Segregation analysis reveals tight genetic linkage between the spontaneously arising neural tube defect gene splotch (Sp) and Pax-3 in an intraspecific mouse backcross. Concurrent research has recently characterized Sp2H, a radiation induced mutation at the splotch (Sp) locus, and found alterations in the murine paired box gene, Pax-3, in homozygous Sp2H DNA. It was proposed that Sp and Pax-3 are the same gene. This report presents additional genetic evidence in support of this finding through linkage studies. Southern blot analysis of genomic DNAs from a panel of 125 intraspecific [(Sp/+ x CBA/J)F1-Sp x CBA/J] backcross mice reveals no crossover between Pax-3 and the spontaneously occurring splotch allele, Sp. This positions Pax-3 within 2.9 cM of the Sp locus (95% confidence interval) and suggests tight genetic linkage between the two marker genes.


The gene map of the pig (Sus scrofa domestica L.): a review. A review of the present status of the porcine gene map is given with references. A total of 84 loci have now been studied, and genes have been assigned to 17 chromosomes. Among them, six chromosomes are defined by only one marker. No loci have been attributed yet to three chromosomes.


Assignment of a porcine male-specific DNA repeat to Y-chromosomal heterochromatin. Primers were designed to amplify by PCR a 509-bp genomic fragment from male pig DNA, using the porcine male-specific repeat sequence described by McGraw et al. (1988). This PCR product showed male-specific hybridization in Southern blots. Nonradioactive in situ hybridization localized it to the entire length of the heterochromatic portion of Yq. The assignment was confirmed using the PCR primer pDYZ1-S for primed in situ labeling.


Microchromosomal assignment of the chicken ovotransferrin and adenylate kinase genes. Ovotransferrin, an egg-white protein implicated in the transfer of trace elements from the hen oviduct to the developing avian embryo, and cytosolic adenylate kinase, an essential enzyme involved in the interconversion of adenine nucleotides in energetically active tissues, have been mapped to two separate chicken microchromosomes by fluorescent in situ hybridization. Considering present and previous data, the possibility of loss of intron material resulting in the compactation of genes in chicken microchromosomes is briefly discussed.


The genes for protamine 1 and 2 (PRM1 and PRM2) and transition protein 2 (TNP2) are closely linked in the mammalian genome. The genes for two protamines (PRM1 and PRM2) and for two transition proteins (TNP1 and TNP2) have been characterized in several mammalian species. In the human, boar, and bull, the genes for PRM1, PRM2, and TNP2 are closely linked over a stretch of DNA 13-15 kb long. Although similar data are not yet available for the mouse and rat, our results suggest that the three genes are similarly linked in these species. The gene for TNP1 in all species studied is located on another chromosome.


A satellite III sequence shared by human chromosomes 13, 14, and 21 that is contiguous with alpha satellite DNA. We report the isolation of a clone (pTR9) from a human chromosome 21 lambda phage library, which was found to contain two distinct components: (1) a previously unreported subfamily of human satellite III (pTR9-s3; 1,485 bp) and (2) an alpha satellite sequence (pTR9-alpha; 250 bp) containing 1.5 copies of a 171-bp alphoid unit that shows 88.4% homology to a previously reported alpha satellite consensus sequence. The two components are separated by two direct repeats of 9 bp. Use of the polymerase chain reaction (PCR) to amplify across the junction between pTR9-s3 and pTR9-alpha established that these two sequences are contiguous in total human genomic DNA and in DNA derived from somatic cell hybrids carrying human chromosomes 13, 14, or 21. A related, but considerably more diverged, sequence was also detected on chromosome 15. Southern analysis of somatic cell hybrids at high stringency revealed a common structure of the pTR9-s3 sequence on chromosomes 13, 14, and 21 but not on 15 or 22. This sequence should be useful for the study of the structural organisation of the centromere of these chromosomes and the mechanism of their involvement in Robertsonian translocations.


Molecular characterization of a mouse Y chromosomal repetitive sequence that detects transcripts in the testis. 145SC5 is a Y chromosomal repetitive sequence isolated from a BALB/c mouse and is unique in that it detects poly(A)-containing transcripts in the testis. We determined nucleotide sequences of 145SC5 and a related cDNA clone designated PC11 and compared their sequences to that of pYMT2/B, another related cDNA clone. 145SC5 and PC11 are almost identical (97%), while PC11 and pYMT2/B share 84% identity. In situ hybridization and Southern blot analysis with XXSxr male mice demonstrated that 145SC5-related sequences were distributed over the entire length of the Y chromosome including the short arm. Two types of Y chromosome are present in inbred mouse strains: the Mus musculus musculus type and M.m. domesticus type. Among 26 inbred strains surveyed, 145SC5 detected polymorphims only in the M.m. domesticus Y chromosome.


Detection of cell-cycle stage by fluorescence in situ hybridization: its application in human interphase cytogenetics. Distinct cell-cycle-dependent changes in the conformation of centromeric chromatin in a specific human chromosome containing alpha-satellite DNA have been demonstrated by fluorescence in situ hybridization (FISH). This method, based upon specific FISH signal morphology, allows simultaneous analysis of chromosomal aneuploidy and detection of specific cell-cycle stage(s) of human tumor and/or normal cell populations in a single preparation of interphase cells. This interphase cytogenetic procedure might prove useful for both basic and clinical research involving human cells.


Sister chromatid differentiation and chromosomal in situ suppression hybridization: a combined methodology for analyzing cell proliferation and SCEs in individual chromosomes. A technique combining sister chromatid differentiation (SCD) with chromosomal in situ suppression (CISS) hybridization is described. This combined methodology allows simultaneous analysis of cell-proliferation kinetics and sister chromatid exchanges (SCEs) in chromosomes identified by probes. To demonstrate the usefulness of this approach, cultured fibroblasts from a patient with Pallister-Killian syndrome, mos46/47,+i(12p), a chromosome mosaicism disorder, were studied. The fibroblasts were cultured in the presence of 5-bromodeoxyuridine (BrdU) for 72 h. Chromosome preparations were stained by a modified fluorescence-plus-Giemsa method to obtain SCD. For identification of the normal chromosome 12 and the i(12p), CISS hybridization with a biotin-labeled chromosome 12-specific library probe (LA 12NS01) was carried out after SCD. The hybridization was detected by an indirect immunofluorescence technique. For the analysis of cell kinetics and SCEs, the technique allows rapid, reliable identification of abnormal and normal cell populations. It also allows analysis of SCEs in individual chromosomes.


Amiodarone pneumonitis. Bronchoalveolar lavage findings in 15 patients and review of the literature. Amiodarone (Am) pneumonitis is currently a common and potentially severe adverse reaction, the accurate diagnosis of which remains difficult to establish. To determine the contribution of bronchoalveolar lavage (BAL) in the diagnostic workup of patients suspected of having Am pneumonitis. Diagnosis of Am pneumonitis was established on the basis of (1) development of recent symptoms and pulmonary opacities while receiving the drug, (2) exclusion of other possible causes, and (3) improvement following cessation of Am and/or steroid therapy. (4) Confirmatory changes were obtained by histopathologic examination in eight cases. BAL was performed in each patient at the time of initial evaluation. Am pneumonitis was diagnosed in 15 consecutive patients between 1985 and 1991. The disease was associated with significant morbidity and mortality. Six patients died; four died of Am pneumonitis. A neutrophilic BAL was found in nine patients (average PMN = 26.6 percent). A mixed pattern (lymphocytic + neutrophilic) was seen in four patients (average: Ly = 19.9 percent; PMN = 11.9 percent). Two patients had a normal BAL. No patient had a lymphocytic pattern. A low CD4+/CD8+ ratio was seen in two patients. A literature survey indicated 70 cases of Am pneumonitis with detailed information on BAL. The BAL pattern was mixed in 23 (33 percent), neutrophilic in 18 (26 percent), lymphocytic in 15 (21 percent), and normal in 14 (20 percent). No correlation was found between BAL pattern and prognosis. Also, BAL pattern was related neither to daily or total dose of Am nor to duration of treatment with Am. The cellular profile of BAL in Am pneumonitis is highly variable, and no cellular pattern of BAL seems to be predictive of a detrimental outcome or of irreversible fibrosis. Aside from excluding other illnesses, and due to its extreme variability, the contribution of BAL differential in the initial workup of patients suspected of having Am pneumonitis is limited.


Does achalasia predispose to cancer of the esophagus? In a follow-up study of 147 patients with achalasia of the esophagus treated by myotomy, 146 patients were traced (58 female and 88 male patients aged 4 to 83 years [median, 46 years]). The living persons were contacted in writing or by telephone. The mean follow-up time after the operation was 23.2 years (range, 6 to 41 years). The cause of death was established for 71 patients. There were three postoperative deaths and two deaths following recurrence. In comparison with the Danish population, the 66 remaining patients were found to have a relatively higher cancer mortality (33.8 percent). Contrary to the expected less than one, ten of 23 patients who died of cancer had a malignant tumor in the esophagus. The mortality rate after 30 years was 66.1 percent, 11.9 percent of the deaths caused by esophageal cancer. It is concluded that there is a connection between achalasia and cancer of the esophagus that ought to be considered in the treatment and follow-up of patients with achalasia.


Improved ventilatory response to exercise after cardioversion of chronic atrial fibrillation to sinus rhythm. The purpose of this study was to assess hemodynamic and respiratory measures of submaximal and maximal exercise performance in patients with chronic atrial fibrillation, before and one month after cardioversion to sinus rhythm. Restoration of sinus rhythm (n = 16) produced significant reductions in resting and exercise heart rates, 14 percent to 20 percent (p < 0.01). Due to a proportionately larger increase in stroke volume, cardiac output increased by 9 percent during low-level exercise (p < 0.01) and by 7 percent during exercise above the anaerobic threshold (p < 0.05). Minute ventilation was reduced by 7 percent during low-level exercise (p < 0.01) and by 9 percent above the anaerobic threshold (p < 0.05). The ratio between minute ventilation and carbon dioxide elimination was significantly reduced (p < 0.01). Maximum oxygen uptake (+8 percent; p < 0.01) and maximal tolerated work load (+6 percent; p < 0.05) increased. Hemodynamic changes during exercise were similar in patients with (n = 7) or without (n = 9) disopyramide prophylaxis. Restoration of sinus rhythm induced improvement in hemodynamics and in efficiency of ventilation, thereby reducing the ventilatory demand during submaximal exercise.


