[Is approval of a multidisciplinary course by the Medical Society inappropriate?].
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Biomedical subjects
Publications and source records attributed to M Borg.
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The purpose of this report was to investigate the efficacy of hyperbaric oxygen treatment in the management of a persisting radiation induced ulcer following standard breast irradiation. A 57-year-old Caucasian patient was referred following partial mastectomy and axillary node clearance for a T2N0 grade 3 infiltrating ductal carcinoma of the left breast. She received 45 Gy in 25 fractions at 1.8 Gy per fraction to the isocentre to the whole breast using tangential fields and 4 MV photons, in conjunction with intravenous chemotherapy (cyclophosphamide, methotrexate and 5 fluorouracil). Treatment was interrupted for 3.5 weeks because of a grade 4 skin and subcutaneous reaction. Treatment resumed to the tumour bed alone. Chemotherapy was abandoned. The tumour bed received 14 Gy in 7 fractions at 2 Gy per fraction prescribed to the 100% using 10 MeV electrons and a direct field, completing treatment on 7 July 1998. The radiation induced a painful 8x4 cm ulcer which persisted in spite of rigorous treatment including Gentian Violet, Silvazine Cream, Duoderm and antibiotics. The patient received 30 hyperbaric treatments, six times a week, completing treatment on 15 December 1998. The patient required insertion of bilateral ear grommets under local anaesthetic. The breast ulcer showed a response to treatment with early healing after 7-8 days and clinical evidence of re-epithelization. At completion of 30 treatments the patient was left with a small shallow faintly discharging multilocular 3-4 cm ulcer. The ulcer had completely healed by 14 January 1999. The patient has been symptom free since completion of treatment. This report highlights the efficacy of hyperbaric oxygen therapy in the management of persisting radiation-induced ulcers.
OBJECTIVE: Perfusion-related parameters obtained by intravoxel incoherent motion (IVIM) MR imaging (MRI) were compared with cerebral blood volume and flow (CBV and CBF), retrieved by dynamic susceptibility-contrast (DSC) MRI. MATERIAL AND METHODS: Twenty-eight volunteers (average age 68.5 years) were investigated. Spin-echo echo-planar imaging with IVIM-encoding gradients was employed (36 different b values, 0-1200 s/mm2). The perfusion fraction and the pseudo-diffusion coefficient were calculated for regions in thalamus gray matter and frontal white matter, using asymptotic and full fitting. In DSC-MRI, a Gd-DTPA-BMA contrast-agent bolus was monitored using simultaneous-dual FLASH. Deconvolution of the measured tissue concentration-versus-time curve with an arterial input function from the carotid artery was applied, and maps of CBV and CBF were calculated. RESULTS: The correlation between the perfusion fraction and CBV was r=0.56 (p<0.0000006) using asymptotic fitting, and r=0.35 (p<0.0004) when full fitting was applied. Average CBF was 41.5 ml/(min 100 g), to be compared with the IVIM-based value of 63.6 ml/(min 100 g), obtained from the median value of the pseudo-diffusion coefficient in combination with assumptions about capillary network structure. CONCLUSION: The IVIM concept provided results that agreed reasonably with conventional CBV and CBF. The non-linear fitting to noisy signal data was problematic, in accordance with previously presented simulations.
