Parainfluenza Virus Infection in Adult Lung Transplant Recipients: An Emergent Clinical Syndrome with Implications on Allograft Function

Parainfluenza virus is a common cause of seasonal upper respiratory tract infections in children and adults. Studies indicate that parainfluenza virus may play an important role in the etiology of respiratory tract infections in lung transplant recipients with an estimated incidence of 5.3 per 100 patients. Parainfluenza virus type 3 is the most frequent serotype in lung transplant patients. The rate of lower respiratory tract infections with parainfluenza virus among lung transplant recipients is between 10 and 66% of cases. In addition, trans-bronchial biopsy at the time of parainfluenza infection shows signs of acute allograft rejection. Subsequently, 32% of patients have been found to have active bronchiolitis obliterans at a median time of 6 months (range 1-14) postviral infection. These findings indicate that parainfluenza virus infections may have long-term implications for lung transplant recipients. Further studies are required to identify the mechanisms of immunomodulation of parainfluenza virus among these patients. In addition, controlled studies are needed to evaluate the efficacy of aerosolized ribavarin in the treatment of parainfluenza virus infection and to determine whether vaccines may be effective in these high-risk patients.     

Diagnosis of arylsulfatase A deficiency in intact cultured cells using a fluorescent derivative of cerebroside sulfate

A fluorescent derivative of cerebroside sulfate (12-(1-pyrene)dodecanoyl-sphingosylgalactosyl-0-3-sulfate (P12-sulfatide) has been synthesized as a potential substrate for the determination of cerebroside sulfatidase (or arylsulfatase A) activity. It was administered into cultured human skin fibroblasts and thereby utilized for the diagnosis of arylsulfatase A deficiency. Cultured skin fibroblasts from normal individuals and healthy persons suffering from a pseudoarylsulfatase A deficiency (PD) degraded the P12-sulfatide, while in cells derived from a metachromatic leukodystrophy (MLD) patient it remained essentially intact. This contrasts with in vitro determinations of enzymatic activity, where the MLD or PD-derived arylsulfatase A exhibit similar deficiency, in spite of a profoundly different clinical course. Administration of the fluorescent sulfatide into the intact cells permitted a sensitive and rapid diagnosis of MLD and its distinction from the PD-phenomenon. This might be of particular importance for cases in which a rapid diagnosis is required and for prenatal diagnosis of fetuses from families afflicted with both MLD and pseudo-deficiency mutant genes.     

Neu-Laxova syndrome: Prenatal ultrasonographic diagnosis,clinical and pathological studies,and new manifestations

A diagnosis of the Neu-Laxova syndrome (NLS) was made by ultrasonography at 32 wks of gestation. Ultrasonographic examination showed intrauterine growth retardation (IUGR), Dandy-Walker anomaly, choroid plexus cysts, receding forehead and microcephaly, bilateral cataract without prominent eyes, scalp edema with no generalized edema, retrognathia, curved penis, and flexion deformities of limbs. The findings in this case are consistent with NLS; however, they did not fit any of Curry's [1982] groups. Massive swelling of hands and feet were among the main manifestations in classic NLS cases. In the case presented herein, edema was noted only in the scalp. This might shed further light on the question of variability vs. heterogeneity in the NLS. This case shows the existing possibility of an early diagnosis of NLS and adds Dandy-Walker anomaly and choroid plexus cysts as new findings to this syndrome. © 1992 Wiley-Liss, Inc.     

Therapeutic Effect of Doxycycline in Experimental Subclinical Canine Monocytic Ehrlichiosis: Evaluation of a 6-Week Course

The efficacy of doxycycline treatment (10 mg/kg of body weight every 24 h for 42 days) in eliminating Ehrlichia canis from four subclinically infected dogs was evaluated. One dog remained PCR positive, suggesting that 6 weeks of doxycycline treatment may not be sufficient to clear E. canis parasites from all subclinically infected dogs. Serology (indirect immunofluorescent antibody assay) was shown to be unreliable in assessing recovery from the carrier state, as anti-E. canis antibodies persisted after elimination of the parasite. Our findings suggest that an increase in the platelet count may be an important indicator for dogs that recover from subclinical ehrlichiosis.     

