Immunoglobulin secreting cells in normal human bronchial lavage fluids.

Immunoglobulin secreting cells were quantitated in the bronchial lavage fluids of 12 normal volunteers and compared with immunoglobulin secreting cells in peripheral blood, by a reverse hemolytic plaque assay. The mean number of cells secreting immunoglobulin (Ig)G in bronchial lavage fluids was 489 per million lymphocytes vs. a mean of 175 IgG secreting cells per million lymphocytes in peripheral blood (P < 0.02). The mean number of IgA secreting cells in bronchial lavage fluids was 633 per million lymphocytes as compared to 100 per million lymphocytes in peripheral blood (P < 0.005). Thus, compared to peripheral blood, cells from the lavage fluids were relatively enriched for both IgG and IgA secreting cells. However, IgA secreting cells were the major class of immunoglobulin secreting cells in bronchial lavage fluids, whereas IgG secreting cells predominated in peripheral blood. The prominence of IgA secreting cells in bronchial lavage fluids was further demonstrated by a mean ratio of IgA/IgG secreting cells in bronchial lavage fluids of 1.26 compared to a ratio in peripheral blood of 0.57 (P < 0.02). Cells secreting IgM were identified in only four of seven bronchial lavage fluid samples studied but in all peripheral blood samples. IgE secreting cells were not present in normal peripheral blood but could be demonstrated in 5 of 11 lavage fluid specimens. Thus, cells actively secreting immunoglobulins can be identified in the lower bronchial-alveolar tree of normal human subjects. Cells secreting IgG, IgA, or IgM may function in local lung defenses against infection; cells secreting IgE may contribute to hypersensitivity reactions in the lung.

Dopamine agonist treatment of fluctuating parkinsonism. D-2 (controlled-release MK-458) vs combined D-1 and D-2 (pergolide)

Adjunctive treatment with the very potent and selective dopamine D-2 agonist MK-458 (controlled-release formulation) improved the control of parkinsonism in patients with fluctuating responses to levodopa therapy (with carbidopa). We subsequently switched patients to adjunctive treatment with pergolide, a less potent D-2 agonist. Pergolide therapy controlled parkinsonism more effectively than controlled-release MK-458. Unlike MK-458, pergolide mesylate also has D-1 agonist properties, apparently accounting for its greater antiparkinsonism efficacy. Adjunctive treatment with controlled-release MK-458 elicited less choreiform dyskinesias than either pergolide adjunctive therapy or therapy with carbidopa-levodopa alone; this finding suggests that D-1 receptor stimulation contributes to the elicitation of medication-induced chorea. The highest doses of controlled-release MK-458 resulted in paradoxical freezing of gait in almost one third of patients. This finding suggests that gait freezing, common in untreated parkinsonism, can also be elicited by excessive D-2 stimulation.

The influence of PEEP on survival of patients in respiratory failure: a retrospective analysis.

Positive end expiratory pressure breathing (PEEP) is used to decrease morbidity and mortality in patients who are hypoxemic despite breathing oxygen in concentrations potentially toxic to their lungs. We reviewed the hospital course of 78 patients whose arterial oxygen tension (PaO2) was less than 70 torr despite a fraction of inspired oxygen (FiO2) of 1.0. Only 60 per cent of these patients were treated with PEEP and their clinical illnesses and severity of cardiopulmonary dysfunction were similar to those in patients not treated with PEEP. PEEP increased the length of survival from 4.2 to 9.2 days (P less than 0.05) whereas over-all survival, defined as hospital discharge, was similar at 31 per cent with and 26 per cent without PEEP. An improvement in PaO2 and decrease in shunt fraction following a trial of PEEP portends a favorable outcome, but its continued use appears to prolong life for a few days without affecting hospital mortality. Survival appears related more to the maintenance of adequate tissue oxygenation as manifested by a high mixed venous oxygen than to improved gas exchange as reflected by an increase in PaO2.

Clinical implications of a "nonspecific" transbronchial biopsy.

