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Biomedical subjects

B R Bloem

Publications and source records attributed to B R Bloem.

15 recordsLinked to original sources

Spread of herpes simplex virus to the cerebrospinal fluid and the meninges in experimental mouse encephalitis.

The development of the inflammatory response within the brain, meninges and cerebrospinal fluid (CSF) compartment has been studied for the first time simultaneously in experimental herpes simplex virus (HSV) encephalitis after inoculation via the cornea. Two major viral pathways were found from the eye to the brain: one through the trigeminal nerve to the brain stem and one through the nasolacrimal duct to the olfactory system. Viral antigen was found to be present in the CNS before there were clinical signs or cellular infiltration of brain tissue. Subsequently, the virus spread to all parts of the trigeminal brain stem complex. This phenomenon was accompanied by severe inflammation of the meninges covering the trigeminal root near its entry into the brain stem. The meninges near the entry of the olfactory fila also contained antigen. However, HSV-1 did not spread along meningeal rami of the trigeminal nerve and, consequently, is--at least in this experimental model--not a route to reach the inferior frontal and temporal lobes. The development of CSF changes followed the histopathological development of meningitis and encephalitis closely. HSV-DNA could be detected in the CSF from day 4 post inoculation (p.i.) and HSV-1-specific immunofluorescence in CSF cells was convincingly present on day 5 p.i.; on the same days (4 and 5 p.i.) inflammatory cells were found in apposition to infected cells in the brain. We postulate that HSV is carried to the CSF by infected leukocytes rather than a direct spread to the CSF by simple extension of the encephalitic process to the meningeal surface.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Are medium and long latency reflexes a screening tool for early Parkinson's disease?

We have studied whether assessment of medium latency (ML) and long latency (LL) reflex amplitudes may serve as a marker for early Parkinson's disease. Twenty-three patients with idiopathic Parkinson's disease (Hoehn and Yahr stage 1 to 4) and 24 controls received 20 4 degrees toe-up rotations of a platform upon which they were standing. All antiparkinsonian medication was withheld for at least 12 h before the study. ML reflexes in the stretched gastrocnemius muscle and LL reflexes in the shortened tibialis anterior muscle were recorded from both legs. ML responses were significantly enhanced in patients compared to controls. In contrast to previous studies which studied patients who continued their usual treatment, we observed that LL responses were significantly reduced in patients compared to controls. For the purpose of individual analysis, we subsequently determined the optimal specificity and sensitivity using various criteria for abnormality. The presence of either enhanced ML responses or reduced LL responses (or both) in at least one leg yielded a maximum sensitivity of 65.2% with a specificity of 75.0% (positive likelihood ratio 2.6; negative likelihood ratio 0.5). Abnormal reflexes were almost exclusively present in patients with advanced and long-standing Parkinson's disease. These results show abnormalities of ML and LL responses in advanced Parkinson's disease, but render it unlikely that these abnormalities are a suitable screening tool for early stages of the disease. The fact that LL responses were reduced in patients taken off antiparkinsonian medication raises the possibility that this reflex is under supraspinal dopaminergic control.

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Postural instability in Parkinson's disease.

Postural instability is one of the most disabling features of Parkinson's disease. Many factors contribute to balance impairment of Parkinson patients, including disturbed postural reflexes and poor control of voluntary movement. Additional factors which place Parkinson patients at risk for falls are side-effects of medication (dyskinesias), the poor response of postural instability to antiparkinsonian medication, orthostatic hypotension, gait abnormalities, muscular weakness in leg muscles and superimposed age-related changes such as reduced peripheral sensation. Future studies should not only investigate means of preventing falls in unstable patients, but should also be directed towards development of new treatment. Because accumulating evidence indicates that postural instability is at least partially related to non-dopaminergic lesions, these novel therapeutic approaches should be aimed at overcoming non-dopaminergic neurotransmitter deficiencies.

Humans

Altered postural reflexes in Parkinson's disease: a reverse hypothesis.

In subjects standing on a movable platform, sudden dorsiflexion of the ankle joint elicits a set of reflexes in leg muscles. These responses include a short latency (SL) and medium latency (ML) stretch reflex in the gastrocnemius muscle and a distal to proximal innervation sequence of long latency (LL) reflexes in the shortened tibialis anterior and vastus lateralis muscles. Because of their role in maintaining upright stance these responses have been termed postural reflexes. In patients with Parkinson's disease (PD), the following abnormalities have been described: 1) enhanced ML-amplitudes; 2) a reversed LL innervation sequence; and 3) delayed onset latencies. These abnormalities are thought to be due to defective motor programming and disturbed control of spinal and supraspinal reflex centers by basal ganglia circuits. The altered reflexes have been held responsible for some of the clinical features of PD, including balance impairment and rigidity. In this paper, we argue the reverse hypothesis that postural reflexes are essentially normal in PD, and that the observed alterations are at least in part consequence rather than cause of balance impairment, the stooped parkinsonian posture and rigidity of PD patients.

