To test or not to test? Laboratory support for the diagnosis of Lyme borreliosis: a position paper of ESGBOR, the ESCMID study group for Lyme borreliosis.

BACKGROUND: Lyme borreliosis (LB) is a tick-borne infection caused by Borrelia burgdorferi sensu lato. The most frequent clinical manifestations are erythema migrans and Lyme neuroborreliosis. Currently, a large volume of diagnostic testing for LB is reported, whereas the incidence of clinically relevant disease manifestations is low. This indicates overuse of diagnostic testing for LB with implications for patient care and cost-effective health management. AIM: The recommendations provided in this review are intended to support both the clinical diagnosis and initiatives for a more rational use of laboratory testing in patients with clinically suspected LB. SOURCES: This is a narrative review combining various aspects of the clinical and laboratory diagnosis with an educational purpose. The literature search was based on existing systematic reviews, national and international guidelines and supplemented with specific citations. IMPLICATIONS: The main recommendations according to current European case definitions for LB are as follows. Typical erythema migrans should be diagnosed clinically and does not require laboratory testing. The diagnosis of Lyme neuroborreliosis requires laboratory investigation of the spinal fluid including intrathecal antibody production, and the remaining disease manifestations require testing for serum antibodies to B. burgdorferi. Testing individuals with non-specific subjective symptoms is not recommended, because of a low positive predictive value.

Oral health status and needs of homebound elderly in an urban home-based primary care service.

OBJECTIVES: This study assessed the oral health status, dental utilization and dental needs of the homebound elderly (HBE) care patients within the Mount Sinai Visiting Doctor program. METHODS: Of the 334 eligible patients, 57% agreed to participate and 95.4% completed the clinical examinations, the Dental Utilization and Needs survey and Geriatric Oral Health Assessment Index conducted in each subject's home by a trained research team. RESULTS: Among 75% who were dentate subjects, 40% needed restorative dental care, 45.6% needed dental extractions, and 33% complained of current oral pain. Overall, 92.0% needed some type of dental care and 96% stated that they had not seen a dentist since they became homebound (mean number of years in program = 3.2 ± 2.58). CONCLUSION: Findings show the oral health status of these homebound elderly was poor and their quality of life was significantly affected by the lack of basic dental care.

Are there sensitive time periods for dementia caregivers? The occurrence of behavioral and psychological symptoms in the early stages of dementia.

BACKGROUND: The behavioral and psychological symptoms associated with dementia (BPSD) can be burdensome to informal/family caregivers, negatively affecting mental health and expediting the institutionalization of patients. Because the dementia patient-caregiver relationship extends over long periods of time, it is useful to examine how BPSD impact caregiver depressive symptoms at varied stages of illness. The goal of this study was to assess the association of BPSD that occur during early stage dementia with subsequent caregiver depressive symptoms. METHODS: Patients were followed from the early stages of dementia every six months for up to 12 years or until death (n = 160). Caregiver symptoms were assessed on average 4.5 years following patient's early dementia behaviors. A generalized estimating equation (GEE) extension of the logistic regression model was used to determine the association between informal caregiver depressive symptoms and BPSD symptoms that occurred at the earliest stages dementia, including those persistent during the first year of dementia diagnosis. RESULTS: BPSD were common in early dementia. None of the individual symptoms observed during the first year of early stage dementia significantly impacted subsequent caregiver depressive symptoms. Only patient agitation/aggression was associated with subsequent caregiver depressive symptoms (OR = 1.76; 95% CI = 1.04-2.97) after controlling for concurrent BPSD, although not in fully adjusted models. CONCLUSIONS: Persistent agitation/aggression early in dementia diagnosis may be associated with subsequent depressive symptoms in caregivers. Future longitudinal analyses of the dementia caregiving relationship should continue to examine the negative impact of persistent agitation/aggression in the diagnosis of early stage dementia on caregivers.

Lyme borreliosis: clinical case definitions for diagnosis and management in Europe.

Lyme borreliosis, caused by spirochaetes of the Borrelia burgdorferi genospecies complex, is the most commonly reported tick-borne infection in Europe and North America. The non-specific nature of many of its clinical manifestations presents a diagnostic challenge and concise case definitions are essential for its satisfactory management. Lyme borreliosis is very similar in Europe and North America but the greater variety of genospecies in Europe leads to some important differences in clinical presentation. These new case definitions for European Lyme borreliosis emphasise recognition of clinical manifestations supported by relevant laboratory criteria and may be used in a clinical setting and also for epidemiological investigations.

