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Biomedical subjects

W R Lin

Publications and source records attributed to W R Lin.

At least 19 recordsLinked to original sources
PubMed2002

Bilateral isolated hippocampal malformation in temporal lobe epilepsy.

Hippocampal malformations in patients with epilepsy usually are reported in the context of widespread cortical malformations. Isolated hippocampal malformations are more rarely identified in MRI studies with little documentation of their pathologic appearance. Postmortem examination revealed abnormal position and complex convolutional malformations isolated to the hippocampal formation in an adult with temporal lobe epilepsy in whom MRI demonstrated bilateral hippocampal abnormalities.

Epilepsy, Complex Partial↗
PubMed2001

Multidrug-resistance protein 1 in focal cortical dysplasia.

Drug resistance in epilepsy is poorly understood. We used routine immunohistochemistry to assess overexpression of a multidrug-resistance protein in dysplastic neurons, glia, and around vessels in surgically resected epileptogenic human brain tissue. We showed non-tumoral overexpression of this multidrug-resistance protein, which might contribute to drug resistance in epilepsy caused by focal cortical dysplasia.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2001

Eosinophilic meningitis caused by Angiostrongylus cantonensis: report of 17 cases.

PURPOSE: To describe two outbreaks of Angiostrongylus cantonensis infection that occurred in Kaohsiung, Taiwan, during 1998 and 1999, and to characterize the source of the outbreaks and the clinical manifestations of the disease. SUBJECTS AND METHODS: We performed a retrospective cohort study among Thai laborers with eosinophilic meningitis who ate raw snails (Ampullarium canaliculatus), as well as an environmental surveillance of larvae in snails. RESULTS: We enrolled 17 Thai laborers in whom severe headache and eosinophilia developed within 4 to 23 days after eating raw snails. Twelve (71%) developed eosinophilic meningitis. Third-stage larvae were found in the cerebrospinal fluids of 2 patients and in all 12 tested snails. Specific antibodies to A. cantonensis were detected in serum from 16 of the patients and in cerebrospinal fluid from 5 of the patients. Central nervous system manifestations included headache (n = 17 [100%]), fever (n = 11 [65%]), Brudzinski's sign/stiff neck (n = 11 [65%]), hyperesthesia (n = 3 [18%]), cranial nerve palsy (n = 2 [12%]), diplopia (n = 2 [12%]), and ataxia (n = 1 [6%]). Laboratory findings included peripheral eosinophilia (n = 15 [88%]) and cerebrospinal fluid eosinophilia (n = 12 [71%]); elevated immunoglobulin (Ig) E levels (n = 13 [100%]); and transient increases in white blood cell count (n = 7 [41%]) and in serum levels of creatine kinase (n = 7 [41%]), transaminase (n = 3 [18%]), and lactate dehydrogenase (n = 2 [12%]). The severity of illness and eosinophilia were correlated with the number of ingested snails. Meningeal and basal ganglion enhancement was noted on magnetic resonance imaging in several patients. Treatment with mebendazole combined with glucocorticosteroids appeared to shorten the course of the infection, but not the number of relapses. The eosinophil count fell to normal within 3 months, but IgE levels remained elevated for as long as 6 months. All patients recovered with minimal neurologic sequelae. CONCLUSION: Eosinophilic meningitis caused by A. cantonensis should be considered in patients who have headache or central nervous system manifestations after eating raw snails.

Adult↗
PubMed2001

Persistent reelin-expressing Cajal-Retzius cells in polymicrogyria.

Cajal-Retzius (CR) cells are early-developing cells important in mammalian corticogenesis. Reelin, a protein secreted by CR cells, is essential for completion of neuronal migration and cortical lamination. Lack of reelin causes the 'reeler' phenotype in mice and autosomal recessive lissencephaly with cerebellar hypoplasia in man. Focal increases in reelin and CR cells are associated with thickening and local invaginations of the marginal zone and microgyria in animal studies. It has been suggested that abnormalities of reelin expression may be involved in human polymicrogyria. We have studied CR cells and reelin expression in pathological sections of human polymicrogyria to explore this possibility. Occurrence, distribution, morphology and reelin expression in CR cells were studied in 12 cases of human polymicrogyria, ranging from 21 gestational weeks to 10 years of age. Findings were compared with age-matched controls. Large, reelin-positive CR-like cells were more numerous in the majority of the polymicrogyria cases and persisted for longer than usual, up to 10 years of age. The CR-like cells tended to cluster and were most frequent in fused molecular layers in the polymicrogyria. Reelin-expressing CR-like cells were also found in bridges between the molecular layer and overlying leptomeningeal heterotopia and within the heterotopia itself. Clusters of CR-like cells were also found in adjacent non-polymicrogyric cortex. No clusters were seen in the control subjects. Increased numbers of CR-like cells were seen in both familial and acquired cases. In contrast to previous reports, the findings show that large CR-like cells persisted for longer than usual, up to 10 years of age, and that they may continue to express reelin. Their maximal aggregation in regions of polymicrogyria and overlying leptomeningeal heterotopia suggest an association between the presence of these cells and polymicrogyria, which we interpret in the light of recent findings concerning the roles of reelin and its downstream signalling pathway in neuronal and glial developmental dynamics and post-developmental function.

