Effect of furosemide treatment on the central and peripheral pressor responses to cholinergic and adrenergic agonists, angiotensin II, hypertonic solution and vasopressin. The present study was performed to investigate the effect of treatment with furosemide on the pressor response induced by intracerebroventricular (i.c.v.) injections of cholinergic (carbachol) and adrenergic (norepinephrine) agonists, angiotensin II (ANGII) and hypertonic saline (HS, 2 M NaCl). The changes induced by furosemide treatment on the pressor response to intravenous (i.v.) norepinephrine, ANGII and arginine vasopressin (AVP) were also studied. Rats with a stainless-steel cannula implanted into the lateral ventricle (LV) were used. Two injections of furosemide (30 mg/kg b.wt. each) were performed 12 and 1 h before the experiments. Treatment with furosemide reduced the pressor response induced by carbachol, norepinephrine and ANGII i.c.v., but no change was observed in the pressor response to i.c.v. 2 M NaCl. The pressor response to i.v. ANGII and norepinephrine, but not AVP, was also reduced after treatment with furosemide. These results show that the treatment with furosemide impairs the pressor responses induced by central or peripheral administration of adrenergic agonist or ANGII, as well as those induced by central cholinergic activation. The results suggest that the treatment with furosemide impairs central and peripheral pressor responses mediated by sympathetic activation and ANGII, but not those produced by AVP.


Enriched environment primes forebrain choline acetyltransferase activity to respond to learning experience. Weanling rats were raised in an enriched or an impoverished environment. The enriched rats subsequently learned the Morris water maze faster than their impoverished counterparts. The enriched rats, both maze-trained and untrained, showed higher choline acetyltransferase (ChAT) activity in the caudate than did the impoverished, untrained rats. Maze training increased caudate ChAT in impoverished rats. Enriched but not impoverished rats showed increased hippocampal and anterior cortical ChAT activity after maze training. Thus, enrichment causes a long-lasting increase in caudate acetylcholine (Ach) synthesis and it also primes cortex and hippocampus to respond to a training experience with increased Ach synthesis.


Unilateral EEG activation during sleep in the Cape fur seal, Arctocephalus pusillus. Sleep and wakefulness on the land were studied electrophysiologically in one adult female Cape fur seal (Arctocephalus pusillus). In two 24-h sessions, slow-wave sleep and paradoxical sleep averaged 27.4% and 4.6% of the total recording time. Almost 40% of the total slow-wave sleep time was accounted for episodes with well-defined interhemispheric ECoG asymmetry.


Eyeblinks evoke potentials in the occipital brain region. The subjects performed voluntary eyeblinks under illuminated and dark laboratory conditions. 32-channel EEG recordings were averaged in relation to the eyeblinks and a brain electric source analysis (BESA) was performed. Two dipoles located near the eyeballs and a third dipole in the occipital region of the brain were found to explain the scalp potentials. The frontally located potentials described electromechanical potentials associated with lid movements and simultaneous eye movements. The occipitally located dipole explained a visually evoked potential with a first peak at about 180 ms after the maximum of the frontal blink potential. The visually evoked potential was observed only under illumination and was probably caused by changes in luminance during the eyeblinks.


Glial fibrillary tangles with straight tubules in the brains of patients with progressive supranuclear palsy. A recent report has described the appearance of silver positive, tau-immunoreactive astrocytes in the brains of patients with progressive supranuclear palsy (PSP) (Neurosci. Lett., 135 (1992) 99-102). In this study we confirmed this finding in two cases of PSP by using Bodian silver staining and immunohistochemistry with antibody to human tau protein. By electron microscopy we demonstrated that fibrillary masses present in these unique astrocytes were made up of straight tubules that were indistinguishable from those of neurofibrillary tangles of PSP. The term 'glial fibrillary tangle' was proposed for these structures.


Protease 'Clipsin' extract activity reflects demographic characteristics of human brain. 'Clipsin' and other peptide bond hydrolase activities that appear to be integral membrane proteins, including two implicated in the formation of the histological hallmarks of Alzheimer's disease, were assayed in the frontal and parietal cortex from a large (n = 45) series of postmortem human brains. Tissues were extracted sequentially with detergent-containing and low ionic strength buffers. The final extracts obtained with detergent-high ionic strength buffer were assayed for peptide-bond hydrolase activity using radiolabelled casein and four chromophore-linked peptide substrates. Hydrolysis of N-succinyl-Ala-Ala-Pro-Phe-p-nitroanilide and alpha-casein showed evidence of sensitivity to the presence of Alzheimer's disease (n = 22) and some of the seven other demographic features (postmortem delay; mode of death in the case of one substrate) of the brain samples considered. By contrast, activity towards carbobenzoxy(Z)-Leu-Leu-Glu-2-naphthylamide, Z-Val-Lys-Met-4-methyl-coumaryl-7-amide and Z-Val-Lys-Lys-Arg-4-methoxy-2-naphthylamide were independent of all factors. The results are discussed in terms of damage to a sub-population of protease-containing membranes.


Oestrogen infusions into the amygdala potentiate excitatory transmission from the accessory olfactory bulb to tuberoinfundibular arcuate neurones in the mouse. We have previously shown that oestrogen increases the percentage of tuberoinfundibular (TI) arcuate neurones that respond to electrical stimulation of the accessory olfactory bulb (AOB). This study focuses on the amygdala as a possible site for the hormonal modulation of AOB input to TI arcuate neurones. Local infusions of 17 beta-oestradiol (30 pmol) into the amygdala of ovariectomized female mice significantly potentiated excitatory responses of TI arcuate neurones to AOB stimulation. This effect appeared rapidly (less than 10 min) after infusion. The inactive oestrogen isomer, 17 alpha-oestradiol, infused in the same manner, was without effect. These results suggest that oestrogen acts directly on amygdala neurones, thereby modulating olfactory information relayed along the vomeronasal pathway to TI arcuate neurones.


Two populations of cells that express preprocholecystokinin mRNA in ventral periaqueductal grey. Cells expressing preprocholecystokinin (CCK) mRNA in the rat midbrain periaqueductal grey area and Edinger-Westphal nucleus were analysed using in situ hybridization combined with liquid emulsion techniques. Semi-quantitative image analysis revealed that there were two populations of cells which expressed CCK mRNA. The first group of cells were large and heavily labelled and were confined to the Edinger-Westphal nucleus. The second group of cells were small and lightly labelled and were found scattered throughout ventral parts of the anterior periaqueductal grey.


A possible neural source of nitric oxide in the rat penis. NADPH diaphorase staining was used to indicate the presence of nitric oxide synthase (NOS) in whole mounts of rat major pelvic ganglion (MPG) and sections of rat penis. Many stained neurons were observed in the MPG and were distributed in a manner identical to that of retrogradely labelled penile neurons described previously. Staining was also observed within many axons of the penile (cavernous) nerve and in varicose terminals associated with various tissues of the penis. The results suggest that many, if not all, penile neurons of the MPG contain NOS and that a neural source of NO within the penis is likely.


Post-training medial septal stimulation improves spatial information processing in BALB/c mice. The experiment reported here was designed to highlight the effects of medial septal nucleus electrical stimulation on memory processes. To that end, we have used a learning task carried out in a 4-hole board in which animals were successively presented with the location of 2 baited holes. Under these conditions, the consequence of a weak stimulation (30 microA peak to peak, 80 s in duration) applied 30 s after acquisition of these 2 separate spatial informations was assessed on a retention test 24 h later. The results indicated that performance of stimulated animals was improved by medial septal stimulation as shown by an increase in the time duration of exploration of the second previously baited hole. However, post-training stimulation also produced a significant avoidance of the first previously baited hole not observed in the control groups. These results suggest that medial septal stimulation improves retroactive inhibition involved in working memory processes, thus leading to better retention of this kind of learning situation.


Serotonergic modulation of the respiratory rhythm generator at birth: an in vitro study in the rat. In order to investigate the mechanisms through which serotonin (5-HT) modulates the activity of the respiratory rhythm generator, respiratory activity was recorded from cervical ventral roots of the superfused isolated brainstem-spinal cord preparation of the newborn rat. Replacing the normal bathing medium by a medium containing 5-HT (30 microM) increased the respiratory frequency by 70% of the control value. Intact pontomedullary structures are necessary for this effect to take place, however, since the 5-HT-induced increases in respiratory frequency were no longer observed after elimination (section and electrolytic lesion) of the caudal ventro-lateral pons containing the A5 areas. Local applications of 5-HT (dual bath, microdialysis and microinjection experiments) revealed, however, that 5-HT acts at the medullary level and that its effects are not due to a diffuse action on all the neurons of the medullary respiratory centers but to a specific action focusing on structures located in the rostral ventro-lateral medulla.


Strong immunoreactivity of beta-amyloid precursor protein, including the beta-amyloid protein sequence, at human neuromuscular junctions. At the postsynaptic domain of the human neuromuscular junction (NMJ), we have demonstrated strong concentrations of the N-terminus 45-62, C-terminus 676-695 and beta-amyloid protein sequences of beta-amyloid precursor protein (beta APP). We used well-characterized monoclonal and polyclonal antibodies for co-localization with three other postsynaptic proteins, applying double and triple fluorescence labeling. Strong immunoreactivity of all three beta APP sequences was found at all NMJs identified by bound alpha-bungarotoxin (alpha BT), where they co-localized with alpha BT and with immunoreactive desmin and dystrophin, which are postsynaptic proteins of human NMJs. This appears to be the first demonstration of beta APP sequences concentrated postsynaptically at human NMJs. beta APP may have a role in normal junction biology and possibly in some diseases affecting NMJs.


Allopurinol preserves cerebral energy metabolism during perinatal hypoxia-ischemia: a 31P NMR study in unanesthetized immature rats. The effects of high dose allopurinol (ALLOP) pretreatment on the cerebral energy metabolism of unanesthetized 7-day-postnatal rats during exposure to 3 h of cerebral hypoxia-ischemia were serially quantitated using non-invasive 31P NMR spectroscopy. Adenosine triphosphate, integrated over the last 2 h of hypoxia and expressed as a fraction of baseline, was 0.73 +/- 0.16 with ALLOP pretreatment (200 mg/kg s.c.) compared to 0.52 +/- 0.05 for saline pretreatment (P = 0.001). Inorganic phosphate/phosphocreatine (Pi/PCr), integrated over the same time interval, was 2.63 +/- 1.23 relative to baseline with ALLOP versus 5.13 +/- 1.45 for saline-treated pups (P less than 0.0005). We suggest that the neuroprotection achieved with high dose ALLOP pretreatment may be attributed in part to preservation of energy metabolites.