The diagnostic accuracy of transbronchial biopsy via fiberoptic bronchoscope was reviewed in 127 noncritically ill patients. Biopsy results were analyzed according to whether a "specific" pathologic diagnosis of neoplasm, granuloma or pneumonia, or a "nonspecific" diagnosis of inflammation, fibrosis or normal lung was made. The clinical significance of a "nonspecific" biospy specimen was evaluated by clinical follow-up of at least 12 months (mean 15 months) and by grouping patients according to the type of abnormality found on chest roentgenography. Clinical follow-up was available in 119 of these patients. The over-all "specific" diagnostic yield for biopsy with secretions was 49 per cent, with transbronchial biopsy being the sole means of specific diagnosis in 14 per cent of the patients with a peripheral mass lesion, in 18 per cent of the patients with localized infiltrative processes and in 52 per cent of the patients with diffuse infiltrative processes. In 64 (52 per cent) patients both biopsy specimens and secretions were diagnostically nonspecific. In 16 (77 per cent) patients with peripheral mass lesions but nonspecific biopsy findings and secretions, neoplasm was diagnosed by more invasive procedures. However, 22 (91 per cent) patients with localized and 12 (75 per cent) patients with diffuse infiltrative processes had benign clinical follow-up suggesting that open lung biopsy in such patients should be reserved for patients with obvious clinical or roentgenographic evidence of deterioration.

Preoperative pulmonary function and complications after cardiovascular surgery.

Results of preoperative pulmonary function tests were evaluated in 106 patients who had major thoracic or upper abdominal cardiovascular surgery. These results were related to the occurrence of postoperative complications by comparison of pulmonary function data in patients with an ICU stay of less than 5 days versus patients with an ICU stay of greater than 5 days. However, quantitative analysis of several specific parameters of pulmonary function tests failed to reveal any difference in the incidence of postoperative complications between patients with modest versus severe preoperative dysfunction. The occurrence of atelectasis was related to type of cardiovascular surgical procedure, but not to preoperative pulmonary function tests. Abnormalities on pulmonary function tests were not the major determinants of use of preoperative respiratory therapy, and its use was unrelated to the length of stay postoperatively in the ICU. We conclude that prior to cardiovascular surgery, routine quantitation of clinically apparent pulmonary dysfunction may be of little value in predicting postoperative morbidity and much less important than careful clinical evaluation. When pulmonary function tests are performed in such patients, simple spirometric tests and arterial blood gas levels are adequate.

First pass radionuclide assessment of right and left ventricular ejection fraction in chronic pulmonary disease. Effect of oxygen upon exercise response.

Right and left ventricular ejection fraction (RVEF; LVEF) were determined in patients with severe chronic pulmonary disease (mean +/- SEM [FEV1 percent predicted 36 +/- 3%; PaO2: 64 +/- 3 mm Hg]), utilizing first pass radionuclide angiocardiography. RVEF and LVEF were measured at rest and again during upright bicycle exercise while patients breathed room air, and again during low flow oxygen (O2) administration. Mean RVEF was abnormal (less than 45%) at rest and did not increase with exercise while subjects breathed room air (44 +/- 2 percent vs 44 +/- 3 percent, P = ns), but improved significantly during exercise while patients breathed O2 (45 +/- 5 percent vs 51 +/- 3 percent, P less than .05). Breathing room air, RV exercise ejection fraction was abnormal (less than 5 percent increase in absolute RVEF) in 15 of 18 patients, but only 5 of 10 patients were abnormal during O2 administration. LVEF at rest was normal in all subjects. These data suggest: 1) RV exercise ejection fraction is abnormal in most patients with chronic pulmonary disease; 2) while low flow O2 does not alter RV performance at rest, it improves RV exercise ejection fraction in some patients.

Evaluation of transbronchial biopsy of the lung.

