Ultrastructural mitochondrial alterations in equine myopathies of unknown origin.

BACKGROUND: Very few mitochondrial myopathies have been described in horses. OBJECTIVE: To examine the ultrastructure of muscle mitochondria in equine cases of myopathy of unknown origin. MATERIALS & METHODS: Biopsies of vastus lateralis of the Musculus quadriceps femoris were taken predominantly immediately post mortem and processed for transmission electron microscopy. As a result, electron micrographs of 90 horses in total were available for analysis comprising 4 control horses, 16 horses suffering from myopathy and 70 otherwise diseased horses. RESULTS: Following a thorough clinical and laboratory work-up, four out of five patients that did not fit into the usual algorithm to detect known causes of myopathy showed ultrastructural mitochondrial alterations. Small mitochondria with zones with complete disruption of cristae associated with lactic acidemia were detected in a 17-year-old pony mare, extremely long and slender mitochondria with longitudinal cristae in a 5-year-old Quarter horse stallion, a mixture of irregular extremely large mitochondria (measuring 2500 by 800 nm) next to smaller ones in an 8-year-old Hanoverian mare and round mitochondria with only few cristae in a 11-year-old pony gelding. It remains uncertain whether the subsarcolemmal mitochondrial accumulations observed in the fifth patient have any pathological significance. CONCLUSIONS: Ultrastructural alterations in mitochondria were detected in at least four horses. To conclude that these are due to mitochondrial dysfuntions, biochemical tests should be performed. PRACTICAL APPLICATIONS: The possibility of a mitochondrial myopathy should be included in the differential diagnosis of muscle weakness.

Safety of a probiotic cheese containing Lactobacillus plantarum Tensia according to a variety of health indices in different age groups.

Safety of the probiotic Lactobacillus plantarum strain Tensia (DSM 21380) was tested in vitro, in semihard Edam-type cheese, in an animal model and after consumption of the probiotic cheese in double-blind randomized placebo-controlled human intervention studies with different age groups. The susceptibility of L. plantarum Tensia to 8 antibiotics, and the presence of tetracycline (tet M, S, O, K, L) genes and class 1 integron was assessed by applying epsilometer-test and PCR-based methods. Production of biogenic amines by the probiotic strain in decarboxylation medium containing 1% of l-histidine, l-glutamine, l-ornithine, l-arginine, or l-lysine and in cheese was tested by gas chromatography. The biosafety of L. plantarum Tensia was evaluated on National Institutes of Health-line mice fed cheese containing Tensia at a concentration of 9.6 log cfu/g for 30 consecutive days. In human intervention trials in adults and the elderly, the effects of different doses of Edam-type cheese and the probiotic bacterium on BW, gut functionality indices, and host metabolism were evaluated. The strain L. plantarum Tensia was susceptible to all tested antibiotics and did not possess the tetracycline resistance-determining genes tet(L), tet(S) and tet(O), nor did it contain the integron (Int1) gene. However, the strain was tet(K) and tet(M) positive. Lactobacillus plantarum Tensia did not produce potentially harmful biogenic amines, such as histamine or cadaverine. The amount of tyramine produced in the cheese environment during ripening and after 15 wk of storage was below the clinically significant content. In the animal model, no translocation of the administered strain or other microbes into the blood or organs of mice was detected. No harmful effect was observed on body mass index, inflammatory markers, or serum lipidograms during human intervention trials with different age groups at a daily dose of 10.3 or 8.17 log cfu/serving for 3 wk. No negative effect on gastrointestinal welfare was observed, but the consumption of 100g/d for 3 wk caused hard stools from the second week of the trial. The content of total lactobacilli increased in feces, and the presence of the ingested probiotic strain was confirmed after the consumption of cheese. Thus, L. plantarum strain Tensia is suitable for generally recognized as safe (GRAS) and qualified presumption of safety (QPS) criteria because it did not have any undesirable characteristics. The regular semihard Edam-type cheese (fat content of 26%) with the probiotic additive at a daily dose of 50 g or in excess (100g) and with a probiotic daily dose of 10 log cfu for 3 wk was safe.

Prevalence of antibiotic resistance of Helicobacter pylori isolates in Estonia during 1995-2000 in comparison to the consumption of antibiotics used in treatment regimens.