Heart rate variability during sleep in snorers with and without obstructive sleep apnea. Changes in sympathetic and vagal tone may be the substrate for the development of cardiac arrhythmias in patients with obstructive sleep apnea (OSA). The cardiovascular responses in the traditional autonomic tests show great interindividual and intraindividual variations. During sleep there are repetitive modifications of heart rate (HR) that are not influenced by psychologic factors or the patient's cooperation. For this reason, we evaluated HR modifications in relation to spontaneous body movements (BM) and sleep apneas during nonrapid eye movement (NREM) and rapid eye movement (REM) sleep in habitual snorers with normal and pathologic respiratory disturbance index (RDI). From 132 consecutive patients referred to our sleep center for habitual snoring and/or daytime somnolence, we selected 35 male patients younger than 60 years without clinical evidence of autonomic dysfunction. They were divided into three groups: group A (RDI < 10); group B (RDI > 10 and < 20); and group C (RDI > 20). No significant difference was found among the three groups in the HR variability related to BM. In the evaluation of bradytachyarrhythmias related to apneic events of 20 to 30 s, we found a significant difference between group A and the other two groups. In patients with RDI > 10, a reduced HR variability related to a reduced sympathetic tone in the post-apnea phase was observed. Some authors suggested that an HR increase during the post-apnea period can be used as an index of "brainstem arousal." Our results seem to indicate a reduced apnea-related "arousability" in patients with RDI > 10. This finding might be one of the factors contributing to the worsening of OSA.


Noninvasive determinations of the anaerobic threshold. Reliability and validity in patients with COPD. We compared the intraobserver and interobserver agreement of blood (BGT) and gas exchange (GET) methods for determination of the anaerobic threshold (AT) in patients with COPD. In addition, we determined the sensitivity and specificity of the gas exchange methods for determination of the AT. Two noninvasive methods, the V-slope (VS) and the ventilatory equivalents method (VEM) were compared with two blood sampling methods, the log standard HCO3 (SB) vs log VO2 (SBT) and base excess (BE) vs VO2 (BET). Twenty-nine patients with COPD (FEV1 < 60%) performed incremental exercise tests to exhaustion while breath-by-breath gas exchange measurements were made. Blood samples were drawn at the end of each minute for SB and BE. Two trained observers determined the VO2 at the threshold for each of the four indices on two separate occasions two weeks apart. Our results demonstrated the following: only modest interobserver and intraobserver agreement was noted by Spearman rank correlations; the VEM was as sensitive as the VS in COPD patients; and the presence of a true metabolic acidosis was not reliably predicted by GET methods. Moreover, although the blood methods accurately identified the presence of metabolic acidosis, there was disagreement on the actual point of the BGT. We conclude that gas exchange indices were not helpful for the determination of metabolic acidosis in patients with COPD.


Changes in hospital admissions pattern in patients with human immunodeficiency virus infection in the era of Pneumocystis carinii prophylaxis. Pneumocystis carinii pneumonia (PCP) was the leading cause of hospital admissions in patients with human immunodeficiency virus (HIV) infection before the widespread use of PCP prophylaxis. We studied retrospectively the changes in annual hospital admission patterns after the start of a population-based PCP prophylaxis program in Toronto. The purpose of the study was to identify the cogent diseases requiring hospitalization of HIV patients in the current era of PCP prophylaxis. This information is important for the allocation of health care resources in the future as well as for targeting research in the prevention of specific HIV-related diseases. The annual HIV-related hospital admissions before and after the start of the Toronto aerosol pentamidine program (May 1989) were studied. All admission records due to AIDS-defining illnesses or occurring in patients with known HIV status in three major referral centers were reviewed. The two periods for comparison were May 1988 through April 1989 and May 1989 through April 1990. The data obtained were stratified according to the following: (1) cause of the illness prompting hospital admission; (2) PCP admissions; and (3) admissions according to the major organ system involved. These categoric data were compared by nonparametric chi 2 tests. Population-based prophylaxis of PCP with aerosol pentamidine resulted in a significant reduction in the total number of PCP hospital admissions. Infection remains the principal cause of hospital admission in HIV patients after the start of the PCP prophylaxis program. However, there was an increase in the proportion of hospital admissions due to nonrespiratory-related infections. There was also a modest increase in admissions due to neurologic and gastrointestinal diseases. Central nervous system lymphoma and cytomegalovirus retinitis accounted for the majority of the rise in the nervous system. These data suggest there is a changing pattern of the diseases leading to the hospitalization of patients with HIV infection in the era of PCP prophylaxis.


Yield of bronchoscopy for the diagnosis of tuberculosis in patients with human immunodeficiency virus infection. The efficacy of bronchoscopy for the diagnosis of tuberculosis in patients infected with human immunodeficiency virus (HIV) has not been systematically evaluated. We therefore compared the diagnostic yield of bronchoscopy in 67 HIV-infected and 45 non-HIV-infected patients with culture-proven pulmonary tuberculosis. In all cases, acid-fast smears of sputum were negative or not obtained prior to bronchoscopy. Prebronchoscopic sputum culture yielded Mycobacterium tuberculosis in 34 (89 percent) of 38 HIV-infected patients and 26 (93 percent) of 28 non-HIV-infected patients from whom specimens were obtained. Bronchoscopy provided an early diagnosis of tuberculosis (positive acid-fast smear or granulomata on biopsy) in 23 (34 percent) of the HIV-infected patients and 20 (44 percent) of the patients without HIV infection. The sensitivities of the acid-fast smear and of mycobacterial culture of bronchoscopic specimens and postbronchoscopic sputum were similar in patients with or without HIV infection. In HIV-infected patients, granulomatous inflammation was noted on transbronchial biopsy in 11 (19 percent) of 59 patients with HIV infection, compared to 16 (43 percent) of 37 patients without HIV infection (p = 0.01). Nevertheless, transbronchial biopsy provided the exclusive means for an early diagnosis of tuberculosis in six (10 percent) of 59 HIV-infected patients. We conclude that the yield of bronchoscopy for the diagnosis of pulmonary tuberculosis in HIV-infected patients is similar to that in patients without HIV infection, and that transbronchial biopsy provides incremental diagnostic information not available from evaluation of sputum or bronchoalveolar lavage fluid.


Prospective evaluation of a prognostic score for Pneumocystis carinii pneumonia in HIV-infected patients. Serum lactate dehydrogenase levels, alveolar-arterial oxygen gradient, and percentage of neutrophils in bronchoalveolar lavage correlate most strongly with early mortality in Pneumocystis carinii pneumonia (PCP) in HIV-infected patients. However, the individual outcome can not be predicted by these parameters due to a considerable overlap between survivors and nonsurvivors. We prospectively investigated a PCP severity score, which has been developed earlier based on a retrospective analysis. Seven of 94 consecutively examined HIV-infected patients died within 14 days after diagnosis of PCP. A PCP severity score greater than 7 had a positive predictive value for early fatal outcome of 66.7 percent (6/9) and a negative predictive value of 98.8 percent (84/85). The overall diagnostic accuracy was 95.7 percent (90/94). The positive predictive value for early fatal outcome of a P(A-a)O2 > 35 mm Hg was 24 percent (6/25); the negative predictive value was 98.6 percent (68/69). However, the overall diagnostic accuracy was only 78.7 percent (74/94). The PCP severity score is a valuable tool for clinical decision making, for the early identification of patients with a prognostic unfavorable course, and for the comparison of patient populations in future studies of HIV-associated PCP.


Interleukin 6 activity in pleural effusion. Its diagnostic value and thrombopoietic activity. We measured interleukin 6 (IL-6) concentrations in the pleural fluid of various patients to determine its role in pathophysiology and diagnosis by using specific functional bioassay. IL-6 levels were significantly higher in exudate than in transudate (79.3 +/- 176.2 U/ml [n = 55] vs 1.7 +/- 1.8 U/ml [n = 12]; p < 0.01). Tuberculous effusion contained a significantly higher amount of IL-6 than malignant effusion (181.3 +/- 176.2 U/ml [n = 13] vs 29.4 +/- 71.5 U/ml [n = 29]; p < 0.005). Pleural IL-6 levels were invariably higher than serum IL-6 levels, and both were significantly correlated (n = 21, r = 0.632; p < 0.02). Pleural IL-6 levels were significantly correlated with lactate dehydrogenase (LDH) in pleural fluid (r = 0.392; p < 0.01), ratio of pleural/serum LDH (r = 0.571; p < 0.01), pleural adenosine deaminase activity (r = 0.599; p < 0.01), and serum C-reactive protein (r = 0.494; p < 0.01). Furthermore, IL-6 levels were significantly correlated with peripheral blood platelet counts (r = 0.447; p < 0.001). These results suggest that (1) IL-6 is produced locally in pleural space, (2) pleural IL-6 level is helpful for differential diagnosis, and (3) locally produced IL-6 could leak to circulation and cause systemic effects such as the induction of C-reactive protein and thrombocytosis.


Pleural SC5b-9 in differential diagnosis of tuberculous, malignant, and other effusions. A monoclonal antibody against soluble phase-terminal complement complex (SC5b-9) was used to try to differentiate pleural effusions of tuberculous vs malignant and other origin. Effusions of tuberculous origin showed a significantly higher SC5b-9 level than did plasma, suggesting activation of complement in the pleural space. All 26 patients with tuberculous effusions showed SC5b-9 levels in pleural fluid exceeding 2.0 mg/L, while 20 with malignant effusions had levels less than 2.0 mg/L. However, rheumatoid, some parapneumonic, and treated malignant effusions showed SC5b-9 levels above 2.0 mg/L. Considering a value exceeding 2.0 mg/L, the specificity and sensitivity of the SC5b-9 estimation in tuberculosis were 0.74 and 1.0, respectively. The mean values for C4d and Bb fragments of complement were significantly (p < 0.05) higher in the tuberculous than in the malignant effusions. However, the values for Bb in 16 (62 percent) of the 26 patients with tuberculous or malignant effusions were in the same range. The activity of adenosine deaminase (ADA) was higher in the tuberculous than in the malignant effusions. While 18 of 26 patients with tuberculous effusions showed an ADA value exceeding 50 mU/ml, the estimated cutoff point (sensitivity = 0.69), 35 of the 36 nontuberculous effusions showed a true negative value (specificity = 0.97). A correlation between ADA and SC5b-9 values was observed in pleural effusions. These observations suggest that the estimation of SC5b-9 in pleural fluid presents a new approach to differentiating tuberculous vs malignant effusions.


From apnea of infancy to obstructive sleep apnea syndrome in the young child. Obstructive sleep apnea syndrome (OSAS) and heavy snoring during sleep, without sleep apnea, has been well described in children and adults. We report a case series of 25 full-term infants, prospectively obtained from a database of nearly 700 "apparent life-threatening event" (ALTE) cases, who presented between 3 weeks and 4 1/2 months of age an ALTE and who progressively developed more florid symptomatology and polygraphic findings. All of them were classified as OSAS patients by five years of age. These index cases are compared with two other ALTE infant groups followed in parallel during the first year of life but whose symptoms were short-lived. The index cases presented more frequently a positive family history of OSAS and an early report of snoring or noisy breathing during sleep. Usage of an esophageal balloon to monitor esophageal pressure (Pes) and usage of nasal continuous positive airway pressure (CPAP) as a test may help in the early recognition of these infants, who appear to make more effort to breathe during sleep, based on the indirect evidence of Pes measurements. It is suggested that anatomic features, including a small posterior airway space leading to an abnormal degree of upper airway resistance, may be the cause of the symptoms presented by these infants. Considering the parental anxiety generated by persistence of symptoms after the first year of life in ALTE infants, recognition of this subgroup is important.