Humans

Polymerase chain reaction for early detection of HSV-DNA in cerebrospinal fluid: an experimental mouse encephalitis study.

A series of experiments was carried out using a mouse HSV-1 encephalitis model for detecting HSV-DNA in CSF by the polymerase chain reaction (PCR). The results were correlated with the time period after corneal inoculation, clinical signs and symptoms, and progression of infection in brain tissue (antigen detection and histopathology), and were compared with virus isolation by spin-amplified culture (SAC/IF). The PCR proved to be superior to SAC/IF, both with respect to early detection and the percentage of positive samples. The results of PCR did not correlate with signs of disease, nor with the interval post-inoculation. A correlation with the spread of HSV within the brain tissue was found. The possible pathways for virus spread from brain parenchyma to the CSF as well as a possible explanation for the low amounts of virus and viral-DNA within the CSF are discussed.

Animals

Electrophysiological correlates of postural instability in Parkinson's disease.

Postural reflexes in response to sudden toe-up tilts of a supporting forceplate platform were studied in free-standing patients with stage III (N = 5) and stage IV (N = 5) Parkinson's disease and compared to 5 age- and sex-matched normals. Latencies of the short (SL), medium (ML) and long latency (LL) responses were normal in the patients. The normalized mean amplitudes of the ML responses were significantly increased only in the stage IV Parkinson patients (P less than 0.0005). The distal-proximal activation sequence of LL responses observed in all 5 controls was reversed in 1 of the stage III and 4 of the stage IV Parkinson patients. Both the enlargement of the ML response (P less than 0.01) and the inverted activation sequence of LL responses (P less than 0.01) were significantly correlated with severity of the disease. The data establish an association between abnormal modulation of postural reflexes in the lower extremity and clinically rated balance impairment in Parkinson's disease.

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Long latency postural responses are functionally modified by cognitive set.

We examined how cognitive set influences the long latency components of normal postural responses in the legs. We disturbed the postural stability of standing human subjects with sudden toe-up ankle rotations. To influence the subjects' cognitive set, we varied the rotation amplitude either predictably (serial 4 degrees versus serial 10 degrees) or unpredictably (random mixture of 4 degrees and 10 degrees). The subjects' responses to these ankle rotations were assessed from the EMG activity of the tibialis anterior, the medial gastrocnemius, and the vastus lateralis muscles of the left leg. The results indicate that, when the rotation amplitude is predictable, only the amplitude of the long latency (LL) response in tibialis anterior and vastus lateralis varied directly with perturbation size. Furthermore, when the rotation amplitude is unpredictable, the central nervous system selects a default amplitude for the LL response in the tibialis anterior. When normal subjects are exposed to 2 perturbation amplitudes which include the potential risk of falling, the default LL response in tibialis anterior appropriately anticipates the larger amplitude perturbation rather than the smaller or an intermediate one.

Adult

Postural reflexes in patients on long-term neuroleptic medication.

It is not conclusively known whether the amplitude of medium latency postural reflexes is controlled by dopamine. To further assess the influence of supraspinal dopaminergic pathways on postural reflexes, we studied short (SL), medium (ML) and long latency (LL) reflexes in the lower extremity of 10 patients on long term (greater than 6 months) neuroleptic medication, 5 with and 5 without mild drug induced parkinsonism. A control group consisted of 10 age and sex matched healthy volunteers. In both patient groups, latencies and amplitudes of all 3 responses were identical to normal controls. These findings suggest that a moderate postsynaptic inhibition of central dopaminergic pathways is insufficient to cause enhanced amplitudes of ML responses.

Adult

Cognitive function after spinal or general anesthesia for transurethral prostatectomy in elderly men.