Development of an adaptive multimedia program to collect patient health data.

BACKGROUND: Direct entry of personal health survey information into a computer by patients could streamline clinical data collection, improve completeness and accuracy of health information available to providers, and provide data for tailoring health education messages. Few computerized programs, however, have been developed to adapt the interface to diverse literacy levels, language, computer skills, and health literacy levels of the broad spectrum of patient populations. METHODS: To develop such a program, we conducted cognitive response interviews with a diverse sample of 21 adult participants from two North Carolina health clinics. Participants were placed into one of three interview categories: (1) low reading skill level, low computer skills; (2) high reading skill level, low computer skills; and (3) high reading skill level, high computer skills. The "think-aloud" technique was employed to elicit feedback on a series of computer interface screens and health risk assessment questions. RESULTS: Interface-related findings showed that preference for touchscreen versus keyboard data entry was not strongly related to computer skill level but was related to question type. Respondents with limited education indicated that they would not click on a "help" or hyperlink option to get more information and that frequent reminders of directions on the screen were needed. Content-related findings showed numerous misperceptions regarding meanings of common health questions and terminology (e.g., seat belt use and intravenous drugs). CONCLUSIONS: These findings have implications for health literacy and may have an impact on the accuracy of information obtained. Study results will be incorporated into the development and testing of an innovative, adaptive multimedia program.

Mechanisms of action of beta-glucan in postprandial glucose metabolism in healthy men.

OBJECTIVE: To assess whether beta-glucan (which is fermented in the colon) lowers postprandial glucose concentrations through mechanisms distinct from a delayed carbohydrate absorption and inhibits de novo lipogenesis. DESIGN: Administration of frequent small meals each hour over 9 h allows a rate of intestinal absorption to be reached which is independent of a delayed absorption. A group of 10 healthy men received either an isoenergetic diet containing 8.9 g/day beta-glucan or without beta-glucan for 3 days. On the third day, the diet was administered as fractioned meals ingested every hour for 9 h. SETTING: Laboratory for human metabolic investigations. SUBJECTS: Ten healthy male volunteers. MAIN OUTCOME MEASURES: Plasma glucose and insulin concentrations, glucose kinetics, glucose oxidation, de novo lipogenesis. RESULTS: On the third day, plasma glucose and free fatty acid concentrations, carbohydrate and lipid oxidation, and energy expenditure were identical with beta-glucan and cellulose. Plasma insulin concentrations were, however, 26% lower with beta-glucan during the last 2 h of the 9 h meal ingestion. Glucose rate of appearance at steady state was 12% lower with beta-glucan. This corresponded to a 21% reduction in the systemic appearance rate of exogenous carbohydrate with beta-glucan, while endogenous glucose production was similar with both diets. De novo lipogenesis was similar with and without beta-glucan. CONCLUSION: Administration of frequent meals with or without beta-glucan results in similar carbohydrate and lipid metabolism. This suggests that the lowered postprandial glucose concentrations which are observed after ingestion of a single meal containing beta-glucan are essentially due to a delayed and somewhat reduced carbohydrate absorption from the gut and do not result from the effects of fermentation products in the colon.

Characterization of Lyme borreliosis isolates from patients with erythema migrans and neuroborreliosis in southern Sweden.