Aging↗
PubMed2001

Herpes simplex encephalitis: involvement of apolipoprotein E genotype.

It was previously found that herpes simplex type 1 virus (HSV1) when present in the brain, is a risk factor for Alzheimer's disease in carriers of the type 4 allele of the gene for apolipoprotein E (apoE epsilon4), and apoE epsilon4 is a risk factor for herpes labialis. Whether a specific allele of the gene is involved in susceptibility to another disorder caused by HSV1-herpes simplex encephalitis (HSE)-has now been investigated. DNA was prepared from formalin-fixed, paraffin-embedded blocks of specimens from the brain or spleen of 14 United Kingdom patients with HSE, confirmed by necropsy, and from the CSF of seven United Kingdom clinical patients with HSV1 in their CSF detected by polymerase chain reaction (PCR). ApoE genotype of the DNA from blocks was determined by seminested PCR, and of the DNA from CSF by one step PCR, followed by restriction endonuclease digestion. The apoE allele frequencies were compared with values previously obtained for 238 normal people from the United Kingdom. The apoE epsilon2 allele frequency of the patients with HSE was 26%, significantly higher than the value of 7% for the normal subjects (OR=4.6, 95% confidence interval (95% CI) 2. 0-10.8). The apoE epsilon3 and epsilon4 allele frequencies did not differ significantly between the two groups. Thus, it seems that apoE epsilon2 is a risk factor for HSE.

Adolescent↗
PubMed2001

An outbreak of meningitis caused by Angiostrongylus cantonensis in Kaohsiung.

Eight Thai laborers developed meningitis after eating raw snails (Ampullarium canaliculatus) during the period from September 27 to October 6, 1998. The diagnosis of Angiostrongylus cantonensis infection was established in all patients by serologic studies of serum and cerebral spinal fluid (CSF). Clinical manifestations included meningitis, radiculitis and cranial nerve palsy. Symptoms included fever, headache, orbital pain, gastrointestinal upset, hyperesthesia, muscle weakness, skin rash and diplopia. Laboratory abnormalities included peripheral eosinophilia, CSF eosinophilia, transient elevation of liver enzymes and creatinine phosphokinase, elevation of IgE. No space occupying lesions were detected by magnetic resonance imaging of the brain. None of the patients developed severe sequelae during the 6-month follow-up except for occasional headache in one patient. This report also provides evidence that third stage larvae were present in the intermediate host, A. canaliculatus, which the laborers had eaten.

Adult↗
PubMed2001

Comparative study of the efficacy and safety of valaciclovir versus acyclovir in the treatment of herpes zoster.

Acyclovir, a specific and selective inhibitor of the replication of Herpesviridae family, has well-documented efficacy and tolerability in the treatment of herpes zoster. Its limited oral bioavailability and short half-life, however, necessitates frequent dosing. Valaciclovir, the l-valyl ester of acyclovir, could be rapidly converted to acyclovir after oral administration, resulting in a three- to five-fold increase in acyclovir bioavailability compared with oral acyclovir in humans. Valaciclovir allows less frequent dosing and maintains the safety profiles of the parent drug. During the period from October 1996 through May 1998, a randomized, prospective study was performed in the Kaohsiung Veterans General Hospital to compare the safety and efficacy of valaciclovir with acyclovir in the treatment of herpes zoster in Taiwanese patients. Patients presenting with herpes zoster within 72 h after the onset of rash were enrolled and randomized to receive one of the following treatments: 1000 mg valaciclovir three times daily for 7 days or acyclovir 800 mg five times daily for 7 days. Patients were followed up for 29 days beginning with the start of therapy. A total of 57 patients were enrolled and randomized to receive valaciclovir (n = 32) or acyclovir (n = 25). Five patients in the valaciclovir group and three in the acyclovir group did not complete the study. The intent-to-treat analysis (57 patients) showed that valaciclovir significantly accelerated the resolution of herpes zoster-associated pain compared with acyclovir; on day 29, the valaciclovir group was 23% superior to the acyclovir group. There was no clinically significant difference in the nature, frequency or severity of adverse events between these two groups, although one and three adverse events were reported in the acyclovir and valaciclovir group, respectively. Thus, we conclude that in the management of herpes zoster, valaciclovir accelerates the resolution of pain and offers a simpler dosing, and maintains the favorable safety profile of acyclovir.