OBJECTIVE: To find a possible relation between the dynamics of antibiotic resistance of Helicobacter pylori isolates and the consumption of antibiotics during the last several years in Estonia. METHODS: Helicobacter pylori isolates were collected from the gastric mucosa of patients with peptic ulcer (153) and gastritis (68) and isolated on the Columbia Agar Base. From 1995 to 1997 the disk-diffusion method was used for testing of H. pylori susceptibility to metronidazole (115 isolates), erythromycin (119 isolates), tetracycline (119 isolates) and amoxicillin (119 isolates). From 1998 to 2000 the susceptibility of H. pylori to metronidazole (106 isolates), amoxicillin (30 isolates), clarithromycin (106 isolates) and ciprofloxacin (30 isolates) was assessed by E tests. Data from the Estonian State Agency of Medicines were used to determine the antibiotic consumption rate. RESULTS: Up to the year 2000 all the investigated H. pylori isolates were susceptible to ciprofloxacin; the resistance to clarithromycin, tetracycline, amoxicillin and erythromycin was 3%, 1.7%, 0.7% and 2.5%, respectively. Forty-six percent of H. pylori isolates were resistant to metronidazole. During 1995-2000 the consumption of amoxicillin, erythromycin and ciprofloxacin increased and the consumption of tetracycline decreased. The increasing consumption of amoxicillin reached a level 5.7 times than that of the consistent use of metronidazole. The resistance to amoxicillin appeared to be very low and resistance to metronidazole was continuously high. The increase of clarithromycin consumption (from 0.002 to 1.119 defined daily doses/1000) during three years was associated with the appearance of the first clarithromycin-resistant isolates in 2000. CONCLUSION: No relation was observed between the antibiotic consumption rate and the resistance pattern of H. pylori to metronidazole, amoxicillin, erythromycin, tetracycline and ciprofloxacin during recent years among the in population.

Health status of the older population in Estonia.

AIM: To assess the prevalence of physical, depressive, and cognitive disorders in the elderly population in Estonia. METHODS: The prevalence of various common morbidities was determined by a questionnaire sent to 200 general practitioners (GP). GPs were asked to collect data, use medical records, and interview five randomly selected patients (a total of 1,000 people aged 65 years or older). Physical morbidities of older persons were assessed according to their self-reports and reports of their general practitioners. Depressive symptoms and cognitive status were determined by 15-item Geriatric Depression Scale and Mini Mental State Examination, respectively. Response rate was 81%. RESULTS: The prevalences of diseases were as follows: hypertension 63.2%, arthritis 61.3%, ischemic heart disease 56.5% (history of myocardial infarction, 9.8%), heart failure 41.4%, heart rhythm disorders 37.5%, hypercholesterolemia 25.4%, kidney and/or urinary disorders 20.5%, osteoporosis 15.5%, diabetes mellitus 14.9%, chronic airway diseases 13.8% (emphysema 5.8%, asthma 5.5%), hypotension 11.1%, gastroduodenal peptic ulcers 10.6%, thyroid diseases 8.9%, malignant tumors 8.1%, psychiatric disorders 5.7%, and stroke 5.3%. Depressive symptoms were found in 40.3% and cognitive impairment in 22.5% of the elderly persons. CONCLUSIONS: The general structure of diseases in the Estonian elderly population is similar to that of other European countries, but the prevalence of cardiovascular, depressive, and cognitive disorders is much higher.

Does agrammatic speech constitute a regression to child language? A three-way comparison between agrammatic, child, and normal ellipsis.

When children are in the process of learning their mother tongue, they show frequent use of nonfinite clauses, even though they produce finite clauses at the same time, thereby demonstrating the availability of the functional domain associated with finiteness. In this study the hypothesis was tested that this behavior results from an overuse of the normal elliptical repertoire that has also been observed in agrammatic aphasia. The purpose of this overuse is prevention of computational overload. In support of the hypothesis it was found that children behaved very similar to aphasics and normal adults with respect to the following parameters: (a) distribution of types of ellipsis, (b) elaboration of ellipses, (c) word order, (d) subject omission, (e) frequency of weak subject pronouns, and (f) verb type (eventivity). The results also support the Jackson/Jakobson regression hypothesis, at least at the grammatical level.