PURPOSE: To evaluate prospectively the prevalence and pathophysiology of anorectal dysfunction following radiation therapy (RTH) for localized carcinoma of the prostate. METHODS AND MATERIALS: The following parameters of anorectal function were evaluated in each of 35 patients (aged 55-82 years) with localized prostatic carcinoma treated with RTH either to a dose of 55 Gy/20 fractions/4 weeks (18 patients) or 64 Gy/32 fractions/6.5 weeks (17 patients), before RTH and 4-6 weeks and at a mean (+/- SD) of 1.4 (+/- 0.2) years after its completion: (1) anorectal symptoms (questionnaire), (2) anorectal pressures at rest and in response to voluntary squeeze and increases in intra-abdominal pressure (multiport anorectal manometry), (3) rectal sensation (balloon distension) and (4) anal sphincteric morphology (endoanal ultrasound). RESULTS: All but 1 patient completed three series of measurements. RTH had no effect on anal sphincteric morphology. The increase in frequency of defecation and fecal urgency and incontinence scores previously reported in the patients 4-6 weeks after RTH were sustained 1 year later (p < 0.001, p < 0.001, and p < 0.05, cf. baseline, respectively). At this time, 56% (19 of 34), 50% (17 of 34) and 26% (9 of 34) of the patients had increased frequency of defecation, fecal urgency, and incontinence, respectively. Decreases in anal sphincteric pressures at rest and in response to voluntary squeeze recorded in the patients 4-6 weeks after RTH were not sustained 1 year later but the volumes of rectal distension associated with perception of the stimulus and desire to defecate were lower compared with baseline volumes (p < 0.01 and p < 0.05, respectively), reflecting heightened rectal sensitivity in the patients. There was no difference in measurements between the two radiation dose regimens. Univariate logistical regression analysis was performed on patients who had experienced increased symptom scores or decreases in recorded motor and sensory manometric parameters at 1 year, cf. baseline. The predictor variables used included individual patient tumor and treatment characteristics as well as individual patient symptom scores and parameters of anorectal motor and sensory function at baseline and 4-6 weeks after RTH. The results of the univariate logistical regression analysis showed that (1) frequency of defecation at 4-6 weeks and (2) rectal volumes at baseline both for (a) perception (p < 0.001) and (b) desire to defecate (p < 0.001), predicted significantly for the patients who had symptoms and signs of anorectal dysfunction at 1 year. Individual patient tumor and treatment-related variables tested, in contrast, had no predictive significance. CONCLUSIONS: Anorectal symptoms following RTH for prostatic carcinoma are common and persist at least until 1 year after its completion and are associated with objective evidence of heightened rectal sensitivity.
The Pacific Islands Internet Project (PIIP) aims to expose interested parties to emerging technologies by creating initial, core national Internet-based information systems, and by training users on how to take advantage of such systems for sustainable development purposes. PIIP works closely with Small Islands Development States Network SIDSNET (http://www.sidsnet.org) and Asia and Pacific Development Information Programme APDIP (http://www.apdip.net), both UNDP initiatives in this field. The Target Beneficiaries are 15 countries in the sub-region including Tuvalu, Niue and Tokelau which are still without Internet access. PIIP will assist these three countries in their connectivity needs and all other countries in other components of the project. Priority is given to the smaller island states. There are four components to the project. These are: Connectivity (WWW access for Tuvalu, Niue and Tokelau); Training and Awareness (through national seminars and training programmes); Internet Applications (in areas such as telemedicine, distance education, SIDSnet and other fields in the private sector); and Policy (work with telecom and regional organisations in facilitating national telecommunications policies that provide a basis for development of an ICT strategy). Some of the progress made since the inception of PIIP are covered in this paper.
PURPOSE: The aim of this study was to evaluate any possible effects of brain motion, CSF pulsations and other possible sources of physiological motion in electrocardiographic (ECG) triggered and non-triggered single-shot echo-planar imaging (EPI) measurements of diffusion. MATERIAL AND METHODS: Three different triggering protocols were evaluated in 6 healthy volunteers: 1) ECG triggering with time delay (TD) 100 ms; 2) ECG triggering with TD 400 ms; and 3) no triggering at all. RESULTS: The results obtained showed that white matter mean apparent diffusion coefficient (ADC) values were similar for all triggering protocols and that the reproducibility in ADC measurements using diffusion-weighted (DW) EPI was good. The average standard deviation of the ADC values was, however, higher for ADC maps obtained without ECG triggering. CONCLUSION: The use of prospective diastolic ECG triggering significantly improves the accuracy of quantitative diffusion measurements but for routine clinical diffusion imaging, where quantitative data is of less importance, the accuracy obtained without ECG triggering can be considered adequate.