Endobronchial irradiation with 192Ir in the treatment of malignant endobronchial obstruction. From Jan 1, 1983 to April 30, 1989, 32 patients underwent 38 endobronchial treatments with 192Ir, bronchoscopically inserted for treatment of endobronchial obstructions secondary to bronchogenic carcinoma. Thirty-four of the 38 treatments were far enough apart to allow separate response analysis. Thirty of the 34 patients were symptomatically improved or stable; 22 of 24 patients who could be evaluated roentgenographically showed improved or stable chest roentgenograms, and ten of 12 patients evaluated bronchoscopically demonstrated improved patency of bronchial lumen.


Extended monitoring of oxygen saturation in chronic lung disease. The goal was to determine values of oxygen saturation from oximetry measurements over extended time periods in the context of prescribing or discontinuing supplemental oxygen. For group 1, when supplemental oxygen therapy was not in use, mean SpO2 values were significantly lower than when it was in use. Without supplemental oxygen, six of eight patients spent greater than 10 percent of the time at or below 88 percent saturation. For group 2, three of the nine patients spent 10 percent of the time at or below 88 percent SpO2. In 16 of 17 patients, lowest room air recorded values of SpO2 were less than 88 percent. We conclude that in many patients with chronic respiratory illness, prolonged monitoring of SpO2 will disclose the presence of hypoxemia. There may be substantial differences in health care cost and outcome depending upon the criteria chosen to prescribe or continue supplemental oxygen.


Utility of repeated fiberoptic bronchoscopy for suspected malignancy. We retrospectively evaluated records of 1598 fiberoptic bronchoscopies (FBs) performed on 1,391 patients (PTs) between Jan 1, 1986 and Dec 31, 1990. We found a progressive increase from 11 percent to 20 percent in the use of repeated fiberoptic bronchoscopy (RFB). Of the 254 RFBs, 151 were done in PTs with known or suspected intrathoracic malignant neoplasms. The 78 (of 151) RFBs performed in PTs with previously diagnosed malignant neoplasms were used to guide additional therapy. The other major indication for RFB (67 of 151) was to evaluate new suspicious lesions that had not been diagnosed on the initial FB. RFB specimens were positive in 36, false-negative in 24, and true-negative in 7 PTs. For some PTs, RFB could probably have been avoided if at initial FB physicians had (1) used fluoroscopy to direct transbronchial lung biopsies in PTs expected to have normal airways, (2) performed transbronchial needle aspiration in all PTs with extraluminal disease or mediastinal adenopathy, and (3) obtained bronchial biopsy specimens from all PTs with endobronchial lesions. In PTs whose initial FB specimens were nondiagnostic despite visualization of endobronchial or extraluminal abnormalities, RFB was associated with a significant diagnostic yield and obviated the need for more morbid, surgical staging procedures.


Production of collagenase and tissue inhibitor of metalloproteinases by fibroblasts derived from normal and fibrotic human lungs. Several experiments have demonstrated low collagenolytic activity during the development of pulmonary fibrosis. In order to determine if fibroblasts play a role in this alteration, procollagenase and tissue inhibitor of metalloproteinases (TIMP) were quantified in fibroblasts derived from 12 human lung specimens (normal = 6, idiopathic pulmonary fibrosis [IPF] = 6). Under basal conditions, three cell strains from normal and three from fibrotic lung specimens did not synthesize collagenase and a similar number of normal and IPF-derived fibroblast strains produced the enzyme. However, the rate of enzyme synthesis among normal and fibrotic collagenase producing fibroblasts exhibited significant differences. Thus, whereas normal fibroblasts produced more than 300 ng/ml, fibrotic lung fibroblasts secreted approximately half of this amount (115 +/- 67 ng/ml). Phorbol myristate acetate (PMA) enhanced collagenase production in all of the 12 lung fibroblast lines tested. In four IPF fibroblasts, PMA increased collagenase secretion close to those of normal stimulated lung fibroblasts; however, a lower induction was observed in cell strains from two fibrotic lung specimens. There was a wide variation in TIMP production both in normal and fibrotic lung fibroblasts, and no statistically significant difference was observed. Under basal conditions, TIMP levels ranged from 329 to 16,911 ng/ml in normal lung cells, and from 377 to 17,557 in fibrotic lung fibroblasts. PMA induced a severalfold increase in all cell lines. These results suggest that there are subpopulations of lung fibroblasts with different potential to produce collagenase and TIMP in vitro, and that the predominance of low collagenase-producing subsets may contribute to the development of fibrosis.


Use of intermittent, intravenous cyclophosphamide for idiopathic pulmonary fibrosis. To determine the safety and efficacy of intravenous cyclophosphamide for patients with idiopathic pulmonary fibrosis. Nonrandomized, open-labeled study of efficacy in symptomatic patients. Patients were treated as outpatients in a referral clinic. All patients had idiopathic pulmonary fibrosis with symptoms of dyspnea on exertion. Patients had either worsening disease or contraindication to corticosteroids. Thirty-three patients were treated with intravenous cyclophosphamide every two weeks. Initial dosage was 500 mg, and the dose was escalated provided the total white blood cell count remained > 3,000 cells per cubic millimeter. The maximum dose administered was 1,000 to 1,800 mg of cyclophosphamide. Corticosteroid therapy was tapered as tolerated by the patient. Patients were treated for at least six months or until death. For the 33 patients, 18-month probability of survival was > 50 percent. For those patients surviving six months, there was a significant rise in the vital capacity (from 1.6 +/- .61 L [mean +/- SD] to 1.8 +/- .52 L, p < 0.01) which persisted for at least 18 months of treatment. This was associated with a significant fall in the average prednisone dosage from 32 +/- 13.0 mg/day to 4 +/- 10.4 mg/day (p < 0.01) by 12 months. Only one patient required hospitalization for possible drug-related toxic reaction. Intermittent, intravenous cyclophosphamide therapy was associated with improved pulmonary function and reduced corticosteroid dosage in patients with idiopathic pulmonary fibrosis who survived at least six months after institution of therapy.


Reduction of alveolar-capillary diffusion after inhalation of endotoxin in normal subjects. Normal subjects were exposed to an aerosol of Escherichia coli endotoxin. Carbon monoxide diffusion (Dco), spirometry, blood neutrophils, white blood cells, and platelets were determined at various times thereafter. A significant decrease in Dco and an increase in blood neutrophils was found, with a maximum effect 4 to 8 h after exposure. Exposure to distilled water caused a tendency for Dco to decrease and a significant increase in blood neutrophils. No effect on spirometry or body temperature was detected. It is suggested that the changes observed represent an inflammation at the alveolar level that appears at dose levels of endotoxin below those which cause bronchoconstriction and fever.


Metabolic effects of inhaled fenoterol in normal subjects. Although the hypokalemic effect of inhaled beta 2-adrenergic agonists has been well documented, little is known as to their effect on plasma magnesium. We therefore examined in ten healthy young volunteers the effect of the inhalation of 2 mg of nebulized fenoterol on plasma potassium (Kpl), plasma magnesium (Mgpl), and intraerythrocytic magnesium (MgIE) levels, as well as on plasma insulin and C peptide concentrations, measured before and serially up to 110 min after fenoterol inhalation. In all subjects, fenoterol inhalation caused a reversible reduction in Kpl (range, 0.2 to 1.1 mEq/L), which was progressive, reaching a statistically significant nadir 30 to 60 min following fenoterol inhalation (largest dip in Kpl, 0.55 +/- 0.29 mEq/L; p < 0.05). The nadir in Kpl levels was preceded by a peak in plasma insulin levels in all subjects. No significant changes in Mgpl or MgIE were observed in any of the subjects. We conclude that fenoterol inhaled at a dosage used in clinical practice significantly reduces Kpl but not Mgpl nor MgIE levels in healthy subjects, indicating a lower sensitivity of Mg++ ions to beta 2-adrenergic stimulation than K+ ions. Beta 2-adrenergic-induced insulin secretion probably contributes to the hypokalemic effect of inhaled fenoterol.


Is asymptomatic bronchial hyperresponsiveness an indication of potential asthma? A two-year follow-up of young students with bronchial hyperresponsiveness. To determine the possibility that asymptomatic bronchial hyperresponsiveness (BHR) develops into symptomatic asthma, a two-year follow-up study was conducted in 81 students (48 male, 33 female; 11 to 17 years) who were found to have BHR in a 3,067 population survey (BHR group). Eighty-eight age-matched students (48 male, 40 female) with normal bronchial responsiveness served as control subjects. Daily symptom cards were recorded. Peak expiratory flow rate was measured for 24 h when symptoms occurred. Histamine inhalation tests were performed at the beginning of the study and at the end of the first and the second year. In the BHR group, 58 students remained bronchial hyperresponsive at the end of follow-up. Nine of 31 students with initially diagnosed bronchial asthma had their symptoms relieved entirely, but ten asymptomatic students developed asthma. The incidence of newly diagnosed asthma (12.5 percent in the BHR group or 20 percent in the asymptomatic BHR group) and the total percentage of diagnosed asthma (39.5 percent) in the BHR group were significantly higher than those (2.27 percent, 2.27 percent) in the control group. FVC and FEV1 showed no significant difference between two groups. PD20 FEV1 values in newly diagnosed asthmatics were significantly lower than those in asymptomatic students both at the beginning (3.05 +/- 1.56 mumol vs 6.14 +/- 1.60 mumol, p < 0.05) or the end (3.47 +/- 1.73 mumol vs 6.55 +/- 1.51 mumol, p < 0.05). The percentage of early respiratory illness was significantly higher in those with newly diagnosed asthma (80 percent) than in asymptomatic students (22.3 percent), but atopic index and the percentage of parental asthma showed no difference between two groups. In nine asthmatics whose symptoms were relieved entirely in the two-year follow-up, PD20 FEV1 was undetectable within the cumulative dose of 7.8 mumol of histamine in three students and rose from 4.58 +/- 1.85 mumol to 7.62 +/- 1.02 mumol in the remaining six. The higher the BHR, the more likely the students developed asthma. About 45 percent of asymptomatic students with PD20 < or = 3.2 mumol developed asthma in the following two years and 80 percent of them had a history of early respiratory illness, suggesting that they may have subclinical or potential asthma.


The role of closed pleural needle biopsy in the diagnosis of malignant mesothelioma of the pleura. Malignant mesothelioma of the pleura is a disease that requires a biopsy procedure for a definitive diagnosis. In the past, closed pleural needle biopsy (CPNB) has given poor yields due to the small amount of tissue obtained, and the patient has subsequently been subjected to a diagnostic thoracotomy. In recent years, the availability of more accurate histopathologic tests have enabled the pathologist to make a diagnosis more easily on samples obtained at CPNB. In this retrospective study of 20 consecutive cases of malignant mesothelioma of the pleura diagnosed between 1980 and 1990, we found that a blind CPNB was diagnostic in five of seven procedures and CT-guided CPNB was diagnostic in five of six procedures. An open pleural biopsy (OPB) was diagnostic in ten of ten procedures performed. There were no complications associated with any of the CPNB procedures. We conclude that CPNB is a safe and effective manner of diagnosing malignant mesothelioma of the pleura, and should be attempted prior to OPB.


