Interleukin-2 treatment potentiates induction of oral tolerance in a murine model of autoimmunity.

The present study addresses the feasibility of potentiating oral tolerance by immunomanipulation, using the murine model of experimental autoimmune uveoretinitis (EAU) induced by immunization with the retinal antigen interphotoreceptor retinoid binding protein (IRBP). Three feedings of 0.2 mg IRBP every other day before immunization did not protect against EAU, whereas a similar regimen of five doses was protective. However, supplementing the nonprotective 3x regimen with as little as one injection of 1,000 U of human recombinant interleukin-2 (IL-2) resulted in disease suppression that was equal to that of the protective 5x regimen. The protective effect was maintained across a range of IL-2 doses and times of administration; none of the IL-2 regimens tested resulted in disease enhancement. Peyer's Patch cells of 3x-fed and IL-2-treated mice showed greatly increased production of TGF-beta, IL-4, and IL-10 compared with animals given the nonprotective 3x regimen and to animals given the protective 5x regimen. We propose that IL-2 treatment enhances protection from EAU at least in part by stimulating production of antiinflammatory cytokines by regulatory cells in Payer's Patches. Moreover, the observed lymphokine production patterns suggest that whereas protection induced by the 3x + IL-2 regimen is likely to involve antiinflammatory cytokines, protection induced by the 5x regimen might involve anergy or deletion of the uveitogenic T cells. These results could have practical implications for use of IL-2 as a safe and effective way of potentiating oral tolerance.     

Spontaneous cerebrospinal rhinorrhea. Etiology--differential diagnosis--therapy

CSF rhinorrhea is called spontaneous if it is due neither to a trauma, nor an intracranial tumour or a congenital malformation. Spontaneous CSF rhinorrhea is extremely rare: the fistula is usually found in the roof of the ethmoid sinus, less often in the walls of the sphenoid sinus. There is a striking prevalence of female patients. We describe a female patient who showed spontaneous CSF rhinorrhea from a leak in the anterior roof of the sphenoid sinus. The possible aetiology, diagnostic measures and therapy are discussed. Areas of reduced resistance in the anterior skull base may be congenital, or may be acquired due to later focal atrophy. The diagnosis of CSF rhinorrhea can be established by the glucose test, isotope scanning, immunoelectrophoresis and fluorescence endoscopy. The most reliable methods of distinguishing between a traumatic or neoplastic lesion and a spontaneous CSF rhinorrhea are high-resolution computed tomography (CT) and magnetic resonance tomography. High-resolution CT is also the best method for localization of the bony defect. Elevated intracranial pressure must be ruled out carefully. The treatment of choice is closure of the fistula, preferably by the nasal surgeon, using either the endonasal-transseptal, the endonasal-transethmoidal or the paranasal-transethmoidal approach in order to preserve olfaction and to avoid the risk of a frontal lobe lesion which is a complication of the neurosurgical approach. Interposition of a fascial or dural graft is considered to be an important technical detail for achieving a secure closure of the fistula; packing can be avoided by additional sealing of the patch with fibrinogen glue.     

Adult-to-adult living donor liver transplantation using extended right lobe grafts.