Metallothionein immunoreactivity is increased in the spinal cord of patients with amyotrophic lateral sclerosis. Sections of the spinal cord from 10 patients with classic amyotrophic lateral sclerosis and from 10 control cases were examined by immunocytochemical methods to localize metallothionein. Metallothionein immunoreactivity was seen in the nucleus and cytoplasm of a subset of astrocytes, largely confined to the gray matter. Also, diffuse gray matter staining was observed, probably representing small glial fibers. Astrocytic metallothionein immunoreactivity (P less than 0.01) and strong gray matter matrix staining (P less than 0.03) was increased in the spinal cords from patients with amyotrophic lateral sclerosis. Although compatible with induction by metals, increased metallothionein expression in the spinal cords from patients with amyotrophic lateral sclerosis may also have resulted from inflammation or gliosis.


Comparison of spontaneous motor pattern generation in non-hemisected and hemisected mouse spinal cord. Spontaneous electromyogram (EMG) patterns in the gastrocnemius (G) and tibialis anterior (TA) muscles of spinal cord-hindlimb explants from neonatal mice were investigated. Compared to non-hemisected explants, neither longitudinal hemisection of the spinal cord nor hemisection plus transection at L1 significantly altered the incidence of spontaneous motor rhythm. Therefore, not only does each half of the neonatal spinal cord contain sufficient circuitry to generate motor rhythm, but the more reduced preparations were just as likely to produce such activity. Hemisected preparations, however, exhibited slower rhythm, perhaps due to the loss of excitatory commissural connections. No correlation was found between the number of cycles in a rhythmic sequence and cycle period. In hemisected as well as non-hemisected explants, sequences of spontaneous EMG rhythm occurred in either the G or TA muscle, but not in both muscles simultaneously. Consequently, cycle-to-cycle alternation between rhythmic bursting in the G and TA muscles was not observed. The excitability in such preparations was apparently insufficient for maintained activations of both muscles (either for cycle-to-cycle alternation or for co-contraction).


Insulin protects brain tissue against focal ischemia in rats. The influence of insulin on the infarct volume due to middle cerebral artery (MCA) occlusion was investigated in rats. A small dose of insulin (1 unit/kg) was injected i.p. just after MCA occlusion. The infarct areas were measured by planimetry from brains perfused with 2,3,5-triphenyltetrazolium-chloride (TTC) 48 h after the occlusion. Systemic variables were measured before and at various times after ischemia. The comparison between insulin-treated (n = 14) and control (n = 13) rats provided evidence that insulin significantly reduced the infarct volume due to MCA occlusion. As insulin minimally and transiently decreased blood glucose, the present results suggest that insulin exerts a beneficial effect directly on the central nervous system.


Retinal ischemia induced by occlusion of both common carotid arteries in rats as demonstrated by electroretinography. In 2 models of reduced cerebral blood flow-permanent occlusion of the vertebral arteries plus transient occlusion of the common carotid arteries (4VO) and transient clamping of the common carotid arteries (BCCA)-the acute effects on the electrical function of the retina were monitored by recording the photopic electroretinogram. During both 4VO and BCCA the amplitude of the b-wave was reduced. Within 30 min of reperfusion after 4VO and after BCCA the b-wave had fully recovered. In contrast, the a-wave was not affected by either treatment. The data suggest that occlusion of common carotid arteries leads to retinal ischemia and might represent a useful model of amaurosis fugax.


Acetylcholine synthesis is modulated by acetylcholine content of cytosolic fraction but not by that of releasable fraction. Synthesis and release of acetylcholine (ACh) in the rat hippocampal slices were examined to clarify the mechanism of modulation of ACh synthesis. Treatment with 2-(4-phenylpiperidino)cyclohexanol (AH5183, 50 microM), an inhibitor of ACh transport from cytosol to synaptic vesicles, inhibited the increase in ACh content of the membrane-bound fraction which is readily releasable, but did not affect the cytosolic ACh content. Under these conditions, the total ACh content reached a plateau value. These results indicate that ACh synthesis is modulated by cytosolic ACh content but not by the vesicular fraction.


Axonal sprouting induced in the sciatic nerve by the amyloid precursor protein (APP) and other antiproteases. Protease inhibition is the mechanism by which some trophic factors promote the extension of neurites. In the rat sciatic nerve, we assessed the ability to induce sprouts of the APP isoform that embodies the Kunitz antiprotease domain and other antiproteases. With the electron microscope, axonal sprouts were found when antiproteases were supplied but not after administration of inactive substances. We conclude that axons have a drive to sprout which can be released by the unbalance of an extracellular protease-antiprotease system. We propose that this system is involved in the pathogenesis of Alzheimer's disease.


Presence of abnormally phosphorylated Tau proteins in the entorhinal cortex of aged non-demented subjects. An immunoblot study was performed in several cortical samples from non-demented aged controls and compared with those from Alzheimer patients, using antibodies against Tau 55, 64 and 69, which are specific and reliable markers of the neurofibrillary degeneration of the Alzheimer type. The immunodetection of Tau 55, 64 and 69 was positive in all cortical areas from Alzheimer patients, in the entorhinal cortex from each control aged more than 65 but not in cortical samples from younger controls. We demonstrate that the entorhinal cortex is the most vulnerable neuronal population in aging and that the biochemical dysfunctions observed in this area are typically of the 'Alzheimer-type'.


Denervation of dopaminergic neurons with 6-hydroxydopamine increases nerve growth factor content in rat brain. Denervation of dopaminergic neurons by intra nigral injection of 6-hydroxydopamine (6-OHDA) increased nerve growth factor (NGF) content in the cortex and hippocampus, both of which are innervated by cholinergic neurons. The increase continued during an observation period of 0.5-28 days after the lesion. The time course of changes in NGF content was quite different from that of cholinergic neuron denervation. The decreased dopamine content produced in the striatum by 6-OHDA injection was not recovered during the observation period. These results suggest that dopaminergic neuron damage may affect NGF synthesis.


Low calcium/high magnesium medium increases activities of hypothalamic arcuate and suprachiasmatic neurons in brain tissue slices. Extracellular single-unit recording was conducted in hypothalamic arcuate (ARC) and suprachiasmatic nucleus (SCN) in rat brain slices. The perifusion medium was switched from normal artificial cerebrospinal fluid (ACSF) to ACSF containing low Ca2+ and high Mg2+ to test the effect of extracellular calcium on the spontaneous activities of these neurons and their responses to some test agents. It was found that almost all of the ARC and SCN units tested increased their firing rates in low Ca2+, high Mg2+ ACSF, and exhibited more significant responses to excitatory test agents. The effects of low Ca2+, high Mg2+ ACSF were repeatable and reversible. The results suggest that extracellular Ca2+ is essential in maintaining the membrane stability of most hypothalamic neurons and most agents tested are acting postsynaptically on the unit recorded.


The type III calcium/calmodulin-sensitive adenylyl cyclase is not specific to olfactory sensory neurons. A cDNA clone for type III adenylyl cyclase was originally isolated from a rat olfactory cDNA library and Northern analysis using total RNA suggested that the expression of the type III mRNA may be limited to the olfactory epithelium (Bakalyar and Reed, Science, 250 (1990) 1403-1406). In this study, the distribution of type III adenylyl cyclase mRNA in a number of bovine tissues and cultured cells was examined by Northern analysis using poly(A)+ RNA. Type III adenylyl cyclase mRNA was expressed in brain, spinal cord, adrenal medulla, adrenal cortex, heart atrium, aorta, lung, retina, 293 cells and PC-12 cells. Furthermore, the Ca2+ sensitivity of adenylyl cyclase activity in 293 cells indicated the presence of type III adenylyl cyclase. These data indicate that expression of the type III adenylyl cyclase is not limited to olfactory tissues, and that this enzyme probably has a number of physiological functions in addition to olfactory signal transduction.


Local radiolabeling of the 68 kDa neurofilament protein in rat sciatic nerves. Rat sciatic nerve segments, 4.5 cm distal to the dorsal root ganglion (DRG), were incubated in vivo with [35S]methionine. Fluorography of 2-D polyacrylamide gels of the nerve proteins demonstrated the labeling of the 68-kDa neurofilament protein, which was identified by immunoblotting. This experimental design excludes the dorsal root ganglion as the source of the radiolabeled neurofilament protein and suggests that this neuron-specific protein may be synthesized in axons.


Delayed degeneration of the optic tract and neurons in the superior colliculus after forebrain ischemia. Neuronal damage induced by 15-min forebrain ischemia was investigated in adult rats 1-5 days (short-term group) and 1-5 months (long-term group) after the initial ischemic attack. In addition to the vulnerable areas reported previously, we observed that the optic tract was also very susceptible. Degeneration of the optic tract and subsequent transsynaptic cell death in the superior colliculus developed slowly and was observed only in the long-term group. The delayed, progressive neuronal damage in this sensory system may serve as a suitable model to investigate the mechanisms of long-term changes in the injured brain.


Tedisamil blocks a calcium-dependent potassium channel in cultured motoneurons. A calcium-dependent potassium channel K(Ca) has been isolated in mouse motoneurons. With physiological concentrations of potassium across inside-out patches, a 100 pS K(Ca) channel was activated when the bath solution of Ca2+ was in excess of 1 microM. Introduction of the drug tedisamil, a blocker of repolarizing potassium channels in cardiac cells, at concentrations in the range 0.2-10 microM, caused a dose-dependent decrease in the mean open times for K(Ca). The drug action was consistent with open channel block of K(Ca) with an onward (blocking) rate constant of 6 x 10(7) M-1 s-1. Tedisamil, at concentrations of 1 microM and 5 microM, also blocked the K(Ca) channel when applied to outside-out patches with a similar potency as found with internal application. A large conductance K(Ca) channel in hippocampal neurons is also blocked by a number of putative Class III antiarrhythmic drugs, including tedisamil; thus, these agents may have utility in the characterization of the properties of K(Ca) channels in various cells.