Cardiac output determination during progressive exercise in cystic fibrosis. Cardiac output (Q) determination using the equilibrium CO2-rebreathe indirect Fick technique (Equil) to estimate mixed venous PCO2 (Pv-CO2) has been validated during steady state (SS) exercise in subjects with lung disease. A modification of the exponential method using a low concentration of CO2 with an exponential rise in PEt-CO2 (Ex) during rebreathing to estimate Pv-CO2 has been validated during nonsteady state exercise. The purpose of the present study was to validate the Ex method in subjects with lung disease. Q was measured by Ex at every second work load during Prog. Q was measured after 5 min of SS exercise by both Ex and Equil. Arterial PCO2 was estimated from PEtCO2. There was no significant difference in the Q-VO2 relationship during Prog exercise between the combined control and mild (FEV1 > 70%) CF subjects or the moderate and severe CF subjects. Q can be determined in the nonsteady state using the exponential CO2-rebreathe indirect Fick technique in subjects with CF, allowing for noninvasive examination of cardiopulmonary interaction during exercise at a wide range of work loads.


Fick-derived hemodynamics. Oxygen consumption measured directly vs oxygen consumption calculated from CO2 production under steady state and dynamic conditions. Indirect calorimetry is being used increasingly as a tool for hemodynamic monitoring via the Fick equation. This investigation was undertaken to examine the use of carbon dioxide elimination (VCO2A) and related respiratory quotient (RQA) to calculate oxygen uptake (VO2A) and estimate oxygen consumption (VO2) during steady-state and dynamic hemodynamic conditions. Nine patients undergoing abdominal aortic surgery were studied intraoperatively and Fick-derived hemodynamic measurements were made using a monitoring system employing indirect calorimetry, pulse oximetry, and pulmonary artery oximetry. Comparisons were made between measured VO2A and calculated VO2A derived from the VCO2A and the initial RQA (RQi), which is assumed not to change. Prior to aortic crossclamping (steady state), there were no significant differences between the measured and calculated methods with respect to oxygen consumption (184 +/- 24 ml/min vs 185 +/- 17 ml/min), oxygen delivery (753 +/- 141 ml/min vs 769 +/- 178 ml/min), and cardiac output (4.7 +/- 0.6 L/min vs 4.7 +/- 0.7 L/min). However, immediately following aortic unclamping (dynamic state), the RQA changed precipitously from the baseline RQi. Consequently, significant differences between the measured and calculated methods were noted in oxygen uptake (213 +/- 41 ml/min vs 193 +/- 25 ml/min, p < 0.001), oxygen delivery (780 +/- 297 ml/min vs 716 +/- 296 ml/min, p < 0.001), and cardiac output (5.8 +/- 2.2 L/min vs 5.3 +/- 1.8 L/min, p < 0.001). Additionally, following unclamping, the peak VO2A was 242 +/- 49 compared with a cVO2A of only 198 +/- 22 (p < 0.01). We conclude that the use of VCO2A to calculate VO2A may lead to erroneous measurements under dynamic conditions, such as unclamping of the abdominal aorta.


A study of rib biopsy.

A study of rib biopsy. A retrospective study of one decade of rib biopsy in four hospitals in Nashville, Tenn, showed 61 biopsies were done in 60 patients. The typical patient was a male in his seventh decade. Preferred operative technique was open biopsy with general anesthesia. One half of the patients had metastatic malignancy; most of the known primary tumors were lung cancer. About one fifth of specimens were normal ribs. Biopsy was done in nine of these because of false-positive scintigraphy. Accurate preoperative chest wall localization is critical in order to minimize intraoperative decision-making problems. Yield of rib biopsy should be increased by more careful clinical observation, including critical evaluation of bone scans, avoiding overinterpretation of physical findings and observing for healing of possible rib fractures.


Circulating endothelin is not extracted by the pulmonary circulation in man. To determine whether endothelin is extracted from plasma during passage through the pulmonary circulation, we measured its concentration at several points, including the pulmonary artery and the left superior pulmonary vein in seven patients undergoing cardiac surgery. Endothelin concentrations were very similar at all sites sampled. In patients undergoing coronary artery bypass grafting, there is no net pulmonary clearance of endothelin.


Accuracy of respiratory inductive plethysmography during wakefulness and sleep in patients with obstructive sleep apnea. To assess the accuracy of the respiratory inductive plethysmograph (RIP) during sleep in obese patients with obstructive sleep apnea (OSA), we monitored 13 patients with OSA during wakefulness and nocturnal sleep with simultaneous measurements of tidal volume from RIP and integrated airflow. Patients wore a tightly fitting face mask with pneumotachograph during wakefulness and sleep. Calibrations were performed during wakefulness prior to sleep and compared with subsequent wakeful calibrations at the end of the study. Patients maintained the same posture during sleep (supine, 11; lateral, two) as during calibrations. There were no significant differences in calibrations before sleep and after awakening. The mean error in 13 patients undergoing RIP measurements of tidal volume during wakefulness was -0.7 +/- 3.4 percent while that during sleep was 2.1 +/- 14.9 percent (p < 0.001). The standard deviation (SD) of the differences between individual breaths measured by RIP and integrated airflow was 9.8 +/- 5.5 percent during wakefulness and 25.5 +/- 18.6 percent during sleep (p < 0.001). During both wakefulness and sleep, errors in RIP tidal volume were not significantly correlated with body mass index. In 12 patients with at least 10 percent time in each of stages 1 and 2 sleep, SD was greater in stage 2 sleep compared with wakefulness and stage 1 (p < 0.001). In three patients who manifested all stages of sleep, SD was greater in REM sleep than in wakefulness and all stages of non-REM sleep (p < 0.001). In three patients who manifested all stages of sleep, SD was greater in REM sleep than in wakefulness and all stages of non REM sleep (p < 0.001). This was associated with paradoxic motion of the rib cage in two patients during REM. We conclude that, despite increased errors in individual breath measurements during sleep, more marked during stages 2 and REM sleep, RIP is clinically useful to measure ventilation quantitatively in obese patients with sleep apnea. The criterion of a decrease of 50 percent in tidal volume assessed by RIP is appropriate to define hypopneas in such patients.


Analysis of induced sputum for the diagnosis of recurrent Pneumocystis carinii pneumonia. We studied the sensitivity of ISA for diagnosis of second-episode PCP in AIDS patients. We induced sputum in 218 patients who had known or suspected AIDS and who had a presentation suggestive of PCP. All patients with negative sputum smear for PCP underwent BAL. Twenty-five patients were identified who had second-episode PCP at least 30 days after initial diagnosis. Chest roentgenographic infiltrate patterns for these 25 patients were blindly scored as normal, diffuse, upper lobe or focal non-upper lobe. The sensitivity of ISA was 72 percent for the first episode of PCP, 72 percent for the second episode of PCP, 72 percent for patients with second-episode PCP who had initial PCP detected by ISA and 71 percent for patients with second-episode PCP whose first episode of PCP was missed by ISA. Of the ten patients who were treated with AP, only one had a false-negative sputum analysis. A comparison of patients who had second-episode PCP diagnosed by ISA with those who had false-negative sputum analysis showed no difference in time to relapse, chest x-ray film pattern (all diffuse) or use of AP.


The effects of flosequinan on hemodynamics and oxygen delivery in cor pulmonale. The hemodynamic effects of a new orally active vasodilator, flosequinan, were compared with placebo (single blind) over 24 h in eight patients with pulmonary hypertension secondary to severe chronic obstructive pulmonary disease. Mean pulmonary artery pressure was reduced by 5.1 (3.4, 6.7) mm Hg (mean 95 percent CI) (p < 0.003) and pulmonary vascular resistance was reduced by 70 (23, 189) dynes.s.cm-5 (p < 0.013) by active drug compared with placebo. Cardiac output increased significantly with flosequinan by 0.47 (0.03, 0.91) L/min (p < 0.04) and systemic oxygen delivery increased by 90 (50, 120) ml/min/m2) (p < 0.05). A significant reduction in systemic vascular resistance was observed, 132 (35,230) dynes.s.cm-5 (p < 0.02) but no significant changes were seen in systemic arterial blood pressure or arterial blood gas tensions. Flosequinan favorably altered pulmonary hemodynamics relative to systemic and resulted in a significant improvement in oxygen delivery. The hemodynamic and blood gas effects of this compound suggest that it is a promising vasodilator for the treatment of pulmonary hypertension.


A prospective study of pulmonary function and gas exchange following liver transplantation. Pulmonary function and gas exchange were prospectively studied in 95 patients before and 9 to 15 months following liver transplantation. Pretransplant, the most common PF abnormality was impaired efficiency of gas exchange as measured by Dss. As a group, the mean Dss was 78.0 +/- 16.6 percent predicted and was found to be less than 80 percent predicted in 50 patients. As a group, patients with the most severe liver diseases clinically (Child's C classification) had the lowest mean Dss pretransplant. Posttransplant, three findings were of clinical importance: PaCO2 significantly improved posttransplantation, suggesting a resolution of pretransplant respiratory alkalosis. Expiratory airflow obstruction, measured by a change in the FEV1/FVC, was extremely uncommon posttransplant. Mean Dss improved significantly in patients with Child's C severity of liver disease. The most frequent deteriorations in Dss statistically were associated with posttransplant thoracotomy, ARDS, nonspecific pneumonitis, significant pleural effusions and hepatic retransplantation.


Small bronchogenic carcinomas presenting as solitary pulmonary nodules. Bioptic approach guided by CT-positive bronchus sign. To evaluate the utility of the CT bronchus sign in making a choice between transbronchial biopsy (TBB) and transthoracic needle aspiration (TTNA) as the first diagnostic procedure in a patient with a solitary pulmonary nodule (SPN), we reviewed the results of TBB and TTNA in 26 patients who had a bronchogenic carcinoma less than 3 cm, studied with thin-section CT. The patients were divided into two groups. Group 1 included ten cases with a third- to fifth-order bronchus sign. Group 2 included two cases with a sixth-order bronchus sign and 14 cases with absence of a bronchus sign. TBB was performed in all the patients; conversely, TTNA was carried out in 22 patients. In group 1, TBB gave a diagnostic yield in eight (80 percent) of ten patients, while TTNA was positive in three (42 percent) of seven patients (p > 0.05). Conversely, in group 2, results of TBB were normal in all the patients, while TTNA gave a diagnosis in 10 (66 percent) of 15 patients (p < 0.05). We think that TBB should be considered the method of choice in diagnosing SPNs associated with a third- to fifth-order bronchus sign; conversely, TTNA is more useful than TBB in diagnosing SPNs in the presence of a more peripheral bronchus sign or with the absence of a bronchus sign. In conclusion, we suggest routine evaluation with thin-section CT of each SPN to optimize diagnostic management.