The insulin receptor is a transmembrane protein of the plasma membrane, where it recognizes extracellular insulin and transmits signals into the cellular signaling network. We report that insulin receptors are localized and signal in caveolae microdomains of adipocyte plasma membrane. Immunogold electron microscopy and immunofluorescence microscopy show that insulin receptors are restricted to caveolae and are colocalized with caveolin over the plasma membrane. Insulin receptor was enriched in a caveolae-enriched fraction of plasma membrane. By extraction with beta-cyclodextrin or destruction with cholesterol oxidase, cholesterol reduction attenuated insulin receptor signaling to protein phosphorylation or glucose transport. Insulin signaling was regained by spontaneous recovery or by exogenous replenishment of cholesterol. beta-Cyclodextrin treatment caused a nearly complete annihilation of caveolae invaginations as examined by electron microscopy. This suggests that the receptor is dependent on the caveolae environment for signaling. Insulin stimulation of cells prior to isolation of caveolae or insulin stimulation of the isolated caveolae fraction increased tyrosine phosphorylation of the insulin receptor in caveolae, demonstrating that insulin receptors in caveolae are functional. Our results indicate that insulin receptors are localized to caveolae in the plasma membrane of adipocytes, are signaling in caveolae, and are dependent on caveolae for signaling.
PURPOSE: Sialorrhea is the unintentional loss of saliva and other contents from the mouth. Most patients with this condition are elderly, requiring palliative treatment. These patients have neuropathology with associated poor performance status. Treatment prescribed for this disabling and distressing condition has often been of a surgical nature and described in young patients. It would be inapplicable to the elderly. The aim of this study was to review the role of radiation therapy in the management of sialorrhea. Previous reports are few in number and are cautionary because of adverse effects which have been described, including dryness of the mouth. METHODS AND MATERIALS: A total of 34 patients were referred to the Department of Radiation Oncology, Palmerston North Hospital, between 1966 and August 1994, of whom only 1 patient received treatment prior to 1985. Three patients declined treatment and were, therefore, excluded from this review. Thirty-one patients, including 14 males and 17 females, of median age 72 years received 1 or more radiation treatments for sialorrhea. The patients were followed up for a median of 12 months, ranging from 6 months to 27 years. RESULTS: Initially, 82% (28/34) of treatments were associated with a satisfactory response. Six patients relapsed, of whom five experienced relapse within 6 months of initial treatment. Two patients were re-treated, one of whom achieved a complete response. Up to the time of review 64% (23/36) of treatments maintained a satisfactory response. The varied fractionation regimens used were not shown to affect the response rate; low doses were shown to be as effective as higher doses, and were not associated with any significant acute or late side effects. Only 4 patients developed long-term side effects. However, response rates were superior for patients treated with electrons, as opposed to orthovoltage therapy, and in particular when electron energies greater than 7 megavolts were used (76% vs. 38% maintained response, p < 0.05). Responses were also superior for patients treated with radiation fields which encompassed both parotid and submandibular glands (74% vs. 33 % maintained response, p < 0.01). CONCLUSIONS: Radiation therapy has proven to be a safe and effective treatment in this group of patients, thereby avoiding the adverse effects of anticholinergic medication and invasive surgical procedures.