Amplification of Ehrlichial DNA from Dogs 34 Months after Infection with Ehrlichia canis

In order to determine whether dogs in the subclinical phase of canine monocytic ehrlichiosis (CME) are carriers of Ehrlichia canis and to determine the significance of persistent indirect immunofluorescent anti-E. canis antibody titers during this phase, PCR was performed with blood, bone marrow, and splenic aspirates collected 34 months postinoculation from six clinically healthy beagle dogs experimentally infected with E. canis. At least one of the three samples (spleen, bone marrow, and blood) from four of the six dogs was PCR positive. The spleens of all four of these dogs were PCR positive, and the bone marrow and blood of two of the four dogs were PCR positive. Indirect immunofluorescent-antibody titers increased progressively during the first 5 months postinfection, remained high for an additional period of more than 11 months, and declined thereafter, suggesting that the dogs were recovering from the disease. Five of the dogs remained seropositive 34 months postinfection. The data obtained in this study demonstrate for the first time that clinically healthy dogs in the subclinical phase of CME are carriers of the rickettsia. It was shown that dogs can harbor E. canis for years without developing the chronic clinical disease and that dogs can eliminate the parasite and recover from CME without medical treatment. Our findings suggest that the spleen is the organ most likely to harbor E. canis parasites during the subclinical phase and the last organ to accommodate the parasite before elimination. It was concluded that PCR of DNA extracted from splenic aspirates is a reliable method for determining the carrier state of CME.     

Transplantation of hematopoietic stem cells for induction of unresponsiveness to organ allografts

Although it has been recognized since the early days of Owen and Medawar that engraftment of donor stem cells, induced in utero spontaneously or intentionally neonatally, results in life-long unresponsiveness to donor alloantigens. However, successful induction of transplantation tolerance in adult life still represents an unsolved problem. Engraftment of donor stem cells using conventional modalities involves intensive myeloablative or lymphoablative immunosuppression, which is associated with toxicity and mortality and such methods are not suitable for organ allograft recipients. In this chapter, we present an innovative approach for induction of donor-specific unresponsiveness to bone marrow and organ allografts without myeloablative conditioning. Our methods is based on cyclophosphamide-induced, alloantigen-primed lymphocyte depletion. Cyclophosphamide is administered 1 day following infusion of donor hematopoietic cells, thus eliminating predominantly host T lymphocytes reacting against donor cell challenge, and resulting in relative unresponsiveness to donor alloantigens. Subsequently, life-long tolerance to fully mismatched donor skin allografts can be accomplished by a second infusion of stem cells from the same donor, with donor T cells displacing residual alloreactive host cells that may have escaped deletion. Taken together, we believe that induction of true permanent and specific tolerance to organ allografts using donor hematopoietic cells could become a clinical reality in the foreseeable future.     

Permanent Cardiac Pacing in Octogenarians

A significant percentage of patients in need of a permanent pacemaker are older than 80 years. The implantation policy may be determined either by the patient's physical activity or by chronologic age. The trend in pacemaker implantation in patients over 80 during the last 10 years in our institution was evaluated and compared with the trend in the patients younger than 80 at the time of implantation. Of 519 patients who had primary pacemaker implantation, 152 (29%) were older than 80 at the time of the procedure. Another 189 patients had second implantation procedures, and 80% of them were older than 80 years. Complete atrioventricular block was the indication for pacing in 44 ?+/- 11% and sick sinus syndrome in 25 ?+/- 7%. The tendency to implant dual-chamber pacemakers increased from 0% during 1985 to 76% in 1994, including 69% DDD and 31% DDDR, but the transition was faster in the younger group. By 1994, there was no difference in the incidence of advanced pacing systems in the 2 age groups. During 1985, only VVI pacemakers were replaced, and during 1994, less than 10% were replaced with simple ventricular pacing units. Pacing system upgrading was frequent during the second half of the decade. The success and complication rate of implantation did not differ in the 2 groups.     

Multivariate Analysis of Left Ventricular Mass Determinants in Adults: Different Patterns in Men and Women

Echocardiographic left ventricular mass (LVM) estimates are strong predictors of subsequent mortality and cardiovascular events. It is known that blood pressure (BP), weight (WT), and age are significantly correlated with LVM. We hypothesized that stroke volume (SV) measured by Doppler echocardiography would also be correlated with LVM. Two hundred and thirteen patients referred for routine echocardiography had determination of LVM, cuff BP, and Doppler SV. Those with localized LV disease, valvular disease, or cor pulmonale were excluded. In both men and women, systolic BP (SBP) was more closely correlated with LVM than was diastolic blood pressure or mean arterial pressure, and SV was more closely correlated with LVM than cardiac output or cardiac index. Stepwise regression, followed by multiple regression showed that four variables (WT, SV, SBP, and AGE) explained 32.3% of the variability in LVM in men and 48.5% of the variability in LVM in women. WT and SV were significant determinants of LVM in both men and women. Age was also significant in men and SBP was also significant in women. For both men and women, SV was more significantly correlated with LVM than was SBP. The changes in LVM associated with 1 SD increments of SV and SBP, respectively, were 8 and 5 g for men and 13 and 11 g for women. We conclude that men and women have different patterns of variables influencing LVM. Doppler echocardiographic SV is a newly described determinant of LVM that has a greater correlation with LVM than does SBP. This study reemphasizes the importance of WT as the major determinant of LVM. (ECHOCARDIOGRAPHY, Volume 13, January 1996)