Bronchiolitis obliterans organizing pneumonia associated with systemic lupus erythematosus. Bronchiolitis obliterans organizing pneumonia (BOOP) is a pathologic entity characterized by the formation of plugs of fibrous tissue in bronchioles and alveolar ducts. It has been described in association with several connective tissue diseases including rheumatoid arthritis, polymyositis-dermatomyositis, and mixed connective tissue disease. Well-documented reports of BOOP in patients with systemic lupus erythematosus (SLE) are limited. We report two patients with SLE who presented with subacute respiratory illnesses due to BOOP, adding further strength to the association of this entity with SLE.


Normobaric measurement of arterial oxygen tension in subjects exposed to hyperbaric oxygen. This study demonstrates the ability of an automated blood gas analyzer (Radiometer ABL 330) operated at atmospheric pressure to measure the arterial oxygen tension (PaO2) of ten healthy volunteers exposed to hyperbaric oxygen (HBO2) up to 3.0 atmospheres absolute. Arterial blood samples were aspirated from subjects compressed in a single-person hyperbaric chamber and were analyzed immediately in the blood gas analyzer. The subjects' values for PaO2 correlated with the calculated alveolar O2 tension (PAO2) (measured PaO2 = 0.827 x PAO2-15.1) (r2 = 0.97). Tonometric experiments indicated a difference between saline and blood PO2 measurements. We therefore derived a correction factor for blood measurements (corrected PaO2 = 0.908 x PAO2-52.4) (r2 = 0.98). These results compared favorably with PaO2 measurements made with blood gas analyzers calibrated inside walk-in hyperbaric chambers. We conclude that the PaO2 of normal subjects exposed to HBO2 can be measured accurately at atmospheric pressure with this automated blood gas analyzer. Prior to this study, hyperbaric PaO2 measurements could only be performed within walk-in chambers. Our observations generalize the normobaric measurement of hyperbaric PaO2 to patients treated in single-person and walk-in chambers.


The conduction system in transplanted hearts. This is a serial section examination of the conduction system (CS) in six patients who died seven months, 11 months, two years four months, four years two months, 11 years, and 16 years eight months following cardiac transplantation. The heart was hypertrophied and enlarged in all. There was myocarditis of varying degree in all cases with arteriosclerosis and arteriolosclerosis. These findings were more dominant in the atria than in the ventricles. In the CS, myocarditis with fibrosis was found in all in the approaches to the sinoatrial (SA) node, the SA node, the atria, the atrioventricular (AV) node, and the bundle and bundle branches, to a varying degree. When compared with the endomyocardial biopsy findings, the autopsied cases revealed more myocarditis and fibrosis than those estimated to be present in the biopsy specimen. In summary, this study demonstrates that there are fibrotic changes in the CS with the persistence of inflammatory phenomena of the myocardium and the CS to a varying degree in transplanted hearts. This is accompanied by the ubiquitous coronary artery disease affecting not only the large coronaries but also the small vessels. The pathologic changes in and around the CS may be responsible for arrhythmias and sudden death in some cases of cardiac transplantation.


Oral vs intravenous dipyridamole echocardiography for detecting coronary artery disease. The usefulness of the intravenous dipyridamole-echocardiography test (12-lead and two-dimensional [2-D] echo monitoring during dipyridamole infusion) in the diagnosis of coronary artery disease recently has been suggested. However, the intravenous form of dipyridamole is not available for clinical use in some countries and therefore the administration of oral dipyridamole has been employed in combination with echocardiography. In order to evaluate the relative usefulness of the oral (300 mg of pulverized tablets) vs the intravenous (up to 0.84 mg/kg in 10 min) dipyridamole-echocardiography test, we performed the two tests, on different days and in random order, in 28 inhospital patients: 21 had coronary artery disease (seven had one-vessel disease, eight had two-vessel disease, and six had three-vessel disease); seven patients had no significant coronary artery disease. For both tests, the diagnostic end-point was the development of a transient dyssynergy of contraction. Sensitivity was 95 percent for the intravenous and 52 percent for the oral dipyridamole-echocardiography test (p < 0.01); in positive cases, the dyssynergy after the dipyridamole administration appeared at 6.5 +/- 2.5 min for the intravenous and at 27.8 +/- 12.4 min for the oral test (p < 0.01). Specificity was 100 percent for both the intravenous and oral dipyridamole-echocardiography test. One or more extracardiac side effects (headache, gastrointestinal upset, flushing, etc) occurred in 61 percent of the intravenous and 68 percent of the oral tests (p = ns). Nine patients with a positive intravenous and oral dipyridamole-echocardiography test also had a positive exercise-electrocardiography test. A significant correlation between exercise time (ie, the time from onset of exercise and 0.1 m V of ST segment shift) and dipyridamole time (ie, the time from onset of dipyridamole administration and the development of frank dyssynergy) was present for the intravenous (r = 0.6, p < 0.05) but not for the oral test. We conclude that the oral dipyridamole-echocardiography test, in comparison with the intravenous dipyridamole-echocardiography test, has a lower sensitivity and requires a substantially longer imaging time. The dipyridamole time is related to exercise time for intravenous but not for the oral dipyridamole-echocardiography test.


Does radial artery pressure accurately reflect aortic pressure? Our objective was to determine whether the systolic, diastolic, and mean arterial pressures measured in the radial artery accurately reflect corresponding pressures in the ascending aorta in narcotic-anesthetized patients with known obstructive coronary artery disease, before being subjected to cardiopulmonary bypass (CPB). This was a prospective study. The cardiac operating room of a large, tertiary-care university medical center. Fifty-one patients (45 men and six women; age range, 48 to 77 years) with documented atherosclerotic coronary artery disease were studied. All patients underwent elective coronary artery bypass grafting after the study. Patients were premedicated with lorazepam and morphine 60 min before administration of Fentanyl-pancuronium anesthesia. The radial artery was cannulated before induction of anesthesia and the aorta approximately 45 min later. Comparisons of radial and aortic pressures were then performed. Radial and aortic pressures were recorded through standard, fluid-filled, high-pressure, 91-cm (36-in) long tubing and disposable transducers, meticulously cleared of air bubbles. Additional measurements included cardiac output, central venous pressure, core temperature, blood gas levels, and hematocrit reading. Radial-aortic pressure differences were as follows: systolic arterial pressure (SAP), 12 +/- 1 mm Hg; mean arterial pressure (MAP), -0.8 +/- 0.3 mm Hg; and diastolic arterial pressure (DAP), -1.0 +/- 0.3 mm Hg. All were significant (p < 0.001), but the SAP difference was more than ten times that of either the MAP or the DAP values. The coefficients of determination (r2) indicated that the radial-aortic dependence was 0.44 for the SAP, 0.90 for the DAP, and 0.98 for the MAP relationship. Plotting the respective differences against the arithmetic mean of simultaneously measured pressures indicated that the radial SAP was 4 to 35 mm Hg higher than the aortic in 42 patients (82 percent) and was 10 to 35 mm Hg higher in 26 patients (51 percent); radial-aortic MAP differences clustered within 3 mm Hg in 47 patients (92 percent); radial DAP was +/- 3 mm Hg different from the aortic in 46 patients (90 percent). The largest MAP difference was -6 mm Hg in one patient. The largest DAP difference was +/- 5 mm Hg in three patients. In this group of patients, who were studied before undergoing CPB, the radial SAP gave a poor estimate of that present in the ascending aorta, since in more than 50 percent of the cases, the radial SAP was 10 to 35 mm Hg higher than that in the aorta. The radial MAP and DAP are reliable, since in 90 percent and 92 percent of the patients, respectively, the pressure differences were within +/- 3 mm Hg of those in the aorta.


Influence of left ventricular filling profile on the effect of atrioventricular synchronous pacing. We correlated the percentage of atrial contribution to left ventricular filling (percent AC) assessed by Doppler echocardiography with the hemodynamic benefit from atrioventricular synchronous pacing assessed by direct hemodynamic measurements. Subjects comprised 40 patients who underwent electrophysiologic catheterization because of unexplained syncope or bradycardia (< 40 beats/min). Femoral arterial and pulmonary capillary wedge pressure were recorded by catheterization, and cardiac output was measured by thermodilution during temporary atrioventricular synchronous (DDD, 70 beats/min with 150 ms of atrioventricular delay) and ventricular (VVI, 70 beats/min) pacing. Mitral inflow velocity by pulsed-wave Doppler echocardiography was recorded during DDD pacing and percent AC was obtained by calculating the ratio of mitral inflow velocity area during atrial systole to total mitral inflow velocity area during early diastole and atrial systole. The mean arterial pressure and the cardiac output increased significantly (99 +/- 16 mm Hg vs 90 +/- 15 mm Hg, p < 0.001; 4.6 +/- 1.0 L/min vs 3.9 +/- 0.9 L/min, p < 0.001), and the mean pulmonary capillary wedge pressure decreased (7 +/- 4 mm Hg vs 10 +/- 4 mm Hg, p < 0.001) during DDD compared with VVI pacing. A significant positive correlation was observed between the percent AC and the increase in cardiac output (r = 0.58, n = 40, p < 0.01) or the increase in mean arterial pressure (r = 0.62, n = 38, p < 0.01) during DDD pacing. The percent AC did not significantly correlate with the decrease in pulmonary capillary wedge pressure. In conclusion, patients with larger percent AC may receive major benefit from atrioventricular synchronous pacing.


Acromegalic cardiomyopathy. Left ventricular filling and hypertrophy in active and surgically treated disease. Myocardial hypertrophy and interstitial fibrosis are common in acromegalic hearts and may induce left ventricular (LV) dysfunction. The transmitral flow pattern was examined by pulsed-wave Doppler in 20 patients with active acromegaly and nine with acromegaly cured by pituitary microsurgery. Control groups consisted of 25 normal subjects and 13 patients with systemic hypertension. We related Doppler indices of LV filling (E and A peak velocities and E/A ratio) to the duration of acromegalic disease, the GH plasma levels and LV mass. The LV mass/BSA was significantly greater in active acromegaly (187 +/- 53 g/sq m) and systemic hypertension groups (161 +/- 48 g/sq m) than in cured acromegaly (125 +/- 35 g/sq m) and the normal control group (109 +/- 36 g/sq m) (p < 0.01 for both). No differences were found in the E peak velocity, A peak velocity, and E/A ratio in the groups with active acromegaly (E/A: 0.9 +/- 0.2), cured acromegaly (E/A: 0.9 +/- 0.3), and systemic hypertension (E/A: 0.8 +/- 0.5). An E/A ratio < 1 was found in 13 patients with active and four with cured acromegaly; (p = NS). In the active acromegaly group, the E/A ratio was related to either LV mass or the duration of disease (r:-0.45 and -0.47, respectively; p < 0.05). In the cured acromegaly group, the E/A ratio was related to the duration of disease before surgery (r:-0.70; p < 0.05) and not to LV mass (r:0.12). In conclusion, an impairment in LV filling may be present not only in the patients with active acromegaly but also in those successfully treated by surgery after a long duration of the disease, despite normal LV mass. These LV filling abnormalities may be in part determined by nonreversible myocardial changes, such as interstitial tissue fibrosis.