GABAergic afferents modulate proenkephalin mRNA expression in the guinea pig hypothalamic magnocellular dorsal nucleus. The proenkephalin (PE) gene expression within Met-enkephalin (ME) neurons of the guinea pig magnocellular dorsal nucleus (MDN) was measured following activation of GABAergic transmission by aminooxyacetic acid treatment (AOAA). A combination of preembedding ME immunocytochemistry and PE in situ hybridization was used to investigate PE mRNA and enkephalin immunoreactivity levels. In perikarya of the MDN, chronic AOAA-treatment resulted in an important decline in PE mRNA signal (-128%). In double-labeled neurons, the PE mRNA decrease was associated to an increase in ME immunoreactivity. These results indicate that the increase in ME immunoreactivity in the MDN following AOAA-treatment is not due to a rise in PE gene transcription. This study provides additional morphological evidence supporting a role for GABA in modulating the enkephalinergic hypothalamoseptal tract of the guinea pig.


Mapping of c-fos expression elicited by pure tones stimulation in the auditory pathways of the rat, with emphasis on the cochlear nucleus. C-fos expression was mapped in the auditory pathways of rats, stimulated acoustically with pure tones. In the cochlear nucleus, two clusters of c-fos-like immunoreactive neurons, located respectively in the caudal part of the dorsal cochlear nucleus and in the granular cell region, did not show clear systematic shift in their position as a function of the tones frequency. On the other hand, more rostrally in the dorsal cochlear nucleus, a cluster of c-fos-like positive neurons moved progressively from dorsal to ventral for decreasing tones frequency. In the posteroventral cochlear nucleus, another cluster of c-fos-like positive neurons was observed, whose position also varied with tones frequency. Surprisingly, no or very rare c-fos-like immunoreactive neurons were present in the anteroventral cochlear nucleus and in the superior olivary complex. In the inferior colliculus, however, c-fos-like immunoreactive neurons formed clear isofrequency contours, shifting from dorsolateral to ventromedial for increasing tones frequency. In the medial geniculate body c-fos-like immunostaining was restricted to the medial and dorsal divisions while the ventral division was free of labeling. The cause of this differential labeling along the auditory pathways is at present unknown but may eventually provide clues as to physiological differences in parallel auditory pathways.


Increased brain concentrations of a neurotoxin, 3-hydroxykynurenine, in Huntington's disease. Concentrations of the neurotoxic tryptophan metabolite, 3-hydroxykynurenine, were determined in brain tissue taken post-mortem from patients with Huntington's disease and Alzheimer's disease. 3-Hydroxykynurenine was substantially and significantly increased in all three brain areas studied in Huntington's disease, but not significantly increased in the cortex in Alzheimer's disease, when compared to matched controls. These results demonstrate a possible dysfunction of tryptophan metabolism, via the kynurenine pathway, in Huntington's disease.


Histamine stimulates exocytosis in a sub-population of bovine adrenal chromaffin cells. Both nicotinic stimulation and histamine are able to raise cytosolic free calcium concentration in the majority of cells in a population of bovine adrenal medullary chromaffin cells to comparable levels. Nevertheless, histamine induces much less catecholamine secretion than does nicotine. In order to test whether this is due to heterogeneity in the responses of chromaffin cells to histamine we examined exocytosis in response to nicotine and histamine using an immunofluorescence method based on staining with anti-DBH to detect inserted secretory vesicle membrane. The results show that while up to 98% of the chromaffin cells in culture undergo exocytosis in response to nicotine, histamine stimulates exocytosis in only a sub-population of cells.


D2 dopamine receptor localization on striatonigral neurons. Two major pharmacological classes of dopamine receptors exist in the central nervous system. These receptors have been designated as D1 or D2 based upon their differing pharmacology and influence on the cyclic AMP second messenger system. Different genes for the D1 and D2 dopamine receptors have been isolated and are found to be expressed in high abundance. Within the neostriatum, however the cellular distribution of the dopamine receptors is equivocal. Dopamine receptors are the targets for drugs used to treat neurological dysfunctions such as Parkinson's disease and schizophrenia, and thus knowledge of their specific cellular location is important for devising future therapeutic manipulations. Using retrograde labeling methods combined with immunofluorescence of various receptor amino acid sequences, this study has examined the postsynaptic distribution of striatal D2 dopamine receptors. We have found that the D2 dopamine receptor can be visualized on a minimum of 60% of the neurons projecting from the neostriatum to the substantia nigra. However, some 65% of all D2 receptor positive cells are represented by other intrinsic neurons of this basal ganglia nucleus.


Cell adhesion molecule L1 guides cell migration in primary reaggregation cultures of mouse cerebellar cells. We demonstrate a new assay in vitro using reaggregated cerebellar neurons in order to test the role of the L1 molecule in migration events. Cells other than neurons were eliminated in these cultures. Cerebellar neuron reaggregates plated on L1 molecule substrates migrated at rates similar to those observed in vivo. This migration was blocked by anti-L1 antibody. These findings suggest that this culture could provide a useful system with which to directly study relationships between neuron migration and adhesion molecules.


Expression of the mRNA for the rat NMDA receptor (NMDAR1) in the sensory and autonomic ganglion neurons. The distribution of NMDA receptor (NMDAR1) on neurons in the peripheral ganglia was examined in the adult rat by in situ hybridization. NMDAR1 mRNA was expressed in all neurons in the sensory and autonomic ganglia examined; in the dorsal root, trigeminal, nodose, superior cervical, and sphenopalatine ganglia. Possible roles of the NMDA receptor on the sensory and autonomic ganglion neurons are discussed.


Glutathione prevents 2,4,5-trihydroxyphenylalanine excitotoxicity by maintaining it in a reduced, non-active form. 2,4,5-Trihydroxyphenylalanine (TOPA) in aqueous solution has been shown to form an non-N-methyl-D-aspartate (non-NMDA) agonist and neurotoxin, TOPA quinone. We examined whether the endogenous chemical reductant glutathione (GSH) could abolish the agonist properties of TOPA and block its excitotoxicity in rat cortical neurons in culture by preventing the formation of TOPA quinone. The oxidative formation of TOPA quinone from TOPA (30-500 microM) at pH 7.2 was measured spectrophotometrically. Using glutathione (0.05-3 mM) as the reducing agent, we found that the optimal [GSH]:[TOPA] ratio which significantly retarded TOPA quinone formation was 10:1. Thus, 3 mM GSH prevented whole-cell currents induced by a solution of 300 microM TOPA but did not affect currents elicited by 300 microM kainate. In addition, 2 mM GSH protected neurons from the toxic effects of 200 microM TOPA, but was not effective against 200 microM NMDA. These results suggest that the presence of endogenous reductants may limit the toxicity of TOPA.


IGF-II mRNA expression in LI human glioblastoma cell line parallels cell growth. A human glioblastoma cell line was found to express in vitro mRNA transcripts specific for insulin-like growth factor-II (IGF-II) and growth-hormone releasing-hormone (GHRH). In the absence of gross morphological changes, retinoic acid reduced the growth rate without major change of IGF-II mRNA expression, while alpha-difluoromethylornithine produced a complete growth arrest and a sharp decrease of IGF-II mRNA expression. Both reagents increased the expression of GHRH mRNA. Also in this glioblastoma cell line, like other neuroectodermal tumours, IGF-II mRNA is expressed independently from GHRH and seems to be parallel to growth rate.


Sexual differences and seasonal variations in vasoactive intestinal peptide immunoreactivity in the suprachiasmatic nucleus of jerboa (Jaculus orientalis). The sexual differences and the seasonal variation in the vasoactive intestinal peptide (VIP) content of the suprachiasmatic nucleus (SCN) of a desert rodent, the jerboa (Jaculus orientalis) were studied using immunocytochemical techniques. During the period of sexual activity (spring-early summer), the VIP immunoreactivity in the SCN was higher in females than in males. In the period of sexual quiescence (autumn), both males and females exhibited an even more intense VIP immunoreaction in the SCN as compared to spring. However, during this period, the sex-related differences in the VIP content of the SCN observed in spring were no longer detectable. The direct possible influence of sex hormones on the VIP content in the SCN, and the physiological significance of the seasonal variation observed in the VIP immunoreactivity in the SCN in this species remains to be determined.


Characterization of amyloid fibril protein from a case of cerebral amyloid angiopathy showing immunohistochemical reactivity for both beta protein and cystatin C. We isolated and carried out a chemical analysis of the amyloid fibril protein from the leptomeningeal vessels of a case with non-hereditary cerebral amyloid angiopathy (CAA) showing dual immunohistochemical reactivity with antibodies to both beta-protein and cystatin C. A crude amyloid fibril fraction reacted only with anti-beta-protein antibody, and cystatin C immunoreactivity was observed in the first PBS supernatant. Complete amino acid sequence of this cystatin C-immunoreactive protein showed a homologous structure to that of normal cystatin C. It is concluded that cystatin C is not an intrinsic component of the amyloid fibril in this type of CAA.


Secretory pathway of beta/A4 amyloid protein precursor in familial Alzheimer's disease with Val717 to Ile mutation. To determine whether the secretory pathway of beta/A4 amyloid protein precursor (APP) was altered in familial Alzheimer's disease (FAD) with a mutation of Val717 to Ile, cerebrospinal fluid was studied by Western blotting. The ratio of the density of the bands labeled with the antibody against the amino-terminal part of beta/A4 protein to that with the antibody against amino-terminal part of beta/A4 protein to that with the antibody against amino-terminal part of APP was not decreased. The present result suggests that the secretory pathway is not altered by the mutation in such a way that amyloidogenic full-length beta/A4 protein is generated.


A novel but non-pathogenic mutation in exon 4 of the human amyloid precursor protein (APP) gene. Mutations in the beta-amyloid precursor protein (APP) gene have been associated with both familial Alzheimer disease (FAD) and with hereditary cerebral haemorrhage. The polymerase chain reaction was used to both amplify and sequence exon 4 of the APP gene from genomic DNA of subjects with FAD and normal control subjects. A novel, rare, conservative DNA sequence variant was discovered at nucleotide 459 of codon 153 (valine) in exon 4 of the APP gene in an affected member of a large FAD pedigree. Segregation studies indicate that this mutation is likely to be non-pathogenic, but must be recognized and discriminated from pathogenic mutations during sequencing studies of the APP gene in patients with FAD.


