Lung transplantation for cystic fibrosis: current concepts and one center's experience.

BACKGROUND: Although new approaches to the treatment of patients with cystic fibrosis (CF) are significantly prolonging their lives, most patients will eventually develop respiratory failure due to progressive bronchiectasis caused by chronic lung infection and inflammation and die from to respiratory failure. We examined our center's (University of Wisconsin Hospital and Clinics) experience with lung transplantation for patients with CF and reviewed the literature to examine current and evolving approaches to transplantation for this indication. METHODS: We reviewed all published literature pertaining to lung transplantation for CF through 2006, and we reviewed all aspects of transplantation for patients with CF at our institution from 1994 to 2005. RESULTS: Major complications following lung transplantation include acute rejection, bacterial infection, and bronchiolitis obliterans. Five-year survival at UWHC (Kaplan-Meier) is 67%, and survival was not adversely affected by transplanting patients receiving mechanical ventilation. The major cause of death for transplant recipients was bronchiolitis obliterans syndrome (BOS). CONCLUSIONS: Lung transplantation for CF is associated with acceptable survival rates and can improve quality of life. Lung transplant should be offered to all patients with advanced CF lung disease if they meet currently accepted inclusion and exclusion criteria.

Rationalizing endpoints for prospective studies of pulmonary exacerbation treatment response in cystic fibrosis.

BACKGROUND: Given the variability in pulmonary exacerbation (PEx) management within and between Cystic Fibrosis (CF) Care Centers, it is possible that some approaches may be superior to others. A challenge with comparing different PEx management approaches is lack of a community consensus with respect to treatment-response metrics. In this analysis, we assess the feasibility of using different response metrics in prospective randomized studies comparing PEx treatment protocols. METHODS: Response parameters were compiled from the recent STOP (Standardized Treatment of PEx) feasibility study. Pulmonary function responses (recovery of best prior 6-month and 12-month FEV1% predicted and absolute and relative FEV1% predicted improvement from treatment initiation) and sign and symptom recovery from treatment initiation (measured by the Chronic Respiratory Infection Symptom Score [CRISS]) were studied as categorical and continuous variables. The proportion of patients retreated within 30days after the end of initial treatment was studied as a categorical variable. Sample sizes required to adequately power prospective 1:1 randomized superiority and non-inferiority studies employing candidate endpoints were explored. RESULTS: The most sensitive endpoint was mean change in CRISS from treatment initiation, followed by mean absolute FEV1% predicted change from initiation, with the two responses only modestly correlated (R2=.157; P<0.0001). Recovery of previous best FEV1 was a problematic endpoint due to missing data and a substantial proportion of patients beginning PEx treatment with FEV1 exceeding their previous best measures (12.1% >12-month best, 19.6% >6-month best). Although mean outcome measures deteriorated approximately 2-weeks post-treatment follow-up, the effect was non-uniform: 62.7% of patients experienced an FEV1 worsening versus 49.0% who experienced a CRISS worsening. CONCLUSIONS: Results from randomized prospective superiority and non-inferiority studies employing mean CRISS and FEV1 change from treatment initiation should prove compelling to the community. They will need to be large, but appear feasible.

Long-term treatment with oral N-acetylcysteine: affects lung function but not sputum inflammation in cystic fibrosis subjects. A phase II randomized placebo-controlled trial.

PURPOSE: To evaluate the effects of oral N-acetylcysteine (NAC), which replenishes systemic glutathione, on decreasing inflammation and improving lung function in CF airways. METHODS: A multicenter, randomized, double-blind proof of concept study in which 70 CF subjects received NAC or placebo orally thrice daily for 24 weeks. ENDPOINTS: primary, change in sputum human neutrophil elastase (HNE) activity; secondary, FEV(1) and other clinical lung function measures; and safety, the safety and tolerability of NAC and the potential of NAC to promote pulmonary hypertension in subjects with CF. RESULTS: Lung function (FEV(1) and FEF(25-75%)) remained stable or increased slightly in the NAC group but decreased in the placebo group (p=0.02 and 0.02). Log(10) HNE activity remained equal between cohorts (difference 0.21, 95% CI -0.07 to 0.48, p=0.14). CONCLUSIONS: NAC recipients maintained their lung function while placebo recipients declined (24 week FEV1 treatment effect=150 mL, p<0.02). However no effect on HNE activity and other selected biomarkers of neutrophilic inflammation were detected. Further studies on mechanism and clinical outcomes are warranted.