Transbronchial biopsy of the lung through the fiberoptic bronchoscope is becoming a widely utilized clinical diagnostic technic. The authors reviewed the histologic features of 109 consecutive cases. The primary problem is the small size of the pulmonary tissue samples obtained, which is further compounded by an apparent mechanical inability to enter the biopsy forceps into dense nodules of neoplastic tissue. The diagnosis of carcinoma can best be made by examining the periphery of the cancer for microscopic extension into adjacent pulmonary parenchyma; however, multiple levels of the tissue block are needed to find such foci. A second problem reflects the use of transbronchial biopsy in the early clinical evolution of various infectious diseases in which pulmonary tissue may contain organisms without a fully developed inflammatory response, which would ordinarily provide the clue to the infective agent. The latter problem appears in cases of infections by Pneumocystis carinii. Close cooperation between the clinician and the pathologist is particularly important in all of these clinical situations.

Pulmonary coccidioidal pseudomycetoma.

Coccidiomycosis is rarely associated with a pulmonary mycetoma. We report a patient with progressive cavitary coccidiomycosis, whose initial radiographic and clinical appearance simulated a mycetoma. Examination of the surgically resected lung showed necrotizing Coccidioides immitis granulomas with spherules and arthroconidialike structures, but no evidence of a mycetoma. We propose the term pulmonary coccidioidal pseudomycetoma as the best descriptor for this patient's clinical, radiographic, pathologic, and microbiologic presentation.

Epidermal growth factor receptor up-regulation is associated with lung growth after lobectomy.

BACKGROUND: We hypothesized that compensatory lung growth after lobectomy is characterized by a combination of cellular hyperplasia and hypertrophy and that up-regulation of epidermal growth factor receptor (EGFR) is involved in these processes. METHODS: Age-matched mature pigs were divided into four groups. The control group (group C) did not have operation. Two groups underwent left upper lobectomy and were studied 2 weeks (group L2) or 3 months (group L3) later. The last group underwent a sham left thoracotomy, and the left lower lobe was harvested 2 weeks later for EGFR analysis. Left lower lobes were studied using wet weight, cell proliferation index through immunostaining for 5-bromo-2'-deoxyuridine, morphometry, and Western blot analysis for EGFR. Content of protein and DNA (deoxyribonucleic acid) in the lung tissue was also determined. RESULTS: Left lower lobe weights were elevated in both groups L2 and L3 compared with group C. We noted a significant rise in the proliferation index, with a concomitant increase in EGFR expression, in group L2 compared with group C. In group L3, there was an increase in the protein to DNA ratio compared with group C. CONCLUSIONS: We conclude that compensatory lung growth after lobectomy comprises an early increase in the cell proliferation index (ie, cellular hyperplasia) and a late increase in the protein to DNA ratio (ie, cellular hypertrophy). The early proliferative phase is associated with EGFR up-regulation.

The value of preliminary traction in the treatment of congenital dislocation of the hip.

In forty-one children who had forty-seven congenitally dislocated hips, the results of attempted closed reduction with general anesthesia, but without preliminary traction, were studied. Twenty (43 per cent) of the hips could not be reduced closed, and an open reduction was needed. After the reduction, all of the involved hips were immobilized in the so-called human position (marked flexion and slight abduction). At a minimum follow-up of two years, osteonecrosis of the femoral head had developed in only two hips (4 per cent). Patients who were more than one year old when the hip was reduced had a higher incidence of osteonecrosis of the femoral head and were more likely to need reconstructive procedures later. Patients who were more than eighteen months old at the time of the attempted closed reduction were more likely to need an open reduction of the hip. Treatment of congenital dislocation of the hip in young children remains an extremely complex problem. It has not been clearly established that the use of preliminary traction decreases the incidence of osteonecrosis of the femoral head or improves the outcome of treatment. In our experience, uncomplicated (non-teratological, postnatal) congenital dislocation of the hip has been safely treated with either open or closed reduction without preliminary traction in patients who were younger than two years old, provided that the reduction could be obtained without excessive force.

A comparison of manual versus computer-assisted radiographic measurement. Intraobserver measurement variability for Cobb angles.