Development of speed of repetitive movements in children is determined by structural changes in corticospinal efferents. This study was aimed to determine the relationship between the maturation of corticospinal efferents, determined by transcranial stimulation of motor cortex, and the development of fastest repetitive voluntary motor activity in children. The development of fastest repetitive voluntary motor activity was assessed for 3 different types of movements including fastest repetitive tapping movements, aiming movements and a pegboard transportation task. These 3 motor activities were chosen as they were different as to their dependence on detailed sensory guidance. Despite these differences the speed of all 3 movements showed a very similar developmental profile, which was matched, however, by the developmental slope of the fastest cortico-motoneuronal efferents. Hence the development of central conduction times determines the speed of repetitive movements in children. In contrast, we could not observe significant effects of repetitive training on speed of these movements. We show for the first time that the development of fastest voluntary movements is a structure-bound phenomenon, being independent from learning.


Thyrotropin-releasing hormone analogue and serotonin interact within the dorsal vagal complex to augment gastric acid secretion. The effects of serotonin (5HT) and a thyrotropin-releasing hormone (TRH) analogue, RX77368, on vagal control of gastric acid secretion were studied. Microinjection of RX77368 (0.66 pmol in 10 nl), but not 5HT (8 pmol in 10 nl), into the dorsal vagal complex (DVC) evoked a significant increase in acid output. When the same doses of RX77368 and 5HT were co-injected, the amount of acid secreted was significantly greater than that due to RX77368 alone. Thus, 5HT and the TRH analogue interact within the DVC to enhance vagal stimulation of acid secretion. The study suggests a possible functional significance of raphe TRH/serotonergic tracts projecting to the DVC.


The long-acting cholinesterase inhibitor heptyl-physostigmine attenuates the scopolamine-induced learning impairment of rats in a 14-unit T-maze. Heptyl-physostigmine (heptyl-Phy), a new carbamate derivative of physostigmine (Phy), has been assessed for potential clinical value by evaluating its in vitro activity against human erythrocyte acetylcholinesterase (AChE) and plasma butyrylcholinesterase (BChE), its duration of in vivo activity against rat plasma AChE, and its effects on attenuating a scopolamine-induced impairment in learning performance of young rats in a 14-unit T-maze. Heptyl-Phy demonstrated potent cholinesterase inhibition, with activity similar to that of Phy against AChE, IC50 values 21.7 +/- 2.0 nM and 27.9 +/- 2.4 nM, respectively, and significantly greater than that of Phy against BChE, IC50 values 5.0 +/- 0.1 nM and 16.0 +/- 2.9 nM, respectively. Heptyl-Phy achieved maximum AChE inhibition of 92.5% at 60 min and maintained a high and relatively constant inhibition for more than 8 h. For analysis of effects on learning performance, heptyl-Phy at 1.0, 1.5, 2.0 or 3.0 mg/kg, or vehicle was administered i.p. to 52 3-month-old male Fischer-344 rats 60 min prior to maze training. Thirty minutes prior to training, each animal received either 0.9% NaCl or scopolamine hydrochloride (0.75 mg/kg). Only a 2.0 mg/kg dose of heptyl-Phy significantly reduced the number of errors in scopolamine-treated rats. The other doses did not improve any aspect of maze performance. Although the therapeutic window of heptyl-Phy did not appear wide enough for clinical use, the longer duration of action of heptyl-Phy would appear beneficial.


L-aspartate-beta-hydroxamate exhibits mixed agonist/antagonist activity at the glutamate metabotropic receptor in rat neonatal cerebrocortial slices. L-aspartate-beta-hydroxamate, a glutamate uptake inhibitor, was investigated for activity at a glutamate metabotropic receptor (mGluR) in neonatal rat cerebral cortical slices. Stimulation of phosphatidylinositol hydrolysis by 100 microM (1S,3R)-ACPD was inhibited only very weakly, to a maximal extent of 28%, L-aspartate-beta-hydroxamate did however exhibit agonist activity (EC50 = 760 microM) and, although much less potent than (1S,3R)-ACPD (EC50 = 20 microM), its efficacy was approximately 70% of the latter. These results indicate that, at least in this preparation, offspartate-beta-hydroxamate is of little value as an antagonist at the mGluR receptor.


Localization of mRNA for beta-adrenergic receptor kinase in the brain of adult rats. A cDNA encoding rat beta-adrenergic receptor kinase (beta-ARK) was cloned and sequenced. By in situ hybridization histochemistry of adult brain, beta-ARK mRNA was expressed intensely in the cerebellar granule cell layer and moderately in the hippocampal pyramidal cells and dentate granule cells. The neocortex and piriform cortex expressed it moderately to weakly, whereas the thalamus and hypothalamus expressed it weakly to faintly. No significant expression of the mRNA was detected in the caudate-putamen. Weak expression of beta-ARK mRNA was detected in several nuclei of the brainstem and in the spinal gray matter.


Neuronal responses of the anterior commissural nucleus to osmotic stimulation and angiotensin II in hypothalamic slices in the rat. The firing rate and pattern of activity of neurons in the anterior commissural nucleus (ACN), which was rich in oxytocin-containing neurons, were studied electrophysiologically in hypothalamic slices. Extracellular recording showed that most ACN neurons exhibited irregular or regular continuous spontaneous unit activity. Other neurons showed short burst patterns of activity or were silent. The majority of ACN neurons were activated by bath application of angiotensin II, and a substantial number of them showed inhibitory or excitatory responses to hypertonic bathing medium. These results indicate that magnocellular neurosecretory neurons in the ACN may participate in the regulation of water balance.


Non-independent quantum bumps in Limulus ventral nerve photoreceptors--a new insight in the light transduction mechanism. Single photon-induced transient currents, called quantum bumps were stimulated by short flashes in dark-adapted ventral nerve photoreceptors of Limulus. Flash intensities were set to activate 3 or more bumps. In most cases, current bumps were activated with a constant rate. The frequency of bump occurrence was between 9 and 17 Hz. Results show that consecutive bumps are not independent and that some of them are not activated by a photon. The periodic bump activation indicates a molecular mechanism which quantifies the transmitter release not only by a light quantum, but also by a late phase of the transduction cascade. A model is proposed, in which Ca2+ ions released from intracellular stores transiently block the further Ca2+ release by inositol trisphosphate in an all-or-none manner.


Sudden infant death syndrome in 1992: the known and unknown. Sudden infant death syndrome (SIDS) continues to be the leading cause of death in infants from one month to one year of age. We present the results to the Fifth Annual Perspectives on SIDS. This program is one component of the educational services of the New Jersey SIDS Resource Center.


Sudden infant death syndrome in New Jersey: 1991. Sudden infant death syndrome (SIDS) is the leading cause of death in infants one month to one year of age. The New Jersey Sudden Infant Death Syndrome Resource Center gathers epidemiological data on all SIDS deaths in New Jersey, noting differences in population and countries.


Medium chain acyl-coenzyme A dehydrogenase deficiency. Medium chain acyl-coenzyme A dehydrogenase deficiency (MCADD) was the first metabolic disorder found to be associated with sudden infant death syndrome. This review covers recent advances in the biochemical and molecular understanding of MCADD.


Sudden infant death syndrome: loss and bereavement. Clinical perspectives of sudden infant death syndrome (SIDS) and family responses to loss and bereavement are addressed. The author discusses factors such as family stage, parental dyad issues, and the needs of young children, friends, and caregivers.


Sudden infant death syndrome and subsequent siblings. Studies indicate that at least 98 (SIDS) in subsequent siblings, summarizes the results of percent of all subsequent SIDS siblings will have a normal outcome. While the data regarding a single SIDS occurrence can be viewed as encouraging, 2 percent mortality is not trivial. Parents of SIDS siblings are in need of appropriate counseling and support. In the unfortunate case of subsequent sibling SIDS deaths, the mortality rate may be as high as 18 percent. Regretably, all attempts at prospective identification of infants destined to die of SIDS have proved futile. The development of a prospective screening test has been hindered by insufficient understanding of the specific cause or causes of SIDS. Attention, thus, has been directed at the development of effective home intervention. Cardiorespiratory monitoring has been identified as one means of home intervention, and a comprehensive support program has resulted in the successful home monitoring of many infants at high risk for SIDS. Studies aimed at making prospective identification a clinical reality continue. Accordingly, we must persist in our efforts to provide support to parents who have experienced one of life's worst tragedies.


Neurodevelopmental outcome in infants with apnea. The neurodevelopmental outcome of term infants with acute life-threatening events (ALTE) and preterm infants with persistent apnea of prematurity were compared to matched control populations. No differences in developmental outcomes were seen between the study and control populations.


NJ SIDS Resource Center: program for bereaved families. The New Jersey Sudden Infant Death Syndrome Resource Center counsels approximately 120 bereaved families each year, conducts l medical and community education programs, and manages the sudden infant death syndrome database for New Jersey.


Sudden infant death syndrome: an overview. The diagnosis of sudden infant death syndrome (SIDS) depends on a thorough and complete autopsy. Many of the infants who die of SIDS have common findings. There are certain steps to be taken for prevention and diagnosis of SIDS. Further investigation of this syndrome still is necessary.


High dose refractoriness to the neuromuscular toxicity of dithiobiuret in rats. Increasing the daily dose of dithiobiuret (DTB) given to rats from 0.5 to 1 to 5 mg/kg shortened the latency to onset of treadmill failure and associated flaccid muscle tone from 7 to 5 to 3 days, respectively. Death generally did not follow treadmill failure for at least 2-3 days. After 3 consecutive days of treatment with 5 mg/kg, gastrocnemius muscle contractions elicited by high frequency trains of nerve stimulation were lower in peak tension and more susceptible to tetanic fade (rapid tension decline in tetanus) than were contractions from control rats. Conversely, rats given 12 mg/kg of DTB for 3 days did not exhibit treadmill failure, flaccid skeletal muscle tone, or tetanic contractile abnormalities. Additional treatment with this dose for 2-3 days was required to produce treadmill failure which was not accompanied by flaccid muscle tone. Refractoriness to development of toxicity with DTB was limited in its spectrum; decreased feed and water intake, weight loss, diuresis, dehydration, chromodacryorrhea, and production of mucoid feces occurred even in the absence of flaccid muscle tone. Tissue distribution of DTB-derived [14C] determined 3 hr after injection of [14C]-DTB (12 mg/kg) was largely unaffected by prior treatment with unlabeled DTB (12 mg/kg/day x 2 days). Conventional microelectrode recording studies using end-plates of extensor digitorum longus muscles indicated that abnormalities occurred in quantal release of acetylcholine (ACh) after 5mg/kg/day but not 12 mg/kg/day of DTB. Specifically, reduced quantal content, increased amplitude and prolonged decay of miniature end-plate potentials were observed. The mechanism by which large daily doses overcome or prevent the expected development of flaccid muscle tone and depressed release of ACh typically associated with treatment with DTB does not involve compensatory increases in quantal release of ACh, or altered distribution of the compound.


