Scleral fibroblasts. Human leukocyte antigen expression and complement production

The authors investigated the ability of recombinant human gamma-interferon (rhIFN-gamma) to influence production of complement and expression of human leukocyte antigens (HLA) by human scleral fibroblasts in culture. Cell cultures were established by explanting sclera from normal human donor eyes. To study complement production, fibroblasts were treated with 500 units/ml rhIFN-gamma in cell culture, and media were tested for complement components by hemolytic assay after 0, 1, 3, 6, 9, and 11 days. To induce Class II HLAs, fibroblasts were exposed to rhIFN-gamma at concentrations ranging from 10-500 units/ml and incubated for 1, 3, and 6 days. The HLAs were detected by immunofluorescence in conjunction with flow cytometry. Class I antigen was detected using a monoclonal antibody directed against beta 2-microglobulin. Class II histocompatibility antigens were identified using monoclonal antibodies specific for HLA-DR, -DP, and -DQ. Although complement component C1 was produced constitutively in cell culture, the addition of rhIFN-gamma resulted in an increase in production. Complement components C2 and C4 were detected only after treatment with rhIFN-gamma. Complement production was completely inhibited by cycloheximide, and C3, C5, C6, and C7 were not present in cell culture media with or without rhIFN-gamma. Class I antigen was present on all cells before induction, and an increase in expression was noted after exposure to rhIFN-gamma. Class II antigens were absent before induction with rhIFN-gamma. After treatment with rhIFN-gamma, scleral fibroblasts expressed HLA-DR, -DP, and -DQ in a dose-dependent, time-related fashion. These findings suggest that rhIFN-gamma has multiple effects on scleral fibroblasts: (1) increased production of C1, (2) production of C2 and C4, (3) up-regulation of Class I antigen expression, and (4) expression of Class II antigens. They also suggest that scleral fibroblasts have the potential to participate in immunologic diseases of the eye.     

Is There an Advantage to Repairing Infected Mitral Valves?

Background. The therapy for native mitral valve endocarditis is in evolution. Antibiotics have significantly improved survival rates, but patients with complications of endocarditis may require surgical treatment.

Methods. Between January 1985 and December 1995, 146 patients underwent surgical therapy (repair or replacement) for native mitral valve endocarditis. All patients had documented bacterial endocarditis. Univariate and multivariate analyses were performed to determine predictors of hospital death, long-term event-free survival, and probability of repair. Patients were evaluated in three groups: all patients, patients with acute endocarditis, and patients with chronic endocarditis.

Results. There were ten hospital deaths (6.8%). Patients undergoing repair had a lower hospital mortality rate (p = 0.008) then those having replacement. Event-free survival was improved after mitral valve repair in the overall group (p = 0.02) and in the group with healed (chronic) endocarditis (p = 0.05). Although the acute endocarditis group demonstrated an improved event-free survival rate after mitral valve repair versus replacement (74% versus 20% at 6 years), this did not reach statistical significance.

Conclusions. We conclude that mitral valve repair is preferable to mitral valve replacement when possible, in patients with complications of endocarditis, as repair results in a lower hospital mortality and an improved long-term survival.     

Intestinal permeability after single dose gluten challenge in coeliac disease.

The changes of intestinal permeability before and after a gluten load were studied. The study group comprised 27 patients with coeliac disease (mean age 12.3 years) and 19 healthy controls matched by sex and age. Intestinal permeability was studied by measuring the urinary excretion of two sugars, lactulose and L-rhamnose, before and six hours after the ingestion of five palatable biscuits made with 50 g of gluten powder. The patients with coeliac disease had been on a gluten free diet during the previous two years. After the gluten load lactulose and L-rhamnose urinary excretion changed significantly in patients, and a significant increase in the lactulose: L-rhamnose ratio was also observed. No significant changes were observed in the controls. In view of the modification of the three biopsies diagnostic protocol made by the European Society for Paediatric Gastroenterology and Nutrition, permeability tests associated with single gluten challenges may be an added contribution to the accuracy of the diagnosis in childhood.     

The mentored clinical casebook project at Harvard Medical School.

An excellent physician must be aware of the countless issues that affect each patient's health. Many medical education programs expose students to a broad spectrum of disparate knowledge and hope they will integrate all the pieces into a coherent whole. The authors describe an explicit approach to integration used at Harvard Medical School since 2003 that aims to enhance students' learning in medical school and throughout their medical careers: the Mentored Clinical Casebook Project (MCCP). The MCCP is constructed on the premise that such integration does not occur suddenly but, rather, is an unending process. A first-year student is assigned to one clinician and follows one patient for one year. The student is expected to spend as much time with the patient as possible, in both clinical and nonclinical settings, seek help from the clinician, and consult other experts and sources to develop a complete picture of the patient's life. The student must produce a casebook that includes, but is not limited to, the patient's history; basic science, clinical, socioeconomic, and cultural issues; and self-reflection. The MCCP is intended to allow students to develop a deeper and more diverse understanding of what comprises a patient's health care life, to discern the patient as a person and the person as a patient. This educational project has been popular with students since its inception, providing them with a personal framework from which to address the needs of future patients and introducing them to how much they will continue to learn from their patients.     

Increased numbers of interleukin-12-producing cells in human tuberculosis.

Numbers of interleukin-12 (IL-12) producing cells were quantitated in the peripheral blood of healthy donors and tuberculosis patients by the ELISPOT assay. We observed that (i) stimulation with mycobacteria increases numbers of IL-12 producers from healthy donors and (ii) tuberculosis patients have larger numbers of IL-12 producers than healthy donors. Our data emphasize the importance of Il-12 in immunity to tuberculosis.     

Living related liver transplantation. Progress or regress?

The impetus for the devolopment of living related liver programmes lies with donor shortage, which relates inversely to the success of generating cadaveric donors. A shrinking or non-existent cadaveric donor pool leads to an increased death rate among potential recipients awaiting transplantation. The living related liver programmes have by and large been successful, though it is accepted that there is potentially a significant risk to the donors. The technique of live donor liver transplantation is clearly here to stay, but the selection of suitable donors is between the family and the unit. Consequently, because of the lack of international guidelines, the programmes are open to abuse. Steps should be taken to establish either mechanisms of control or a worldwide register to combat this potential.     

Measurement of post-operative pain and narcotic administration in infants using a new clinical scoring system

We developed a clinical neurologic and behavioral scoring system composed of 10 items to measure the post-operative pain levels in infants: (1) sleep during preceeding hour, (2) facial expression of pain, (3) quality of cry, (4) spontaneous motor activity, (5) Spontaneous excitability, (6) flexion of fingers and toes, (7) sucking, (8) global evaluation of tone, (9) consolability and (10) sociability. Using this system, a group of infants ranging from one to seven months in age and undergoing minor surgical procedures was studied. The infants were randomly assigned to two groups: Group I received Fentanyl intravenously (3 g/kg) prior to surgery, and Group II received a placebo. The infants then were studied post-operatively in the recovery room at 30, 60, 90 and 120 min intervals. Over the entire post-operative observation period, 54% of the infants in Group I had satisfactory analgesia compared to 18% in Group II. There were no significant differences in Group I and Group II in oxygenation, carbon dioxide elimination, blood pressure, heart rate or temperature.