Working memory constraints on syntactic processing: an electrophysiological investigation.

Event-related potentials (ERPs) and reaction times (RTs) were used to study how the processing of sentences with morphosyntactic violations is constrained by working memory (WM) capacity. The available WM capacity was varied by three orthogonal manipulations: (1) syntactic complexity; (2) additional WM load; and (3) verbal WM span. The processing of the morphosyntactic violations was reflected in longer RTs in ungrammatical compared with grammatical sentences, and in an anterior negativity and a centroparietal positivity in the ERPs. While the behavioral grammaticality effect was not influenced by the WM manipulations, the ERP effects were. The amplitude of the anterior negativity was modulated by the combination of complexity and load, and by WM span. The onset of the centroparietal positivity was delayed in the high-load condition, and for the low-span group. ERPs over the course of the sentences showed a frontal negative slow wave under high WM load, largest for the low-span group. The finding that online syntactic processing is related to WM span and to additional WM load does not support the theory that there is a WM capacity specific for syntactic processing.

Error monitoring in speech production: a computational test of the perceptual loop theory.

A theory of speech monitoring, proposed by Levelt (1983), assumes that the quality of one's speech is checked by the speech comprehension system. This system inspects one's own overt speech but would also inspect an inner speech plan ("the inner loop"). We have elaborated and tested this theory by way of formalizing it as a computational model. This model includes a new proposal concerning the timing relation between planning the interruption and the repair: the proposal that these two processes are performed in parallel. We attempted to simulate empirical data about the distribution of error-to-cutoff and cutoff-to-repair intervals and the effect of speech rate on these intervals (these intervals are shorter with faster speech). The main questions were (1) Is an inner monitor that utilizes the speech perception system fast enough to simulate the timing data? (2) Can the model account for the effects of speech rate on these intervals? We conclude that including an inner loop through the speech comprehension system generates predictions that fit the empirical data. The effects of speed can be accounted for, given our proposal about the time course of planning interruption and repair. A novel prediction is that the error-to-cutoff interval decreases with increasing position in the phrase.

Prearticulatory and postarticulatory self-monitoring in Broca's aphasia.

The present study examined to what extent patients with Broca's aphasia and healthy controls rely upon prearticulatory and postarticulatory monitoring processes for detecting and repairing errors in speech production. Monitoring skills were investigated in a speaking situation with normal auditory feedback, a speaking situation with white noise, and a situation in which errors had to be detected in other-produced speech. The results demonstrated that the Broca's aphasics repaired a lower percentage of errors than the controls in the situation with normal auditory feedback, whereas their performance in the noise-masked condition was comparable. In contrast to the controls, the aphasics did not suffer from the presence of white noise. In addition, the proportion of covert repairs was higher for the Broca's aphasics than for the healthy controls. These findings indicate that Broca's aphasics concentrate primarily on prearticulatory monitoring. Possible explanations for this strong reliance on prearticulatory monitoring processes are discussed.

Metronidazole and clarithromycin susceptibility and the subtypes of vacA of Helicobacter pylori isolates in Estonia.

The prevalence of metronidazole and clarithromycin resistance of Helicobacter pylori strains under different growth conditions (microaerophilic or anaerobic preincubation) was tested in 56 patients suffering from gastritis and peptic ulcer. vacA subtypes were detected in 46 H. pylori strains and were subsequently compared with the antibiotic resistance pattern. From 56 isolates, 26 proved resistant and 30 sensitive to metronidazole. The patients with peptic ulcer and gastritis were infected with both metronidazole-sensitive and metronidazole-resistant strains. In anaerobic preincubation all the strains were sensitive to metronidazole (MIC < 8 mg/l). All the strains were clarithromycin-sensitive (MIC < 2 mg/l). In the patients with gastritis and peptic ulcer s1 was the predominant vacA subtype. Comparison of vacA subtypes with the diagnoses revealed no correlation; different virulence factors such as vacA subtypes and antibiotic resistance to metronidazole in a microaerophilic milieu proved unrelated.

Accidental fenitrothion intoxication in young broilers.

Death from fenitrothion intoxication in young broiler chicks has never been reported. The mortality in this instance was 16.4% in the first week. The dead birds were found lying in a ventral position resting their heads on the floor. Prior to death dyspnea and paralysis occurred. A concentration of 120 mg fenitrothion/kg of litter (dry weight) was found.

