The OKT3 Antibody Response Study: a multicentre study of human anti-mouse antibody (HAMA) production following OKT3 use in solid organ transplantation

Human anti-murine antibody titres following patient exposure to the monoclonal antibody Orthoclone OKT3 (muromonab-CD3) are determined by laboratories using diverse analytical methods which are not standardized and whose concordance is not established. A multicentre study group therefore compared testing for IgG anti-OKT3 antibody among seven laboratories. A set of 270 sera was obtained from 30 heart, 30 kidney and 30 liver transplant recipients with no previous exposure to OKT3 who were receiving OKT3 for induction immunosuppression. Sera were collected from each patient prior to and at 24 +/- 2 days and 31 +/- 2 days following initial OKT3 exposure. Identical aliquots of all 270 sera were tested for IgG anti-OKT3 antibody by each laboratory. In addition, the limit of detection of each laboratory's method was estimated by titration of an affinity-purified IgG anti-OKT3 reference material of known concentration. Anti-OKT3 antibody formation differed greatly among the three organ groups. Cardiac patients demonstrated the least sensitization and almost exclusively lower titres, while kidney recipients had more frequent and higher titre antibody formation. Liver recipients yielded the highest sensitization rate and the most frequent high titre sera. Importantly, the seven laboratories differed widely in the number of pretreatment sera reported as positive (ranging from 0% to 41% among laboratories), the number of post-OKT3 sera reported as positive (17-63%), the number of post-OKT3 samples with titre > or = 1000 (2-31%), and the number of patients sensitized 19-69%). Concordance among laboratories was highly variable, with interlaboratory agreement ranging from 38% to 83% on the sample titres assigned to 180 post-OKT3 sera. Many of the discordant results were consistent with differences in the limit of detection of the analytical methods, which ranged from 0.19 microgram/ml to > or = 15 micrograms/ml, a nearly 100-fold difference among laboratories. This study demonstrated the presence of both good concordance and significant discordance among laboratories in determining human anti-mouse antibody titres, and demonstrated that common titre categories (100, 1000, 10,000) were not equivalent among laboratories. The level of concordance among methods should be considered when comparing anti-OKT3 antibody results from different centres and their correlation with clinical events. Universal comparative testing, patterned after proficiency testing programmes, is needed to assess differences among laboratories and to bring uniformity and a sound interpretative basis to this field of testing.     

Prevalence and severity of the dementia syndrome in homes for the aged and nursing homes. A study in elderly from a rural area near Zwolle

In the Netherlands both nursing homes and homes for the aged serve as a residence for demented elderly. Although these institutions differ considerably regarding financing and care facilities, specific functions of each institute concerning demented elderly have not been clearly defined. In order to know to what extent residential facilities serve demented elderly, the prevalence and severity of dementia among residents aged 65 and over was studied as part of a prevalence study among elderly people in a rural area of the Netherlands. The target population existed of all persons aged 65 and over who were registered in eight general practices. Patients who had to leave the practice on account of ill-health and were admitted to nursing homes were included in the study. In a two stage study the MMSE was applied as a screening instrument. Based on MMSE-score a non-proportional stratified random sample was drawn for the second, diagnostic stage, which existed of the CAMDEX. Prevalence estimates for DSM-III-R-dementia were 21% among residents of homes for the aged, 48% among residents of somatic wards of nursing homes and 100% among those admitted to psychogeriatric wards of nursing homes. Severity of dementia was highest among residents of psychogeriatric wards of nursing homes and lowest among those living in homes for the aged. Prevalence of dementia among residents of homes for the aged can be fully attributed to the age-distribution. The high frequency of dementia among residents of somatic nursing home wards can be explained in several ways: First, admission can be necessary due to a combination of dementia and somatic illness.(ABSTRACT TRUNCATED AT 250 WORDS)     

Noise and machine failures: determining factors in the acceptance and behavior of O2 concentrator. The Asturias project

Whether a sulfonylurea may be used together with insulin for treating NIDDM has been controversial. One view, based on older studies, has been that the additional benefit is too small or the level of glucose control achieved usually too poor to recommend this method. More recent studies of a more specific way of combining a sulfonylurea with insulin are more supportive. When a single injection of insulin taken in the evening is added to a sulfonylurea at the time of secondary failure of the sulfonylurea alone, glycemic control is quite simply and consistently restored to acceptable levels. At this time in the natural history of NIDDM, evening insulin combined therapy is more effective than a single injection of insulin alone, and just as effective as a more complex multiple-injection regimen without an oral agent. A recent multicenter trial of a new sulfonylurea, glimepiride, in combination with a single injection of 70/30 insulin before dinner has confirmed that this approach is safe and more consistently effective than insulin alone for obese patients beginning insulin in a setting resembling clinical practice. The available evidence suggests this form of combined therapy is suitable for routine use.     

