Subclinical neurotoxicity of mercury vapor revealed by a multimodality evoked potential study of chloralkali workers

Pattern visual, brainstem auditory, and somatosensory evoked potential (EP) studies were performed on 26 chloralkali workers. The intensity of mercury vapor exposure in these workers was estimated from the individual working history. Mercury levels in blood, urine, and hair were determined with atomic absorption spectrometry. The EP findings were compared with those from individually matched normal subjects. In brainstem auditory and somatosensory EP studies, prolonged neural conduction times in the central nervous system (CNS) were found in workers exposed to mercury vapor. In the pattern visual EP study, mercury workers had higher interpeak amplitudes. Findings of this study suggested that chronic exposure to mercury vapor would affect the CNS functions. A multimodality EP study is a useful adjunct in evaluation of chronic mercury neurotoxicity, especially in an epidemiological study.     

Postictal Language Dysfunction in Patients with Right or Bilateral Hemispheric Language Localization

Summary: Purpose : As shown previously, when temporal lobe complex partial seizures (TLCPS) originate from the language dominant hemisphere, patients cannot read a test phrase correctly within 60 s of the end of the ictal discharge. We wished to assess whether postictal language testing results discordant with this pattern identified patients with non-left (right hemisphere or mixed) language dominance.
Methods : Since 1988, all patients undergoing video/EEG monitoring at our institution have been given a test phrase to read aloud as soon as a seizure is detected. Inclusion criteria for this study were (a) postictal language testing within 60 s of seizure end for at least one TLCPS, (b) >90% seizure reduction after anterior temporal lobectomy with 2-year minimum follow- follow- up, and (c) language localization by either intracarotid amobarbital test (IAT) or direct electrical stimulation of left hemisphere cortex.
Results : Two hundred twenty-four seizures in 64 patients were analyzed. Discordant postictal language patterns were noted in 10 of 11 patients with IAT documented non-left language dominance and in 15 of 53 with left dominance (p = 0.006; sensitivity 90.9%, specificity 71.7%).
Conclusions : Postictal language testing accurately identifies patients with non-left language dominance and may be useful in selecting appropriate patients for IAT.     

Catabolic effect in premature infants with early dexamethasone treatment

To evaluate the catabolic effects of dexamethasone therapy on protein metabolism, amino acid concentrations and urinary 3-methylhistidine (3MH) were measured in 28 premature infants who were included in a double-blind controlled study using early dexamethasone therapy in the prevention of bronchopulmonary dysplasia. Fifteen infants received dexamethasone (0.5mg/kg/day i.v.) and 13 infants received normal saline as control. Heparinized venous blood samples for amino acid analysis were obtained before the study and again at day 5 after starting the study. Urinary 3MH was measured on days 1, 3, 5, 7, 14, 21, and 28 of treatment. A substantial increase in amino acid concentrations was observed in infants receiving dexamethasone. Alanine, glutamine, citrulline, ornithine and cystine concentrations increased twofold or more. The 3MH:creatinine ratio was increased in the treated group. These metabolic effects were most likely due to an increase in protein catabolism.     

Effects of age and chronic renal failure on the urinary excretion kinetics of famotidine in man

Summary The plasma and urine concentrations of famotidine, a new, potent H₂-receptor antagonist, have been measured in 16 healthy young adults, 8 healthy elderly people and 18 patients with varying degrees of renal dysfunction after intravenous administration.Both the plasma elimination and renal excretion of famotidine were decreased in the elderly volunteers and renal patients. The renal clearance of famotidine averaged 4.43 ml/min/kg (310 ml/min) in normal young volunteers, which exceeded the mean creatinine clearance 1.55 ml/min/kg (109 ml/min), suggesting net secretion is a significant mechanism for elimination of famotidine.The ratio of famotidine renal clearance to creatinine clearance decreased as creatinine clearance decreased; these results suggest that the deterioration in the secretion process was much faster than that in glomerular filtration and are incompatible with the intact nephron hypothesis. Nevertheless, both total body clearance and renal clearance were significantly correlated with creatinine clearance.The apparent half-life was also significantly correlated with creatinine clearance. Since famotidine is essentially free of dose-related adverse effects, dose adjustment in patients with mild renal insufficiency and in elderly people is not required; however, either a prolonged dosing interval or a decrease in daily dose during long-term therapy may be adapted for the patients with severe renal insufficiency to avoid accumulation and the potential undesirable effects.     

