The range and specificity of antinuclear antibodies in systematic lupus erythematosus

Antibodies to nine calf thymus nuclear antigens were sought by complement fixation methods in twenty-four sera from sixteen patients with systemic lupus erythematosus. These antigens included whole nuclei, native and heat denatured DNA, particulate and soluble nucleoprotein and Sm antigen. Soluble antigens were also tested by tanned red-cell agglutination tests. A wide variation in the presence and titres of antibodies to these various antigens was found in the sera studied even when from the same patient but at different times. To further test the range and specificity of antinuclear antibodies in SLE, nineteen ribonucleosides, nucleotides and monophosphoric dinucleotides were coupled to human serum albumin and used as antigens in precipitin studies. A wide variation of reactivity was also found in each serum. Exquisite specificity became apparent, capable of reacting with a nucleoside but not with the corresponding nucleotide or vice versa, with a dinucleotide but not with the nucleotides or nucleosides which it contained, with a given dinucleotide but not with the opposite sequence.

Antinuclear antibodies in systemic lupus are, therefore, markedly heterogeneous. Those to a `single' antigen such as DNA may be directed to antigenic sites which may variously be at the bases, single or in sequence, at the site of union of base and sugar–phosphate moiety, at the backbone of deoxyribophosphate or actually dependent on the secondary structure.

     

Early and frequent histological recurrence of Crohn's disease in small intestinal allografts

BACKGROUND: Recurrence of Crohn's disease in small intestinal allografts, although rarely described, can cause serious morbidity and jeopardize graft survival among transplant recipients with Crohn's disease. However, systematic studies to determine the frequency, predictors, and clinical implications of recurrent Crohn's disease have not been reported METHODS: We analyzed our transplant program's experience with small intestinal allografts in patients with Crohn's disease based on retrospective review of clinical and pathological records and corresponding pathology slides. RESULTS: Of 67 patients undergoing 70 transplantations between 1998 and 2004, six adults (three males, three females; mean age 48.1 years) had Crohn's disease complicated by short gut syndrome and total parenteral nutrition failure. Four survivors surveyed endoscopically for a mean 29 (range, 20-40) months and underwent a mean 37 endoscopic examinations with biopsies (range, 31-44) while on maintenance immunosuppression. Despite absence of any endoscopic or clinical manifestations of Crohn's disease throughout this period, two patients had granulomatous enteritis characteristic of Crohn's disease in multiple biopsies, one patient in 8/44 examinations (18%) ranging from 34 days to 20 months postoperatively and the other in 6/32 examinations (19%) ranging from 20 days to 22 months postoperatively. No comparable changes occurred in 57 other patients without Crohn's disease followed endoscopically under the same protocol CONCLUSIONS: Histological recurrence of Crohn's disease may occur in small intestinal allografts despite the absence of endoscopic and clinical disease manifestations. Such recurrences are probably not rare, may occur as early as 3 weeks after transplantation, and do not necessarily portend early clinical recurrence or mandate aggressive therapy to prevent allograft loss.     

Orthotopic small bowel transplantation in mice

On the basis of our experience with rat small bowel transplantation (SBT), we established a model of orthotopic SBT in mice. The immediate success rate was approximately 50%. Indefinite survival was obtained in the syngeneic group. The effect of different immunosuppressive treatments was also investigated: mean survival was 10.2+/-1.2 days in untreated mice receiving allogeneic grafts, 14.2+/-1.6 days with cyclosporine, 24+/-5.1 days in the rapamycin group, and 73.6+/-29.1 days with tacrolimus-treated animals. From this study, we conclude that although the model is technically difficult, it may provide an excellent tool to further investigate the physiology and immunology of small-intestinal transplantation.     

Management of a small bowel transplant with complicated central venous access in a patient with asymptomatic superior and inferior vena cava obstruction

During the past few years, small bowel transplantation (SBT) has become a realistic alternative for patients with irreversible intestinal failure who have or will develop severe complications from total parenteral nutrition (TPN). Transplantation can be associated with large fluid shifts and massive blood loss necessitating rapid infusions of large quantities of crystalloid and/or blood products. Invasive monitoring and large-bore venous access are necessary in order to manage these patients intraoperatively. Because patients with irreversible intestinal failure are often managed with total parenteral nutrition via a central venous catheter, thrombotic intraluminal obstruction of major vessels may develop over time. Additionally, this may lead to superior vena cava (SVC) syndrome as well as challenging problems with vascular access. We present a 34-year-old woman with a past medical history for long-standing Crohn's disease with multiple small bowel resections and short gut syndrome who presented for an SBT. The patient had a long history of TPN use, complicated by SVC syndrome and inferior vena cava (IVC) obstruction. She was presently asymptomatic from her SVC obstruction. Central venous access was obtained by an interventional radiologist. A 7-French double-lumen Hickman minicatheter was placed in the left femoral vein with the tip of the catheter positioned just distal to the IVC narrowing. A left radial 20-gauge arterial line was placed for hemodynamic monitoring and frequent blood sampling. The patient's left and right dorsal-saphenous veins were cannulated with 16-guage catheters and adequate flow was observed. Lower extremity pressure was measured via the Hickman catheter in the left femoral vein. A multiplane transesophageal echo was used to assess ventricular volume. The options and intraoperative management of such patients are discussed.     

Multiple sources of dietary calcium-some aspects of its essentiality

The increasing recognition of the important role of calcium in the myriad regulation of cellular processes in the health and well being throughout one's lifetime has focused on the need to ensure a sufficiency of its intake for nutritional, physiological, and medical reasons. Additionally, the recognition of the dynamic dietary changes and preferences of various populations in terms of their consumption of calcium-containing products coupled with large variations of food patterns and availability of calcium, highlights the need to consider and evaluate multiple sources of calcium (dairy, non-dairy, fortified foods, and supplemental). Aspects of the essentiality of calcium are thus considered via an initial consideration of: the salient aspects of absorption and bioavailability, changes in individual and societal dietary habits and preferences and the evaluation of various RDAs, AIs, and DRIs for calcium.