Failure to induce organ-specific autoimmunity by breaking of tolerance: importance of the microenvironment

Peripheral tolerance is considered to be a safeguard against autoimmunity. Using a TCR-transgenic mouse system displaying peripheral tolerance against a liver-specific MHC class I Kb antigen, we investigated whether the breaking of tolerance would result in autoimmunity. Reversal of tolerance was achieved by simultaneous challenge with cells expressing the Kb autoantigen and IL-2. Tolerance could not be broken with IL-2 alone or when Kb- and IL-2-expressing cells were applied to different sites of the mice. However, despite the presence of activated autoreactive T cells that were able to reject Kb-positive grafts no autoaggression against the Kb-positive liver was observed. These results indicate that breaking of tolerance per se is not sufficient to cause liver-specific autoimmunity. However, when in addition to breaking tolerance the mice were infected with a liver-specific pathogen, autoaggression occurred. Thus, in this system at least two independent steps seem to be required for organ-specific autoimmunity: reversal of peripheral tolerance resulting in functional activation of autoreactive T cells and conditioning of the liver microenvironment which enables the activated T cells to cause tissue damage.     

Organization of direct hippocampal efferent projections to the cerebral cortex of the rhesus monkey: projections from CA1, prosubiculum, and subiculum to the temporal lobe

This study investigates direct hippocampal efferent projections to the temporal lobe of the rhesus monkey. Tritiated amino acid injections were placed into the hippocampal formation to identify terminal fields, and complementary fluorescent retrograde tracer injections were placed into the cortex to identify the cells of origin. Tritiated amino acid injections into CA1, prosubicular, or subicular subfields produced anterograde label over parts of the parahippocampal gyrus and temporal pole. Injections of fluorescent retrograde tracers demonstrated that these projections originate from longitudinal strips of neurons that occupy part of the CA1 subfield as well as from strips of neurons in adjacent prosubicular and subicular subfields. Thus, an injection into area TH of the posterior parahippocampal gyrus labeled neurons in a longitudinal strip of proximal CA1 (i.e., near CA2) as well as a strip in the subiculum; injections into areas TF, TL, 35, or Pro labeled neurons in a longitudinal strip of distal CA1 (i.e., near the prosubiculum) as well as one in the prosubiculum; and an injection into area TFO labeled neurons in a longitudinal strip in the middle of CA1. These strips of neurons extended longitudinally throughout the entire rostrocaudal length of the hippocampus. These results demonstrate that, in the monkey, CA1 projections to cortex arise topographically from longitudinally oriented strips of neurons that occupy only a part of the transverse extent of CA1 but that cover most of the anteroposterior extent of the hippocampus. Thus, in the monkey, CA1 is not a single uniform entity and may have a unique role as a source of direct hippocampal projections to the cerebral cortex.     

Amalgam vs. composite resin: 1998

PURPOSE: The aim of this study was to compare the incidence of surgical complications between two different surgical techniques for intestinal anastomosis in children. METHODS: This was a clinically controlled, randomized study with blind follow-up from 18 to 36 months performed at the Reference Government Hospital in Mexico City. Eighty-six children required intestinal anastomosis, ages ranged between 1 month and 16 years, with emergency or elective surgery. Anastomoses of duodenum, rectum, with enteroplasty or protected with a proximal stoma were excluded. Two randomized groups were formed: (1) anastomosis with one layer of suture (Gambee stitches) and (2) with two layers of suture (first with Connel-Mayo stitches then with Lembert). Both groups were controlled in the principal variables without differences, and the follow-up concerning postoperative recovery was blind for the surgical team. RESULTS: Forty-two cases in group 1 and 44 in group 2 were compared. Intestinal dehiscence was found in 5 of 86 (5.8%), two from group I and three from group II (P value, not significant). Surgical time for anastomosis with one layer was an average of 26 minutes versus 43 minutes with two layers (P<.001). There were no stenoses within the follow-up period. CONCLUSIONS: This study proves that intestinal anastomosis with one layer of suture is as safe as anastomosis with two layers in children, and the time spent for completion of the procedure is significantly less with one plane of suture. For those reasons, it is the method of choice for intestinal anastomosis in children.     