Delayed neurotoxicity of trixylenyl phosphate and a trialkyl/aryl phosphate mixture, and the modulating effect of atropine on tri-o-tolyl phosphate-induced neurotoxicity. Two hydraulic fluids, Fyrquel EHC (trixylenyl phosphate) and Reofos 65 (trialkyl/aryl phosphate mixture), were examined for effects of organophosphorus-induced delayed neurotoxicity (OPIDN) in hens using the OECD Test Guideline (1984). Furthermore, the influence of atropine and the concentration of tri-o-tolyl phosphate (TOTP) in the oil vehicle on the development of OPIDN were investigated. For Fyrquel EHC a neurotoxic effect was demonstrated with single oral doses of 5, 10 and 15 g/kg. Reofos 65 caused no clinical neurotoxic effect after single oral doses of 5, 10 and 15 g/kg. Redosing at day 22 with Reofos 65 did not result in clinical delayed neurotoxicity, but minor histopathological changes were found in the spinal cord and peripheral nerves. Atropine 10 mg/kg im delayed the onset of OPIDN caused by TOTP 1 g/kg po without affecting the final neurotoxic effect. Dilution of TOTP in large amounts of soybean oil vehicle reduced its neurotoxic effect. In conclusion, the neurotoxic potential of the hydraulic fluids was very low. The effect of atropine and the concentration of the test compound in oil vehicle should be taken into consideration when designing experiments on OPIDN.


Phenylmethylsulfonyl fluoride alters sensitivity to organophosphorus-induced delayed neurotoxicity in developing animals. The serine/cysteine hydrolase inhibitor phenylmethylsulfonyl fluoride (PMSF) markedly intensifies the clinical expression of organophosphorus-induced delayed neurotoxicity (OPIDN) in adult chickens when administered after organophosphate exposure. In this study, we have examined the ability of PMSF post-treatment to affect sensitivity to OPIDN in developing animals at ages normally showing resistance. Chickens (35, 49 or 70 days of age) were treated with diisopropylphosphorofluoridate (DFP, 2 mg/kg, sc) and then treated four hours later with PMSF (90 mg/kg, sc) or vehicle only and examined for clinical signs of ataxia and incoordination. Chickens treated with DFP alone showed a marked age-related increase in the severity of motor deficits. Birds treated with DFP followed by PMSF showed more extensive clinical deficits relative to those treated with DFP only, but relatively similar degrees of motor dysfunction among the age groups. Cervical spinal cord samples processed by the Fink-Heimer degeneration method indicated that PMSF post-treatment induced more extensive axonal degeneration in all age groups relative to treatment with DFP only. As the DFP treatment alone caused greater than or equal to 90% inhibition of neurotoxic esterase activity (NTE, the putative molecular target site for OPIDN), interaction with NTE by PMSF does not appear to be involved in potentiation. We hypothesize that PMSF potentiates OPIDN through impairment of a physiological process which normally imparts resistance to young animals and which regresses during development.


Functional/metabolic modulation of the brain stem lesions caused by 1,3-dinitrobenzene in the rat. To determine whether neuronal activity plays a role in the localisation of brain stem lesions in 1,3-dinitrobenzene intoxication we produced asymmetrical changes in auditory input by rupturing the left tympanic membrane in Fischer rats. This raised the auditory threshold on that side from 57-63 dB to 104-122 dB. It also decreased glucose utilisation in the ipsilateral cochlear nucleus and significantly increased utilisation in the contralateral nucleus, resulting in a relative deficit of 72 +/- 6%. Similarly, tympanic membrane rupture led to decreased glucose utilisation in the contralateral and increased utilisation in the ipsilateral inferior colliculus. Additional exposure to "white noise" prevented the decrease in glucose utilisation in the contralateral inferior colliculus. Dosing with dinitrobenzene (10 mg/kg in 4 doses over 48 hr) to otherwise normal rats produces symmetrical vasculonecrotic lesions in these regions, but in animals with left tympanic membrane rupture the severity of morphological changes in the ipsilateral cochlear nucleus and the contralateral inferior colliculus were substantially reduced. Additional exposure to "white noise" increased the degree of damage in the ipsilateral cochlear nucleus and contralateral inferior colliculus. These findings indicate that altered auditory function in rats, with its associated metabolic consequences exercises a significant role in the development of brain stem damage in auditory pathways following dinitrobenzene intoxication.


Mitochondrial glutathione and methyl iodide-induced neurotoxicity in primary neural cell cultures. The status of both cytosolic and mitochondrial glutathione was studied in primary cultured cerebrocortical cells from fetal mice using the selective membrane-solubilizing properties of digitonin and after exposure to the monohalomethane methyl iodide. A correlation was found between cell injury (assessed by lactate dehydrogenase leakage 24 hr after exposure) and early loss of mitochondrial glutathione (2 hr after exposure), while cell death did not appear directly dependent on cytosolic glutathione depletion. The antioxidants BW 755C (3-amino-1-[m-(trifluoromethyl)phenyl]-2-pyrazoline) and DPPD (N,N'-diphenyl-p-phenylenediamine), and the glutathione precursor N-acetyl-L-cysteine were used to modify cellular responses to methyl iodide. Prevention of cell injury by these reagents was obtained only under conditions where at least 50% of the normal level of mitochondrial glutathione was preserved after methyl iodide exposure. Mitochondrial metabolic activity (reduction of 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide, MTT) was affected by exposure to methyl iodide and correlated with mitochondrial glutathione depletion and cytotoxicity. These findings indicate that the mitochondrial glutathione pool and mitochondrial functions may be the most significant intracellular targets of methyl iodide in neural cultures. Moreover, the present work exemplifies the dependence of neural cell viability on the status of mitochondrial functions and suggests that, as in the liver, mitochondrial glutathione is an important component of cellular homeostasis in nervous tissue.


Corticosterone hypersecretion in preweanling rats exposed neonatally to trimethyltin. Developmental neurotoxicity may be influenced by effects of a compound on endocrine function. Here we report that developmental exposure to TMT increases the corticosterone (CS) response to stress in developing rat pups. Long-Evans rat pups were injected i.p. with either 6 mg/kg TMT hydroxide (in 10 microliters/g BW NaCl) or vehicle on Postnatal Day 5 (PND5) or 10 and were then tested for their CS response to restraint stress on PND12, 16, or 20. In the stress test, pups were maternally deprived in individual compartments of an incubator for 24 hr, and then blood sampled by decapitation either immediately (basal), or 30, 60 or 90 min after the onset of a 15-min period of restraint in a wire-mesh holder. Regardless of TMT exposure or age of testing, this procedure produced a peak in plasma CS at 30 min which then recovered to basal levels by 90 min. TMT exposure on PND5 (Experiment 1) resulted in CS hypersecretion relative to vehicle-injected controls on PND12 and 16 but not PND20. TMT exposure on PND10 (Experiment 2) had no effect at PND12 but elevated CS over vehicle controls at PND16 and 20. PND15 exposure to TMT resulted in CS hypersecretion in pups tested on PND20. Neonatal organotin exposure appears to alter CS secretion in a manner that is influenced by age of exposure and age of testing.


Effects of trimethyltin on repeated acquisition (learning) in the radial-arm maze. Trimethyltin (TMT) was used as a positive control neurotoxicant to evaluate a repeated acquisition procedure for the 8-arm radial maze. Ten male Long-Evans rats were trained to collect a single food pellet at the end of each baited arm on each trial of a daily 12-trial test session. Four of the eight arms were baited on all trials of a given session. The set of four baited arms was changed each day: thus the rats were required to learn a new set of baited arms in each session. In trained rats, error frequencies (entries into unbaited arms) declined from about 4 on Trial 1 to less than 1 on Trials 4-12 in each session: this within-session error reduction thus defined an acquisition baseline which was evaluated for its sensitivity to TMT. Learning was impaired after 7 mg/kg (iv) TMT, as shown by a slower decline in within-session error frequencies in all treated rats. Errors and response times were elevated for 5 weeks after TMT but returned to control levels thereafter. Histological examination of hippocampi showed damage in all treated rats 18 weeks after treatment; however, no significant relationship between degree of damage and behavioral effect was observed. Analysis of errors showed that TMT more strongly impaired the rats' ability to avoid arms in the current unbaited set than those baited arms already entered on a given trial (i.e., working memory). These dissociations between behavior and hippocampal morphology in terms of time course, magnitude of effect across animals, and error type suggest that performance of this task does not depend upon hippocampal integrity, as do other tasks involving spatial working memory. Recovery of function in this kind of task may shed light on processes of neural plasticity after exposure to neurotoxic compounds.


Effects of pre- plus postnatal exposure to methylmercury in the monkey on fixed interval and discrimination reversal performance. Female monkeys were dosed with 0, 10, 25 or 50 micrograms/kg/day of mercury as methylmercuric chloride. When blood levels reached equilibrium, females were bred to untreated males. A total of 5, 1, 2, and 5 live infants were born in the four dose groups, respectively. Infants were separated from their mothers at birth, and dosed with the same dose their mothers had received. Maternal blood mercury levels averaged 0.33, 0.78, or 1.41 ppm for the three dosed groups respectively. Infant blood mercury levels averaged 0.46, 0.93, or 2.66 ppm at birth, and decreased slowly to steady state levels of 0.20, 0.25, or 0.60 ppm. Behavior was assessed during infancy on a nonspatial discrimination reversal task and fixed interval performance, and when monkeys were juveniles on a series of nonspatial discrimination reversal tasks. During infancy monkeys were tested 7 days per week, 16-21 hr per day in a home-cage environment. As juveniles, they were tested five days per week in a standard operant test environment. For the discrimination reversal tasks, there were no strong indications of differences between treated and control monkeys either as infants or juveniles. Treated monkeys tended to perform transiently better than controls when first introduced to the task both as infants and juveniles. On the Fl, treated monkeys received more reinforcements, and had shorter pauses and lower quarter-life values than control monkeys. Analysis of feeding behavior over the session during infancy revealed marginally longer periods of feeding in methylmercury-treated infants. These results suggest that pre-plus postnatal exposure to methylmercury did not result in gross intellectual impairment in these monkeys, but may have interfered with temporal discrimination.


