Clinical complaints and their handling: a time for change?

Objectives: To assess the performance of the hospital complaints procedure for complaints proceeding to peer review and the quality of responses to complainants.

Design: Retrospective study of data on clinical complaints proceeding to peer review during 1986-91 from clinical records, correspondence, reports of the complaints investigations, and expert review of written responses to complainants.

Setting: Northern Regional Health Authority, covering three million people.

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%.

Improved resolution in three-dimensional constant-time triple resonance NMR spectroscopy of proteins.

Two new protocols for the three-dimensional, triple resonance, constant-time HCA(CO)N NMR experiment are presented that significantly increase the experimental resolution attainable in the C alpha frequency dimension. Experimental verification of the new experiments is provided by spectra of the IIA domain of glucose permease from Bacillus subtilis.

Vascular factors in the neurotoxic damage caused by 1,3-dinitrobenzene in the rat.

Using a 3 x 10 mg/kg dose schedule of 1,3-dinitrobenzene (DNB) over two days in Fischer rats, we have found the following changes in vascular function and structure during the early phase of the symmetrical brain stem lesions. 1. Marked increase in cerebral blood flow generally but especially in the inferior colliculi, from 6 h after the final dose of DNB.

Uniform labeling of a recombinant antibody Fv-fragment with 15N and 13C for heteronuclear NMR spectroscopy.

The expression of functional antibody fragments in Escherichia coli enables a detailed analysis by NMR spectroscopy. This is demonstrated with the uniform labeling of an Fv-fragment (25 kDa) comprising the antigen binding site of an antibody against 2-phenyloxazolone with 15N and 13C. The antigen-complexed Fv-fragment was analysed for a potential assignment by heteronuclear multi-dimensional NMR spectroscopy.

Polypeptide backbone resonance assignments and secondary structure of Bacillus subtilis enzyme IIIglc determined by two-dimensional and three-dimensional heteronuclear NMR spectroscopy.

The enzyme IIIglc-like domain of Bacillus subtilis IIglc (IIIglc, 162 residues, 17.4 kDa) has been cloned and overexpressed in Escherichia coli. Sequence-specific assignment of the backbone 1H and 15N resonances has been carried out with a combination of homonuclear and heteronuclear two-dimensional and heteronuclear three-dimensional (3D) NMR spectroscopy.

What have we learnt from Graham Frederick Young? Reflections on the mechanism of thallium neurotoxicity.

The recent death of the psychopathic poisoner, Graham Frederick Young, prompts the question: has our knowledge of the toxic effects of thallium been increased as a result of his activities? The answer is 'yes' but very little. However, the poisonings led to a re-examination of the topography and pathogenesis of thallium intoxication and the suggestion that there are close similarities with chronic thiamine deficiency neuropathy and arsenical neuropathy. They might be termed chronic energy deprivation neuropathies and are associated with damage to other organs with high energy requirements, namely skin and its appendages, testis and heart.

Selective degeneration of cerebellar cortical neurons caused by cycad neurotoxin, L-beta-methylaminoalanine (L-BMAA), in rats.

Both the racemate and the L-form of BMAA (beta-methylaminoalanine), when injected intraperitoneally into young rats, produced acute signs of cerebellar dysfunction and degeneration of cerebellar stellate, basket, Purkinje and Golgi cells, but not granule cells. Degenerative changes were also occasionally seen in cerebellar roof nuclei which may be secondary in nature. No other changes were found in the remainder of the central nervous system.

Pregnancy reduces noradrenaline but not neuropeptide levels in the uterine artery of the guinea-pig.

Using histochemical, immunohistochemical and biochemical techniques, noradrenaline-, neuropeptide Y-, vasoactive intestinal polypeptide-, substance P- and calcitonin gene-related peptide-containing nerve fibres were studied in the uterine artery of virgin, progesterone-treated and pregnant guinea-pigs. Morphological changes following hormone treatment or in pregnancy were also evaluated in a quantitative study on semithin sections of the uterine artery. In late pregnancy, the number of noradrenaline-containing nerve fibres, which formed the densest plexus in virgin animals, was significantly decreased, a finding supported by a significant reduction in noradrenaline levels.

Long-term chemical sympathectomy leads to an increase of neuropeptide Y immunoreactivity in cerebrovascular nerves and iris of the developing rat.

Short-term (surgical) and long-term (chemical) sympathectomy have revealed the presence of a population of neuropeptide Y-like immunoreactive nerve fibres which do not degenerate in parallel with noradrenaline-containing nerves supplying cerebral vessels and the iris of the rat. Two days after bilateral removal of the superior and middle cervical ganglia of 7-week-old rats, noradrenaline-containing nerves could not be detected along any of the arteries of the rat circle of Willis or of the iris, but 18-32% of neuropeptide Y-like immunoreactive nerves remained. Long-term treatment (6 weeks) with guanethidine commencing in developing 1-week-old rats caused degeneration of the sympathetic neurons in cervical ganglia and disappearance of 5-hydroxydopamine-labelled nerves (that showed dense-cored vesicles at the electron microscope level) from rat cerebral vessels, but did not significantly change the density of neuropeptide Y-like immunoreactive axons on the vessels.

Glial cell intrusions actively remove detritus due to toxic chemicals from within nerve cells.