STUDY DESIGN: A comparison between computer-assisted measurement using digitized radiographs, which has the potential to reduce error, and manual measurement using standard radiographs. OBJECTIVE: To assess measurement variability for the Cobb method on digital radiographs and compare it with that of manual measurements on standard radiographs. BACKGROUND DATA: Studies of the Cobb method have demonstrated multiple sources of error leading to significant intraobserver measurement variability. Estimates for the 95% confidence interval for intraobserver variability range from 2.8 degrees to 10 degrees. METHODS: Twenty-four scoliosis radiographs were measured by six examiners. Two measurement sets were done manually ("manual set"), and two measurement sets were done on digitized images using a computer mouse ("computer set"). RESULTS: For the manual set, the 95% confidence interval for intraobserver variability was 3.3 degrees (range, 2.5-4.5 degrees). For the computer set, the value was 2.6 degrees (range, 2.3-3.3 degrees). This difference in 95% confidence intervals between the manual and computer sets was statistically significant (P < 0.001). CONCLUSIONS: The results of this study demonstrate that intraobserver variability for manual and computer Cobb angle measurements yield a 95% confidence interval of approximately 3 degrees, with the computer having a slightly lower variability. The computer technique removes sources of intrinsic error, e.g., the variability introduced by using different manual protractors, the inaccuracy of standard protractors, and the use of wide-diameter radiographic markers. Identical digital images can be shared electronically between centers, without having to duplicate and mail films. Multicenter studies in which different examiners will be measuring Cobb angles may consider using the computer as a measuring device to reduce intrinsic measurement errors.

A long-term review of shelf arthroplasty.

Shelf arthroplasty is briefly reviewed in historical perspective and the results in 45 hips (39 patients) which had undergone this procedure at the Royal Children's Hospital are presented. The majority of these patients were adolescents who had previously been treated for congenital dislocation or subluxation of the hip. The indications for operation and the operative technique are discussed. Clinical examination was carried out upon 33 of the 39 patients at an average of 11 years after operation. The results suggested that where pain had been an indication for operation almost 80 percent of the hips remained relatively free of symptoms at the time of follow-up and in those patients where acetabular dysplasia had been an indication, the coverage remained good and pain had not appeared. It is concluded that the shelf operation is useful for dealing with both pain and dysplasia in the adolescent.

Closed reduction and percutaneous pinning of displaced supracondylar humerus fractures in children: description of a new closed reduction technique for fractures with brachialis muscle entrapment.

A retrospective review of 43 displaced extension-type supracondylar humerus fractures in children was performed. Thirty-four fractures were completely displaced (type III). Ninety-one percent (39 of 43) of the fractures were managed by immediate closed reduction and percutaneous pinning. Ten type III fractures exhibited clinical or radiographic evidence of brachialis muscle penetration. A closed reduction maneuver designed to "milk" the entrapped brachialis muscle off of the proximal fracture spike was developed and was successful in all eight cases in which it was attempted. At mean follow-up of 35 months, 97% (38 of 39 patients) achieved a good or excellent result based on the Flynn grading scale.

Coxa vara: another option for fixation.

Coxa vara is a progressive childhood deformity that is best remedied by a valgus intertrochanteric osteotomy. By restoring the femoral neck and its physis to a more anatomic position, hip mechanics are normalized, with consequent beneficial effects upon hip motion, limb lengths and acetabular development. In the pediatric age group, there is no implant specifically designed for this purpose. Therefore, in addition to the challenge of obtaining adequate correction, inadequate fixation may contribute to recurrent varus deformity, a problem that, according to the literature, has a 30% to 70% prevalence. We are presenting a new technique using a modified veterinary plate for osteosynthesis in children in the 5-year-old to 11-year-old age group. The rationale, implant design, surgical technique and results in a group of nine patients (12 hips) are described.

Studies on the disposition of a 5-nitroimidazole in laboratory animals.