Effects of complexed iron and aluminium on brain calcium. Ferric lactate increases Ca(2+)-uptake by Ehrlich carcinoma ascites cells as well as in vitro and in vivo Ca(2+)-uptake by the liver. Iron and aluminium are increased in the substantia nigra of patients with Parkinson's disease and aluminium is suspected to be involved in the pathophysiology of Alzheimer's disease. This study was conducted to determine if there is any relationship between iron and aluminium uptake and a possible calcium influx into brain tissue. Groups of Swiss mice were injected in the tail vein with 100 microliters of 0.05 M ferric lactate plus 2 microCi45CaCl2, or 100 microliters of 0.05 M aluminium lactate plus 2 microCi45CaCl2, or 100 microliters of saline plus 2 microCi45CaCl2. Twenty-four hr later they were sacrificed by decapitation. Samples of blood and the total brain were weighed and ashed. The ashes were dissolved and the solution transferred to counting vials evaporated to dryness. A scintillation solution was added to the vials and the radioactivity was counted. To accurately assess brain uptake in each animal the value of brain specific activity was related to blood specific activity. When compared to those of control animals, these values gave the 24 hr increase of 45Ca-uptake by brain of ferric lactate or aluminium lactate-treated animals. A significant increase of 45Ca-uptake was observed for ferric lactate (136% of control value, p less than 0.005), which is more important for aluminium lactate (163% of control value, p less than 0.001). The nature of the complexed metal-brain tissue interaction is not known, several mechanisms are discussed.


The influence of dietary fat on food intake and body weight. Excessive intake of dietary fat is associated with a number of nutrition-related disorders, including obesity, heart disease, and cancer. The over-consumption of fat may be related to its palatability, high energy density, or physiological effects. This article reviews possible reasons why fat intake is high, examines the relationship between diet composition and body weight, and explores potential fat reduction strategies. It is concluded that low-fat or fat-free products could be useful in reducing the percentage of calories derived from fat, although this assertion needs to be further tested in controlled laboratory experiments and validated on a population basis.


Low serum retinol is associated with increased severity of measles in New York City children. Children with no known prior vitamin A deficiency exhibited a significant decline in their serum retinol levels during the acute phase of measles. This decline in circulating retinol was associated with increased duration of fever, higher hospitalization rates, and decreased antibody titers.


What is the physiological origin of free D-amino acids in mammals? A previously unknown metabolite of vitamin B6, tentatively identified as adenosine-N6-diethylthioether-N1-pyridoximine-5'-phosphate, accounts for up to 30% of the total intracellular vitamin B6 observed in tumor cells cultured in the presence of radiolabeled pyridoxine. When various animal and human tumor cells were incubated with radiolabeled pyridoxine, the formation of this metabolite was greatest in rapidly growing cells that were the least differentiated. If analytical methods are verified, the presence of the compound in serum may provide an indicator of in vivo tumor growth.


A novel vitamin B6 metabolite may be a circulating marker of cancer. A previously unknown metabolite of vitamin B6, tentatively identified as adenosine-N6-diethylthioether-N1-pyridoximine-5'- phosphate, accounts for up to 30% of the total intracellular vitamin B6 observed in tumor cells cultured in the presence of radiolabeled pyridoxine. When various animal and human tumor cells were incubated with radiolabeled pyridoxine, the formation of this metabolite was greatest in rapidly growing cells that were the least differentiated. If analytical methods are verified, the presence of the compound in serum may provide an indicator of in vivo tumor growth.


Cooperative relationships between professional societies and the food industry: opportunities or problems? A variety of cooperative relationships may potentially exist between professional or voluntary organizations and food companies: endorsements of food products, health messages, or educational and informational materials; certification of nutrient components of food products that meet a certain standard of a society; and acceptance of food advertising in society publications and the display of food products at society meetings. We queried the American Heart Association, the Society for Nutrition Education, the American Cancer Society, the American Diabetes Association, and the American Dietetic Association about past and present policies on these various relationships. Specific examples of cooperative relationships are discussed, weighing risks and benefits to the food company, the professional or voluntary organization, and the public. Guidelines are suggested for professional societies in evaluating different cooperative relationships, with the public's health and nutritional well-being as the primary consideration.


HIV-infected pregnant women and their infants. Primary health care implications. Human immunodeficiency virus infection in women and infants is a significant and growing health care problem in the United States. Young adult black or Hispanic women are at particular risk, especially if they use intravenous drugs or are the sexual partner of someone who does. However, acquired immunodeficiency syndrome/HIV infection is a significant cause of mortality in women of reproductive age (i.e., 15 to 44 years). In addition, the incidence of AIDS in infants directly correlates to the incidence of AIDS in childbearing women. HIV-infected pregnant women need on-going comprehensive prenatal care with a special focus on HIV management. Antepartum care should include an HIV-focused history and physical examination, as well as additional laboratory assessments to screen for viral and bacterial infections. Intrapartum care should focus on avoiding contact with infected or potentially infected secretions and body fluids. Postpartum care should emphasize development of a comprehensive and integrative plan of care for mother, baby and family unit prior to discharge. Avoidance of breastfeeding and strategies to prevent further HIV transmission must be stressed.


A guide to primary care of iron-deficiency anemia. Iron deficiency, the most common cause of anemia, is prevalent in 10 percent to 30 percent of the world's population. Inadequate intake of iron may be an important causative factor, particularly when the body requires more iron than usual (e.g., during infancy, early childhood, adolescence, pregnancy and periods of blood loss). The popular increase of fiber in diets may increase the incidence of iron-deficiency anemia because too much fiber in the diet renders available iron unabsorbable. Symptoms in children include skin or conjunctival pallor, excessive sleepiness, learning disabilities, diminished attention span, tiredness, irritability or inappropriate behavior, and pica. Adults may have shortness of breath, decrease in exercise tolerance, palpitations, tachycardia, angina, congestive heart failure, orthopnea and edema. Iron deficiency occurs in sequential states and is measured by many laboratory tests. The levels of hemoglobin and hematocrit are both decreased, while the red blood cell count may be normal initially, but will decrease as the iron-deficiency state continues. The steps of treatment include correction of the underlying disorder, administration of the amount of iron needed and observation of the response to treatment.


Pap smear histories in a medical clinic: accuracy of patients' self-reports. Women using the medical clinic of a public hospital were interviewed about their Pap smear histories to assess the accuracy of self-reported smears and to identify groups in need of further screening. Interview data from 263 women were compared with cytology files and hospital records. In spite of considerable agreement between patient report and record, patients reported significantly more recent smears than were documented. Accuracy of recall was not dependent on age or birthplace, but on the length of time since the last smear. About half the women had been screened within the past two years, whereas one tenth had never been screened. Women aged 65 years or older had fewer recent smears than younger women, while foreign born women were more likely never to have had a Pap smear than were United States born women. We conclude that self-reported information is useful in assessing Pap smear histories, but the screening rates that result should be treated as high estimates. Significant opportunities for screening exist in ambulatory care sites in low-income communities.


Extracranial carotid arterial disease: a prognostic factor for atherothrombotic brain infarction and cerebral transient ischemic attack. A prospective study investigated the prevalence of extracranial carotid arterial disease by carotid duplex ultrasonography, and evaluated its correlation with the incidence of atherothrombotic brain infarction or cerebral transient ischemic attack in 949 patients, mean age 82 +/- 8 years. The mean follow-up period was 45 months. Of 949 patients, 37 (4%) had 80%-100% extracranial carotid disease (mean follow-up, 24 +/- 15 months), 113 (12%) had 40%-80% extracranial carotid disease (40 +/- 19 months follow-up), and 799 (84%) had 0%-40% extracranial carotid disease (47 +/- 14 months follow-up). The average annual incidence of atherothrombotic brain infarction was 37% in patients with 80%-100% extracranial carotid disease, 9% in patients with 40%-80% extracranial carotid disease, and 4% in patients with 0%-40% extracranial carotid disease. The average annual incidence of transient ischemic attack was 3% in patients with 80%-100% extracranial carotid disease, 2% in patients with 40%-80% extracranial carotid disease, and 1% in patients with 0%-40% extracranial carotid disease. The Cox proportional hazard model showed that among the variables evaluated, the severity of extracranial carotid disease correlated with the highest relative risk of developing atherothrombotic brain infarction (2.5x higher relative risk) or transient ischemic attack (2.8x higher relative risk). Patients with an earlier atherothrombotic brain infarction had a 2.1x higher probability of developing atherothrombotic brain infarction and a 1.9x higher chance of developing transient ischemic attack than those without an earlier atherothrombotic brain infarction. Age was a prognostic variable for new atherothrombotic brain infarction, and male sex was a prognostic variable for new transient ischemic attack.


From hospital to community: a follow up of community placement of the long term mentally ill. To evaluate the planned movement of long stay patients with chronic mental disorders from Sunnyside Hospital into staffed residential accommodation in the community. Sixty-nine long stay psychiatric patients were followed up over 18 months to assess their social functioning, psychiatric symptomatology, resource use, relapse rate, satisfaction with their care, and impact on the community. Social functioning and psychiatric symptomatology scores on the social behaviour schedule remained stable overall. Relapse rates were low, and rehospitalisation rare. Use of community and area health board resources tended to decrease. Over 90% of patient responses indicated satisfaction with their new living arrangements. Over 50% reported no contact with outside friends, though over the follow up period about 70% maintained at least monthly contact with relatives. Careful community placement of the long term mentally ill, with ongoing supervision, can have a successful outcome from clinical, patient and community perspectives.


The quality of a laboratory test in general practice: the throat swab example. To measure the repeatability, the flow of information, and the data entry error of the throat swab test from a suburban general practice. A prospective study of consecutive patients seen in routine consultation for a sore throat as their primary complaint. Repeated throat swabs were taken for each patient. Carbon copies of routine laboratory forms were collected. The kappa statistic for reproducibility of the throat swab test was 0.63 (95% CI 0.50-0.77). In 5.8% of patients, one swab was positive and the other negative. Information took one day or less to travel to and from the laboratory for 25.7% of patients with a beta-haemolytic streptococcal growth compared to the 9.9% of patients with no growth (chi 2 = 6.17, p < 0.02). The laboratory received 53% of the swabs on the day they were taken. Delays in getting the swabs to the laboratory occurred when swabs were taken in the afternoon session or on weekends. Monday morning gave the quickest return. Data entry errors were found on 15.9% of patient forms. The quality of the throat swab test needs improvement in the suburban general practice context.