Dose-response curves of homovanillic acid in pre-frontal cortex and caudate following antipsychotic drugs: relation to clinical potencies

Dose-response curves for the elevation of homovanillic acid (HVA) levels, determined by high performance liquid chromatography using electrochemical detection, in the pre-frontal cortex and caudate of rats after acute treatment with 12 antipsychotic drugs are presented. The order of potency in both brain regions was: haloperidol fluphenazine > loxapine > trifluoperazine > thiothixene > molindone > clopenthixol > chlorpromazine > metoclopramide > thioridazine > clozapine > sulpiride. This ranking is roughly correlated with that based on clinical potencies. The relative elevation of the content of HVA was weaker in the pre-frontal cortex than in the caudate for all drugs tested, except clozapine at a high dose.     

Irregular connexin43 expressed in a rare cardiac hamartoma containing adipose tissue in the crista terminalis

Cardiac hamartomas are very rare and are demarcated masses of enlarged, hypertrophied, mature myocytes and collagen tissue. Cardiac hamartomas are generally circumscribed in the right ventricle or atrium, but not reported in the crista terminalis (CRT). The CRT is crucial in electrophysiology, is related to arrhythmogenesis, and is targeted by radiofrequency catheter procedures. Previous works only described the benign natures of prominent CRT using non-invasive methods. This study describes an unusual cardiac hamartoma originating from the CRT and extending toward the tricuspid valve. Microscopically, this hamartoma comprised dense collagen and adipose tissue, mixed with hypertrophy, but with disarrayed cardiomyocytes. An irregular gap junction, connexin43, was demonstrated in this cardiac hamartoma.     

Androgen receptor YAC transgenic mice carrying CAG 45 alleles show trinucleotide repeat instability

X-linked spinal and bulbar muscular atrophy (SBMA) is caused by a CAG repeat expansion in the first exon of the androgen receptor (AR) gene. Disease-associated alleles (37-66 CAGs) change in length when transmitted from parents to offspring, with a significantly greater tendency to shift size when inherited paternally. As transgenic mice carrying human AR cDNAs with 45 and 66 CAG repeats do not display repeat instability, we attempted to model trinucleotide repeat instability by generating transgenic mice with yeast artificial chromosomes (YACs) carrying AR CAG repeat expansions in their genomic context. Studies of independent lines of AR YAC transgenic mice with CAG 45 alleles reveal intergenerational instability at an overall rate of approximately 10%. We also find that the 45 CAG repeat tracts are significantly more unstable with maternal transmission and as the transmitting mother ages. Of all the CAG/CTG repeat transgenic mice produced to date the AR YAC CAG 45 mice are unstable with the smallest trinucleotide repeat mutations, suggesting that the length threshold for repeat instability in the mouse may be lowered by including the appropriate flanking human DNA sequences. By sequence-tagged site content analysis and long range mapping we determined that one unstable transgenic line has integrated an approximately 70 kb segment of the AR locus due to fragmentation of the AR YAC. Identification of the cis - acting elements that permit CAG tract instability and the trans -acting factors that modulate repeat instability in the AR YAC CAG 45 mice may provide insights into the molecular basis of trinucleotide repeat instability in humans.      

Automated, quantitative cytopathic effect reduction assay for interferon.

A rapid, cytopathic effect reduction assay for human interferon (IFN) is described. Dilutions of IFN were made with an automated diluter in 96-well microtiter plates. Total incubation time was 26 h. IFN titers were calculated from optical density readings of crystal violet-stained monolayers in an automated spectrophotometer, which required less than 1 min to read each plate.     

Serologic and molecular detection of granulocytic ehrlichiosis in Rhode Island.

A new indirect fluorescent-antibody (IFA) assay with antigen produced in vitro in the human promyelocytic leukemia cell line HL60 was used to identify the first recognized case of human granulocytic ehrlichiosis in Rhode Island. This IFA assay was used to detect granulocytic ehrlichiae in white-footed mice and in a dog inhabiting the area surrounding the patient's residence. Host-seeking Ixodes scapularis ticks found in the same habitat also were infected. I. scapularis ticks collected from other locations were fed on dogs and New Zealand White rabbits to assess the competency of these species as hosts of granulocytotropic Ehrlichia. Tick-induced infections of dogs were confirmed by serologic testing, tissue culture isolation, and PCR amplification, whereas several rabbits seroconverted but were PCR and culture negative. PCR amplification of the 16S rRNA gene and DNA sequencing of the PCR products or culture isolation was used to confirm granulocytic Ehrlichia infections in humans, dogs, white-footed mice, and ticks.