Biomedical subjects
Publications and source records attributed to J McEwan.
Vascular anomalies can cause epistaxis in children. The authors present two cases of recurrent epistaxis secondary to rare causes and discuss their presentations. Both cases were managed conservatively since intervention in these vascular lesions carries a high risk of damaging adjacent structures.
Drooling is an important factor affecting the quality of lives of neurologically impaired children, and surgery often has to be performed. Submandibular duct relocation is a relatively simple procedure with a low complication rate, and has been carried out on 37 patients at the Sheffield Children's Hospital between 1986 and 1998. To determine the short-term and long-term outcome of this procedure, a questionnaire was sent to the parents/wards of the patients. Feedback was also obtained on complications, parents'/carers' perceptions and main concerns about the operation, particularly in those cases which did not improve. Both short-term (82.4%) and long-term (76.5%) control rates were high, and there were few complications, none of which had any long-term adverse effects. The most significant area of parental/carer dissatisfaction and concern in 'failed' cases was 'pain', and it was felt that proper preoperative counselling about analgesia and chances of failure is very important. We conclude that this is a safe, highly successful procedure which significantly improves the quality of lives of the majority of drooling children.
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Cat-scratch disease (CSD) is a relatively common entity, particularly in children. The most common sites of involvement are the axillary lymph nodes, followed by cervical, pre-auricular and submandibular lymph nodes. We present a case of cat-scratch disease in which the initial clinical features were indistinguishable from those of acute bacterial tonsillitis with jugulodigastric lymphadenopathy. This previously unreported apparent mode of presentation is discussed with reference to the current understanding of the disease.
The vestibulo-collic reflex represents a promising test for evaluating the integrity of otolith function. We have investigated the threshold of this response in a group of normal subjects, and the effect of a conductive hearing loss. A positive response was recorded in 31 of 32 normal subjects. The threshold of the vestibulo-collic reflex varied from 80 to 97 dBHL in these subjects with a 95% response rate at a threshold at 96 dBHL. A total of 23 ears with a conductive hearing loss in 17 patients were also investigated. The average conductive hearing loss (at 0.5, 1, 2 and 4 kHz) ranged from 8.75 to 40 dBHL (average 24.46 dBHL). A positive response was recorded in only two ears. Therefore, the vestibulo-collic reflex has a high stimulus threshold which is dependant on reliable transmission of the click stimulus to the inner ear thus limiting is clinical use.
In the brain of the honey bee, dopamine receptors have been identified by using the vertebrate D1 dopamine antagonist [3H]-SCH23390 and the vertebrate D2 dopamine antagonist [3H]-spiperone. This study uses light microscope autoradiography to investigate the anatomical distributions of the binding sites labelled by [3H]-SCH23390 and [3H]-spiperone in tissue sections cut at three depths from the anterior surface of the brain. The binding of these radioligands differed significantly, in both density and distribution. Specific binding of [3H]-SCH23390, defined by using 5 x 10(-6) M cis-(Z)-flupentixol, was densest in regions of somata, such as the deutocerebral somatal rind, the somatal layer beneath the calyces of the mushroom bodies and the ventral protocerebral somatal group. High levels of [3H]-SCH23390 binding were also measured in the lateral protocerebrum. [3H]-Spiperone binding site density estimates were consistently lower than those of [3H]-SCH23390. Specific binding of [3H]-spiperone, determined by subtracting binding in the presence of 10(-4) M domperidone from the total binding, was highest in the alpha lobes, beta lobes, and calyces of the mushroom body neuropil. Relatively high binding was also measured in the central body and lateral protocerebral neuropil. These results suggest that the distribution of dopamine receptors in the brain of the bee is subtype specific, and they support the view that dopamine plays many roles in the insect central nervous system.