OBJECTIVE: The authors report their experience with living donor liver transplantation (LDLT) using extended right lobe grafts for adult patients under high-urgency situations. SUMMARY BACKGROUND DATA: The efficacy of LDLT in the treatment of children has been established. The major limitation of adult-to-adult LDLT is the adequacy of the graft size. A left lobe graft from a relatively small volunteer donor will not meet the metabolic demand of a larger recipient. METHODS: From May 1996 to November 1996, seven LDLTs, using extended right lobe grafts, were performed under high-urgency situations. All recipients were in intensive care units before transplantation with five having acute renal failure, three on mechanical ventilation, and all with hepatic encephalopathy. The median body weight for the donors and recipients was 58 kg (range, 41-84 kg) and 65 kg (range, 53-90 kg), respectively. The body weights of four donors were less than those of the corresponding recipients, and the lowest donor-to-recipient body weight ratio was 0.62:1. The extended right lobe graft was chosen because the left lobe volume was <40% of the ideal liver mass of the recipient. RESULTS: Median blood loss for the donors was 900 mL (range, 700-1600 mL) and hospital stay was 19 days (range, 8-22 days). Homologous blood transfusion was not required. Two donors had complications (one incisional hernia and one bile duct stricture) requiring reoperation after discharge. All were well with normal liver function 5 to 10 months after surgery. The graft weight ranged from 490 g to 1140 g. All grafts showed immediate function with normalization of prothrombin time and recovery of conscious state of the recipients. There was no vascular complication, but six recipients required reoperation. One recipient died of systemic candidiasis 16 days after transplantation and 6 (86%) were alive with the original graft at a median follow-up of 6.5 months (range, 5-10 months). CONCLUSIONS: When performed by a team with experience in hepatectomy and transplantation, LDLT, using an extended right lobe graft, can achieve superior results. The technique extends the success of LDLT from pediatric recipients to adult recipients and opens a new donor pool for adults to receive a timely graft of adequate function.     

Direct detection of Molluscum contagiosum virus in clinical specimens by in situ hybridization using biotinylated probe.

Molluscum contagiosum virus (MCV) is an unclassified poxvirus which has recently become recognized as causing a major sexually transmitted disease. At present no assay is available for specific detection of MCV because the virus cannot be serially propagated in cell culture. Since MCV produces an abortive, limited growth with some cytopathic effect in certain cell lines, we were able to develop an in situ hybridization assay for detection of MCV genome in clinical specimens. Human fetal diploid lung cell monolayers were infected with clinical specimens, and after proper incubation and fixation in paraformaldehyde, hybridization was performed under full stringency conditions with a molecularly cloned biotinylated probe. Only MCV infected cells showed homology to the MCV probe with a purple-brown cytoplasmic staining. Additionally, we have described an in situ hybridization assay for direct detection of MCV genome in formalin-fixed, paraffin-embedded biopsies. Characteristic intracytoplasmic Molluscum bodies (Henderson-Paterson bodies) were detected in stratum spinosum cells of the epidermis. Striking staining similarities have been observed between in situ hybridization and haematoxylin-eosin cytostaining. These procedures are the first successful identification of MCV genome in clinical samples by molecular hybridization, with sensitivity and specificity equal to or greater than electron microscopy.     

HTLV-1 associated T cell lymphoma in South East Asia: case report and family study.

Geographic clustering of human T cell lymphoma/leukaemia virus type 1 (HTLV-1) infection is well recognised, particularly in south western Japan, parts of West and Central Africa, the south eastern United States and the Caribbean islands. Sporadic cases have been reported in many other parts of the world. The first case of HTLV-1 associated leukaemia/lymphoma (ATLL) in South East Asia is reported. Contact tracing showed a high incidence of carriers among the relatives.     

Masseter spasm and malignant hyperthermia: a retrospective review of a hospital-based pediatric otolaryngology practice.

It has been claimed that the combination of halothane and succinylcholine, commonly used for anesthetic induction during short pediatric otolaryngologic procedures, is associated with a 1% incidence of masseter spasm (MS) which may be an early sign of malignant hyperthermia (MH). An 18-month retrospective chart review of all patients undergoing general anesthesia at the Children's Hospital of Pittsburgh (n = 14, 112) was conducted to assess the incidence of MS and its management. In addition, a separate subgroup of patients identified as being at risk for MH was also evaluated. In the otolaryngology service, the incidence of developing MS was 2 of 206 (1%) in children who were anesthetized with halothane and received succinylcholine, patients were identified in the MH high-risk group, and none developed MH. The findings affirmed the risks of using this combination of anesthetic and neuromuscular blocking agents during induction and the need for establishing management guidelines.     

