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Biomedical subjects

A Kennedy

Publications and source records attributed to A Kennedy.

At least 145 records · Page 8Linked to original sources

Pleural involvement in the carcinoid syndrome.

Tissue fibrosis is a recognized complication of the carcinoid syndrome but pleural changes have not been described. Prompted by the finding of severe pleural thickening in two patients with the metastatic carcinoid syndrome but no thoracic metastases or previous pleural disease we reviewed the chest radiographs and CT scans in 50 patients with the carcinoid syndrome investigated from 1981 to 1990. Pleural abnormality was noted in 14 of the 50 patients (28%), five of whom had other possible causes for pleural disease. However, nine (18%) patients had 'idiopathic' pleural thickening. Pleural disease had developed within 2 years of the diagnosis in all cases, and seven of the nine patients had fibrosis elsewhere (heart valves, skin or mesentery). There were no features to suggest a more rapid disease progression in the patients with pleural disease. We suggest that the pleural abnormality is a complication of metastatic carcinoid disease.

Humans↗

Effects of a high-galactose diet on the interphotoreceptor matrix of two strains of rat.

PURPOSE: The authors previously reported that a diet containing 30% galactose retards the development of the late-onset photoreceptor dystrophy in the spontaneously hypertensive (SHR) rat. It was suggested that the dystrophy might result from faulty galactosylation of a critical glycoprotein or glycosaminoglycan (GAG) in the interphotoreceptor matrix (IPM). In the current study, this hypothesis was tested by studying IPM protein and GAG composition in SHR and normotensive Wistar-Kyoto (WKy) control strain rats fed a standard or a high-galactose (30%) diet. METHODS: The authors performed biochemical analyses of the IPM of SHR and of WKy control rats fed either the basal diet or a 30% galactose diet for 14 mo and labeled at the termination of the experiment with 3H-glucosamine and 35S-sulfate. Analyses included high-performance liquid chromatography and two-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and isoelectric focusing (IEF) of extracted proteoglycans with identification of the GAG by selective enzymatic degradation and immunoblotting of SDS-PAGE gels for interphotoreceptor retinol-binding protein (IRBP), with slot blots for additional quantitation. RESULTS: Although several differences were detected in GAG radiolabeling between the two strains, only one, a decreased overall synthesis of 3H-glucosamine-labeled GAG in the WKy rats, was altered by the high-galactose diet. There was no apparent difference in the protein patterns of the IPM as evaluated by two-dimensional SDS-PAGE and IEF. However, slot blots of that portion of the IPM extracted from the neural retinas showed less reactivity per microgram of protein for IRBP in the galactose-fed animals of both strains than for the rats fed a basal diet. This was statistically significant, however, only in the WKy rats. CONCLUSIONS: The composition of the IPM of these two strains of rat appears similar to the composition of the IPM of other species that have been studied. Whether the quantitative alteration in IRBP that appears to be produced by galactose feeding has functional significance, with particular relevance to retarding the development of the photoreceptor cell dystrophy of the SHR rat, is unclear at this time.

Animals↗

Effects of endothelin on cultured bovine retinal microvascular pericytes.

PURPOSE: The endothelins, a recently discovered family of peptides, include endothelin-1, the most potent vasoconstrictor known. Retinal microvascular pericytes are thought to be contractile cells analogous to the smooth muscle cells of larger vessels, but the physiologic stimulus for their contraction is unknown. We hypothesized that the endothelins might serve as such stimuli. METHODS: The intracellular free/bound Ca++ ratio increases rapidly immediately before muscle cell contraction. We evaluated changes in this ratio in cultured bovine retinal microvascular pericytes and, for comparison, three other types of ocular cells. We loaded the cells with the calcium-sensitive, fluorescent dye Indo-1. Using a laser cytometer, we monitored the time course of changes in fluorescence of individual cells in response to several putative vasoactive agents, including, in particular, endothelin-1, 2, and 3. RESULTS: Endothelin-1 (ET-1) produced a rapid rise in the free/bound Ca++ ratio, followed by a slow decline. The response occurred at ET-1 concentrations as low as 1 x 10(-12) mol/l, and was graded in amplitude and concentration dependent. After an initial application of ET-1, repeat applications yielded no response. Endothelin-2 was less effective than ET-1, and ET-3 had no effect at all, but both agents blocked the response to ET-1. Several other agents also raised the free/bound Ca++ ratio, but were substantially less effective than ET-1. When any of these agents, except for histamine, was added after even a submaximal concentration of ET-1, no response was observed, but ET-1 applied after these agents produced a large response. Histamine could elicit a rise in the free/bound Ca++ ratio after application of ET-1 to cultured pericytes. The ET-1 response occurred in Ca(++)-free medium and in medium containing 10(-4) mol/l verapamil or nifedipine, indicating that the results we observed are due primarily to the release of free Ca++ from bound intracellular stores. Endothelin-1 produced a similar change in the free/bound Ca++ ratio in cultured bovine RPE cells, but not in retinal microvascular endothelial cells or lens epithelial cells. CONCLUSIONS: ET-1 is at least three orders of magnitude more effective in producing the release of free intracellular Ca++ than other agents tested. It appears to act through specific cell surface receptors, which can be blocked by prior application of other endothelin isopeptides, but not by structurally dissimilar molecules. However, with the exception of histamine, all of these agents appear to act through a common intracellular pathway, because application of ET-1 blocks the subsequent effect of the other agents tested, except histamine. Alternatively, ET-1 may be capable of desensitizing the receptors for these agents without occupying the receptor sites. Because cultured retinal pericytes are extremely sensitive to ET-1 in a response closely linked to muscle cell contraction, ET-1 must be considered a highly plausible agonist for pericyte contraction in vivo.

