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Biomedical subjects

R Perry

Publications and source records attributed to R Perry.

At least 19 recordsLinked to original sources

Neuroleptic sensitivity in patients with senile dementia of Lewy body type.

OBJECTIVE: To determine the outcome of administration of neuroleptics to patients with senile dementia of Lewy body type confirmed at necropsy. DESIGN: Retrospective analysis of clinical notes blind to neuropathological diagnosis. SETTING: Specialist psychogeriatric assessment units referring cases for necropsy to a teaching hospital neuropathology service. PATIENTS: 41 elderly patients with diagnosis of either Alzheimer type dementia (n = 21) or Lewy body type dementia (n = 20) confirmed at necropsy. MAIN OUTCOME MEASURES: Clinical state including extrapyramidal features before and after neuroleptic treatment and survival analysis of patients showing severe neuroleptic sensitivity compared with the remainder in the group. RESULTS: 16 (80%) patients with Lewy body type dementia received neuroleptics, 13 (81%) of whom reacted adversely; in seven (54%) the reactions were severe. Survival analysis showed an increased mortality in the year after presentation to psychiatric services compared with patients with mild or no neuroleptic sensitivity (hazard ratio 2.70 (95% confidence interval 2.50-8.99); (chi 2 = 2.68, p = 0.05). By contrast, only one (7%) of 14 patients with Alzheimer type dementia given neuroleptics showed severe neuroleptic sensitivity. CONCLUSIONS: Severe, and often fatal, neuroleptic sensitivity may occur in elderly patients with confusion, dementia, or behavioural disturbance. Its occurrence may indicate senile dementia of Lewy body type and this feature has been included in clinical diagnostic criteria for this type of dementia.

Aged

Concentrations of particulate and gaseous polycyclic aromatic hydrocarbons in London air following a reduction in the lead content of petrol in the United Kingdom.

The environmental importance of tropospheric polycyclic aromatic hydrocarbons (PAH) is reviewed. The impact of reducing lead on airborne PAH is indicated and the importance of monitoring both particulate and gaseous-phase PAH is demonstrated. A Brief description of a sampling regime performed from 1985 to 1987 is given. Sampling of 18 PAH was performed and particulate lead concentrations at the kerbside were measured concurrently. Measurements indicate that there is a pronounced seasonality in PAH concentrations and in the distribution of PAH between particulate and gaseous phases. On average, 47% of the PAH measured were in the gaseous phase, indicating the importance of measuring the volatile fraction. The dominance of the common variation of each PAH was also investigated using principal components analysis. An uneven spread of data prior to and following the reduction in lead content, hindered a thorough examination of the effect of this change on PAH concentrations. However, they appeared to indicate only a small change in PAH concentration and this was linked to an increase in aromatic content of the petrol, which was much less than expected.

Air Pollutants

Use of gastrotomy to relieve esophageal obstruction in a horse.

Esophageal obstruction of 1 week's duration in a gelding was diagnosed by contrast radiography and esophagoscopy. A food bolus was found at the junction of the caudal thoracic portion of the esophagus and the cardia. A gastrotomy was performed through a cranial abdominal incision and a phytobezoar was manually broken down and removed. The gelding was started on complete pellet food and water on the fifth day after surgery. The horse remained clinically normal more than 1 year after surgery.

Animals

Distribution of nerve growth factor receptor immunoreactivity in the human hippocampus.

Nerve growth factor (NGF) receptor-like immunoreactivity has been demonstrated in the normal adult human hippocampus, using minimally fixed cryostat sections obtained from snap-frozen tissue and incubated with the mouse monoclonal antibody, ME 20.4. The majority of the reactivity was associated with nerve fibre processes and their terminals. Numerous fibres were apparent in the alveus, originating from the fornix, and extending into the stratum oriens and pyramidal layer of the hippocampal formation. A more diffuse particulate reactivity, presumed to be nerve terminal, was observed around the pyramidal neurons and in the stratum radiatum, stratum lacunosum moleculare and also in the dentate fascia. The pattern of hippocampal NGF receptor immunoreactivity was broadly similar to acetylcholinesterase histochemical localization, indicating a principal localization on cholinergic axons innervating this area. Preliminary observations indicate an overall reduction in NGF receptor-immunoreactive axons and terminals in old age and Alzheimer's disease.