The disposition and metabolism of a 5-nitroimidazole compound (SC 28538) was investigated in the rat, beagle dog and rhesus monkey. The absorption of [14C]-SC 28538 was rapid and essentially complete after oral dosage in male animals, and also after intravaginal dosage in the female rat. Peak plasma levels of radioactivity occurred within 2 h of dosage. In the rat and dog the radioactivity was excreted predominantly in the faeces (greater than 60%) but in the monkey more than 60% was excreted in the urine. In both the male and pregnant female rat radioactivity was concentrated in the gastro-intestinal tract, liver and harderian gland and the concentrations of radioactivity in other tissues was generally lower than in plasma. Radioactivity was cleared more rapidly from plasma than from the majority of tissues. SC 28538 was extensively metabolised to form glucuronide and amino acid conjugates. The half-life of SC 28538 was of the order of 1 h in the dog and 3.7 h in the monkey.

Plasma levels and urinary excretion of orally administered propantheline bromide in man.

After a single oral dose of 30 or 60 mg of propantheline bromide peak plasma levels of the drug were reached within 2 h in six healthy men. Mean peak plasma concentrations were 20.6 and 53.1 ng/ml after 30 mg and 60 mg respectively. The mean apparent absorption and elimination half-lives after 30 mg dose were 0.22 and 1.57 h respectively, and similar half-lives were found at the higher dose level. There was a dose related change in plasma levels and AUCinfinity of the drug, and some 3% to 4% of the administered dose of propantheline bromide was excreted unchanged in urine at each dose level. Comparison of the plasma levels and urinary excretion of the drug with those seen after i.v. administration in an earlier study indicated an apparently low systemic availability of orally administered propantheline bromide. There was tentative evidence of a qualitative relationship between the oral dose administered, plasma concentrations and the effects of propantheline bromide on salivary excretion.

Radiographic distortion of bones: a marker study.

The osseous shadows observed on radiographs are distorted by parallax and magnification error. Parallax may be minimized by proper centering of the subject; magnification error is governed by the subject-to-cassette and exposure distances. The usual assumption that radiographic magnification is 15% is, therefore, erroneous and misleading. A triangular marker was used to assess radiographic distortion of bones on films exposed at "standard" distances of 40 and 72 inches, varying the subject-to-cassette distance to simulate the effect of positioning problems posed by body habitus or joint contracture. Osseous magnification ranged from 6% to 36% on the 40-in exposures and from 3% to 17.5% at 72 in. Using a mid-sagittal marker, true bone size can be more closely determined; once the magnification is known, linear measurements can be normalized for accuracy, permitting valid comparison of quantitative data. Preoperative planning of reconstructive procedures, including implant sizing with templates, is greatly facilitated.

L plate fixation for osteotomies.

It is generally acknowledged that stable fixation of osteotomies offers certain benefits, including maintenance of predictable alignment, while permitting rapid mobilization and rehabilitation. A variety of implants are available which require technical proficiency and familiarity by the surgeon for successful implantation. The ability to customize implants before or during surgery allows the surgeon critical control in a variety of situations. An L plate, which is a pre-bent dynamic compression plate (DCP), applied as a tension band with interfragmentary screws serves this purpose well.

Guided growth for correction of knee flexion deformity: a series of four cases.

Fixed knee flexion deformity can present as an insidious and significant problem in diverse etiologies, most commonly in cerebral palsy. Traditional surgical intervention has included posterior capsulotomy and supracondylar femoral osteotomy, both of which carry significant associated morbidity and risks. In the skeletally immature patient, guided growth may be used to correct or substantially diminish the deformity. We are presenting our early experience encompassing four subjects who completed instrumented gait analysis both prior to and after distal femoral anterior guided growth (hemiepiphysiodesis). Changes in gait and function resulting from surgery in each individual are reported. Outcomes indicate improved knee range of motion and alleviation of crouch at the knee with secondary improvements in the ankle, hip and pelvis. Three subjects with initially slow gait velocity improved to within normal limits by demonstrating increased stride length. A measure of overall gait kinematics showed improvements in all limbs. Anterior guided growth (hemiepiphysiodesis) of the distal femur resulted in positive quantitative changes in all four patients, though degree and types of changes were variable in this small series. Encouraged by these findings, we now prefer guided growth to extension supracondylar osteotomy for the skeletally immature patient with fixed knee flexion deformity.