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OBJECTIVES: We investigated the effects of Photodynamic therapy (PDT) using Aluminium disulphonated phthalocyanine (AlS2Pc) on experimental intimal hyperplasia (FCIH). MATERIALS AND METHODS: (a) Pharmacokinetics: Normal rats were injected with Als2Pc and carotid artery fluorescence was measured. (b) Normal artery PDT: Sensitised rats underwent carotid artery laser irradiation (50J/cm2, 675nm) and were assessed after 3 and 14 days and 1-6 months. (c) PDT: Rats underwent standard carotid artery balloon injury immediately prior to PDT and arteries were assessed at 2 to 26 weeks, together with laser, AlS2Pc, and untreated controls. CHIEF OUTCOME MEASURES: (a) Fluorescence intensity in different arterial layers. (b) Medial smooth muscle cell counts per high power field (light microscopic). (c) Percentage amount of FCIH (area of intimal hyperplasia) as a ratio of the IEL (area enclosed by the internal elastic lamina). RESULTS: (a) AlS2Pc fluorescence intensity increased with increasing dosage, with maximal fluorescence in the arterial media at 30 min. (b) PDT produced medial cell depletion at 3 days and persisted over 6 months without loss of vessel integrity. (c) PDT completely inhibited FCIH at 2 and 4 weeks. This was partial at 6 to 26 weeks (51% of untreated level). PDT inhibition of FCIH was significantly greater than in any of the control groups. p < 0.0001. Mann-Whitney Test. CONCLUSION: Adjunctive AlS2Pc sensitised photodynamic therapy inhibits experimental intimal hyperplasia, by causing medial smooth muscle cell depletion. This offers a new approach to the management of angioplasty restenosis in patients.
Herpes simplex virus 1 (HSV1), while usually thought of as neurotrophic, can also efficiently infect a wide variety of non-neuronal cell types and so might be developed as a vector for gene delivery to non-neuronal as well as neuronal cells. Here we have tested three different disabled HSV vectors for their ability to deliver a lacZ gene to primary cardiac myocytes and vascular smooth muscle cells in vitro, and used the most efficient virus to transfect the rat heart in vivo. We also assessed the degree of cytopathic effect of the various viruses on the cardiac myocytes in vitro by testing the effects on the frequency of beating in synchronously beating myocyte cultures. While an HSV mutant in which the essential immediate-early gene IE2 had been deleted gave high efficiency gene transfer to the cardiac myocytes in vitro and the rat heart in vivo, viruses in which ICP34.5 or ICP34.5 and VMW65 were inactive (and which were also unable to replicate in these cells) gave a much lower efficiency of gene transfer, mirroring the degree of cytopathic effect observed in the beating myocyte cultures. Gene transfer to the vascular smooth muscle cells was considerably less efficient than to the myocytes in all cases. These results indicate that while HSV may be inappropriate for highly efficient gene transfer to the arterial wall, efficient gene transfer can be achieved in the myocardium, and thus that HSV vectors may be suitable for the alteration of cardiac cell physiology in vivo.
BACKGROUND: Although the management of atherosclerotic disease by the use of balloon angioplasty is widespread, the treatment is limited by restenosis in 30% to 50% of cases. Fibrocellular intimal hyperplasia, the main cause of restenosis, arises from proliferation and migration of medial smooth muscle cells (SMC) into the intimal layer. Factors leading to intimal hyperplasia are incompletely understood, and drugs have universally failed to influence clinical restenosis. Photodynamic therapy (PDT), the light activation of photosensitizing drugs to generate cytotoxic mediators, may have potential as prophylaxis for intimal hyperplasia. 5-Amino-levulinic acid-induced protoporphyrin IX (ALA-PPIX), a naturally occurring porphyrin precursor, and its product, -PPIX, offers a novel method of sensitization for PDT. We have investigated the pharmacokinetics of ALA in arteries and the effects of ALA-PPIX-sensitized PDT on normal and balloon-injured arteries. METHODS AND RESULTS: ALA (20 to 200 mg/kg) was injected into healthy rats, and PPIX fluorescence was measured in the carotid arteries. In a second group of rats, the exposed carotid artery was laser illuminated (50 J/cm2, 630 nm) 30 to 90 minutes after sensitization. Three and 14 days after PDT, histological sections from treated arteries were analyzed by light microscopy. Subsequently, two new groups of rats underwent PDT (ALA, 100 mg/kg; laser, 50 J/cm2, 630 nm [at 60 to 90 minutes]). The left carotid arteries underwent balloon angioplasty by intraluminal passage of a Fogarty FG2 catheter immediately before irradiation. These rats were killed at 14 and 28 days together with laser-only, ALA-only, and untreated control rats. The arteries were perfusion-fixed in vivo. ALA-PPIX induced arterial media fluorescence in a dose-dependent manner. In the normal arteries, PDT produced a dose-dependent cellular depletion in the treated arterial segment at 3 days, and this was complete with 100 and 200 mg/kg of ALA. At 14 days, the media remained acellular, although the endothelial lining had regenerated. In the balloon-injured arteries, PDT produced complete inhibition of intimal hyperplasia at both 14 and 28 days (0%). This was significantly greater than that produced by any of the control rats (34% to 69% and 37% to 66% at the two times, respectively). Significance was at 99% using ANOVA and Fisher's PLSD test. No hemorrhage, thrombosis, or aneurysm formation was seen. CONCLUSIONS: ALA-PPIX-sensitized PDT applied at the time of angioplasty effectively inhibits experimental intimal hyperplasia development in rats. This may offer a new approach to the management of angioplasty restenosis in patients.