Acetylcholinesterase

Photodynamic therapy of oncogene-transformed cells.

Photodynamic therapy with dihematoporphyrin ether sensitizes malignant cells to damage by 630 nm light. The in vitro, in vivo photodynamic therapy sensitivity of a cell line transformed by the Kirsten ras oncogene (45342) was studied to establish a new photodynamic therapy model. With the colony formation assay, neither light alone nor dihematoporphyrin ether alone affected 45342 survival. Energy-dependent photodynamic therapy effects were seen in vitro in dihematoporphyrin ether-incubated and light-exposed cells (90% cytotoxicity = 950 joules/m2; 99% cytotoxicity = 1575 joules/m2; p2 less than 0.05). Subcutaneous allografts of 45342 were established in nu/nu mice, and ideal route (intravenous or intraperitoneal) of dihematoporphyrin ether delivery, dihematoporphyrin ether tissue kinetics, and in vivo photodynamic therapy effects were examined. Intravenous administration not only gave higher levels of the sensitizer in various tissues, but also was associated with less variation than the intraperitoneal route. Selective dihematoporphyrin ether retention was documented in the tumors at 24 hours after injection compared with other tissues, and photodynamic therapy with 0.3 W/cm2 to a total dose of 150 joules/cm2 led to progressive coagulative tumor necrosis and tumor regression. These studies confirm that transformed, malignant cells are sensitive to photodynamic therapy, and this model may prove in future studies to increase efficacy to photodynamic therapy (i.e., with dihematoporphyrin ether delivery by monoclonal antibodies).

Animals

Fetal supraventricular tachycardia and hydrops fetalis: combined intensive, direct, and transplacental therapy.

A 25-week fetus with severe hydrops fetalis secondary to supraventricular tachycardia was treated with fetal intramuscular injections of digoxin in conjunction with maternal intravenous digoxin, followed by oral digoxin and subsequently by oral procainamide therapy. Fetal umbilical blood sampling revealed poor placental transfer of digoxin, even after 2 weeks of therapeutic maternal levels. This case suggests that direct fetal therapy is of value in the treatment of some fetuses with supraventricular tachycardia, and lends further evidence that the role of transplacental digoxin therapy is limited in the compromised fetus. It also demonstrates that resolution of hydrops may require a prolonged period.

Adult

Biochemical assay of Alzheimer's disease--associated protein(s) in human brain tissue. A clinical study.

The concentration of Alzheimer's disease-associated protein (ADAP) was measured in postmortem brain tissue samples of temporal or frontal cortex from 111 human brains using a sandwich immunoassay. Alzheimer's disease-associated protein has three major ALZ-50-reactive subunits, including A-68. This assay utilizes ALZ-50 and a rabbit antibody raised against a highly ADAP-enriched brain protein fraction. The frequently observed cross-reactivity of ALZ-50 with normal brain components in direct immunoassays is minimized by this configuration. There were 27 normal controls, 28 neurologic disease controls, and 56 Alzheimer's disease cases. The normal control and neurologic disease control cases had essentially no detectable level of ADAP, while ADAP was clearly detected in 85.7% of the Alzheimer's disease cases. Clinical dementia, neuritic plaques, and old age per se are not correlated with increased ADAP levels. This biochemical assay of ADAP may prove to be helpful as an adjunct in the clinicopathologic diagnosis of Alzheimer's disease.

Aged

Effect of photodynamic therapy on tumor necrosis factor production by murine macrophages.

Photodynamic therapy (PDT) involves the treatment of tumors in the presence of sensitizer, light, and oxygen, causing energy-dependent cytotoxicity. A vascular effect that causes hemorrhagic tumor necrosis has been described with PDT, but its basis remains undefined. To investigate the possible role of tumor necrosis factor (TNF) production in the generation of such a vascular effect and/or a direct tumor effect, we treated thioglycollate-elicited murine macrophages with PDT, and we measured the possible production of TNF using the L929 assay. An energy-dependent production of TNF by macrophage treated with PDT, stimulated or unstimulated with endotoxin, was demonstrated, and TNF production was inhibited at the highest treatment energy levels. These data represent the first description of cytokine production by PDT-treated macrophages, and may serve as another mechanism of PDT cytotoxicity in vivo, either directly by TNF-mediated tumor necrosis, or indirectly by vascular effects on tumor vessels.

