The natural history of multiple sclerosis: a regional study with some longitudinal data.

A regional survey of multiple sclerosis (MS) patients in Wellington, New Zealand in 1983 identified 245 patients, giving a prevalence (all categories included) of 72 per 100,000. Retrospective review of the history and medical records identified a poorer prognosis for disability where there was progressive onset of symptoms, secondary progression after a remitting phase, older age of onset (40 years or more), or a motor syndrome involving the limbs at presentation. In 1983 follow up data were obtained on 96 patients who were seen during a previous survey in 1968. For those with definite or probable MS, progression to severe disability (Kurtzke disability status scale (DSS) 6-9) or death (DSS 10) was seen in 26/34 with moderate disability (DSS 3-5) in 1968 and in only 5/29 with mild disability (DSS 0-2). When the analysis is confined to those with symptoms for at least five years in 1968, severe disability or death from MS occurred in 22/30 with moderate and 4/19 with mild disability (chi 2 = 10.8, p = 0.001). It is concluded that the patient's established disability level after five years of illness is a useful, but not infallible, prognostic indicator. From the follow up of the 1968 patients, the probability of MS-related mortality for a given disease duration was calculated. Using this survival distribution to adjust the disability ratings in the 1983 population, it was found that the proportion with mild disability decreased steadily with increasing disease duration, reaching 14% when the disease duration was more than 25 years.     

The effects of alcohol and benzodiazepines on the severity of ski accidents.

Urine samples from 402 victims of ski accidents were analyzed for the presence of benzodiazepines (BZD) and alcohol. Eighty-one (20%) samples were positive for alcohol; BZD were detected in 34 (8.5%) cases. Ten of the samples (2.5%) were found to be positive for both alcohol and BZD. Subjects who were positive for either alcohol or BZD or both were older than the other persons examined. The prevalence of alcohol was significantly higher among male accident victims. BZD intake could be demonstrated to have a significant influence on the severity of injuries. Besides an increased awareness of the need for skier education regarding drug use, heightened attention of medical caregivers is warranted to inform their patients about potential accident hazards in sport activities when BZD are prescribed.     

Modified extravesical ureteral reimplantation in pediatric renal transplantation: 5 years of experience.

Numerous surgical procedures have been described to reimplant the ureter into the bladder during renal transplantation. Since November 1985 we have used a modified extravesical technique in 19 children. At the time of transplantation patient age ranged from 2 to 17 years (average age 10 years). Of these patients only 2 received a cadaveric kidney. Postoperative followup ranged from 4 to 54 months (average 32 months). No immediate or delayed urological complications were noted, and all but 1 graft has continued to function. This procedure is not only expeditious and safe but it also eliminates a long cystostomy suture line and requires a short ureteral length. Urinary leakage and ureteral obstruction, 2 of the most common urological complications, have not been observed in our patients. Although further experience and longer followup are required, this technique has become our procedure of choice for ureteral reimplantation in children undergoing renal transplantation.     

Immunochemical and biochemical characterization of purified canine interferon-gamma. Production of a monoclonal antibody, affinity purification, and its effect on mixed lymphocyte culture and mixed lymphocyte kidney culture reactions.

We have advanced the hypothesis that the primary autolymphoproliferative response of dog T cells in mixed lymphocyte kidney cultures (MLKC) results from their recognition of tissue-specific (kidney-associated) antigen(s) presented in conjunction with class II MHC antigens. Lymphocyte culture-derived supernatants had been found previously to upregulate class II antigen expression on kidney cells and enhance T cell activation. In the present study we have isolated and characterized dog IFN-gamma, a class II-inducing substance that is secreted in the culture supernatant of activated T lymphocytes. Dog IFN-gamma was induced with A-23187 and PMA and purified stepwise using controlled-pore glass, Mono Q anion exchange chromatography, and Superose 6-gel filtration on FPLC. The purification resulted in two molecules of 42 Kd and 31 Kd molecular weights. An IgG1 monoclonal antibody was engendered to these molecules. With this mAb reagent, in immunochemical experiments, we have developed a sensitive ELISA and a method for purifying dog IFN-gamma by affinity chromatography. Species specificity studies indicated that purified dog IFN-gamma reacted with a polyclonal rabbit antihuman IFN-gamma, but not with a mAb to human IFN-gamma. However, the antidog IFN-gamma mAb that was generated also reacted with recombinant human IFN-gamma. In in vitro biological studies, the purified IFN-gamma (two mol. wt. species) upregulated the expression of canine class II MHC molecules on dog tubular epithelial cells and the dog kidney epithelial cell line (MDCK). The antidog IFN-gamma mAb blocked T cell proliferative response to kidney cell and, by inference, the interaction between endogenously released IFN-gamma in vitro with its cell surface receptor, thus inhibiting the induced upregulation of class II. Interestingly, although antidog IFN-gamma markedly blocked the MLKC (10 micrograms mAb/well), there was no effect on the allogeneic MLC. This observation indicates that the cytokine IFN-gamma may be a uniquely key substance amplifying the immune response of T cells to tissue-associated antigens on surrogate antigen-presenting cells that require induced upregulation of class II MHC antigen expression (MLKC), in contrast to reactions in which these antigens are already constitutively expressed on the antigen-presenting cells (mixed lymphocyte culture).