Some aspects of the automation of perimetry.

Manual perimetry has certain inherent limitations stemming from both the patient and the examiner. Automated perimetry, if properly developed, can offer the advantages of exact reproducibility of the examination strategy, accuracy achieved through averaging of repeated determinations, and systematic application of previous data to the current examination. The history, concepts and clinical practically of automated perimetry are discussed. Several systems capable of performing functions resembling human intellectual activity are commerically available; one, the OctopusTM, is described in detail.

Renin producing Wilms' tumor.

A 4-yr-old boy with Wilms' tumor, hypertension, and hyperreninemia is presented. Three times as much renin was extracted from tumor tissue as from adjacent renal parenchyma, suggesting that the tumor itself was the primary source of the renin and cause of the hypertension. Other reported cases of hypertension and increased renin production with Wilms' tumor are reviewed. Hypertension is a very frequent finding in patients presenting with Wilms' tumor. The possibility that many of these neoplasms may be found to hypersecrete renin if properly investigated is discussed.

Pulmonary cytopathology of an invasive thymoma.

The cytopathology of an invasive thymoma that penetrated the bronchus is presented. As is typical of these neoplasms histologically, both epithelial cells (thymocytes) and lymphocytes were seen cytologically. However, the benign appearance of the thymocytes precluded a neoplastic diagnosis initially. Only with the knowledge that an anterior mediastinal mass is present roentgenographically can this diagnosis be safely made cytologically.

Cytopathologic findings in pulmonary blastoma.

The exfoliative cytologic description of a pulmonary blastoma is reported. The debated histogenesis of these tumors is briefly reviewed. A review of all case reports recording cytopathology findings indicates that these rare tumors yield diagnostic cells in only a minority of cases. In the present case, as in previous reports, only the epithelial component (carcinoma) was recognized prior to the histopathologic diagnosis. The stromal cells were less numerous and not as conspicuous as the epithelial cells. The diagnosis of pulmonary blastoma should be considered whenever nonsquamous carcinomatous cells plus a separate population of smaller malignant cells are seen in a pulmonary cytology specimen.

Preleukemic granulocytic sarcoma of cervix and vagina: initial manifestation by cytology.

Granulocytic sarcoma is an unusual form of tumefaction caused by acute granulocytic leukemia. On rare occasions, the lesion precedes the leukemic phase and presents as a mass with a normal peripheral white cell count. This report describes the initial manifestation of granulocytic sarcoma by vaginal cytology in a 39-year-old female with Down's syndrome. Six days after admission, the patient died of acute peritonitis following spontaneous perforation of the bowel. Autopsy revealed involvement of cervix, vagina, bowel wall and one pelvic lymph node by granulocytic sarcoma. Bone marrow examination confirmed the preleukemic stage of the disease. Cytologically, the malignant cells occurred singly. No nucleoli were seen. The differential diagnosis between malignant lymphoma and granulocytic sarcoma rests upon a positive naphtol AS-D chloroacetate esterase stain in granulocytic sarcoma. This stain may be performed on paraffin-embedded sections or on smears.

Evaluating the protective capacity of two-post ROPS for a seat-belted occupant during a farm tractor overturn.

This study evaluated the effectiveness of a commercial rollover protective structure (ROPS) and size-extended ROPS in protecting a 95th percentile male operator during tractor overturns. Six rear upset tests (commercial ROPS) and ten side upset tests (commercial and size-extended ROPS) were conducted. A 95th percentile instrumented male manikin was used in all tests. Head injury criterion (HIC15), 80 g limit on resultant head acceleration, neck injury criterion (Nij), and peak axial force (extension-compression) were employed to evaluate injury potential. In all rear tests, the manikin's head impact with the ground was within the tolerance limits for head/neck injuries. Based on limited trials in the side tests, the study observed a small to moderate chance of neck injuries under the commercial and size-extended ROPS conditions; the injury risk was not statistically significant between these two test conditions. This study identified a risk of non-fatal injuries for large-size operators in side overturns, although the prevention effectiveness of commercial versus size-extended ROPS cannot be determined without further testing. These findings may have implications for future ROPS designs.