An audit of the safety of an acute pain service

We audited and analysed the adverse effects and safety of postoperative pain management on 2509 consecutive patients under care of the Acute Pain Service at a tertiary referral teaching hospital over a 32-month period. Our standard respiratory monitoring consisted of continuous pulse oximetry, hourly respiratory rate counting, sedation scoring and intermittent arterial blood gas sampling. This protocol was reliable and detected six episodes of bradypnoea, 13 of hypercapnia and 23 of oxygen desaturation occurring in 39 patients (1.8% of all spontaneously breathing patients) . Two patients required naloxone injection and none had long-term sequelae. Hypotension due to epidural bupivacaine 0.0625% and fentanyl 3.3 μg.ml⁻¹ infusion occurred in four patients (1.2%), all with a sensory block higher than T₅. They readily responded to fluid infusion and ephedrine (two patients). Postoperative nausea or vomiting occurred in 723 (28.8%) and 380 (15.1%) patients, respectively. Odds ratio analysis showed that the risk factors for postoperative nausea and vomiting were: female gender, gynaecological operations, nongeriatric patients and systemic analgesia. Postoperative nausea and vomiting decreased analgesic efficacy by discouraging the use of patient-controlled analgesia and was regarded as equally distressing as pain. Other side-effects included: pruritus in 182 patients; dizziness in 333 and lower limb weakness in 73 (21.2% of patients receiving epidural local anaesthetics). It is concluded that a standard monitoring and management protocol, an experienced nursing team and reliable Acute Pain Service coverage is mandatory for the safe use of modern analgesic techniques.     

Ophthalmologic manifestations of genitourinary diseases

There are several urologic disorders which also involve the eye and orbit. We have compiled examples of these and reviewed the literature. Metastasis from genitourinary malignancy (including neuroblastoma), Wilms tumor, Reiter syndrome, tuberous sclerosis, von Hippel-Lindau disease, and oxalosis may all have ophthalmologic manifestations. Urologists need to be aware of these and obtain appropriate consultation in order to fully care for patients with these diseases.     

Renal metastasis from choriocarcinoma: MRI appearance

Choriocarcinoma is the most malignant tumor of gestational trophoblastic neoplasia. It grows rapidly and metastasizes to the lung, liver, and, less frequently, to the brain. Renal involvement is rare. Magnetic resonance imaging (MRI) is a useful modality to image the affected tissues; it contributes to the evaluation and management of the disease. One case of renal choriocarcinoma with MRI evaluation is reported. Received: 24 February 1997/Accepted: 14 April 1997     

A perinatal perspective on South Australia in the 1980s.

OBJECTIVE: To assess changes in sociodemographic characteristics of mothers, their obstetric management and perinatal outcomes in the 1980s. DESIGN: A survey of data recorded in the South Australian perinatal data collection. For singleton births, we compared risks of stillbirth, neonatal death and perinatal death by year of birth, after adjusting for risk factors. SUBJECTS: There were 176,637 births of at least 400 g birthweight (or at least 20 weeks' gestation) notified to the perinatal data collection between 1981 and 1989. MAIN OUTCOME MEASURES: Frequency of risk factors and relative risks of stillbirth, neonatal death and perinatal death by year of birth. RESULTS: There have been changes in the sociodemographic characteristics of mothers, their obstetric management and perinatal outcomes during the 1980s. Crude perinatal mortality rates have not increased, despite increases in the frequency of low birthweight, preterm births, mothers aged 35 years and over, and some other risk factors. After adjusting for risk factors, the risks of stillbirth, neonatal death and perinatal death were lower among singletons in 1987-1989 than in the 1981-1982 reference period. CONCLUSION: Advances in clinical management may be preventing increases in stillbirths, neonatal deaths and perinatal deaths in response to increased numbers of births with low birthweight, preterm delivery and some other risk factors in South Australia.