Residual volume in a general population. Effects of body size, age, cigarette smoking, and respiratory symptoms. Residual volume (RV) was obtained by subtracting vital capacity from total lung capacity determined by the single breath helium dilution (TLCsb) to measure CO diffusing capacity in 2,680 subjects (8 to 64 years old) of a general population sample. There were 712 normal subjects (243 male and 469 female subjects) selected to evaluate the pattern of RV by age and to derive reference values for internal comparisons. From 8 to 20 years old, RV showed an increase because of the cross-sectional body size effect; after 20 to 30 years, RV was still increasing, however, at a lower level. Age and height coefficients were significantly related to RV in younger and older ages, both in male and female subjects. The RV percent predicted and RV/TLC percent were higher in smokers when compared to nonsmokers and exsmokers (the difference was significant in male subjects). A dose-response effect was observed between RV percent predicted, RV/TLC percent, and pack-years. The RV percent predicted and RV/TLC percent were significantly higher in smokers and nonsmokers with FEV1 percent predicted below the normal limit (the difference was significant in male subjects). Moreover, higher values of RV percent predicted and RV/TLC percent were observed in subjects with wheezy symptoms in male smokers and nonsmokers. A negative significant correlation was observed between RV/TLC percent and the diffusing capacity adjusted for lung volume (DL/VA) in smokers, exsmokers and nonsmokers of both sexes, confirming the hypothesis that the decrease in DL/VA may be ascribed to the enlargement of terminal air spaces. In conclusion, determination of RV by the single breath helium dilution method is suitable in epidemiology, and it allows additional important information for understanding the physiopathologic mechanisms related to the pathogenesis of chronic obstructive lung disease.


Validation of a technique to assess maximal inspiratory pressure in poorly cooperative patients. The maximal pressure that can be generated during an inspiratory effort against an occluded airway serves as an index of respiratory muscle strength. We devised a method that permits accurate measurement of MIP, with near maximal values, and does not require patient cooperation. Twenty-two critically ill intubated patients performed MIP maneuvers before and after coaching. For the initial 11 patients, MIP was measured after the airway was occluded in 20 s with a one-way valve that permitted only exhalation. In the latter 11 patients, DS (approximately 1/3 VT) was added in an effort to increase respiratory drive before the noncoached MIP maneuver. We found no significant difference between coached and noncoached MIP maneuvers when P0.1 during the first 100 ms of inspiratory efforts prior to the noncoached MIP maneuver was greater than 2 cm H2O. Thus, MIP can be reliably measured in critically ill patients with or without coaching.


Intrinsic PEEP and unilateral lung hyperinflation. Pathophysiology and clinical significance. Over a 14-month period, three patients developed unilateral lung hyperinflation during mechanical ventilation as a manifestation of intrinsic PEEP. These patients all had a history of CAO and an inflammatory or fibrotic disease process involving the contralateral lung. Physicians caring for patients with CAO need to be familiar with this presentation of intrinsic PEEP due to the associated barotrauma and cardiac dysfunction which can result from it.


Volume-assured pressure support ventilation (VAPSV). A new approach for reducing muscle workload during acute respiratory failure. This study reports the preliminary clinical evaluation of a new mode of ventilation--volume-assured pressure support ventilation (VAPSV)--which incorporates inspiratory pressure support (PSV) with conventional volume-assisted cycles (VAV). This combination optimizes the inspiratory flow during assisted/controlled cycles, reducing the patient's respiratory burden commonly observed during VAV. Different from conventional PSV, VAPSV assures precise control of tidal volume (VT) in unstable patients. Eight patients with acute respiratory failure (ARF) were submitted to assisted ventilation under VAV and VAPSV. Patient's ventilatory workload (evaluated through the pressure-time product, mechanical work per liter of ventilation, and work per minute) and patient's ventilatory drive (occlusion pressure--P0.1) were significantly reduced during VAPSV. This "relief" was more evident among the most distressed patients (p < 0.001), allowing a reduction of more than 60 percent in muscle load, without the need of increasing peak tracheal pressure. Mean inspiratory flow (VT/TI), VT, and effective dynamic compliance were significantly increased during VAPSV, whereas the effective inspiratory impedance decreased. These mechanical advantages of VAPSV allowed a reduction of intrinsic PEEP, whenever it was present. Blood gas values were similar in both periods. We concluded that VAPSV is a promising form of ventilatory support. At the same time that it was able to safely assure a minimum preset VT, VAPSV reduced patient workload and improved synchrony between the patient and the ventilator during ARF.


Maneuver-free determination of compliance and resistance in ventilated ARDS patients. At present, most methods of lung mechanics analysis do not take nonlinearities of compliance and resistance into account. Nevertheless, nonlinearity of compliance is an inherent property of the respiratory system in ARDS and nonlinearity of resistance is an inherent property of the endotracheal tube. Herein we describe a computer-assisted multipoint method (LOOP) for breath-by-breath calculation of total respiratory system compliance (Ctrs) and total respiratory system resistance (Rtrs). Unlike our previously published method, LOOP excludes nonlinearities of compliance and resistance by confining the data used from the P/V/V loop to sequences with constant flow in inspiration and with steadily decreasing flow in expiration. LOOP was applied to five patients ventilated after open heart surgery (HEART group) and 12 patients ventilated for ARDS (ARDS group). The compliance results from LOOP were compared with the semistatic reference values corrected for intrinsic PEEP (CsST,IP). In the ARDS patients the compliance values from LOOP (46 ml/mbar) corresponded well with the semistatic compliance (CsST,IP = 42 ml/mbar). Despite the fact that there is no reference method for resistance known to date, we also determined the semistatic resistance (RsST) at end-inspiratory pause. The resistance values determined with LOOP were 8.5 mbar/L/s (RsST = 7.3 mbar/L/s) in the HEART group and 11.1 mbar/L/s (RsST = 8.6 mbar/L/s) in the ARDS group. LOOP gives a good correspondence between the linear RC model and the measured data in ARDS patients. In conclusion, LOOP requires neither an end-inspiratory pause (EIP) nor additional determination of intrinsic PEEP and gives Ctrs, automatically corrected for IPEEP, as well as Rtrs breath by breath at the bedside.


Modification of the spacer device. Use in the patient with arthritis or an artificial airway. The spacer device minimizes oropharyngeal deposition of metered dose inhaler (MDI) medication and helps ensure consistent delivery of the medications to the bronchial tree. Patients with hand limitations and artificial airways may be unable to use an MDI. We describe several modifications to two currently available spacer devices for use in these populations.


Role of platelet-activating factor in pulmonary edema after coronary ligation in dogs. To evaluate whether PAF is related to the precipitation of pulmonary edema after myocardial ischemia, we studied the effect of a specific PAF antagonist, CV-6209, on the extravascular lung water level measured by the thermal-dye double indicator dilution method, ETV, after coronary ligation in dogs. Eight dogs served as sham control animals (group 1). The proximal left anterior descending coronary artery was ligated for 45 min in eight dogs (group 2), and the coronary artery was ligated after pretreatment with CV-6209 (1 mg/kg) in eight dogs (group 3). The ETV increased significantly after coronary ligation in groups 2 and 3. The amount of increase in ETV in group 2 was significantly larger than in group 3. Thus, CV-6209 can prevent the accumulation of extravascular lung water after coronary ligation without producing changes in pulmonary vascular dynamics, indicating that PAF may play an important role in pulmonary edema after myocardial ischemia.


Evaluation of airway smooth muscle contractions in vitro by high-frequency ultrasonic imaging. To visualize ASM contraction in vitro, we measured changes in cross-sectional area and inner circumference of isolated porcine and human bronchi in response to acetylcholine or carbamylcholine chloride (Carbachol) using high-frequency ultrasound. A mechanical ultrasonic catheter (20 MHz; diameter, 1.7 mm; echo element, 1 mm2) demonstrated three histologic layers (mucosa, cartilage and adventitia) and allowed measurement of dose-dependent contraction of porcine bronchi over time. Acetylcholine (10(-4)M) significantly decreased the cross-sectional area by 17 +/- 2.85 percent but did not change the circumference. The mean initial value for area was 0.6 +/- 0.08 cm2 and for circumference was 3.0 +/- 0.24 cm (n = 5). The EC50 of acetylcholine was 1.5 x 10(-8) M. Carbachol (10(-4)M)-induced contractions of human bronchi were also observed under the same conditions. In conclusion, high-frequency ultrasonic imaging can be used to study the morphology of ASM contractions in vitro, providing valuable information on the natural dynamics of ASM.


Mediastinal lymph node enlargement as a result of mitral valve stenosis. Two patients are described with severe MVS, pulmonary venous hypertension and enlarged mediastinal, pulmonary and hilar lymph nodes. These enlargements were diagnosed on a preoperative chest CT. After MV replacement these enlarged lymph nodes nearly all resolved. The lymphadenopathy should be considered to be secondary to MVS with pulmonary venous hypertension.


Aortico-left atrial fistula in aortic valve endocarditis. Aortic root abscess is a well-known complication of aortic valve endocarditis. This report describes the two-dimensional echocardiographic findings in a patient with aortic valve endocarditis whose course was complicated by a posterior aortic root abscess which ruptured into the left atrium creating an aortico-left atrial fistula, which, to our knowledge, has not been previously reported. These findings were confirmed at surgery.


Bronchial dehiscence associated with a large broncholith in a lung transplant recipient. A 63-year-old man who underwent single lung transplantation for advanced emphysema had a postoperative course complicated by asymptomatic bronchial dehiscence associated with a large broncholith. The stone eventually caused airway obstruction requiring partial fragmentation and incomplete extrication. We suggest that calcified nodes of significant size be removed at the time of surgery in the lung transplant recipient.


Unilateral pulmonary edema. An unusual cause. A patient presented with shortness of breath without fever, cough or sputum production. The patient was hypoxic without leukocytosis and a chest x-ray film demonstrated a right unilateral pulmonary infiltrate. A chest CT showed a large ascending thoracic aortic aneurysm with dissection. During surgical repair, the aneurysm was noted to be compressing the single right pulmonary vein. The infiltrate resolved postoperatively, and the patient has remained symptom-free for one year.


Hamman's sign revisited. Pneumothorax or pneumomediastinum? Louis Hamman described distinctive chest noises and emphasized their association with pneumomediastinum in 1937. However, the etiology of Hamman's sign remains incompletely defined and its association with pneumothorax underemphasized. We present a patient with pneumothorax and Hamman's sign assessed by computed chest tomography. Tomography suggested an alternate genesis of Hamman's sign; free pleural air may be cyclically channeled through a lung fissure thus creating chest sounds.


