A quantitative analysis of eye movements during the cover test – a preliminary report

The aim of this study was to carry out quantitative analyses of eye movements during the cover test on a group ( n = 57) of asymptomatic emmetropes. Eye movements were recorded during an automated cover test while subjects fixated a distance (3.4 m) and near (0.4 m) target. There was a significant difference between the amplitude of phoria measured after 2 s of occlusion compared to 10 s ( P < 0.01). The mean phoria after 10 s of occlusion was 0.1° (eso) for distance fixation and 1.6° (exo) for near fixation. The distribution was approximately normal for both distance and near fixation but the standard deviation was greater for near (2.0°) than distance fixation (1.4°). The pattern of eye movements during the recovery phase was more complex than is often assumed, in many cases consisting of a variety of saccadic and vergence movements involving both the covered and 'fixing' eye. The latency of the first recovery movement was significantly shorter for exophoric than esophoric deviations ( P < 0.01) and the latency of some recovery movements were very short (< 150 ms).     

Cerebellar syndrome in myxoedema revisited: a published case with carcinomatosis and multiple system atrophy at necropsy.

One of six patients in a 1960 paper on "Cerebellar syndrome in myxoedema" was subsequently found to have adenocarcinoma. General post-mortem revealed carcinomatosis and basal pneumonia. Neuropathological examination revealed the changes of multiple system atrophy. The relationship between hypothyroidism, carcinoma, and cerebellar, pontine and striatonigral degeneration is discussed.     

Localization and Quantitative Autoradiography of Glutamatergic Ligand Binding Sites in Chick Brain

The anatomical localization of glutamate receptor subtype-selective ligand binding sites was investigated in 1-day-old chick brain using quantitative autoradiography. Under the conditions used, the regional distributions of [3H]glutamate, [3H]AMPA (a selective quisqualate receptor ligand) and [3H]kainate binding sites are manifestly different. [3H]l-glutamate binding is densely localized in the telencephalon, particularly in the neostriatum (2.8 pmol/mg protein). In addition, [3H]l-glutamate labels the thalamus, the nucleus mesencephalicus lateralis pars dorsalis, the superficial layers of the optic tectum and the molecular layer of the cerebellum. [3H]AMPA binding sites are most densely localized in the hippocampus (0.90 pmol/mg protein), with an otherwise relatively uniform distribution of binding within the telencephalon. [3H]AMPA also labels the striatum griseum et fibrosum superficiale of the optic tectum and the molecular layer of the cerebellum. [3H]Kainate binding sites are extremely densely packed in the molecular layer of the cerebellum (10 pmol/mg protein). Other regions of [3H]kainate binding include the hyperstriatum and the thalamus. The binding of the NMDA receptor channel blocker [3H]MK-801 is increased in the presence of 1 mM l-glutamate. [3H]MK-801 binding is generally widespread in the telencephalon but is notably absent from the ectostriatum. No evidence of [3H]MK-801 binding sites was detected in the cerebellum, even in the presence of 1 mM l-glutamate. The relatively high densities and the well-defined localizations of the glutamate receptor subtype binding sites suggest that chick brain provides a useful system for the further study of excitatory amino acid receptors.     

Progress in the autosomal segmental aneusomy syndromes (SASs): single or multi-locus disorders?

Based on cytogenetic observations, several syndromes have been previously identified as microdeletion-based disorders. In this review, recent progress is presented regarding whether one or multiple genes can be implicated in the pathogenesis of these segmentally aneusomic syndromes. The syndromes discussed include Angelman, Alagille, Williams, Langer-Giedeon, Prader-Willi, Smith-Magenis, Miller-Dieker, and DiGeorge/velocardiofacial or the 22q11 deletion syndromes. For Angelman and Alagille syndromes, single genes have been identified, whereas for Williams and Langer-Giedion syndromes, more than one gene can be implicated. Although there has been significant progress in dissecting the molecular basis for the other disorders, the ultimate answer regarding one versus several genes remains to be determined.      

HLA/Bf haplotypes in a Newfoundland family

HLA/Bf haplotypes were examined in a large three-generation Newfoundland family with a high incidence of Graves' disease. In that family Graves' disease was inherited in association with the haplotype HLA Aw24, Bw39 in some instances and with HLA B8-containing haplotypes in other instances. As all seven members of the family who suffered from Graves' disease were homozygous for the Bf S allele, the study for Bf was uninformative. However, the examination of other HLA/Bf haplotypes disclosed some interesting associations. One-hundred-and-five out of 168 HLA-A, -B, -Bf haplotypes were Bf S. Although numerically deviant, no unusual HLA B/Bf associations were observed. Bf F entered the family only once. A new finding is the association between HLA B27 and Bf S1; the haplotype entered the family once and was passed on to eight family members over three generations. Bf S1 was previously reported in association with HLA B12 or W21. None of these family members had ankylosing spondylitis. The Bf allele F1 entered the family three times, always in association with HLA B18.     

Interactions between cyclosporin A, indomethacin and 16,16-dimethyl prostaglandin E2: effects on renal, hepatic and gastrointestinal toxicity in the rat

Rats were treated for 3 or 14 days with cyclosporin A (CsA, 50 mg/kg) or indomethacin (2 or 5 mg/kg) either alone or in combination, or with CsA plus 16,16-dimethylprostaglandin E2 (DMPGE2, 0.25 mg/kg). Hepatic and renal function were unaffected by treatment with indomethacin at either dose and only at the higher dose was severe intestinal ulceration observed. CsA caused renal and hepatic toxicity, evidenced by increased urine N-acetyl-beta-D-glucosaminidase activity, serum urea, creatinine and bilirubin and decreased serum albumin and total protein. In rats cotreated with CsA and either dose of indomethacin the increases in serum urea and creatinine and decreases in serum albumin and total protein were accentuated, but serum bilirubin was not further increased. Intestinal lesions were present in rats treated for 14 days with CsA plus the lower dose of indomethacin, but not in rats treated with either drug alone. In rats treated with DMPGE2 plus CsA, serum urea and creatinine were normal and urine N-acetyl-beta-D-glucosaminidase activity was reduced compared to rats treated with CsA alone, but DMPGE2 cotreatment had no effect on the CsA induced hyperbilirubinaemia. Hepatic microsomal cytochrome P-450 concentration and aminopyrine N-demethylase activity were lower in rats treated with CsA plus indomethacin than in untreated rats or those treated with either drug alone. Coadministration of indomethacin or DMPGE2 had no effect on serum trough CsA levels. The results are interpreted as showing an exacerbation by CsA of the intestinal toxicity of indomethacin, an increase by indomethacin in the renal toxicity of CsA and a protection by DMPGE2 against CsA renal toxicity. Possible mechanisms involving drug interactions and either hepatic cytochrome P-450, renal cyclooxygenase or other renal sites are discussed.