Animals

Changes in benzodiazepine and acetylcholine receptors in the globus pallidus in Parkinson's disease.

Experiments are described in which the benzodiazepine portion of the gamma-aminobutyric acid (GABA)/benzodiazepine receptor and the muscarinic cholinergic receptor were investigated in Parkinson's disease and control brains. Tritiated flunitrazepam and tritiated quinuclidinyl benzilate (QNB) were used to locate and quantify the receptors by autoradiographic and homogenate binding techniques. Densitometric analysis of autoradiographs of the basal ganglia allowed comparison of receptor densities in the post-mortem control and parkinsonian tissue, while homogenate binding experiments gave information concerning receptor affinity and maximum binding capacity. The results indicate that: 1) Binding of flunitrazepam to the benzodiazepine receptor is reduced in the lateral segment of the globus pallidus in Parkinson's disease. This suggest that the GABA-ergic pathway from the putamen to the lateral pallidal segment is overactive in Parkinson's disease. 2) Binding of QNB to the cholinergic receptors of the medial pallidal segment is increased in Parkinson's disease. This finding suggests underactivity of the cholinergic pathway from the pedunculopontine nucleus of the medial pallidal segment. 3) Binding of these ligands in the caudate and putamen of Parkinson's disease is not significantly different from controls. We reviewed the literature concerning the activity of these projections in parkinsonian conditions assessed by different methods and discuss here their implications for the pathogenesis of parkinsonian symptoms.

Aged

Nager's acrofacial dysostosis. Case report and review of the literature.

Nager's acrofacial dysostosis is a rare congenital anomaly in which mandibulofacial dysostosis is seen in combination with limb deformities, particularly hypoplasia of the radial aspect of the hand. A boy with a severe manifestation of this syndrome is presented. Deformities include severe bilateral mandibular hypoplasia with trismus, malar hypoplasia, downward sloping palpebral fissures, high-arched hard palate, absent soft palate, external auditory and middle ear abnormalities and bilateral hand deformities. The diagnosis and treatment difficulties in this patient are discussed in light of those reported in the literature. An interdisciplinary team approach to the management of patients with Nager syndrome is emphasized.

Fingers

LH and FSH secretion and responses to GnRH and TRH in patients with clinically functionless pituitary adenomas.

Serum concentrations of LH and FSH and their response to the separate administration of GnRH (100 micrograms i.v.) and TRH (200 micrograms i.v.) have been studied preoperatively in 12 patients with a clinically functionless pituitary adenoma, of whom nine (3F: 6M) were found to secrete gonadotrophins in vitro. In three patients with a gonadotrophin-secreting adenoma (GSA) the pulsatile release of LH and FSH was also assessed preoperatively. An elevated serum FSH was recorded in six of nine patients with a GSA, and was subnormal in one, whilst an elevated LH was recorded in only two and was subnormal in six. A doubling of LH occurred in only four of the nine patients after GnRH and in three of six after TRH. None of the three patients with a non-GSA was shown to have an aberrant response to GnRH or TRH. In patients with a GSA, pulsatile release of LH and FSH was usually asynchronous and neither hormone demonstrated any regular harmonic pattern. These data show that in patients with a GSA the serum FSH level is usually elevated but this is not invariable, and the LH may well be low. Pathological responses of LH are frequently found following the administration of either GnRH or TRH and these stimulation tests should be performed separately in patients presenting with a clinically 'non-functioning' pituitary tumour to assist in the preoperative diagnosis. The absence of normal LH and FSH pulsing also appears to be a feature of GS adenomas, and suggests that tumorous gonadotrophin secretion is not under physiological control by hypothalamic GnRH.

Adenoma

Saliva and serum lithium monitoring in hospitalized children.

Serum and saliva lithium levels are presented for 30 inpatients, ages 5.12 to 11.95 years, diagnosed as having conduct disorder of the undersocialized aggressive type. Maintenance doses of lithium carbonate ranged from 600 mg to 1,500 mg/day. Serum and saliva lithium levels were significantly correlated at optimal dose (r = .78, p less than .001) and overall (r = .83, p less than .001), lending support to the use of saliva lithium levels as an adjunct to serum lithium determinations. However, because saliva/serum lithium ratios reveal wide ranges between subjects, the use of saliva levels is limited, and laboratory assessments should be combined with careful clinical monitoring.

Child