AIM: The incidence of anorectal symptoms after radiotherapy (RTH) for localised pelvic malignant disease is unclear. In addition, the effects of pelvic irradiation on both anorectal motility and sensory function are poorly defined. A prospective study was therefore performed on 35 patients (55-82 years of age) with localised prostatic carcinoma before and four to six weeks after RTH to assess its effects on anorectal function. METHODS: Anorectal symptoms were assessed by questionnaire. Anorectal pressures at rest and in response to voluntary squeeze, rectal distension, and increases in intra-abdominal pressure were evaluated with perfused sleeve side hole manometry. Rectal sensation was tested during graded balloon distension. Rectal compliance was calculated by the pressure-volume relation obtained during the testing of rectal sensation. Ultrasound was used to determine anal sphincter structure and integrity. RESULTS: RTH had no effect on anal sphincter morphology. The frequency of defecation increased after RTH (7 (3-21) v 10 (3-56) bowel actions a week; p < 0.01). After RTH, 16 patients had faecal urgency and eight faecal incontinence, compared with five and one respectively before RTH (p < 0.01 for each). Basal and squeeze sleeve recorded pressures were reduced after RTH (54 (3) v 49 (3) mm Hg (p < 0.05) and 111 (8) v 102 (8) mm Hg (p < 0.01), before and after RTH respectively; means (SEM)). Rectal compliance was reduced after RTH (1.2 v 1.4 mm Hg/ml, p < 0.05). After RTH, threshold volumes for perception of rectal distension were lower in the 16 patients who either experienced faecal urgency for the first time (13 patients) or reported worsening of this symptom (three patients) compared with the remaining patients (34 (4) v 48 (5) ml respectively, p < 0.05). CONCLUSION: Faecal incontinence (23%) is a common problem four to six weeks after RTH for prostatic carcinoma and is associated with minor reductions in anal sphincter pressures. The high prevalence of faecal urgency in patients after RTH may be related to alterations in rectal perception of stool.
The involvement of calcium signaling during cold-induction of the kin genes of Arabidopsis thaliana (L.) Heynh. was examined. Treatments with chemicals which either chelate extracellular calcium (EGTA) or block the plasma-membrane calcium channels (La3+, Gd3+) inhibited cold acclimation as well as kin gene expression. Ruthenium red, an inhibitor of calcium release from intracellular stores partially inhibited kin gene expression and development of freezing tolerance. An inhibitor of calcium-dependent protein kinases (CDPKs) and calmodulin prevented cold acclimation as well as the cold induction of kin genes. Using restriction fragment length polymorphism-coupled domain-directed differential display, five CDPK clones were identified which showed differential regulation by cold. The amplified fragments showed homology to known plant CDPKs. The involvement of calcium and calcium-binding proteins in cold acclimation of A. thaliana is discussed.
Five cases of benign fetal arrhythmias presented with dramatic pictures of sustained irregular bradycardias. These cases were not associated with structural heart disease, the development of hydrops fetalis, or maternal autoantibodies. In all but one case, the arrhythmias resolved before delivery. Two fetuses had 2:1 atrioventricular block and the other three showed group beating due to blocked atrial trigeminy. With regular intermittent reevaluation, and if no signs of hydrops occur, watchful waiting is the suggested therapeutic modality.
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We report 3 cases of opercular myoclonic status epilepticus (OMASE), characterized by fluctuating cortical dysarthria without true aphasia associated with epileptic myoclonus involving bilaterally the glossopharyngeal musculature. In this syndrome, the inferior rolandic area of either one or the other hemisphere is involved by an epileptogenic lesion of various etiology. Ictally, clonic expression was consistent with epilepsia partialis continua (EPC) and bilaterally and symmetrically involved palatal muscles (cases 1-3), tongue (cases 2 and 3), lips and chin (case 3), and inferior jaw (case 1) due to bilateral projections of the inferior corticonuclear pathways. Postictally, the main clinical sign was pseudobulbar palsy, consistent with Todd's palsy. In our cases, OMASE was either of vascular (cases 1 and 2) or tumoral origin (case 3). In adulthood, early recognition of OMASE, although nonspecific, may be important for early management of carotid occlusive disease because it usually indicates an acute opercular infarction.
A 40-year-old HIV-positive right handed homosexual man was admitted for progressive mental deterioration coexisting with permanent segmental middle-amplitude arrhythmic, asynchronous and asymmetrical myoclonic jerks. EEG showed fronto-central bursts of rhythmic triphasic 1.5-2 Hz sharp waves similar to the characteristic periodic pattern of Jakob-Creutzfeldt disease. Biological procedures were negative, thus eliminating a metabolic encephalopathy. Dramatic neurological improvement occurred shortly after initiation of i.v. and then oral zidovudine which produced perfect EEG normalisation. This unusual electroclinical presentation of the AIDS-dementia complex underlines the fact that this affection may present a diagnostic challenge, particularly in individuals in whom HIV infection is unknown.