We report the previously undocumented development of an orbital metastasis and skin metastases in a patient with polymorphous low grade adenocarcinoma (PLGA) 15 years after initial presentation. The clinical course, treatment and changing histological features are discussed.
1. The reproducibility of angiotensin converting enzyme inhibitor induced cough was examined in a double-blind cross over study in patients previously shown to have exhibited this side effect. 2. Ninety-seven patients who had experienced angiotensin converting enzyme inhibitor cough within the last 2 years were challenged with enalapril 20 mg daily for 4 weeks to establish eligibility. Eighty-eight of 97 (91%) patients experienced a repeat of their cough symptoms. Sixty-four patients entered the double-blind part of the study where they were treated with enalapril 20 mg and a renin inhibitor for up to 4 weeks in random order. These periods were separated by a minimum 4 week placebo wash out. 3. Of 59 evaluable patients who received enalapril a second time, 37 (62.7%) experienced cough again. Of 62 patients on the renin inhibitor 16 (25.8%) experienced cough, however as it was not equi-efficacious to enalapril no valid comparison could be made. 4. Angiotensin converting enzyme inhibitor cough is not reproducible within patients, as other factors are involved in the aetiology. Objective testing with blinded assessment together with symptom reporting, would give a more accurate measure of the incidence, and mechanism of this side effect.
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BACKGROUND: The optimal management of patients with brain tumors requires knowledge of the tumor characteristics upon presentation and the discovery of recurrence after therapy. Thallium-201 (Tl-201) chloride has shown varying uptake in tumors, depending on their viability and the type and degree of malignancy. This study explores the diagnostic potential of thallium imaging in patients with brain tumors. METHODS: Forty-three Tl-201 single photon emission computed tomographic scintigrams were performed on 40 patients with intracranial neoplasms, nearly equally divided between patients with no prior treatment and patients who had prior treatment and were suspected to have recurrent tumor and/or radiation necrosis. A thallium tumor index was calculated as the ratio of counts for a region of interest drawn in the lesion area and its mirror image in normal brain tissue. A two-tailed Student's t test was performed to compare the thallium index and histopathologic findings. RESULTS: A value of 1.5 for the thallium tumor index allowed for the best correlation between the prediction of malignancy and the histopathologic results. In the pretreatment group, a thallium tumor index greater than 1.5 correlated with high grade malignancy, and less than 1.5 correlated with either a well differentiated astrocytoma or benign cyst. In the posttreatment group, a thallium tumor index greater than 1.5 correlated with recurrent and/or residual malignant tumor. CONCLUSIONS: For those patients undergoing initial evaluation, the thallium study can help in the differential diagnosis of an intracranial mass lesion and offers confirmation of results of biopsy. For those patients who already have received treatment, the study can be used to detect recurrent or residual tumor.
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Tl-201 scintigraphy has been used to visualize thyroid tissue that is suppressed by an autonomously functioning thyroid nodule. Reports have indicated that the sensitivity of this technique rivals that obtained by I-123 scanning after thyroid-stimulating hormone stimulation. We report a case of triiodothyronine toxicosis caused by an autonomously functioning thyroid nodule in which the suppressed thyroid tissue was not visualized on Tl-201 scintigraphy. The suppressed tissue was readily identified with ultrasound imaging, which demonstrates the utility of this technique in differentiating between thyroid suppression and agenesis.