Southern Sweden is an area of Lyme borreliosis (LB) endemicity, with an incidence of 69 cases per 100,000 inhabitants. The most frequent clinical manifestations are erythema migrans (77%) and neuroborreliosis (16%). There was no record of human Borrelia strains being isolated from patients in this region before the prospective study reported here. Borrelia spirochetes were isolated from skin and cerebrospinal fluid (CSF) from LB patients living in the region. A total of 39 strains were characterized by OspA serotype analysis, species-specific PCR, and signature nucleotide analysis of the 16S rRNA gene. Of 33 skin isolates, 31 (93.9%) were Borrelia afzelii strains and 2 (6.1%) were Borrelia garinii strains. Of six CSF isolates, five (83.3%) were B. garinii and one (16.7%) was B. afzelii. Neither Borrelia burgdorferi sensu stricto strains nor multiple infections were observed. The B. afzelii isolates were of OspA serotype 2. Three B. garinii strains were of OspA serotype 5, and the remaining four strains were of OspA serotype 6. All of the B. garinii strains belonged to the same 16S ribosomal DNA ribotype class. Our findings agree with earlier findings from other geographic regions in Europe where B. afzelii and B. garinii have been recovered predominantly from skin and CSF cultures, respectively. To further study the possible presence in Sweden of the genotype B. burgdorferi sensu stricto, which is known to be present in Europe and to occur predominantly in patients with Lyme arthritis, molecular detection of Borrelia-specific DNA in synovial samples from Lyme arthritis patients should be performed.

Preexercise feeding in untrained adolescent boys does not affect responses to endurance exercise or performance.

The effects of preexercise feeding on responses to endurance exercise and performance were investigated. Untrained adolescent boys (N = 13, age 14.9 +/- 0.5 years) completed three endurance test sessions separated by a minimum of 72 hr. Each session consisted of 75 min of cycling at 60% of VO2 max followed by a high-intensity performance test. Dietary conditions were a candy bar (C1: 280 kcal, 36 g CHO), fat-free fig bars (C2: 200 kcal, 44 g CHO), and a nonnutritive sweetened drink (C3: placebo), ingested 10 min prior to exercise. Respiratory gases, heart rate, blood glucose, and lactate concentrations were measured throughout the test. ANOVA results revealed significant time effects for all variables; however, no differences were seen among the conditions. Performance times, 311.9 +/- 38.5 s in C1, 316.2 +/- 37.3 s in C2, and 328.1 +/- 46.4 s in C3, were not significantly different among conditions. Thus, preexercise feeding did not affect responses to endurance exercise or performance in adolescent boys.

A review of racial differences in geriatric depression: implications for care and clinical research.

How racial differences influence depressed elders' seeking and obtaining treatment for depression is poorly understood. Studies in other medical illnesses show older African Americans use fewer health-care services for heart disease, stroke, and renal dialysis. This article reviews the racial composition of Duke University's Clinical Research Center (CRC) for the Study of Depression in the Elderly. Possible explanations for low participation of African Americans in such programs also are discussed. During most of the first year of the CRC project, minority enrollment varied from 5% to 10%, at least one third the African-American population of the area. Active efforts to improve minority recruitment increased this percentage to 15% by the end of the project's second year. Likely explanations for low minority participation rates include 1) elders may recognize depressive symptoms, but do not seek or cannot obtain medical treatment, and 2) depressive symptoms may be attributed to a crisis of the spirit (so help is sought through prayer and the church), the "slowing down" process of aging, or part of life's burden to be endured. Future attempts at both treatment and clinical research recruitment efforts are needed to address these possibilities.

An epidemiologic study of Lyme disease in southern Sweden.

BACKGROUND: Lyme disease is the most common vector-borne infection in some temperate regions of the Northern Hemisphere. However, for most areas of endemic disease reliable epidemiologic data are sparse. METHODS: Over a one-year period, we conducted a prospective, population-based survey of cases of Lyme disease in southern Sweden. The diagnosis was made on the basis of the presence of erythema migrans at least 5 cm in diameter or characteristic clinical manifestations such as arthritis, neuroborreliosis, and carditis. RESULTS: We identified 1471 patients with Lyme disease, for an overall annual incidence of 69 cases per 100,000 inhabitants. The incidence varied markedly according to geographic region, and there were several areas where disease was widely prevalent. The incidence varied according to age, with the highest rates among people 5 to 9 and 60 to 74 years of age, but not according to sex. The most frequent clinical manifestation was erythema migrans (seen in 77 percent of all cases), followed by neuroborreliosis (16 percent) and arthritis (7 percent). Carditis was rare. A preceding tick bite was reported by 79 percent of the patients. Bites in the head and neck region were more common among children than among adults and were associated with an increased risk of neuroborreliosis. CONCLUSIONS: Lyme disease is very common in southern Sweden, with a relatively high frequency of neurologic complications and arthritis. With the exception of the low incidence of carditis, the pattern of disease we found in Sweden was similar to that reported in the United States.