[Advances in the automation of perimetry (author's transl)]. / Fortschritte in der Automatisierung der Perimetrie

The most important improvements and innovations since 1973 in the automatic perimeter Octopus are described. On the one hand, they include instrumental modifications, namely spatial separation of the perimeter from its control panel, the introduction of step motors in order to increase the accuracy of setting of the stimulus coordinates, the tilting of the perimeter cupola and patient in order to increase stability and comfort of the latter, a fully automated fixation control system, the use of a magnetic-tape recording system, providing analytical programs for the computer and recording computer-answers at the same time. On the other hand, progress has been made in the optimisation of threshold determination methods in the visual field and in the design of methods for the graphical display of the sensitivity distribution across the visual field.

Static perimetry: strategies.

In static perimetry the method of limits is widely used for threshold determinations. Its performance is compared with that of a certain modification of the staircase method (repetitive up and down) by means of simulations, where the behaviour of the observer is described by an assumed psychometric function. Systematic and random errors are considerably smaller with the up and down method. Further consideration is given to signal detection theory and to the concept of optimal strategy.

Static perimetry: accuracy and fluctuations.

Threshold fluctuations are divided into short-term and long-term effects applying statistical methods. Sixteen normal and pathological visual fields were analysed in order to obtain values for the short-term, long-term and total fluctuations. Special attention is paid to fortuitous variations between the results obtained at successive examinations. Finally the concept of spatial correlations is introduced.

[Practical experiences with the Octopus automatic perimeter (author's transl)]. / Praktische Erfahrungen mit dem automatischen Perimeter Octopus.

A statistical analysis comparing the results of more than 1000 visual field examinations carried out with the automatic perimeter Octopus and with a conventional Goldman-perimeter, clearly demonstrates the superiority of the automatic instrument in many respects: Apart from a higher precision of the perimetric measurements (smaller fluctuations), a better reproducibility of the results (larger correlation coefficients) is noticed. Due to great ease of operation of the automatic perimeter, the ophthalmologist is discharged from the time-consuming task of perimetric examinations.

Experience with Gleason's histopathologic grading in prostatic cancer.

The inaccuracy of clinical staging as a predictor of the biologic potential of prostatic cancer has prompted evaluation of additional methods of assessment. We reviewed 228 patients with prostatic adenocarcinoma who presented during a 4-year period. Of the 228 patients 144 with no detectable bony disease underwent staging pelvic lymphadenectomy with or without preliminary bilateral pedal lymphangiography. Histopathologic specimens of the primary diagnostic prostatic biopsy were classified with Gleason's grading system of tumor differentiation. Of the patients with Gleason's sum of 8, 9 or 10, 93 per cent had regional nodal metastases, regardless of preliminary clinical stage. Furthermore, no patient with Gleason's sum of 2, 3 or 4 had nodal metastatic disease. The incidences of falsely positive and falsely negative lymphangiograms were 29 and 35 per cent, respectively, reflecting the unreliability of pedal lymphangiography to predict nodal involvement accurately in patients with prostatic cancer. The Gleason system of histopathologic grading was reliable and reproducible, and afforded an accurate prediction of the surgical stage of disease.

IgE myeloma with osteoblastic lesions.

A 69-yr-old man with persistent anemia had multiple myeloma with an IgE-type kappa M component and Bence Jones proteinuria. Bone x-rays revealed occasional lytic lesions associated with a diffuse sclerotic reaction throughout the skeleton. Special bone histologic studies utilizing tetracycline labeling, undercalcified sections, and microradiography confirmed active osteoblastic activity. This case was compared with the four previously reported cases of IgE myeloma, one of which also had osteosclerosis.