Agrammatic production of subject-verb agreement: the effect of conceptual number.

Three experiments tested the hypothesis that the deficit underlying agrammatic sentence production difficulties can be characterized as a limitation of computational resources and that these resources are not restricted to syntactic processing. This hypothesis was tested by eliciting subject-verb agreement errors in a sentence fragment completion paradigm. Sentence fragments were complex noun phrases, containing a subject (head) noun and a modifying prepositional phrase, containing a "local" noun. We varied the number of "tokens" a singular head noun referred to. Therefore, in one condition, grammatical and conceptual number of the head noun mismatched, whereas these numbers were the same in another condition. In Experiments 1 and 2, we observed an effect of this variable (i.e., more agreement errors when conceptual number was plural and grammatical number singular) in normal controls. Broca's aphasics, on the other hand, showed no effect. Experiment 3 consisted of a sentence/picture matching test. This test showed that the lack of effect with Broca's aphasics cannot be attributed to a comprehension deficit. We argue that these results are incompatible with the notion of a limitation in resources specific for syntactic processing. Instead, we interpret this as the result of a trade-off: Broca's aphasics lack computational resources to take into account both grammatical and conceptual information in morphosyntactic processing and rely on grammatical information only.

Syntactic facilitation in agrammatic sentence production.

Recently, proposals have been made to relate processing difficulties in aphasic language performance to limitations in resources for grammatical processing (Carpenter et al., 1994; Hagiwara, 1995; Kolk, 1995; Martin & Romani, 1994). Such proposals may account for a defining characteristic of agrammatic sentence production: reduced syntactic complexity. Syntactic structures that require deep hierarchical processing or reversals of canonical word order make demands exceeding limited resources. In the present study, we investigate the possibility of counteracting hypothesized resource limitations by increasing the availability of relatively complex sentences (i.e., datives and passives). The phenomenon of "syntactic priming" has been observed in a number of studies with healthy adults (e.g., Bock, 1986). With respect to Broca's aphasia, we hypothesized that increased availability of a syntactic structure, due to syntactic priming, results in a lesser demand on (limited) resources for sentence production. We elicited speech from 12 Broca's aphasics and 12 control subjects in three different conditions: spontaneous speech, picture description without priming, and picture description with priming. In addition, we varied instructions, in order to determine the role of strategies. The main findings were that (a) Brocas show stronger syntactic priming effects than controls; (b) the effects are automatic rather than strategic; and (c) in conditions with priming, Brocas produce relatively complex sentences (e.g., passives). We discuss these results in relation to capacity theories.

Syntactic persistence in Dutch.

Three experiments are reported that showed effects of "structure priming," the tendency to repeat syntactic structure across successive sentences. These effects were demonstrated in a previously untested language, Dutch. All experiments studied spoken sentence production. Importantly, pre-experimental baselines were measured for all target structures in order to assess possible effects of frequency on the magnitude of priming effect. We obtained priming with dative sentences, including datives with medially placed prepositional phrases, a sentence type not tested before. In one experiment we obtained priming effects with passives, including passives with sentence-final verbs, which also have never been tested before. However, we failed to obtain priming effects with active transitives. A comparison with the baseline data suggested that priming is not related to baseline frequency. Further, the results allowed us to draw an empirical generalization: Structure priming is a relatively long-term event, lasting at least several trials. The implications of these findings are discussed.

The federated healthcare record to support shared diabetes care.

In this paper the conception of the federated healthcare record server to support shared diabetes care is described. Business process modelling is applied to describe the shared care for diabetes patients. Typical dialogues between the different users (patient, internist, GPs, and diabetic nurses) are analysed and described in terms of use cases. Next to this modelling three incremental steps are defined to realise the record server based upon results of standardisation. It proves to be successful to design and build this record server on modern technologies like CORBA and JAVA.

Supporting shared care for diabetes patients. The synapses solution.

In this paper we discuss the construction of a Federated Health Care Record server within the context of the European R&D project Synapses. We describe the system using the five ODP viewpoints. From an analysis of the business process to be supported by the distributed system (the shared care for diabetes patients) requirements for the server are derived.