Abnormal galactosylation of complex carbohydrates in cultured fibroblasts from patients with galactose-1-phosphate uridyltransferase deficiency.

An abnormality in galactosylation of complex carbohydrates may be important in the pathogenesis of the long-term complications of classic (galactose-1-phosphate uridyltransferase-deficient) galactosemia. The ability of nine galactosemic fibroblast preparations to be galactosylated with a purified galactosyltransferase was measured as an indicator of vacant sites where galactose would normally reside. The amount of galactose transferred to cell protein from galactosemic patients was significantly higher than that transferred to a group of seven controls (p less than 0.005). Galactosyltransferase activity of the galactosemic cell preparation toward N-acetylglucosamine was also significantly higher than normal (p less than 0.01), and there was a linear relationship between these two parameters in galactosemic but not normal cells. These findings suggest that there is defective galactosylation of galactosemic cell complex carbohydrates and that such cells increase their galactosyltransferase levels in an attempt to compensate for the defect. Defective galactosylation may be implicated as an etiologic factor in complications observed in galactosemic patients even when treated with galactose-restricted diets.

Biochemical and radioautographic evidence for dopaminergic afferents of the locus coeruleus originating in the ventral tegmental area.

The dopamine (DA) content of the locus coeruleus (LC) and the uptake of tritiated DA in the presence of desmethylimipramine into fresh vibratome sections of the LC-area were determined in control rats and in rats whose ventral tegmental area (VTA) had been destroyed by local application of 6-hydroxydopamine (6-OHDA). Destruction of the VTA reduced the DA content and the number of dopaminergic fibers visualized by radioautography in the LC area. This indicates that the DA containing afferents of the LC originate, at least partly, in the VTA.

The morphogenesis of stereotyped behavior induced by the dopamine receptor agonist apomorphine in the laboratory rat.

The seemingly unrelated stereotyped locomotor "acts" reported in the literature to be produced by apomorphine in rats are shown to be composites, whose form and sequence are determined by the particular values of a few component variables which form a common denominator in each of the behaviors. Three variables, continuous snout contact, forward progression and turning, account for much of the behavior. In the course of the drug's action these emerge in succession and vary in amount, the latter two successively reaching a peak and subsiding. The interaction between forward progression and turning yields in sequence, forward walking, circling, revolving, tight pivoting and finally side-to-side movements of the forequarters around the relatively stationary hindquarters. Later behaviors in this list are gradually incorporated into the sequence as earlier ones are eliminated. The course of change in forward progression and turning is also reflected in changes in the sequence and in the direction of stepping of each of the four legs. The order in which the behavior unfolds under the drug is opposite to that manifested in ontogeny and in recovery from lateral hypothalamic damage, suggesting that at the particular high dose used, apomorphine is acting not only to activate the behavior but also to shut it down.

Self-stimulation in the brain stem after ipsilateral precollicular decerebration.

Rats were tested for self-stimulation after unilateral removal of the entire forebrain anterior to the superior colliculus. The stimulating electrodes were situated in the peribrachial region, just lateral to the superior cerebellar peduncle. Of 27 animals tested, 8 still self-stimulated after ipsilateral decerebration. Self-stimulation was exhibited from as early as a few hours to as long as 119 days after decerebration. The results are discussed in the context of the search for neural elements that subserve reinforcing brain stimulation.

Snout contact fixation, climbing and gnawing during apomorphine stereotypy in rats from two substrains.

Apomorphine, at doses greater than or equal to 10 mg/kg (intraperitoneally), produced two patterns of stereotypy. In rats from one supplier it induced predominantly gnawing while in those from another predominantly climbing, suggesting that the response to the drug is influenced by genetic and/or experimental factors. At lower doses, apomorphine induced climbing in both groups (ED50 = 1.4 mg/kg in each group) but oral behavior in only one of them (ED50 = 1.3 mg/kg in one, and 8 mg/kg in the second group). Thus, at a given dose of apomorphine, different patterns of stereotypy may result from an interaction between two phenomena: the relative setting of the thresholds to mouth and to climb, and an inverse relation between oral activity and climbing. Analysis of climbing suggests that this response is comprised of two (previously unidentified) fundamental effects of apomorphine: snout contact fixation and bodywise forward progression.