Animals↗

Detection of mRNA by in situ hybridisation and in northern blot analysis using oligodeoxynucleotide probes labelled with alkaline phosphatase.

AIMS: To assess whether a reduction in intensity of signal observed using an alkaline phosphatase labelled oligodeoxynucleotide probe could be explained on the basis of procedural steps rather than reduced sensitivity. METHOD: Signal intensity was assessed on in situ hybridisation for pro-opiomelanocortin (POMC) mRNA in rat pituitary and for somatostatin mRNA in human pancreas and in northern blot analysis for POMC mRNA in the presence and absence of formamide. The direct effects of formamide on the alkaline phosphatase detection step were assessed using histochemical enzyme detection in rat kidney. RESULTS: All signals were reduced in systems containing formamide. CONCLUSIONS: In the absence of formamide clear, strong signals for specific mRNAs can be obtained by in situ hybridisation and northern blot analysis using oligodeoxynucleotide probes directly labelled with alkaline phosphatase. Formamide seems to inhibit the activity of alkaline phosphatase.

Alkaline Phosphatase↗

Factors which influence necropsy requests: a psychological approach.

AIMS: To determine which factors influence a clinician's decision to request a necropsy. METHODS: Patient age, confidence in premortem diagnosis, relatives' attitudes, and conditions of necropsy practice were combined factorially (two levels each) in separate medical and surgical questionnaires based on clinical case histories. The interactions between the factors were measured by a repeated measures factorial analysis of variance for each of the two clinical groups. The influence of the clinician's interest in necropsies on these interactions was also examined by a similar method. RESULTS: Necropsies were more likely to be requested on young patients, when diagnostic confidence was low, and when relatives' attitudes were favourable. Conditions of necropsy practice did not affect the likelihood of a request and there was no apparent overall difference in necropsy requests between the two groups of clinicians. The "patient age" and "relatives" factors had less influence on the decision of the surgical group to request necropsy. This was attributed to the opportunity to "see for themselves" at operation and was supported by the finding that surgeons were very likely to request necropsies in the absence of surgical intervention. Clinicians from both groups with a high pre-existing interest in the necropsy were consistently more likely to request necropsies. CONCLUSIONS: The "case history" based questionnaires successfully measured the relative influence of multiple factors in relation to the decision of clinicians to request a necropsy. These findings suggest that any attempt to reverse the decline in necropsy rates should focus on changing the clinician's perception of the value of the modern necropsy.

Age Factors↗

Nd:YAG laser endometrial ablation: histological aspects of uterine healing.

Laser ablation of the endometrium performed under hysteroscopic control is a novel procedure for the conservative management of menorrhagia in cases of dysfunctional uterine bleeding. The effect this has on the uterine cavity and the mechanism of reepithelialisation and endometrial regeneration have been examined by means of histological examination of endometrial biopsies and four hysterectomy specimens obtained for various indications at varying time intervals after laser endometrial ablation. During the first 3 months, fragments of necrotic and granulation tissue are found surrounded by a limited polymorph response. By 3 months, the uterine cavity appears to be completely reepithelialised. After 6 months, areas of normal-appearing endometrium may persist, but in other areas there is an attenuated cuboidal surface epithelium closely applied, to the underlying myometrium. Stromal fibrosis reminiscent of Asherman syndrome is also apparent.

Adult↗

General practitioners, skin lesions and the new contract.

We reviewed all skin lesions received in our laboratory from general practitioners (GPs) during a three-month period before the introduction of the new contract for GPs and during the same period a year later. For comparison we also reviewed skin lesions received from the general and plastic surgeons. Particular attention was paid to the completeness of excision. There was a significant increase in the number of skin lesions removed in general practice after the introduction of the new contract. Both benign and malignant lesions were more likely to be incompletely excised by GPs compared with surgeons. The GPs first noted to carry out minor surgery after the new contract came into force were less likely to have completely excised lesions than their more experienced colleagues. We suggest the future monitoring of lesions removed in general practice, possibly by the formation of a joint audit group.