Judgments of semantic anomaly in agrammatic patients: argument movement, syntactic complexity, and the use of heuristics.

Two studies on the judgment of semantic anomaly of sentences in agrammatic aphasia are reported. The primary question was whether performance on this task would be negatively affected by sentence complexity. In a first experiment, we repeated part of the study by Schwartz, Linebarger, Saffran, and Pate (Language and Cognitive Processing, 2, 85-113, 1987). With a group of 15 Dutch-speaking agrammatics, we obtained a small but significant negative effect of "lexical padding": sentences like "#the puppy ran around excitedly and accidently dropped the little boy onto the wet grass which upset Louise" elicited more errors than their simple counterparts, "#the puppy dropped the little boy." In our second study, we looked at (a) the effect of sentence embedding (e.g., "the doctor, who was tired of climbing a staircase, examined the patient") and (b) the effect of incorporating a "distractor agent" in the sentences, that is, an NP that could serve as a possible agent of the critical action (e.g., "the doctor, who had talked to the nurse, examined the patient"). In addition we employed sentences with moved arguments (e.g., "it was the patient who the doctor examined"). There were two major conclusions. First, syntactic complexity has a strong negative effect on anomaly judgments. Second, patient use a linear-order strategy to deal with the task. Results are discussed in terms of a range of recent approaches to agrammatic comprehension, not only representational hypotheses, based upon linguistic theory, but also processing accounts.

A time-based approach to agrammatic production.

A time-based approach to agrammatic speech is presented. The paper consists of three parts. In the first part, the literature which deals with agrammatic comprehension as a problem of disrupted timing, that is, as a slow-down of syntactic computation and/or a rapid decay of the results of syntactic processing, is reviewed. In a second part, the hypothesis that similar timing problems cause difficulties in production as well is discussed. Two possible ways in which this can happen are described. First, slow down or rapid decay can lead to desynchronization within the process of syntactic tree formation. Second, a slow down of syntactic processing can cause asynchrony between the production of a syntactic slot and the retrieval of the proper grammatical morpheme from the mental lexicon. This hypothesis predicts that morphemes which are dependent on a relatively complex part of the syntactic tree will elicit relatively many errors. Results from the literature which seem to confirm this prediction are discussed. In the third part of the paper, the possible ways in which a patient can adapt to the reduced temporal window that would result from a timing deficit are discussed. Message simplification will reduce the size of the required temporal window and will therefore have a beneficial effect on the error rate. Restart of the computational process will profit from previously reached activation levels so that synchrony is easier to reach and error rate is reduced. Empirical work which appears to support these hypotheses is reviewed.

On-line sensitivity to subject-verb agreement violations in Broca's aphasics: the role of syntactic complexity and time.

This study examined on-line sensitivity to subject-verb agreement violations in patients with Broca's aphasia and age-matched controls using a word monitoring paradigm. The agreement violations were couched in either simple or complex syntactic frames. In a first experiment, these syntactic frames were immediately followed by the noun phrase containing the target, whereas in the second experiment a 750-msec separation was introduced. The main finding of the first experiment was that patients with Broca's aphasia showed an agreement effect only for simple (i.e., conjoined) sentences but not for complex (i.e., embedded) ones, while controls showed the expected agreement effect for both. The results of the second experiment demonstrated further that the 750-msec delay in target presentation abolished the agreement effect in Broca's aphasics but not in normal controls. The findings are interpreted to suggest that Broca's suffer from a pathological limitation in parsing capacity, giving rise to a faster than normal decay of syntactic information.

The effects of task variation on the production of grammatical morphology in Broca's aphasia: a multiple case study.

Generally task variation is not taken into account in discussions about agrammatism in Broca's aphasia. Both free speech and speech under constrained conditions are classified as "agrammatic speech." In this study, we investigated the effects of task variation on the character of agrammatic speech. We employed three types of task situations, an interview and two picture description tasks, to elicit speech from 16 Dutch and 3 German Broca's aphasics. The two picture description tasks differed in the extent to which they necessitated the production of grammatical morphology. Various task-dependent changes in the character of agrammatic speech were observed. Overall, omission rates of grammatical morphemes went down and substitution rates tended to go up in picture description as compared to free conversation. Results are discussed by contrasting two explanatory concepts, task interaction and strategic variation.