Validity of a self-completed questionnaire measuring the physical demands of work

The aim of this study was to compare the results of open retropubic (OC) and laparoscopic (LC) colposuspension to the Cooper's ligament (Burch operation). We matched retrospectively 72 LC and OC according to their ages, the type of associated operations and the clinical stages of their urinary incontinence. We excluded associated prolapsus, previous surgical procedure for urinary incontinence, maximal urethral closure pressure lower than 30 cms of water and instability of the detrusor. We estimated the comparability of our two series about the other criteria which have an effect upon the post operative results in literature. The mean follow up was 17 months for LC and 46 months for OC. LC operative time was longer than (Mean: LC: 89 minutes, OC: 42 minutes), women considered LC less aching than OC. They needed less postoperative analgesia, mostly given only just the day of the procedure. LC length of hospitalization and return to normal activity was shorter than OC (Mean: LC: 3 days--OC: 6, 7 days; LC: 15 days--OC: 21 days). The graphs of the subjective cure and improvement rates made according to the Kaplan-Meier method could be compared with the log rank test. (Cure after one year: LC 79%, OC 69%--Improvement after one year: LC 85%, OC 82%--Cure after two years: LC 68%--OC 64%--Improvement after two years: LC 80%--OC 75%).     

Management considerations for treating vesicoureteral reflux in children with solitary kidneys

OBJECTIVES: To evaluate the management approach for vesicoureteral reflux (reflux) into a solitary kidney. METHODS: Outcomes of all children with solitary kidneys and reflux managed between 1981 and 1996 were reviewed. Solitary kidneys were documented by nuclear renography and ultrasonography; reflux was graded after cystography. Management consisted of observation and antimicrobial prophylaxis or surgery by ureteroneocystostomy or subureteric injection of polytetrafluoroethylene (STING). Follow-up ranged from 3 months to 14 years and included serial cystography, sonography, and serum creatinine measurement. RESULTS: Twenty-one patients with a median follow-up of 26 months were identified. Etiologies included contralateral renal agenesis (14 children), multicystic dysplastic kidney (5 children), or nonfunctioning ureteropelvic junction obstruction (2 children). Low-grade (I to II) reflux was identified in 6 children, and high grade (III to V) was identified in 15. Reflux resolved in 20 patients. Five children with low-grade reflux were managed without surgery and demonstrated reflux resolution after a mean of 20.5 months. Renal function deteriorated in only 1 child. Ureteroneocystostomy was performed in 13 children with grades III to V reflux, and STING was performed in 1 child with grade II reflux. Every surgical patient maintained stable renal function and was infection-free during a mean follow-up of 56 months. Management by observation in 2 children with grades IV to V reflux resulted in spontaneous resolution in one and stable grade IV in the other. CONCLUSIONS: Reflux into the solitary functioning kidney may be managed by the same strategies used to manage unilateral reflux in children with two normally functioning kidneys: low-grade reflux by observation/ chemoprophylaxis until spontaneous resolution occurs, and higher grades by surgery to protect renal function; however, chemoprophylaxis and serial imaging may be used until well-defined indications for surgery are satisfied. Renal function should be monitored diligently.     

Cyclic, low-dose total body irradiation for metastatic neuroblastoma

Total body irradiation (TBI) can be thought of as a systemic anticancer agent. It therefore might best be given like an adjuvant drug, i.e. in tolerable doses, cyclically. The therapeutic ration between normal bone marrow stem cells and suitably sensitive cancer cells should be widened by these means. Fourteen children with advanced (State IV) neuroblastomas were given 100-150 rad TBI in 50 rad daily fractions along with each three-week cycle of standard triple-agent chemotherapy, (vincristine, DTIC, cyclophosphamide). Two patients died of toxicity and one is still undergoing therapy. Four of the remaining 12 survive free of disease for 12+ to 31+ months. The regimen is well tolerated, but prolonged, pronounced bone marrow depression, especially thrombocytopenia, comonly occurs after doses of 300-450 rad.