It has been observed that when neurons are acutely damaged by toxic chemicals leading to accumulations of effete materials, glial supporting cells insert cytoplasmic processes into neuronal cytoplasm and appear to transfer this material into themselves. Essentially the same phenomenon has now been seen in several situations, namely in peripheral nerve axons in a number of experimental peripheral nerve intoxications, especially in spinal roots, as well as occasionally in normal axons in paranodal regions and more frequently above a nerve ligation. It has been seen, too, in cerebellar Purkinje cells after acrylamide intoxication and in hippocampal pyramidal neurons and in neurons of the pyriform cortex after triethyllead and trimethyltin intoxications.

Regional variations in nerve cell responses to trimethyltin intoxication in Mongolian gerbils and rats; further evidence for involvement of the Golgi apparatus.

The different responses of neurons with distinctive variations in morphology and function, confirm earlier observations of the lack of uniformity in the reaction of nerve cells to trimethyltin. Thus, hippocampal pyramidal and cortical neurons in both rat and Mongolian gerbil (M. unguiculatus) show abundant lysosomal dense bodies and disorganisation of the protein-synthesising apparatus.

Use of enhanced silver staining combined with electron microscopical immunolabelling to demonstrate the colocalization of neuropeptide Y and vasoactive intestinal polypeptide in cerebrovascular nerves.

The combination of immunolabelling at the electron microscope level and enhanced silver staining has been used to demonstrate the colocalization of neuropeptide Y and vasoactive intestinal polypeptide in perivascular nerves supplying cerebral arteries of the rat. This has been shown in control tissue, but it is easier to demonstrate after long-term sympathectomy since that leads to an enhancement of neuropeptide Y in vasoactive intestinal polypeptide-containing parasympathetic nerves supplying these vessels. Immunolabelling of the antigens for these peptides was performed sequentially with the biotin streptavidin diaminobenzidine method, and the end product to the first antiserum was gold-silver intensified before the visualization of the second antigen.

Complete assignment of the 1H NMR spectrum of a synthetic zinc finger from Xfin. Sequential resonance assignments and secondary structure.

A 25-residue synthetic peptide corresponding to zinc finger 31 of the Xenopus protein Xfin adopts a compact, folded conformation in the presence of zinc. Complete 1H resonance assignments have been made. The peptide contains a helix, beginning as an alpha-helix and ending as a 3(10)-helix, that extends from residue 12 to 23.

Trichloroethylene cranial neuropathy: is it really a toxic neuropathy or does it activate latent herpes virus?

The mechanism of the cranial neuropathy associated with heavy exposure to trichloroethylene (or dichloroethylene) is unknown. In severe cases there is destructive spread of the neuropathic process from the Vth cranial nerve nuclei up and down the brain stem in a manner that is difficult to explain on accepted neurotoxicological principles. However, there is a close association reported of this form of trigeminal neuropathy with reactivation of orofacial herpes simplex that suggests the possibility that the chemical, which readily gains entrance into the nervous system, may be responsible for reactivating the latent virus.

Involvement of the MN blood group antigen in shear-enhanced hemagglutination induced by the Escherichia coli F41 adhesin.

An adhesin from Escherichia coli F41 with an apparent subunit molecular weight of 28,000 daltons was isolated by using (NH4)2SO4 precipitation at pH 10 and Sephacryl S-500 gel filtration. The hemagglutination (HA) properties of the native high-molecular-weight adhesin were studied by using a viscometric assay, which provided a quantitative index of the degree of agglutination present as a function of time at a known rate of shear. Shear was found to enhance the degree of agglutination over a 20-min period.

Motoneuron disease: a disorder secondary to solvent exposure?

There seems to be a statistically significant association between work in the leather industry and subsequent development of motoneuron disease. The reason for this association may be occupational exposure to solvents, which may damage motoneurons either directly or through activation of latent virus.

Persistent mercury in nerve cells 16 years after metallic mercury poisoning.

A male subject, after exposure to mercury metal at work in 1968, developed classical signs of mercurialism from which he made a slow clinical recovery. He subsequently developed psychoneurotic symptoms and became an alcoholic; he never returned to work and died in 1984. No histological changes relevant to mercury intoxication were found in the brain, but staining by Danscher & Schroeder's method for mercury showed many positively staining lysosomal dense bodies in a large proportion of nerve cells, and the presence of mercury was confirmed by elemental X-ray analysis.

Lesion localisation: implications for the study of functional effects and mechanisms of action.

In some toxic neuropathies we see only distal "dying back" of longer and larger diameter axons, the perikaryon appearing to be intact. Some of these are the result of chronic energy deprivation, others are not. In other neuropathies sensory and autonomic neuron cell bodies are damaged without apparent selectivity.

Nuclear and nucleolar damage in adriamycin-induced toxicity to rat sensory ganglion cells.

A single dose (10 mg/kg) of Adriamycin was given to 23 adult Wistar rats and the spinal ganglia were studied from 6 h to 15 days after. As previously described, this drug results in the appearance of 'clear' areas in the nuclei of rat spinal ganglion cells as seen by light and by electron microscopy. The 'clear' areas become less conspicuous during the week before the onset of cytoplasmic degeneration.