Clozapine protocol: a collective approach to use of an unregistered medicine. We describe a protocol for the use of an unregistered antipsychotic medicine, clozapine, in a mental health service. Traditionally, prescribing of unregistered medicines has been a matter between prescriber and patient alone. However, clozapine carries a high risk of agranulocytosis and its use requires strict adherence to monitoring procedures. Persons most likely to benefit from it include many who, because of their psychosis, may be unable to give truly informed consent or to react appropriately to adverse reactions. We have designed a protocol which seeks to ensure that this medicine is given only to those whose severity of illness and lack of response to all other reasonable treatment outweighs the risk of agranulocytosis, that it is used with maximum safety and that only persons who have been shown to benefit from the medicine continue to receive it after an initial trial. Although this protocol has been accepted by the medical staff, questions of clinical autonomy and liability in the event of medical misadventure remain.


Ondansetron antiemetic therapy for chemotherapy and radiotherapy induced vomiting in children. To evaluate ondansetron as the sole antiemetic in children treated with emetogenic chemotherapy and irradiation. Fifteen children aged 3-11 years were studied. Seven had acute lymphoblastic leukaemia, two acute myeloid leukaemia, two lymphoma and four had other tumours. Ondansetron 5 mg/m2 IV or 4 mg by mouth was given immediately before chemotherapy or radiation treatment and continued eight hourly for 24 hours. Nausea and vomiting was assessed during treatment and for the next 48 hours, and graded using WHO criteria. Thirty-eight courses of chemotherapy were assessed, 27 severely emetogenic and 11 moderately emetogenic. Two included total body irradiation. The most severe nausea and vomiting was grade 2 (transient vomiting) reported in six children. Nausea and vomiting was abolished on subsequent courses in four of these children by increasing the ondansetron dose frequency to six hourly. The remaining children experienced no nausea or vomiting (n = 7) or only nausea (n = 2). Nausea and vomiting were each completely controlled in 27 courses. Ondansetron is a cost effective and safe antiemetic in children receiving chemotherapy and total body irradiation, minimises weight loss on treatment and enables outpatient chemotherapy in some cases.


Residential care for the long term mentally ill in Canterbury: options, costs and funding sources. To obtain estimates of the costs of the main options of care for the long term mentally ill and to compare different approaches to costing. Resources used by samples of residents in extended hospital care (EC, n = 43), community staffed houses (SH, n = 30), boarding houses (BH, n = 43) and group homes (GH, n = 100) were identified and costed using both the expenditure and total resource concepts of cost estimation. Using the expenditure concept of cost SH was the most expensive at $773 per person per week, compared to $700 for EC, $189 for BH and $155 for GH. Using the resource cost approach, valuing all resources used, SH and EC were similar at $790, compared to $184 and $169 for BH and GH care. Nursing was the most costly input with striking differences between nursing costs in the four modes of care. The results indicate a gap in the spectrum of residential care options, between high and low cost care. Future funding arrangements will require improved linkage between needs assessment and resource provision.


Viral hepatitis in the Christchurch community. To determine the relative frequency of known causes of viral hepatitis in the Christchurch community. Serum samples were collected at a private laboratory from patients aged 15-75 years who had an elevated transaminase of at least twice normal. One hundred and thirty-three subjects entered the study of whom 32 were positive for Epstein Barr virus, three for cytomegalovirus, nine for hepatitis A virus, and eight for hepatitis B virus. Paired convalescent samples were obtained from 64 of the remaining 81 subjects (17 lost or declined) and seven of these were positive for hepatitis C. Assuming a similar percentage in the lost/declined group this corrects to nine. The relative frequency of viral agents causing hepatitis was Epstein Barr virus 52%, cytomegalovirus 5%, hepatitis A virus 15%, hepatitis B virus 13% and hepatitis C virus 15%. Hepatitis C virus is a common cause of viral hepatitis in the Christchurch community.


Immunisation status of children in the eastern Bay of Plenty. To assess the status of immunisation of children in the eastern Bay of Plenty. Survey of general practitioner records and case notes of all resident children born over a period of two years and aged from five to 29 months. Immunisation was considered up to date if received within a reasonable period of the expected time. One thousand five hundred and ninety-three children were studied (97% of those known to be resident). The six week immunisations were received by 91%, 88% received the three month, and 81% the five month vaccines. Delivery of second year immunisation was much less successful, only 72% receiving measles or MMR vaccine despite publicity about a current measles epidemic and 61% the eighteen month vaccines. Forty-three percent children of two years of age had not received the full recommended immunisation schedule. Some of the contributing factors were identified and measures that could improve immunisation uptake are discussed.


The effect of emergency department policy change on Hutt district general practices. To determine the impact of the new Hutt Hospital emergency care policy as perceived by general practitioners and measure the level of general practitioner emergency services provided. Postal survey one year after policy instituted of Hutt district general practitioners. Sixty-three general practitioners replied (93% response). Eighty-one percent of general practitioners were in favour of the new policy or wanted it extended further, although 79% had noticed a slight increase in patient numbers. Most surgeries were less than 10 km from the hospital, 44% had one general practitioner, 38% had no practice nurse, 84% were staffed between 40-59 hours a week. No practice had staff on the premises between the night time hours of 8 pm and 8 am but all had after hours cover by telephone. Most practices were equipped to manage at least some emergency conditions: all had peak flow meters, 94% had nebulisers, 69% oxygen cylinders, and 47% had an ECG machine. Only two practices had slit lamps and plaster of paris facilities, and one a defibrillation machine. Almost all general practitioners suture wounds, strap ankles, and most treat fractures and pack noses. Seventy-five percent of general practitioners expressed a need for better communication with the Hutt Hospital emergency department. A general acceptance of the policy change by Hutt general practitioners although more research is needed to determine the impact of this change on patients.


Ceftriaxone for paediatric bacterial meningitis: a report of 62 children and a review of the literature. The purpose of this prospective study was to document the efficacy of ceftriaxone in the treatment of childhood bacterial meningitis in a general paediatric unit. All children presenting with bacterial meningitis to Christchurch Hospital between January 1987 and June 1991 were enrolled in this prospective study and received ceftriaxone 100 mg/kg/d for seven days. Outcome was defined by parameters including mean time to fever defervescence, prolonged fever, days in hospital, seizures, and other acute neurological sequelae, requirement for ventilation, mortality and morbidity. Audiology was performed at six weeks and again at three months if abnormal. Neurodevelopmental assessment was performed at three months. Side effects were recorded. There were 62 evaluable children. The mortality rate was 4.8% (3 children). Two children (3.4%) had clinically detectable neurological sequelae at the three month assessment. The mean duration of stay was 8.7 nights. Five children (8%) required ventilation. Mild self limiting diarrhoea occurred in 29%. Ceftriaxone is an effective, safe and well tolerated antimicrobial for the treatment of childhood meningitis. It compares favourably with other equipotent antimicrobials. With a relatively long half life once daily administration is possible with a cost advantage.


Sexually transmitted diseases amongst a sample of people seeking HIV testing. To examine the incidence of sexually transmitted diseases according to gender, age, sexual orientation, sexual behaviour and drug use. Data were collected from 814 clients attending anonymously for HIV testing at the Burnett Centre in Auckland. During pretest counselling clients were asked questions designed to assess their risk of HIV infection including a detailed history of sexually transmitted diseases (STDs). Amongst attenders 44% reported at least one lifetime STD including 16% reporting more than one. Multiple STDs were not associated with gender or sexual orientation but they were associated with the practice of anal sex and with a history of multiple sex partners. Alcohol and drug use were also related to multiple STDs. For men the most common STD was NSU with 20% of them reporting it whereas for women genital warts was the most common reported by 18%. Amongst those under 20 years 9% reported genital warts, 7% NSU and 6% chlamydia. The findings confirm that it is sexual practices which put people at risk of infection from STDs rather than their sexual orientation. They also draw attention to the role that drugs and alcohol play in the practice of unsafe sex and the consequent transmission of STDs. Finally they suggest that screening for STDs as well as HIV in AIDS clinics should be encouraged.


Child passenger fatalities and restraint use in Auckland. To determine the proportion of children killed as passengers in car crashes who were unrestrained and to estimate the reduction in mortality that might result from increasing child restraint utilisation. All children killed as passengers in car crashes, over the period 1980-90, were identified from the Auckland coroners records. Data were recorded on sex, age, use and type of restraint, position within the motor vehicle, pattern of injuries and place of death. There were 49 children (25 male, 24 female) killed as passengers in car crashes over the study period (2.14/100,000/year). The median age was eight years (range 0-14 years). Of the 38 children for whom restraint use could be determined, 31 (81.6%) were unrestrained and seven (18.4%) were restrained. None of the children aged 0-2 years were restrained. Thirty-five children (71.4%) died at the scene of the crash, three (6.2%) died during transport to hospital, and 11 (22.4%) died in hospital. Based on overseas reports of the efficacy of child restraints, close to half (49%) of all child passenger deaths in Auckland could have been prevented with appropriate child restraint use.


Elderly people referred for institutional care--is prior assessment necessary? To determine whether requests for placement of an elderly person into rest home or hospital care accurately predicted the final outcome and to identify factors influencing a move to institutional care. Three month audit of all referrals to an assessment and rehabilitation unit for the elderly requesting rest home or hospital placement. Requests for medical advice or rehabilitation were excluded. Two hundred patients were studied (24.6% of all referrals). Placement was requested in a rest home in 132 and hospital in 68. Seventy-one (54%) patients referred for rest home placement were able to return to their own home and 64 remained there at six month follow-up. Hospital level care was assessed as appropriate in 62% of requests for this initially and at six month follow up. Age and diagnosis were not significant predictors of patients requiring placement. Overall, of 158 patients living at home referred for rest home or hospital care, 67 (42%) were managing at home six months later. Accurate assessment and treatment/management of elderly patients is necessary before recommending higher levels of care. Patients can be maintained in their current environment for longer than perceived by the referring doctor. This has important social and financial benefits.