Barriers to providing case management to older rural persons

This article analyzes data from a national sample of 356 agencies on barriers to providing case management to rural older persons. Although considerable variation is found regarding the degree of difficulty attributed to various barriers, several areas are reported by respondents as problematic, such as a lack of resources to pay for case management and services, a lack of services, and a lack of transportation. On the other hand, a lack of rural case management standards, qualified persons to conduct case management, and opportunities for staff training, as well as staff turnover and professional isolation, are generally not seen as particularly troublesome. More support from families and personal knowledge of clients and service providers are most likely to be seen as advantages in providing case management to rural elders. These findings both support and contradict the current gerontological literature on the types of barriers that impede the development and provision of services to rural older persons. Additional research is needed on the barriers to providing case management to rural older persons before policies directing scarce resources are put into place.     

Preoperative pulmonary evaluation of the thoracic surgical patient

A test designed to separate those undergoing thoracic surgery without complications and those with complications must be both highly specific and sensitive. Clearly, the difference between patients at opposite ends of the population curves is easy to identify. Spirometry can be helpful for screening, although it is not a very discriminating test. If patients fall in the overlap region between the populations, however, it is impossible to discern the risks with any certainty using low-yield tests. A test with higher sensitivity, specificity, and predictive values is necessary to ascertain such marginal differences. With this kind of analysis at hand, preoperative testing can be divided into three predictive value groups. Calculating the predictive value of each preoperative test can provide a comparative measure of usefulness of discriminative power (Table 1). In this way, spirometry, blood gas analysis, and stair climbing tolerance are shown to be poor predictors of outcome. An intermediate predictive value can be achieved using diffusion capacity, exercise-induced decreases in O2 saturation, and exercise PVR. High predictive value can be accomplished with combination indexes (PPP, possibly PRQ), measurement of VO2 at 40 watts of exercise, or VO2max. Logic dictates a step-wise preoperative evaluation using prediction value analysis (Fig.4). A flow decision chart for the preoperative evaluation of patients for pulmonary resection begins with exercise oximetry, spirometry, and blood gas analysis as general screening tests to separate those patients at minimal or no risks for complications from those patients that require further evaluation. Functional indexes (PPP, PRQ) or exercise testing can aid further in the selection of those patients in whom a nonsurgical option should be considered. Flow decision chart for the preoperative evaluation of patients for pulmonary resection should continue to evolve as new information about outcome studies is gathered. Examination of outcome data will provide us with reduction of the size of the nonoperable population, so that we can deny only those patients who truly pose a prohibitive risk.     

Ovarian aging and hormone replacement therapy. Hormonal levels, symptoms, and attitudes of African-American and white women

The purpose of the study was to identify psychiatric symptoms, neurological impairments, and situational factors associated with the emergence of violence and with its persistence. Psychiatric symptoms were assessed in newly admitted physically assaultive psychiatric patients and nonviolent controls. Patients were than evaluated for 4 weeks to determine the persistence or resolution of these physical assaults. Patients who showed marked resolution of assaults were classified as transiently violent (n = 41), and those who remained assaultive throughout were categorized as persistently violent (n = 34). At the end of 4 weeks, all patients received a comprehensive psychiatric and neurological assessment. Physical assaults were associated initially with prominent positive psychotic symptoms. Both transiently and persistently violent patients were more psychotic than the nonviolent controls; however transiently violent patients showed better resolution of these symptoms over the 4 weeks. They also evidenced less frontal lobe impairment on the neurological examination than the persistently violent patients. The two violent groups differed in their susceptibility to environmental influences: the surrounding ward agitation fostered physical assaults in transiently but not in persistently violent patients. This differentiation between transiently and persistently violent patients has major implications for the comprehensive treatment of violent behavior.     

Therapy of Crohn's disease in childhood

The aim of therapy in Crohn's disease in childhood is to induce and to maintain a remission of disease activity so that normal growth and development of the child may occur. Enteral nutrition may now be recommended as the first-line treatment for most children with Crohn's disease. However, the evidence for remission is better for children with Crohn's disease of the small intestine rather than of the large intestine. There is evidence that amino acid feeds (elemental), whole protein (polymeric) and protein hydrolysate feeds (semi-elemental) may all be successful. Such a therapeutic approach can lead to healing of the mucosa and down-regulation of inflammation. However, in some cases surgery is required, particularly in children with growth failure and delayed puberty. Drug therapy also continues to have a role in therapy especially with severe colonic disease.