Pulmonary capillaritis and hemorrhage. A clue to the diagnosis of systemic necrotizing vasculitis.

Patients with systemic necrotizing vasculitis frequently present as diagnostic dilemmas. In previous series of patients with polyarteritis nodosa, less than one third were diagnosed antemortem. Although current clinical awareness of systemic necrotizing vasculitis is greater than in the past and procedures for the diagnosis of these diseases have improved, patients commonly present with atypical features. The diagnosis of a systemic necrotizing vasculitis frequently remains unsuspected or unproven until an involved tissue is biopsied. We report an unusual case of systemic necrotizing vasculitis in which the diagnosis was confirmed by a transbronchial biopsy of the lung which demonstrated pulmonary capillaritis with hemorrhage.

Fat embolism, ARDS, coma, death: the four horsemen of the fractured hip.

The pathophysiology of fat embolism syndrome (FES) is presented in the context of total joint arthroplasty. The current literature is reviewed with recommendations for surgical technique, anesthetic and pulmonary management. Diagnosis is quite difficult but can be established by imaging techniques such as MRI, SPECT, and transcranial Doppler sonography. Early steroid treatment may limit morbidity.

Central airway obstruction due to cytomegalovirus-induced necrotizing tracheitis in a patient with AIDS.

Cytomegalovirus (CMV) infection in patients with the acquired immunodeficiency syndrome (AIDS) can present as either disseminated disease, pneumonitis, retinitis, gastroenteritis, neuropathy, or a subclinical infection. We report a patient whose initial manifestation of CMV infection was severe central airways obstruction due to necrotizing tracheitis. At bronchoscopy, the lesion appeared deeply ulcerated, distinctly different from previously described airway lesions in patients with AIDS. Mucosal biopsies showed characteristic intranuclear and intracytoplasmic inclusions and cultures yielded only CMV. The patient responded partially to ganciclovir, steroids, and antibiotics against suspected anaerobic superinfection but died as a result of central nervous system disease believed due to toxoplasmosis or lymphoma. CMV infection of the upper airway should be considered in the patient with AIDS presenting with atypical cough or stridor and ulcerated endobronchial lesions.

Kidney function in heart-lung transplant recipients: the effect of low-dosage cyclosporine therapy.

The indices of kidney function of all discharged heart-lung transplant survivors were examined before and after the introduction of a triple-drug immunosuppressive regimen comprised of low dosages of cyclosporine (to maintain a trough serum level of 75 to 100 ng/ml by radioimmunoassay), azathioprine (1 to 1.5 mg/kg/day), and prednisone. A comparison of survivors treated with either high dosages of cyclosporine (n = 19) or low dosages of cyclosporine (n = 8) revealed a lower early creatinine level postoperatively (1.84 versus 0.96 mg/dl), a higher creatinine clearance (46.33 versus 62.47 ml/min), and a lower cyclosporine level (337.96 versus 204.30 ng/ml) in the latter group. The findings from the outpatient period were similar to the above, and all findings were statistically significant (p less than or equal to 0.05). Another comparison of a subgroup of survivors (n = 11) before and after conversion to the low dosage cyclosporine triple-drug regimen demonstrated no significant difference in kidney function for nine patients and equivocal evidence of improvement in the other two patients for creatinine levels and creatinine clearance. Overall, despite the lower cyclosporine dosage used, we have not encountered an increased prevalence of acute heart or lung rejection. We conclude that early implementation of low dosages of cyclosporine, as part of a triple-drug immunosuppression regimen, is associated with preservation of kidney function while maintaining adequate immunosuppression. Patients with chronic azotemia from long-term cyclosporine therapy may still reap some benefit from this regimen.

The role of right ventricular endomyocardial biopsy in the long-term management of heart-lung transplant recipients.

Right ventricular endomyocardial biopsy remains the gold standard for the diagnosis of acute rejection of the heart allograft. Surveillance right ventricular endomyocardial biopsies are performed routinely at 3-month intervals in heart-lung transplant patients with uncomplicated conditions who have long-term follow-up. Recent observations of asynchronous heart and lung rejection, plus the impression that acute rejection was a rare phenomenon in long-term heart-lung transplant survivors, led us to analyze our experience with this technique to determine its clinical role. During the first 6 years of the heart-lung transplantation program at Stanford University Medical Center, only one episode of moderate acute rejection has occurred at greater than 4 months after heart-lung transplantation, despite greater than 160 surveillance right ventricular endomyocardial biopsies. This was in a patient who was recovering from a viral illness and had a subtherapeutic cyclosporine level of 38 ng/ml (as measured by radioimmunoassay). Fourteen patients (40%) have never had acute rejection, but freedom from acute rejection did not correlate with freedom from obliterative bronchiolitis or concentric coronary artery intimal hyperplasia. We conclude that in the long-term management phase (greater than 6 months after heart-lung transplantation), right ventricular endomyocardial biopsy should be performed for specific indications, rather than as a surveillance procedure.

The distribution of MHC class I and II antigens on bronchial epithelium.

The distribution and degree of expression of Class I and Class II major histocompatibility (MHC) antigens on human lower respiratory tract epithelium were evaluated in five freshly obtained pneumonectomy and lobectomy specimens using an immunoperoxidase technique. Multiple sites were examined from each specimen, and two independent observers graded each sample as positive, equivocal, or negative compared with control slides. Interobserver agreement was high. From a total of 120 grade determinations, 114 showed complete concordance and only one showed a positive/negative discordance. Both Class I (HLA-A,B,C) and Class II (HLA-DR) antigens were uniformly and strongly expressed throughout the major, lobar, and segmental bronchi of each sample, the bronchiolar epithelium, and the alveolar epithelium. Paired samples of adjacent lower respiratory tract epithelium harvested with the fiberoptic bronchoscope and during pathologic examination, respectively, revealed an identical staining pattern for these antigens. Staining for HLA-DQ expression (a subset of MHC Class II antigens) was generally weaker and appeared more variable, with four negative, six equivocal, and 30 positive samples. Our observations demonstrate the widespread expression of Class I antigens on airway epithelium and reveal for the first time the ubiquitous nature of Class II MHC antigen (HLA-DR) expression throughout the lower respiratory tract. Furthermore, they attest to the adequacy of bronchoscopically obtained samples for immunologic staining. These results provide a basis for both a putative mechanism of bronchocentric rejection phenomena after human heart-lung transplantation and for the means to monitor it prospectively.