Acyclovir↗
PubMed2001

Legionnaires' disease in an immunocompetent young adult.

Infection with Legionella pneumophila (LP) is a rare cause of pneumonia in previously healthy young adults. Pleural effusion is relatively common in Legionnaires' disease but is usually clinically insignificant. Herein we describe an immunocompetent, 19-year-old female with LP respiratory infection that presented with pleural effusion and mild interstitial infiltrates in the lower lungs. She received 3 weeks' treatment with erythromycin and rifampin and recovered completely. Diagnosis was based on serology testing with a four-fold rise of the antibody titer in the acute and convalescent phase. Legionnaires' disease should be considered in the differential diagnosis of culture-negative pleural effusion in immunocompetent young adults.

Adult↗
PubMed1999

Apolipoprotein E and herpes virus diseases: herpes simplex keratitis.

Our previous studies showed that herpes simplex type 1 virus (HSV1) is present in a high proportion of the brain of elderly normal people and Alzheimer's disease (AD) patients. We subsequently discovered that the combination of HSV1 in brain and carriage of the type 4 allele of the gene for apolipoprotein E (apoE-epsilon 4) is a strong risk factor for AD, and also that apoE-epsilon 4 is a strong risk factor for herpes labialis. In this study we have examined apoE genotypes of sufferers from another disorder caused by HSV1, namely, herpes simplex keratitis (HSK), to find if an apoE allele is involved in the disorder. In 46 HSK patients the apoE-epsilon 4 allele frequency was 15%-the same as that found in 238 unaffected controls. The apoE-epsilon 2 allele frequency was 13%-higher than the value of 7% for unaffected people, but the difference is not statistically significant.

Adolescent↗
PubMed1999

Once daily isepamicin treatment in complicated urinary tract infections.

Isepamicin is a new aminoglycoside, derived from gentamicin B, which is more stable than other aminoglycosides against inactivating enzymes, and is less nephrotoxic. We evaluated the efficacy and safety of a once daily isepamicin in the treatment of complicated urinary tract infections (UTIs), as compared with amikacin. During the period May, 1997, to January, 1998, a total of 52 patients with similar demographic and baseline characteristics were enrolled into a prospective, randomized, open-label, single-center trial at the Veterans General Hospital-Kaohsiung. Eleven patients were excluded for protocol violation. The remaining 41 patients were included in the efficacy analysis. Study subjects included 16 men and 25 women, with a mean age of 57.9 (range 18-95) years. Clinical improvement was noted in 100% of patients in both the isepamicin and amikacin group. No statistically significant difference was observed between the 2 groups in regard to the rapidity of defervescence, relief of dysuria and urinary frequency, and clearance of bacteriuria and pyuria. Bacteriological cure rates were 89.4% for the isepamicin group and 100% for the amikacin group. Fifteen of 25 subjects who received isepamicin and 16 of 27 subjects who received amikacin had an adverse effect, all of which were considered to be mild except for one in the amikacin group, who had an adverse event of moderate severity (vomiting). Seven (3 isepamicin and 4 amikacin) adverse events were considered probably or possibly related to the study drug, which included eosinophilia (2 isepamicin), liver function impairment (1 isepamicin, 2 amikacin), renal function impairment (1 amikacin) and flushed face (1 amikacin). However, none of the patients had a life-threatening or severe adverse event that required discontinuation of the drug. These results show that once daily administration of isepamicin is as effective and safe as amikacin in treatment of complicated UTIs.

Adolescent↗
PubMed1997

Herpes simplex virus type 1 in brain and risk of Alzheimer's disease.