External stabilization of flail chest using continuous negative extrathoracic pressure. On rare occasions after total sternectomy, patients develop persistent flail chest deformities requiring long-term mechanical respiratory assistance. We report the use of a temporary external chest shell to deliver constant negative extrathoracic pressure (CNEP) to a long-term ventilated patient with flail chest. The patient's anterior thoracic cage stabilized, and significant improvement in pulmonary function was observed. With these data in hand, an operation was done to permanently stabilize the anterior chest wall by bone grafting.


Unusual cause of hemoptysis. Hickman-induced cava-bronchial fistula. A 56-year-old man with metastatic prostatic carcinoma underwent placement of a Hickman catheter. Approximately two months after the procedure, he was admitted to the hospital with hemoptysis and in respiratory distress. A contrast computed tomographic (CT) scan confirmed the diagnosis of a cava-bronchial fistula. The fistula was surgically repaired, and the patient made a satisfactory recovery.


Ventilatory dysfunction in severe anorexia nervosa. A 25-year-old woman suffering from chronic anorexia nervosa lost more than 50 percent of her body weight and presented with generalized muscle weakness. Pulmonary function tests showed a severe restrictive defect, and she had marked impairment of respiratory muscle strength and endurance, peripheral muscle function, and hypercapnic ventilatory responses, all of which improved following refeeding. The interaction and response to treatment of these effects on respiratory function are discussed.


Thoracoscopic resection of a posterior mediastinal neurogenic tumor. Advances in endoscopic instrumentation and a growing enthusiasm for minimally invasive surgical techniques have sparked renewed interest in therapeutic thoracoscopy. We report the successful thoracoscopic resection of a posterior mediastinal nerve sheath tumor. A 35-year-old asymptomatic woman was found to have a posterior mediastinal mass on chest roentgenogram. Computed tomography and magnetic resonance imaging confirmed the presence of the lesion and showed no evidence of intraspinal extension. Exploratory thoracoscopy revealed a localized lesion without intraspinal extension. Thoracoscopic resection of the lesion was then performed. The patient's postoperative course was uncomplicated and she was discharged on the fifth postoperative day. The therapeutic potential of thoracoscopy continues to be realized as experience with the technique grows.


Upper airway dysfunction in olivopontocerebellar atrophy. We report the findings in a patient known to have olivopontocerebellar atrophy who developed respiratory distress, inspiratory stridor, and maximum inspiratory and expiratory flow volume loops. Treatment with carbidopa-levodopa gave symptomatic relief.


Thrombosed pulmonary artery aneurysm. A rare cause of a high-probability lung scan. The high-probability ventilation-perfusion lung scan is accepted as supportive of pulmonary embolism and often negates further diagnostic evaluation; however, there are processes that mimic the clinical presentation and radiographic findings of pulmonary emboli, including a unilateral segmental or greater perfusion defect. We present the findings in a patient whose presentation and ventilation-perfusion scans over a three-month course were suggestive of pulmonary embolism, yet pulmonary angiography revealed a thrombosed pulmonary artery aneurysm. The interpretation of a unilateral segmental perfusion defect as high probability does not secure the diagnosis of pulmonary embolism and should not preclude further evaluation for alternative etiologies.


Tricuspid valve regurgitation following blunt thoracic trauma. Valvular lesions following blunt thoracic trauma are uncommon. Tricuspid valve regurgitation occurs very rarely. We report a successful tricuspid valve reconstruction for rupture of the chordae tendineae in a young man nine years after a motor vehicle accident. The value of echocardiography and transesophageal echocardiography for the diagnosis and quantification of this valve lesion is stressed.


Interleukin-5 levels of pleural fluid and serum samples in a patient with PIE syndrome. An increased production of IL-5 was detected in the pleural fluid (7.2 ng/ml) and in the serum samples (53 pg/ml) of a patient with PIE syndrome. Following steroid therapy, pleural fluid disappeared, eosinophilia improved and serum IL-5 concentration became undetectable. These results suggested that eosinophilia in the PIE syndrome is a consequence of increased production of IL-5, especially in the lung.


Extreme hypercapnia in a fully alert patient. A patient is described with decompensated chronic obstructive lung disease (COLD) and extreme hypercapnia. Despite an arterial CO2 level of 160 mm Hg, the patient remained awake and alert. This indicates that CO2 narcosis is not an invariable finding in severe hypercapnia.


Periaortic hematoma formation leading to aortic valve failure. A complication of homograft placement for second valve surgery. The aortic homograft has become the replacement valve of choice in the treatment of complicated endocarditis involving native and prosthetic aortic valves. Complications are rare, typically involving chronic leaflet degeneration causing valvular insufficiency or rarely chronic calcific stenosis. We present a case in which functional stenosis of the homograft valve was caused by compression and distortion by blood transmitted directly from the left ventricle into a space between the homograft and an external cavity formed by a Dacron wrap. The latter had been placed to help control suture-line bleeding. This case presentation demonstrates an unusual cause of homograft failure and suggests that wrapping of a homograft conduit by native aorta or an external Dacron wrap is not a substitute for meticulous surgical technique to assure a hemostatic suture line.


Diffuse alveolar hemorrhage secondary to superwarfarin ingestion. A 27-year-old woman with severe vitamin K deficiency presented with hemoptysis and diffuse pulmonary infiltrates. She rapidly developed respiratory failure requiring ventilatory support. Surreptitious ingestion of brodifacoum, a long-acting warfarin derivative, was ultimately found to be the cause of her coagulopathy and DAH.


Endobronchial tuberculosis. Clinical and bronchoscopic features in 121 cases. The clinical and bronchoscopic features of endobronchial tuberculosis in 121 patients were retrospectively investigated. The peak incidence occurred in the second decades, with 3.8 times higher incidence noted in female than in male subjects. A barking cough with sputum was the most common chief complaint in 61.1 percent. Parenchymal infiltration and/or consolidation was the most common roentgenographic finding of the chest in 58.6 percent. Hypertrophy with luminal narrowing was the most common bronchoscopic finding in 43 percent. Bronchoscopically, right upper and right main bronchus were the most frequently involved in 30.5 percent. It was concluded from these data that using fiberoptic bronchoscopy allows not only substantial meaningful assessment of endobronchial tuberculosis but also relieves atelectasis eventually resulting in successful treatment with antituberculosis drugs.


Fiberoptic bronchoplasty. Description of a simple adjunct technique for the management of bronchial stenosis following lung transplantation. Bronchostenosis is a well-recognized complication of pulmonary transplantation occurring at the site of the anastomosis and occasionally spreading distally from the original site of obstruction. The management of these airway complications has relied heavily on stent placement that usually involves the use of a rigid bronchoscope and is a relatively complicated procedure in the patient requiring mechanical ventilation. Another has been the use of laser therapy in selected patients. We report three cases of postoperative bronchostenosis managed with bronchoscopically directed balloon dilatation. This relatively simple procedure performed under local anesthesia using a fiberoptic bronchoscope and a modification of the Seldinger technique for balloon placement permitted accurate and atraumatic dilatation of significant posttransplant stenosis. This technique may have potential for emergency and/or palliative management of postoperative, posttraumatic, or malignant airway obstruction.


Bronchoalveolar lavage cell count and differential are not reliable indicators of amiodarone-induced pneumonitis. Amiodarone-induced interstitial pneumonitis is a serious, frequently fatal untoward effect of a commonly used antiarrhythmic agent. Recent reports suggest that bronchoalveolar lavage (BAL) fluid cellular analysis might be used to diagnose amiodarone-induced pneumonitis. The purpose of this study was to determine if the diagnosis of amiodarone-induced pneumonitis could be made by patient history, pulmonary function evaluation, and examination of BAL fluid. We studied five groups of patients. Three of the five groups received amiodarone: patients receiving amiodarone without evident lung toxic reaction, patients with amiodarone-induced pneumonitis, and amiodarone-treated patients diagnosed as having other pathologic processes involving the lung. The two other groups examined were healthy volunteers and patients with interstitial lung disease from causes other than amiodarone. Pulmonary function tests included vital capacity (FVC), first second forced exhaled volume (FEV1), total lung capacity (TLC), and diffusing capacity for carbon monoxide (DCO). BAL fluid analysis included total and differential cell counts. We found that amiodarone-induced interstitial pneumonitis was not associated with an alteration in pulmonary function or BAL cellular composition which could permit its distinction from amiodarone-treated patients diagnosed as having an unrelated pulmonary process or patients with interstitial lung disease from other causes. The most frequent abnormality encountered in patients with amiodarone toxicity was a reduction in the percentage of macrophages in the differential cell count. The sensitivity, specificity, and predictive value of this finding was 82 percent, 69 percent, and 69 percent, respectively. The sensitivity, specificity, and predictive value of a > or = 15 percent reduction in DCO was 44 percent, 50 percent, and 36 percent, respectively. We conclude that amiodarone-induced interstitial pneumonitis remains a diagnosis of exclusion, and the role of BAL fluid analysis is to narrow the differential diagnosis through microbiologic culture and cytologic examination.


A six-year survey of immunogenicity and efficacy of hepatitis B vaccine in infants born to HBsAg carriers. Although the efficacy of hepatitis B vaccine is well documented, the duration of immunity of healthy infants after vaccination is unknown. 99 infants born to hepatitis B surface antigen (HBsAg)-carrier mothers were studied and found to have positive anti-HBs (titer: greater than or equal to 10 mIU/mL) after a first injection of vaccine at the ages of 1 to 6 years. The infants were randomly divided into four groups of recipients treated with the vaccine of the National Institute of Allergy and Infectious Diseases (NIAID), U.S.A. or that of the Beijing Biological Products Research Institute (BBPRI), BBPRI vaccine in combination with hepatitis B immune globulin (HBIG) and placebo. The results showed that the protective efficacy dropped considerably after 5 years with NIAID vaccine, after 3 years with BBPRI vaccine and after 4 years with BBPRI vaccine plus HBIG. This suggests that a booster injection is needed 5 years after the first injection of NIAID vaccine, 3 years after BBPRI vaccine, and 4 years after BBPRI vaccine plus HBIG.


Elimination of immune tolerance to hepatitis virus in an animal model. Four-day old ducklings were infected with duck hepatitis B virus to simulate perinatal transmission of hepatitis B virus. Immune tolerance was characterized as persistent viremia, antigenemia, without detection of anti-DHBs or anti-DHBc. A synthetic peptide, P125-146, mimicking one of the epitopes of the native DHBV Pre-S protein was used to cross-link to tetanus toxoid or phytohemagglutinin. These 'novel' antigens were used to immunize immune tolerant ducks, aimed at bypassing T cell tolerance. After 5 injections, though no anti-DHBV Pre-S was detected, around 50% of the immunized ducks showed seroconversion to DHBV DNA negative.