Biopsy↗

Epilepsy: disappearing lesions appearing in the United Kingdom.

OBJECTIVE: Investigation of spontaneously resolving lesions associated with epilepsy. DESIGN: Observational study during one year. SETTING: One neurology department. PATIENTS: 4 cases in patients (one of Indian parents, one African, one white English, and one Afro-Caribbean) resident in the United Kingdom, who presented with transient epilepsy. MAIN OUTCOME MEASURES: Findings on computed tomography and on screening for infections. RESULTS: In all four cases a small mass lesion in one cerebral hemisphere was observed on computed tomography, which resolved after 9, 4, 3 and 1.5 months respectively without surgery. CONCLUSIONS: The number of cases seen in one year suggests that the lesions may be more common in the United Kingdom than previously recognised and that research into their cause is warranted.

Adolescent↗

Cisplatin and 5-fluorouracil for advanced locoregional and metastatic squamous cell carcinoma of the skin.

Seven patients with advanced locoregional or metastatic squamous cell carcinoma of the skin were treated with cis-daimminedichloroplatin (cisplatin) and 5-fluorouracil (5-FU). Responses were seen in six of seven patients (three partial responses [PR] and three complete responses [CR]). One patient is alive and disease-free at 2 years. These results indicate that cisplatin and 5-FU is an effective combination regimen that should be used in future clinical trials in squamous cell carcinoma of the skin.

Aged↗

The effects of flicker on eye movement control.

Groups of typists with extensive experience of screen-based editing and groups of students with no such experience carried out a reading task under three conditions of illumination (50-Hz flicker, 100-Hz flicker, and steady illumination). Subjects read a sentence, which was followed by the presentation of a single stimulus word on the same line to the right-hand side of the display. The task was to decide whether or not the stimulus was present in the sentence. Subjects were free to re-inspect the sentence when making the decision. Eye movements were measured as subjects completed the task. In comparison with students, typists adopted a more cautious reading style, making more right-to-left saccades, shorter saccades, and more corrective eye movements. Flicker affected the performance of both groups of subjects in the first pass, leading to shorter saccades. In the second pass, its effect for students was to shorten the extent of large saccades made to check the presence of the stimulus word. In the group of typists, flicker led to an increase in the variability of saccade extent and a doubling in the number of small corrective saccades. The results are consistent with the view that flicker has two distinct effects on reading, both of which are potentially disruptive. The first relates to an increase in the number of prematurely triggered saccades, which are, as a result, less accurate. The second is an increase in the number of saccades perturbed in flight, which land short of their intended target. These two mechanisms may have different consequences for readers, depending on their reading style.

Adult↗

Case report: cisplatin-induced hemolytic uremic syndrome.

Two patients developed noncardiogenic pulmonary edema (NCPE), following red blood cell transfusion in a setting of acute cisplatin nephropathy. One manifested the full picture of hemolytic uremic syndrome, the other had transient features following blood transfusion. We further reviewed the clinical records on blood transfusion for all patients with cisplatin nephropathy. A third case of (NCPE) was identified in a patient with acute renal dysfunction. However, none of the 16 patients with cisplatin-induced, mild stable chronic renal impairment had pulmonary dysfunction or other laboratory evidence for microangiopathy following transfusion. Hemolytic uremic syndrome may be a rare manifestation of cisplatin toxicity. Caution is indicated in transfusing patients with acute platinum nephropathy even in the absence of overt microangiopathy. The pathogenesis of this syndrome and the cause for NCPE is unclear. The literature is reviewed and discussed.

Adenocarcinoma↗

A comparative study of ethamsylate and mefenamic acid in dysfunctional uterine bleeding.

The effects of ethamsylate and mefenamic acid on menstrual blood loss were compared in a double-blind trial in 34 women with menorrhagia. Both drugs produced statistically significant reductions in blood loss during the 3 months of treatment; the overall reduction was 20% in the ethamsylate group and 24% in the mefenamic acid group. Compared with pretreatment values, blood loss was significantly less in each of the 3 treatment months in the mefenamic acid group, but only in the second and third months of treatment in the ethamsylate group. However, more women had a clinically useful reduction in blood loss (greater than 40%) in the ethamsylate group. The onset of effect of mefenamic acid was rapid but ethamsylate showed a comparatively greater effect as the trial progressed. Cessation of treatment was followed by an increase in blood loss, more pronounced in mefenamic acid group who reverted to pre-treatment levels. A greater number of side-effects were reported with mefenamic acid.

Adolescent↗

Should eye protection be worn when performing necropsies?

One hundred necropsies were performed by four junior pathologists wearing safety spectacles. The number of blood splashes on the spectacle surfaces were counted after each necropsy. Splashes were found after 22 necropsies (range 10-34%), with higher numbers being seen among the more junior grades of pathologist. This suggests that the use of safety spectacles should be considered by all pathologists performing necropsies.

Autopsy↗