Choledochoscopic stone removal through a T-tube tract: experience in 75 consecutive patients

Retained biliary stones remain a common clinical problem in patients after surgery. Since 1984, the authors have used choledochoscopy in the treatment of suspected retained biliary stones in 75 patients. These procedures were performed in the radiology department with use of local anesthesia supplemented by an intravenously administered sedative and analgesic. A 15-F flexible fiberoptic choledochoscope was used. Fifty-one of the 75 patients were treated as outpatients. Treatment was successful in 74 of 75 patients; in one patient, intrahepatic stones were not completely removed. Electrohydraulic lithotripsy was used to fragment calculi in 11 patients (15%). Biopsies were performed in four patients (5%). Five minor complications occurred; three required overnight admission. Choledochoscopic-assisted removal of retained biliary calculi is a highly effective and safe procedure. Advantages over standard fluoroscopic stone removal include the ability to directly visualize and fragment adherent or impacted stones and visualize noncalculous filling defects, such as air bubbles, mucus, and biliary tumors.     

Managing self-injection difficulties in patients with relapsing-remitting multiple sclerosis.

Difficulties with self-injection, including inabillity to self-inject, are common for individuals taking home-administered injectable medications. In relapsing-remitting multiple sclerosis (MS), all of the currently available disease-modifying medications are injectables marketed for self-injection. Problems with self-injection pose a barrier to treatment adherence for many patients. Clinicians at the University of California, San Francisco (UCSF) Multiple Sclerosis Center have developed a number of strategies to help patients who experience anxiety associated with self-injection. These strategies have been empirically tested and found to be effective and easily implemented by mental health professionals and nurses. This article offers case examples and discussion of the principles of the techniques developed at UCSF to remediate patients' difficulties with self-injection. Nurses are most often the healthcare providers responsible for training MS patients in self-injection and monitoring their compliance. Nurses who are familiar with these tools have the opportunity to have a significant positive impact on patient comfort, confidence, and, ultimately, successful long-term adherence to disease-modifying medications.     

Identification of T cell epitopes within a 23-kD antigen (P24) of Toxoplasma gondii.

Among the potentially vaccinating antigens, the products excreted/secreted by the parasite T. gondii have been demonstrated to be excellent candidates. The molecular cloning of one of these antigens (P24) present in excreted/secreted antigens (ESA) has recently been carried out in our laboratory. The recombinant antigen P24 corresponds to a native molecule of 23 kD. We were interested in determining the main epitopes of the P24 antigen eliciting a T lymphocyte response using synthetic peptides derived from the primary structure of P24. Five peptides: 64-79, 88-109, 170-193, 194-208 and 231-250 were synthesized according to their hydrophobicity, mobility and accessibility profiles. The presence of T lymphocyte epitopes in these peptides has been examined in the rat model. The determination of T cell epitopes was carried out using T lymphocytes from infected rats, and from ESA and P24 expression vaccine virus immunized rats. The results showed that the stimulation of T cells with these peptides varied according to the period after Toxoplasma infection. The main T cell stimulation was obtained with the 88-109, 170-193 and 194-208 peptides. When Fisher rats were immunized with ESA, a most significant stimulation was achieved with the 170-193 and 194-208 peptides. In addition, T lymphocytes primed with P24 expressed vaccine virus immunization were more stimulated with the 88-109 and the 194-208 peptides. This study showed that P24-derived peptide-specific T cells were elicited in the three experimental situations, although no antibody response against the 23-kD native antigen was evidenced in the Fisher rat model. However, the native antigen (presented by irradiated parasites) can induce a proliferative response of the 170-193 peptide-specific T lymphocytes, confirming that this peptide contains an important T cell epitope. The adoptive transfer into athymic rats of T helper cells recovered from 170-193 peptide-immunized Fisher rat conferred a significant protection to infected nude rats despite the fact that no antibody production was observed.     

Patients' recollections of therapeutic paralysis in the intensive care unit.