BACKGROUND: The apolipoprotein E epsilon 4 (APOE-epsilon 4) allele is a risk factor for Alzheimer's disease (AD), but it is neither essential nor sufficient for development of the disease. Other factors-genetic or environmental-must therefore have a role. By means of a PCR we have detected herpes simplex virus type 1 (HSV1) in latent form in brains of elderly people with and without AD. We have postulated that limited reactivation of the virus causes more damage in AD patients than in elderly people without AD because of a difference in the hosts. We now report the APOE genotypes of AD patients and non-AD sufferers with and without HSV1 in brain. METHODS: DNA was extracted from 84 samples of brain from 46 AD patients (39 temporal lobe, 39 frontal lobe, three hippocampus) and from 75 samples of brain from 44 non-AD elderly people (33 temporal lobe, 36 frontal lobe, six hippocampus). PCR amplification was used to detect HSV1 thymidine kinase gene and the host APOE gene. FINDINGS: By multiple logistic regression, the APOE-epsilon 4 allele frequency was significantly higher in the patients positive for HSV1 in brain than in the HSV1-negative AD group, the HSV1-positive non-AD group, or the HSV1-negative non-AD group (52.8% vs 10.0%, 3.6%, and 6.3%, respectively). The odds ratio for APOE-epsilon 4 in the HSV1-positive AD group compared with HSV1-negative non-AD group was 16.8 (95% CI 3.61-77.8) and in the HSV1-negative AD group, 1.67 (0.21-13.4). We also compared APOE genotypes of 40 people who had recurrent cold sores and 33 non-sufferers; the APOE-epsilon 4 allele frequencies were 36% and 9%, respectively (p < 0.0001). INTERPRETATION: These findings suggest that the combination of HSV1 in brain and carriage of an APOE-epsilon 4 allele is a strong risk factor for AD, whereas either of these features alone does not increase the risk of AD. The findings in people with cold sores support our hypothesis that APOE-epsilon 4 and HSV1 together are damaging in the nervous system.

Aged↗
PubMed1997

Neurotropic viruses and Alzheimer's disease: a search for varicella zoster virus DNA by the polymerase chain reaction.

BACKGROUND: In studies on the possible role of viruses in the aetiopathogenesis of Alzheimer's disease, herpes simplex virus type 1 (HSV1) DNA was detected by the polymerase chain reaction (PCR) in a high proportion of normal elderly people and of patients with Alzheimer's disease. The combination of HSV1 and a host factor, the type 4 allele of the gene for apolipoprotein E, is a strong risk factor for the disease. METHODS: Brain specimens were examined for another herpes virus, varicella zoster (VZV), which, like HSV1, is neurotropic, has a predilection for residing latently in the peripheral nervous system, and can reactivate. RESULTS: Using primers for sequences in the VZV origin of replication gene or thymidine kinase gene, VZV DNA was not found in any of 24 samples (18 HSV1 positive), from 17 patients with Alzheimer's disease, nor in 20 samples (12 HSV1 positive from 12 aged normal people. Hybridisation of the PCR products with a radiolabelled oligonucleotide probe capable of detecting less than 10 copies of the target sequence, confirmed the absence of VZV DNA. CONCLUSION: The presence of one neurotropic virus--HSV1--and the absence of another--VZV--in aged human brains is consistent with a role for HSV1 in the aetiology of Alzheimer's disease.

Aged↗
PubMed1993

Hippocampal CRF, NE, and NMDA system interactions in memory processing in the rat.

In the present study, we investigated the neural mechanisms of corticotropin-releasing factor (CRF) and the interactions among CRF, norepinephrine (NE), and N-methyl-D-aspartate (NMDA) systems in the dentate gyrus (DG) of hippocampus in modulating the memory process of rats. One-way passive avoidance task was adopted. Results indicated that CRF (80 ng), when directly injected into the DG, consistently and significantly enhanced memory retention in rats. The noradrenergic neurotoxin DSP-4, at a high dose (4 micrograms), impaired memory. DSP-4 at a moderate dose (2 micrograms), which did not affect retention alone, antagonized the memory-enhancing effect of CRF. Similarly, the beta-adrenergic antagonist propranolol, at a high dose (8 micrograms), reduced retention. At a low dose (80 ng), which did not markedly affect retention by itself, propranolol also prevented the memory-improving effect of CRF. Moreover, direct NE infusions to the DG significantly improved retention performance in a dose-sensitive manner. Coadministration of CRF and NE did not further enhance retention. These results together suggest that CRF and NE facilitated memory probably through the same instead of independent mechanisms. In contrast, the selective NMDA receptor antagonists 2-amino-5-phosphonopentanoate (AP5) and MK801, at high doses markedly impaired memory retention (0.8 and 3.2 micrograms for AP5, 2 and 10 micrograms for MK801). At a dose of MK801 that did not significantly alter retention alone (80 ng), it completely blocked the memory-facilitating effect of CRF. These results indicate that CRF enhanced memory indirectly through NMDA receptor mediation also. Finally, MK801 at 80 ng also successfully antagonized the memory-facilitating effect of NE in the DG. We have demonstrated that MK801, at the dose chosen for interaction studies, did not markedly alter locomotor activity. These results together suggest that CRF, through a presynaptic facilitation mechanism, possibly facilitates NE release in the DG; increased NE release and stimulation of beta-adrenergic receptors in the DG result in NMDA receptor activations in the same area. This sequence of events enhance the memory consolidation process in the hippocampus and explained the neural mechanism of CRF in facilitating retention performance in rats. The same neuropeptide/neurotransmitter interactions may have other physiological and neuropathological implications.

Adrenergic Agents↗