Splanchnic transplantation. An approach to the infant dependent on parenteral nutrition who develops irreversible liver disease.

Two infants with short-bowel syndrome and liver failure associated with obligatory parenteral nutrition received a composite allograft that consisted of en bloc liver, stomach, duodenum, pancreas, jejunum, and ileum. Solutions to the fatal complications in the first case resulted in a functioning composite splanchnic system in the second case. Despite a number of early complications, the small intestine and liver developed near-normal function until a monoclonal, malignant, B-cell lymphoproliferative disorder appeared. The analysis of these two cases supports three summary observations: the operative procedure can be safely performed in a metabolically compromised infant; intestinal allograft rejection, in this model, is controllable with existing immunosuppressive drugs; and this procedure appears to be associated with a uniquely high incidence of lymphoma. Since transplantation is a feasible solution to this devastating infantile disease, further development of this therapy must incorporate means of preventing lymphoma.

Bilateral trephine bone marrow biopsy for staging non-Hodgkin's lymphoma--a second look.

Several reports have suggested that bilateral bone marrow biopsy is better than unilateral biopsy in staging non-Hodgkin's lymphomas. Therefore since 1975, bilateral iliac crest bone marrow biopsy has been part of our standard initial staging investigation of non-Hodgkin's lymphomas. The present study is to determine the relative value of bilateral marrow biopsy compared to the unilateral procedure. We studied 176 patients who had evaluable adequate bilateral biopsies and tumor histology. Among 57 patients with low-grade lymphoma, 7 (12%) were unilaterally positive for lymphoma and 25 (44%) were bilaterally positive. Among 119 patients with intermediate and high-grade lymphoma, 6 biopsies (5%) were unilaterally positive and 10 (8%) were bilaterally positive for lymphoma. Doing the second (contralateral) biopsy changed the disease stage as assessed by bone marrow biopsy in 6.1% of patients with favorable histologies and in 2.5% of patients with unfavorable histologies. These changes are small. Moreover, treatment would not have been significantly altered in the majority of patients as a result of the changes. We conclude that the routine use of bilateral trephine biopsy in initial staging of non-Hodgkin's lymphomas needs to be reappraised. We believe that its use should be limited to selected patients in whom the finding of bone marrow involvement may influence the choice of treatment.

Cat scratch disease. Identification of bacteria in seven cases of lymphadenitis.

A retrospective study of lymph node biopsy specimens from nine patients with the clinical findings and histologic features of cat scratch disease was undertaken to determine whether the recent report by Wear et al. that pleomorphic bacteria are present in the lymph nodes of cat scratch disease could be confirmed. In seven of our nine cases, pleomorphic bacteria were demonstrated with the Warthin-Starry (WS) silver stain. These were gram-negative with the Brown-Hopps tissue Gram stain and were almost at the limit of microscopic resolution. Lymph node specimens from 13 additional patients with nonspecific lymphadenitis who had neither clinical nor histologic findings of cat scratch disease were studied similarly; in none of these were bacteria demonstrated with the WS silver stain. After examining the distribution of the organisms and the related morphologic features in cat scratch disease, we conclude that demonstration of pleomorphic, gram-negative, WS-positive bacteria in the appropriate clinical and histologic setting can firmly establish the diagnosis of cat scratch disease.

Red cell comets: ultrastructure of axial elongation of the membrane skeleton.

In order to study intact red cell membrane skeletons, we developed two methods for the electron microscopic study of stress-ruptured and partially opened glutaraldehyde pre-fixed Triton shells of red cell ghosts. Both methods showed continuous networks of fine filaments decorated and apparently crosslinked by elongated particles. Our electron micrographs show a filamentous component that is morphologically consistent with F-actin. Quantitative considerations, including the dimensions of the elongated particles and published estimates of the number of particles in situ, suggest that compact spectrin decamers or dodecamers may exist in intact red cells. Long filaments consistent with F-actin appear to be decorated with the putative spectrin particles.

Burkitt cell acute lymphoblastic leukemia with partial expression of T-cell markers and subclonal chromosome abnormalities in a man with acquired immunodeficiency syndrome.

A 45-year-old white male, bisexual, with a 2-year history of acquired immunodeficiency syndrome (AIDS) prodrome, developed a Burkitt cell-like acute lymphoblastic leukemia (ALL). Marker studies of marrow blasts show an unusual and possibly unique pattern, in that an unequivocal monoclonal B cell leukemia, having K-IgM with HLA-DR and B cell subset antigen (BA-1) expression, was superimposed with a mature suppressor T cell marker profile (pan-T, mature T, and suppressor/cytotoxic T antigens). The leukemic blasts were totally negative for terminal deoxynucleotidyl transferase (TdT), human T cell leukemia-lymphoma virus (HTLV) p19 antigen, and other immunoglobulin isotypes. Chromosome analysis of marrow cells disclosed that 70% of the cells had 47,XY, + 12,t(8;14)(q24;q32) chromosome complement, and 30% of the cells had a 47,XY, + 12,dup1q + (q22-31),t(8;14)(q24;q32). The consistent finding of the specific chromosome rearrangement (8/14 translocation) in all abnormal cells suggests that the cells were derived from a common precursor. With regard to the partial T cell marker expression, the significance of these markers in B cell leukemia is unclear, as is their relation to the additional chromosome abnormalities that apparently developed in the process of clonal evolution.

Congenital central hypoventilation syndrome: a pathologic study of the neuromuscular system.

An infant with congenital central hypoventilation was managed by bilateral phrenic nerve pacing for 3 months. He died at 8 months of age, following 19 days of continuous bilateral pacing necessitated by the eventual loss of voluntary as well as autonomic ventilatory control. The phrenic nerves showed axonal dystrophy at the site of electrode implantation and more severe distal degeneration. Focal neurogenic atrophy was seen in the diaphragmatic muscle. These changes were attributed to electrical injury resulting from the period of continuous pacing. The most significant neuropathologic finding was a mild generalized decrease in the density of neurons and myelinated nerve fibers in the respiratory centers of the medulla. These morphologic abnormalities were attributed to a sublethal intrauterine lesion that would be the first example of a morphologic correlation with the functional abnormality in congenital central hypoventilation.

Central hypoventilation syndrome: experience with bilateral phrenic nerve pacing in 3 neonates.

Successful long-term phrenic nerve pacing has been reported in adults with acquired central hypoventilation syndrome. This report summarizes our experience with phrenic nerve pacing in 3 infants with congenital central hypoventilation syndrome. The electrodes were implanted in the lower thoracic portion of each phrenic nerve. In all patients. bilateral simultaneous pacing was required to maintain an adequate arterial PO2, tidal volume, and minute ventilation during quiet sleep. Case 1 died of problems primarily related to the severe cor pulmonale that had been present before pacemaker insertion; at autopsy, the pacemaker system was intact and there were no significant phrenic nerve abnormalities. Case 2 later developed failure of awake ventilatory control and died because of extensive phrenic nerve damage incurred by 19 days of continuous pacing. Case 3 has received quiet sleep pacemaker support since September 1977 and has been able to maintain normal quiet sleep ventilation in this manner. Phrenic nerve pacing can be successful in infants as long as continuous pacing is not required. Bilateral simultaneous pacing appears to be an appropriate alternative to home-based intermittent positive-pressure breathing for long-term management of children with central hypoventilation syndrome.