BACKGROUND: Neuromuscular blocking agents used for therapeutic purposes, such as facilitating mechanical ventilation and relieving life-threatening agitation, paralyze patients but leave them fully conscious. Aggressive sedation or analgesia is necessary to reduce awareness, relieve fear, produce comfort, decrease anxiety, induce unconsciousness, and minimize possible complications such as posttraumatic stress syndrome. Little information is available on the extent to which patients experience awareness during therapeutic paralysis. OBJECTIVES: To determine and describe the remembered experiences of critical care patients who were given neuromuscular blocking agents and sedatives and/or analgesics to facilitate mechanical ventilation, improve hemodynamic stability, and improve oxygenation. METHODS: A phenomenological approach with in-depth interviews with 11 patients was used. Data were analyzed by using the constant comparative approach. RESULTS: A total of 4 themes and 3 subthemes were identified. The first theme was back and forth between reality and the unreal, between life and death; the subtheme was having weird dreams. The second theme was loss of control; the 2 subthemes were (1) fighting or being tied down and (2) being scared. The third theme was almost dying, and the fourth theme was feeling cared for. CONCLUSIONS: Patients can remember having both negative and positive experiences during neuromuscular blockade. Steps to improve the experiences of patients receiving neuromuscular blockers include improving assessment parameters, developing and using sedation/analgesia guidelines, and investing in quality improvement programs to provide assessment of awareness during therapeutic paralysis and follow-up and referral as necessary. Ways to decrease the use of neuromuscular blockers would also be useful.     

Structure of an autoimmune T cell receptor complexed with class II peptide-MHC: insights into MHC bias and antigen specificity

T cell receptor crossreactivity with different peptide ligands and biased recognition of MHC are coupled features of antigen recognition that are necessary for the T cell's diverse functional repertoire. In the crystal structure between an autoreactive, EAE T cell clone 172.10 and myelin basic protein (1-11) presented by class II MHC I-Au, recognition of the MHC is dominated by the Vbeta domain of the TCR, which interacts with the MHC alpha chain in a manner suggestive of a germline-encoded TCR/MHC "anchor point." Strikingly, there are few specific contacts between the TCR CDR3 loops and the MBP peptide. We also find that over 1,000,000 different peptides derived from combinatorial libraries can activate 172.10, yet the TCR strongly prefers the native MBP contact residues. We suggest that while TCR scanning of pMHC may be degenerate due to the TCR germline bias for MHC, recognition of structurally distinct agonist peptides is not indicative of TCR promiscuity, but rather highly specific alternative solutions to TCR engagement.     

Anti-P30 IgA antibodies as prenatal markers of congenital toxoplasma infection

This study extends a previous study and confirms that the detection of anti-P30 IgA antibodies is very helpful in the diagnosis of acute acquired or congenital toxoplasmosis. Moreover, we demonstrate that an anti-P30 IgA response can be mounted in the fetuses infected by Toxoplasma gondii during their intra-uterine life as early as week 23 of gestation. A double-sandwich ELISA described in our previous work was used to detect anti-P30 IgA antibodies in 1378 human serum samples collected from 551 patients, including 162 fetuses whose mothers had been infected by T. gondii during pregnancy, 46 congenitally infected and 90 uninfected newborns and 253 women suspected of having been infected during pregnancy, including the mothers of fetuses and newborns previously described. Anti-P30 IgA antibodies were detected in all cases of acute toxoplasmosis but in no case of chronic toxoplasmosis: in the majority of cases, the IgA antibody titre fell below cut-off in 3-9 months. Among the 46 congenitally infected newborns, anti-P30 IgA antibodies were detected in sera of 41 infected newborns (38 at birth, two in the first months of life, one in the seventh month of life), while anti-P30 IgM antibodies were detected in only 30 cases at birth and in one case during the first month of life. Among 162 fetuses, anti-P30 IgA response was observed in five infected fetuses, but was not detected in either 152 uninfected fetuses or in five fetuses considered as infected. The absence or presence of anti-P30 IgA antibodies in the fetus is discussed in relation to the date of maternal infection and collection of the fetal blood. It clearly appears from our study that the combined testing of both IgM and IgA in the fetus and the newborn is essential for a more efficient diagnosis of infection.