Do access factors affect utilisation of general practitioner services in south Auckland? To describe basic features of access to general practitioner services in south Auckland, and to examine the effect of different factors on utilisation of general practitioner services with particular attention to access issues. A random population survey of relatively established residents was undertaken with the sample drawn from electoral rolls. A questionnaire was administered face-to-face by trained interviewers. Ninety-eight percent of respondents claimed to have a regular family doctor. The median travelling time to a respondent's general practitioner was 10 minutes. Ninety-five percent of respondents' general practitioners operated appointment systems. The median waiting time was 20 minutes, 30% felt the doctors fees stopped them going to the doctor sometimes. The average reported visiting rate was 6.9 visits per year. Poor perceived health, longer times with a given doctor and long waiting times were associated with decreased utilisation. Demographic factors were not associated with utilisation. Patient fees were not associated with utilisation in the sample. Only 23% of the variation in utilisation could be explained by the model. Long waiting times are associated with decreased utilisation in this population. Although there is significant dissatisfaction with general practitioner fees, this does not manifest itself in decreased utilisation. Only a small proportion of the variation in utilisation can be explained by linear models of the variables studied.


Air cushion mower foot injuries.

Air cushion mower foot injuries. This study was undertaken to identify significant physical, social and psychological problems resulting from injuries caused to the feet by air cushion mowers. Thirty-four patients seen with air cushion mower injuries were reviewed, either by personal assessment, or by questionnaire. A large number of patients had significant symptoms relating to their soft tissue or bone injuries, the majority experiencing some pain, and those who had amputations difficulty in some aspects of walking. Better education of the dangers of the misuse of these mowers may reduce the incidence of significant forefoot injuries.


Incidence of cancer among Pacific Island people in New Zealand. to describe the epidemiology of new cancer registrations among Pacific Island people in New Zealand with a view to identifying important cancers for preventive activities. new cancer cases registered with the New Zealand Cancer Registry of the Health Statistical Services for the decade 1979-88 were analysed. Cancer cases among Pacific Island people were compared with cancer cases among Maori and the remainder of the New Zealand population (other). while the number of cases reported among Pacific Island people was relatively small (1884), age standardised rates for cancer of all sites were much higher than age standardised rates for Maori and other populations. The age standardised rate (per 100,000 person years) for cancer of all sites among males in all age groups was 400 for Pacific Island, 308.8 for Maori and 295.3 for others. The age standardised rate for cancer of all sites among women in all age groups was 373.3 for Pacific Island women, 324.2 for Maori and 313.4 for other women. Liver cancer was more common among Pacific Island men than could be explained by temporary migration from the Pacific Islands for treatment. The age standardised rate for liver cancer was 28.2 for Pacific Island men, 11.4 for Maori and 1.9 for other men. Cancer of the cervix was the leading site among Pacific Island women as in Maori women, compared with breast cancer among women in the rest of the population. The age standardised rate for cervical cancer was 61.8 for Pacific Island, 69.0 for Maori and 59.3 for other women. in the decade 1979-88 there was an excess number of new registrations for some cancers described among Pacific Island people compared with Maori and other ethnic groups. Temporary migration from the Pacific Islands for treatment may explain some of the excess cases.


Increase in selenium status of Christchurch adults associated with deregulation of the wheat market. to determine whether there have been changes in the plasma selenium status of Christchurch adults between 1981 and 1992, and likely causes of any such changes. selenium analyses were performed on plasma samples collected during the period. Changes in agricultural practices and importation policies were also examined. mean plasma selenium levels ranged between 46 and 54 micrograms/L (0.59-0.69 mumol/L) until 1987, after which there was a dramatic and sustained increase to between 66 and 70 micrograms/L (0.84-0.88 mumol/L) for 1988-91, with a 1992 mean of 80 micrograms/L (1.01 mumol/L). This increase closely follows the deregulation of the New Zealand wheat market and greater South Island consumption of wheat imported from Australia and the United States. Whereas flour was made from South Island wheat prior to 1988 and contained about 15 micrograms/kg selenium, flour manufactured by Christchurch mills in 1991 contained between 80 and 140 micrograms/kg. these results imply that as a result of current government policy, the population of Christchurch no longer has particularly low selenium levels. It follows that if there is an association between low selenium and any form of ill health, a declining incidence or severity in this population might be expected.


Autologous blood transfusion in Auckland. To review autologous blood collection and transfusion practice in Auckland over the last five years. Records of autologous blood collections were obtained from blood collection centre records and results of transfusions on patients from hospital notes. One hundred and sixty-four units of blood were collected from 77 patients. Seventy-five percent of the units collected were transfused. Most autologous blood was transfused to private hospital patients. Only 8% of patients required homologous blood. There has been a slow increase of autologous blood collection and transfusion in the Auckland area, as well as in the rest of New Zealand. The present risks of homologous transfusion, particularly since the introduction of hepatitis C testing, appear very low. A further expansion of the present autologous blood programme would entail increased expenditure and it is suggested that a critical cost benefit analysis would be useful before the programme is expanded.


The bequest of human bodies for dissection: a case study in the Otago Medical School. To explore why and by whom body bequests to the Otago Medical School have been made since the 1960s. We sent out a questionnaire to people who have bequeathed their bodies to the medical school, the people being randomly selected on the basis of the inclusion of the initial J in a forename. The questionnaire sought information on sex, marital status, age, occupation at the time of bequest and bequest information source, as well as reasons for the bequest, expectations of cadaver use and attitudes towards organ donation. The most common reasons for making a bequest were--to aid medical science, and gratitude to the medical profession. There was, however, widespread confusion between cadaver use for medical teaching and for research. These center around the ethical implications of our findings for organ donation and attitudes towards usage of the dead body.


Financing oral health care. Can dentistry diversify the portfolio? One of the easiest ways to measure socioeconomic status in 20th-century America is to look in the mouth. Socioeconomic status is directly related to access to oral health care. And access to oral health care is directly related to financing oral health care.


Dental practices in New York State counties in the 1980s. The number of dental practices, population per dental practice, dental employees and employee salaries in New York State counties changed during the 1980s. The following is a review of these developments.


Fathers and sons. Practices not necessarily made in heaven. Partnerships result in many pluses to a dental practice. Interpersonal relationships result in many minuses to the partners' rapport. This is magnified manyfold when the relationship is father and son. This article attempts to resolve some of the problems.


Dental fellowships in developmental disabilities help broaden care of disabled. Continuation of the national trend toward deinstitutionalization and community placement for persons with developmental disabilities, physical handicaps and other medical problems will mean increased demand for dentists trained to care for this segment of the population. The New York State Office of Mental Retardation and Developmental Disabilities now offers dental fellowships in developmental disabilities to help fill the learning gap.


The single compartment model applied to the large renal pelvis: a preliminary study. Diuresis renography should exclude or confirm pelvi-ureteric junction obstruction. Numerous equivocal cases seen here had large renal pelves with slow emptying on frusemide diuresis. An attempt was made to relate the rate of emptying to the volume of the renal pelvis. The fully distended renal pelvis during frusemide diuresis appears to satisfy the criteria of the single compartmental model which predicts a linear relationship between volume and flow rate, i.e. F = [0.693 V0]/t1/2 where F is the flow rate, V0 is the volume and t1/2 the time at which half the tracer has disappeared. Clearance half-time was measured from the diuresis renogram curve. Volume was estimated from a longitudinal ultrasound image at the end of the procedure, using a volumetric version of Simpson's rule as a sequential slice technique, given a roughly circular transverse image. Of 18 kidneys in 14 adult patients, three had large volume pelves and short emptying times. The remaining 15 showed a roughly linear relationship between volume as estimated and clearance half-time. This appears to validate both the theory and the method and permits calculation of the pelvic outflow rate. An hypothesis to explain the large unobstructed renal pelvis is advanced.


The effect of captopril on glucoheptonate uptake in experimental renal artery stenosis. This study attempted to evaluate the role of glucoheptonate (GHA) in captopril renography in an in vivo laboratory investigation in which postcaptopril glucoheptonate uptake was analysed in awake 2KlC hypertensive rats. Clamped kidney uptake in a previous study was greater in the poststenotic kidney than in the normal kidney (P = 0.01) in rats with mild renal artery stenosis. A glucoheptonate renogram protocol was developed for use in rats anaesthetized with sodium pentobarbital. An 123I-hippuran scan was performed to determine the relative renal function, followed by a control 99Tcm-GHA scan. Five minutes after administering captopril, another 99Tcm-GHA scan was performed. Relative renal uptake was determined between 30 and 90 s postinjection. 99Tcm-GHA uptake in the clamped kidney was more than 50% of total uptake in 3/9 of the abnormal rats' control scans. No abnormal rats clamped kidney 99Tcm-GHA uptake was greater than 50% in the postcaptopril scans. Captopril reduced GHA uptake in all nine of the animals with baseline scans. These findings suggest that the laboratory observation of captopril induced paradoxically increased 99Tcm-GHA uptake in renal artery stenosis may not be observed scintirenographically. Moreover, the data support a potential value of glucoheptonate in captopril renography.


Further characterization of iodide-induced hyperthyroidism based on the direct measurement of intrathyroidal iodine stores. Clinical, scintigraphic and laboratory findings in a group of 23 hyperthyroid patients with inappropriate total intrathyroidal iodine pool (ITI), measured by X-ray fluorescence, were compared to those of 25 hyperthyroid patients with low ITI. Differences are discussed which may be useful in the diagnosis of this clinical entity.


Challenges for nuclear medicine in the 1990s. This article discusses the problems facing nuclear medicine in the coming decade and outlines the areas in which new developments or expansion can be expected. The questions considered include legislative requirements, the need to educate the public and the medical profession on the strengths of nuclear medicine, approaches to cost-benefit analysis, and development of new technologies and new radiopharmaceuticals. There is also an evaluation of expansion in nuclear medicine using both existing methodology and new methodologies.


The use of a new radiopharmaceutical, 97Ru-DISIDA, and of 99Tcm-sulphur colloid for the simultaneous evaluation of duodenogastric reflux and gastric emptying. There is no consensus or a uniform technique for measuring gastric emptying and numerous modalities have been reported. We report here the results obtained using a modification of the published techniques for the simultaneous measurement of duodenogastric reflux and gastric emptying utilizing simultaneously the recently developed radiopharmaceutical 97Ru-DISIDA, intravenously, and the oral administration of 99Tcm-sulphur colloid incorporated in a 'solid' test meal.