Hepatitis D virus infection in liver tissues of patients with hepatitis B in China. 2,346 liver samples from 17 cities of China for intrahepatic hepatitis D antigen (HDAg) were studied by direct enzyme-labelled technique. HDAg was detected in 167 out of 1,764 samples of HBsAg positive individuals making a detection rate of 9.47%. Hepatitis D virus (HDV) infection existed in all the examined districts with no significant difference in the HDAg detection rate. It was found that the intrahepatic HDAg detection rate was related to the pathologic type of the liver disease. The HDAg detection rate in chronic liver diseases and severe hepatitis was higher than in other liver diseases. It suggests that HDV infection is associated with the progression and chronicity of the liver disease. Studies on the relationship between HDV infection and HBV replication showed that HBV replication might be suppressed by HDV infection. Both HDV and HBV, however, could replicate in the same hepatocyte simultaneously.


Preliminary report on seroepidemiology of HCV and HBV infection in northern China. 1 141 serum samples from various population groups in north China were examined for C100-3Ab by ELISA. Antibody to C100-3 antigen derived from HCV genome (C100-3A) and HBsAg were measured in 438 normal population in Beijing. The C100-3Ab positive rate was 2.1% and the HBsAg positive rate was 2.5%. There is increased occurrence with age. In 649 cases of chronic liver diseases, the HBsAg positive rate was 87.1% in chronic persistent hepatitis (CPA), 88.8% in chronic active hepatitis (CAH), 64.9% in liver cirrhosis (LC) and 67.3% in hepatocellular carcinoma (HCC). The C100-3Ab positive rate was 10.5% (CPH), 12.1% (CAH), 42.6% (LC) and 38.4% (HCC). It is noteworthy that the C100-3Ab positive rate significantly increased with disease progression from CPH to CAH, LC and HCC. Prevalence of cases positive for both C100-3Ab and HBsAg was 0% in the normal population, 6.7% in CPH, 8.4% in CAH, 31.1% in LC and 28.8% in HCC. Investigation of patients with HCV infection showed that only 36.8% had blood transfusions. HCV and HBV infection may play important pathogenic roles in CPH, CAH, LC and HCC in north China.


Ultrastructural study on extrahepatic infection of duck hepatitis B virus in ducks. Kidney and pancreas tissues from congenitally infected Ma ducks with duck hepatitis B virus (DHBV) were examined by immunohistochemical staining technique and electron microscopy. The immunostaining showed that DHBV antigen was localized in the cytoplasm of tubular epithelial cells of kidney and acinar cells of pancreas of infected ducks. Under electron microscope, we found that complete and incomplete DHBV particles existed in the dilated cisternae of rough endoplasmic reticulum of both the cells. The size of complete and incomplete virus particles was nearly uniform in both the cells, 50-65 nm and 40-50 nm in diameter respectively. Therefore, extrahepatic infection and replication of DHBV were directly demonstrated ultrastructurally.


A study of Chinese knee joint geometry for prosthesis design. This study for the first time provides the geometric parameters of the knee joint of Chinese, which is indispensible to the design of knee prosthesis used for compatriotic patients. Thirty-five items, including linear, radial and angular measurements, were taken from 105 cadaveric knees and knee X-ray films of 1,100 subjects. The method and calculation for proper correction of the X-ray image magnification and joint cartilage space was established. Correlation was found to exist between the X-ray correction coefficients and the body weight, which formed the basis for individualized correction of X-ray measurements. Statistical analysis revealed that most of the linear and radial measurements were highly related while the angular measurements were independent of others. Principal component analysis showed that the width of femoral condyle might be taken as the leading index in determining the dimension of the knee, and regression functions were established to supply the serial parameters for prosthetic design. Multivariate discriminate functions could aid the selection of knee prosthesis.


A clinical study on diabetic retinopathy. A clinical research on the diabetic retinopathy(DR) is reported. In the 662 cases of diabetes mellitus examined, the prevalence of DR was 51.3%, of which 7.6% were preproliferative and 7% proliferative. The study showed that when the disease progressed to the preproliferative and proliferative DR, laser photocoagulation could be the best treatment of choice, and panretinal photocoagulation was also quite effective in the treatment of pregnant patients with proliferative diabetic retinopathy.


The arch structure of trabeculae in normal femoral head and its biomechanical significance. The microstructure of the normal human femoral head was observed under light and electron microscope. Most of the trabeculae were seen in the form of arch structure, and the collagen fibers and mineral columns among the trabeculae were arranged in different directions. These findings provide a new explanation of the mechanism by which the femoral head can bear high stress without collapse.


DNA content and its relationship with pathology and prognosis of colorectal carcinoma. The DNA content of 181 colorectal cancers was investigated by flow cytometry on paraffin-embedded specimen. The relationship of flow cytometric DNA patterns of colorectal cancer to Dukes's stage, histological type and grade, tumor size and patient's prognosis were analysed. The DNA aneuploid carcinomas were found in 53.04% of the patients (hypodiploid 22.10%, hyperdiploid 20.99%, polyploid 9.94%). Diploidy was found in 46.96% of the patients with colorectal cancer. The proportions of aneuploidy were significantly lower in the patients with Dukes' stage A (25.00%) and B (47.14%) than those with Dukes' stage C (64.71%) and D (68.42%). Aneuploid frequency was higher in the patients with poorly differentiated adenocarcinoma (84.62%), mucinous adenocarcinoma (62.50%) and tubular adenocarcinoma (52.75%) than those with villous adenocarcinoma (22.86%). The proportion of aneuploidy was significantly higher in the patients with poorly differentiated tumor (71.79%) than in those with moderately (50.00%) and well differentiated tumors (44.83%). Five-year survival rate of the patients with DNA aneuploid tumors was 33.80% compared with 66.67% of those with diploid tumors. Analysis of Cox regression revealed that DNA ploidy and Dukes' stage significantly influenced the patient's prognosis. It is suggested that DNA ploidy might be an important prognostic factor in colorectal cancer.


Transcoronary chemical ablation of ventricular tachycardia. Transcoronary chemical ablation of ventricular tachycardia was recently performed in one patient with refractory ventricular tachycardia in our hospital. The procedure was successful. The arrhythmia was cured and no recurrence occurred in a 24-month period. The clinical application and mechanism of transcoronary chemical ablation were discussed.


Pelvic lymphadenectomy with stripping technique in 43 cases. Pelvic lymphadenectomy with stripping technique--Gao's stripping pelvic lymphadenectomy (GSPL) was introduced. From January to December 1989, this operation was performed on 43 patients (36 patients with cervical carcinoma, 5 endometrial carcinoma and 2 ovarian carcinoma). The mean time of the operation was 12.56 minutes for the left side, and 13.33 minutes for the right side. No severe complications were found. The bleeding during operation was minimal. The main advantages of GSPL include high-speed operation, clean and integral lymphnodes stripped, less bleeding and complications, and easy performance of operation.


Full-valve annuloplasty in treatment of primary deep venous valvular incompetence of the lower extremities. Full-valve annuloplasty of superficial femoral venous valves was performed successfully in 139 extremities affected with primary deep venous incompetence of the lower limb. Chronic ulcerations in 43 affected extremities healed after operation. Postoperative venography showed that the recovery rate of valvular function was 97%, and no serious complication was noted. Follow-up for a mean of 3.5 years showed no varicosed vein and no recurrence of ulceration. The principles of operation, the optimum site, number and degree of annuloplasty, indications and results of the operation were discussed.


[Endosonography of esophageal cancer. Results of a clinical study and in vitro analysis]. From April 1989 to June 1991 63 patients with esophageal cancer were investigated by endosonography with the object of ascertaining the depth of intrathoracic tumor infiltration and lymphnode involvement. The sensitivity in diagnosing tumor infiltration amount to 0.74; the sensitivity for involvement of regional lymphnode was 0.84, specificity 0.44. In an in-vitro analysis endosonographic criteria for the assessment of regional lymphnodes are proved. Echogenic structure seems not to be a valuable criterium.


[Importance of sonography in diagnosis of ileus. A retrospective study of 459 patients]. In a retrospective trial we investigated the significance of ultrasound in the diagnosis of intestinal obstruction in 459 patients. The overall sensitivity was 93.7%. In paralysis the correct diagnosis was obtained in 98% of all. Mechanical obstruction was identified in 91%. In cases of incomplete mechanical obstruction sensitivity was 89%. The corresponding value for complete obstruction was 95%. In all patients with negative findings on abdominal x-ray (10%) the correct diagnosis was established by ultrasound. Only in 71% of cases ultrasound was successful differentiating small bowel from large bowel obstruction. The underlying cause of ileus was yielded by ultrasound in 45% of the cases. On the basis of our experience ultrasound is proven to be of significant importance in the diagnosis and differentiation of ileus.


[Surgery of blunt heart trauma].

[Surgery of blunt heart trauma]. Between 1972 and 1990 11 patients--all but one of them with multiple injuries--were treated surgically for blunt cardiac trauma caused by traffic accident in about 90%. Myocardial rupture (n = 3), laceration of the pericardial sac (n = 1), mitral insufficiency (n = 5; one of them in combination with atrial septal defect), ventricular septal defect (n = 1) and myocardial aneurysm (n = 1) occurred. Patients with myocardial rupture and pericardial laceration died within 2 h after admission to hospital; the other patients were successfully treated by mitral valve replacement (n = 4), mitral valvuloplasty and repair of ASD, suture repair of VSD and resection of myocardial aneurysm in one case, respectively. The interval to operation was 8 months to 12 years. Whereas pericardial tamponade caused by rupture of the atrial or ventricular wall and injuries of main coronary vessels require immediate surgical intervention, valve insufficiencies, septal defects or myocardial aneurysms may be mostly treated at a later date. Improvement of logistic measurements and the suspicion of blunt cardiac trauma followed by immediate surgical intervention may reduce the mortality rate in cases of cardiac rupture.


[New histomorphologic prognostic parameters in stomach cancer. A uni- and multivariate analysis of 445 patients]. In a retrospective series of 445 gastric cancer patients, the prognostic significance of classical histological parameters such as T-category, tumor size, lymphnode involvement and tumor grading was compared with the prognostic value of vascular invasion and the degree of tumor cell dissociation (TCD) at the invasion front. As shown in a Cox regression analysis, T-category had the highest prognostic value. Nevertheless, vascular invasion and TCD proved to be independent new parameters in a multivariate analysis, exceeding the prognostic information obtained by the combination of T-category and lymph-node involvement. In contrast, tumor grading provided no significant information. The determination of TCD at the invasion front as well as a careful search for vascular invasion may therefore provide additional useful information for identifying those patients who are at high risk and who may be candidates for adjuvant therapy in future clinical trials.


[Technique of dynamic support suture and palisade closure]. In 35 cases a dynamic supporting suture was applied. The technique of a palisade closure and of a dynamic supporting suture is introduced as shown in three cases of complicated abdominal wall conditions. This allows a differentiated operative-tactical procedure in the treatment of complicated laparotomy wounds following peritonitis, re-operation and wound dehiscence.