Cognitive functions in 53 elderly men who underwent a transurethral prostatectomy were assessed pre-operatively and 4 days and 3 months post-operatively. Thirteen patients had a preference for one particular type of anesthesia, and the remaining 40 were randomly allocated to receive either spinal or general anesthesia. Cognitive function was not different between the groups receiving different types of anesthesia at either time point and did not decrease post-operatively. No pre- or perioperative variable could distinguish the subgroup of patients who had a post-operative decrease of 2 points or more on the Mini-Mental State Examination. No difference in post-operative performance was found in the patient groups with pre-operative Mini-Mental State Examination scores above or under their age-specific norm. It is concluded that neither hospitalization nor the two forms of anesthesia investigated cause a decrease in cognitive function in elderly men.

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Detection of herpes simplex virus in the ependyma of experimentally infected mice.

Forty-five Swiss albino mice were inoculated with HSV-1 (strain McKrae) by the corneal route. The spread of HSV to the brain stem and the ventricular ependyma was investigated. The polymerase chain reaction (PCR) was used to detect HSV-DNA in the CSF during the course of infection. The ependyma of the third and fourth ventricle and the central canal contained viral antigen at a late stage of infection in up to 60% of mice. At this stage we found that many animals gave a positive PCR in the CSF although no antigen could be detected in the ependymal cells. The presence or absence of antigen containing cells could not be related to detection of HSV-DNA in the CSF. The results show that infection of the ventricular wall is not important for the spread of HSV to the CSF.

Animals

Hereditary cerebral hemorrhage with amyloidosis--Dutch type. Tc-99m HM-PAO single photon emission computed tomography.

We performed single photon emission computed tomography (SPECT) and cerebral CT-scans in nine patients with hereditary cerebral amyloid angiopathy. CT-scans showed 23 focal hypodense lesions, 13 of which were visible on SPECT as a CBF-defect. One patient showed a CBF-defect on SPECT without CT-scan lesion and had a cerebral hemorrhage three months later in that particular region. In two additional patients, who were 50% at risk for this autosomal dominant disease, CBF-defects on SPECT, but no cortical lesions on CT-scan were found. CT-scans may be more sensitive than SPECT to detect chronic lesions caused by cerebral hemorrhages, but another possibility is that hemorrhages do not always lead to persistent CBF-defects. SPECT can show the effect of amyloid deposits on CBF before the angiopathy causes clinical symptoms.

Amyloidosis

The MPTP model: versatile contributions to the treatment of idiopathic Parkinson's disease.

In human and subhuman primates, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) produces irreversible clinical, biochemical and neuropathological alterations highly reminiscent of those observed in Parkinson's disease. The MPTP model has provided the best available tool to date for the assessment of efficacy and side-effects of symptomatic treatments of Parkinson's disease. In addition, the mechanism of action of MPTP has offered a basis for the development of novel therapeutic strategies aimed at the prevention of Parkinson's disease.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine

Polymerase chain reaction and viral culture techniques to detect HSV in small volumes of cerebrospinal fluid; an experimental mouse encephalitis study.

A technique is described for the detection of HSV-DNA in very small volumes (5-10 microliters) of cerebrospinal fluid (CSF). The method was evaluated in CSF samples of 4-6-week-old mice inoculated with HSV-1 via the corneal route. The sensitivity of the PCR assay was compared with results of spin-amplified viral culture with immunofluorescent visualization (SAC/IF), routine viral culture (RVC) and radioactive dot-blot hybridization (DBA) in CSF samples obtained from other mice. The results show the PCR to be superior over the other techniques: infectious virus or viral DNA in CSF was demonstrated by PCR, SAC/IF, RVC and DBA in 68, 55, 20 and 2.5%, respectively. These results show the feasibility of the PCR for a rapid, non-invasive diagnosis of human HSV-encephalitis.

Animals

Investigation of gait in elderly subjects over 88 years of age.

To evaluate senile gait patterns in octagenarians and nonagenarians, we provided a standardized questionnaire on gait disabilities to 153 elderly subjects over 88 years of age. Subjects represented a relatively healthy subgroup of noninstitutionalized residents who participated in a gerontological survey of all inhabitants of the city of Leiden who were 85 years of age or older. Of the 142 subjects who responded to this questionnaire, 87 persons (61%) claimed distinct diseases as a cause of gait impairment. Forty-two of the remaining 55 persons were investigated neurologically and received a standardized assessment of gait. Twenty-five persons (18% of all responders) had a completely normal gait, whereas a wide spectrum of gait abnormalities--mainly with ataxic features--was encountered in the remaining persons. It is concluded that a surprisingly high number of very old community residents can have a completely normal gait. Gait disorders in this age group are most frequently associated with common distinct diseases. In addition, many elderly have a gait disturbance of variable clinical nature and unclear pathologic basis, which may represent the "idiopathic senile gait."

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