions, and symmetry versus asymmetry of C-band heteromorphisms on chromosomes 1, 9, and 16 in peripheral blood lymphocytes from 52 prostatic cancer patients and 183 healthy individuals. There were no differences in C-band heteromorphism on chromosomes 1, 9, and 16 between the patients and the controls. Neither were there any differences when patients with early-stage disease were compared with patients with more advanced cancer. Younger (aged less than 70 years) cancer patients had significantly higher frequencies of larger C-bands on chromosomes 1 (p less than 0.01) and 16 (p less than 0.001) than did patients aged more than 70 years at diagnosis. This could indicate a possible relationship between the amount of constitutive heterochromatin on chromosomes 1 and 16 and susceptibility to early development of prostatic cancer but could also result from the age differences between the two patient groups.

Chromosome analysis of a newly established renal carcinoma cell line.

A renal cell carcinoma has been established as a cell line in vitro. Repeated chromosome analyses of the cell line revealed a stable clone with the modal chromosome number 80 and three pairs of marker chromosomes, M1-M3. M1 and M2 resulted from a translocation between a chromosome #3 deleted in band p14 and a normal #7: M1 = der(3)t(3;7) (:3p14----cen----3q24::7q21----7qter), and M2 = der(7)t(3;7)(3qter----3q24::7q21----cen----7pter ). M3 was a small metacentric chromosome, probably consisting of the centromeric portion of a #3: del(3)(:p14----cen----q12:). No other structural changes were present. Our findings are in agreement with those of previous studies, stating that rearrangements of 3p12-14 are primary cytogenetic events in renal cell carcinomas, even though this can only be inferred in this case. Thus, this cell line may be useful for further molecular and biochemical studies.

Multiple structural chromosome rearrangements, including del(7q) and del(10q), in an adenocarcinoma of the prostate.

Cytogenetic analysis of a poorly differentiated adenocarcinoma of the prostate revealed the complex karyotype: 76-86,X, -Y, +X, +X, +del(X)(q24), +t(1;10) (p22;q24), -2, +der(2) t(1;2;?)(p32;q24p13;?), +der(2)t(1;2;?) (p32;dq24p13;?), +3, +3, +4, +5, +5, +6, +7, +del(7) (q22), -8, +der(8)t(8;?)(q24;?), + der(8)t(8;?)(q24;?), +9, +10, +10, +der(10)t (1;10)(q24;q22), +del (10)(q23), +11, +11, +12, +der(12)t(4;12)(q11;p11), +der(12)t(4;12) (q11;p11), +14, +der (15)t(1;15)(q21;p11), +t(16;?) (q21;?), +17, +18, +19, +19, +20, +20, +21, +22, +2-5 mar. The karyotype contains deletions of both 7q and 10q, abnormalities that also have been described previously in prostatic adenocarcinomas, and which hence may represent primary chromosomal rearrangements in this type of cancer.

Double minutes in two primary adenocarcinomas of the prostate.

Double minute chromosomes were found in metaphases from short-term tissue cultures of two primary prostatic adenocarcinomas. This is the first cytogenetic evidence of gene amplification in this tumor type.

Cytogenetic analysis of upper urinary tract transitional cell carcinomas.

Ten primary (nine regular and one post-radiation) upper urinary tract transitional cell carcinomas (TCC), i.e., tumors of the renal pelvis and ureter, were obtained from 10 patients following nephroureterectomy and processed for cytogenetic analysis after short-term culturing. Clonal chromosomal aberrations were found in eight tumors. While 10 karyotypically related and/or unrelated clones were detected in the post-radiation tumor, cytogenetic monoclonality was seen in all other tumors. With the exception of two tumors with loss of the Y chromosome as the only change, chromosome 9 was invariably involved, either with loss of the entire chromosome or with partial loss from the short arm. Our findings indicate that the karyotypic profile of upper urinary tract TCC is identical to that of bladder TCC, an indication that the same pathogenetic mechanisms are at work in both regions.

An improved technique for short-term culturing of human prostatic adenocarcinoma tissue for cytogenetic analysis.

An improved technique for cytogenetic analysis of malignant prostatic tissue is described. This method is based on 1) prolonged mild collagenase treatment, 2) careful washing and repeated centrifugation and sedimentation of the disaggregated material to isolate viable prostatic epithelial cells, 3) short-term culture on collagen R-coated chamber slides with PFMR-4 medium supplemented with mitogenic factors, and 4) daily inspection of the cultured cells to determine the optimal time for harvesting. Twenty consecutive primary prostatic adenocarcinomas were cultured and processed for cytogenetic analysis. Outgrowth of pure epithelial colonies was obtained in 16 cases; in three there was a mixture of epithelial colonies and fibroblasts, and in one there was no cell growth. More than 25 metaphases with chromosomes of high banding quality could be analyzed per case, in particular in cultures from the final pellet fraction. Clonal chromosome aberrations were present in four tumors, and nonclonal structural changes were present in nine. Six tumors showed only normal diploid karyotypes.

Chromosomal abnormalities in two bladder carcinomas with secondary squamous cell differentiation.

Two secondary squamous cell carcinomas of the bladder (i.e., tumors that originated from primary transitional cell carcinomas) were examined cytogenetically. Both tumors showed complex karyotypes with many of the same aberrations that have formerly been described in transitional cell carcinomas. Monosomy 9, trisomy 7, and rearrangements of chromosomes 3, 8, 10, 13, and 17 were common to both tumors. Among other changes that have been implicated in bladder carcinogenesis, an isochromosome for 5p was seen in one tumor and loss of 11p material in the other. Our findings indicate that secondary squamous cell carcinomas of the bladder are karyotypically indistinguishable from advanced transitional cell carcinomas of the same organ. The putative genetic changes that steer the differentiation of the neoplastic epithelium in the direction of squamous cells thus remain unknown.

On the significance of trisomy 7 and sex chromosome loss in renal cell carcinoma.

Cytogenetic analysis of 30 renal cell carcinomas showed 3p aberrations in nine tumors, trisomy 7 in 17 tumors, and clonal loss of one sex chromosome in 14 tumors. The 3p aberrations and trisomy 7 were present in the same clone in two tumors and in separate clones in three tumors. Loss of one sex chromosome was present together with 3p aberrations in the same clone in one tumor and occurred in seemingly unrelated clones in two tumors. It occurred as the sole change in five tumors. Clones with trisomy 7 as the only change were present in six tumors. Trisomy 7 and loss of one sex chromosome were present in separate clones in four tumors and in the same clone in one tumor. Because +7 and -X/-Y were thus rarely present together with clonal structural abnormalities, in particular 3p changes, our findings make it highly unlikely that loss of one sex chromosome or trisomy 7 represents a primary change in renal cell carcinoma. We instead suggest that there is a tendency for normal kidney cells to lose an X or a Y chromosome and also to gain an extra copy of chromosome 7. This tendency is retained by renal carcinoma cells; therefore, trisomy 7 and sex chromosome loss should not be viewed as tumor-specific abnormalities in this context. Whether these simple numerical aberrations reflect in vivo mosaicism or are acquired in vitro remains unresolved.