We studied mitochondrial respiratory chain function in skeletal muscle taken from 27 patients with idiopathic Parkinson's disease (PD; 21 Dopa-treated PD patients and 6 de novo patients), 5 patients with multiple system atrophy (MSA) and from 43 age-matched controls in order to determine the occurrence of mitochondrial respiratory chain abnormalities in parkinsonian syndromes. In our control subjects, we found a significant age-related decrease in the activity of respiratory chain complex I. As compared to carefully age-matched control subjects, activity of complex (NADH:ubiquinone reductase) was significantly lower in muscle mitochondria from patients with PD and MSA and a mean remaining activity < 30% of controls was observed. Mean activities of complexes III (ubiquinol:cytochrome c reductase) and IV (cytochrome c oxidase) were also lower in PD patients than controls, but a low activity (remaining activity < 30% of controls) was observed in only 5 PD patients for complex I and III or I and IV. No deficit in complex II activity (succinate:ubiquinone reductase) was observed. Our results support the hypothesis of a wide-spread mitochondrial complex I deficiency in PD and MSA as compared to age-matched controls, who showed age-related deficiency. This deficit can be found in de novo PD patients as well as in treated patients. The observed respiratory enzyme chain deficiency could not be explained by the dose and duration of L-Dopa or dopaminergic agonist treatment, the severity of the disease, anxiety or depression since no significant correlation was found between these parameters and enzyme complexes activities.
1. Enterocyte development of microvillus structure has been measured in intestinal biopsies obtained from children suffering from coeliac disease, cow's milk protein intolerance and microvillus atrophy, and the results compared with similar measurements carried out in control children. 2. All types of enteric disease caused a significant 30% reduction in the length of microvilli present on undifferentiated basal crypt enterocytes, here referred to as potential stem cells. 3. Microvillus growth measured in control enterocytes took place mainly over the basal third of the villus. There was then little further change in structure during subsequent enterocyte migration to the villus tip. 4. Microvillus length in diseased tissue remained more or less constant during enterocyte migration to the crypt-villus junction. Microvillus length then decreased slightly during subsequent enterocyte migration over stunted villi. 5. The present results are discussed in relation to the supposed properties of potential stem cells. Comparisons are also made between profiles of microvillus development measured in healthy children and mature adults.
The extracellular acid proteinase of Candida albicans and Candida tropicalis was monitored in vitro during phagocytosis by murine peritoneal macrophages. Fungal blastospores were quickly ingested by the thioglycolate-elicited macrophages and the intracellular blastospores partly resisted killing and started to grow out after 6 h incubation, causing destruction of the macrophage. Proteinase antigen appeared on fungal cells after 30 min in culture medium containing 10% fetal calf serum. The antigen was detected on ingested blastoconidia and filamentous cells of C. albicans serotype A. The proteinase antigen was also expressed by blastoconidia of C. albicans serotype B but was missing on the filamentous cells of this serotype. Isolates of C. tropicalis behaved similarly to C. albicans serotype A. The acid proteolytic activity of Candida cells was confirmed by the haemoglobin test on culture supernatants. Lysates of infected and noninfected phagocytes showed a differential acid proteolytic activity; noninfected macrophages revealed rising activity, while infected macrophages showed a distinct reduction of activity. The proteolytic activity of lysates of noninfected cells is due to lysosomal cathepsin-D. Cathepsin-D was also most likely to be responsible for the declining proteolytic activity in lysates from infected phagocytes; such lysates contained increasing amounts of fungal proteinase antigen. The differential kinetics of this antigen and the total acid proteolytic activity in the lysates suggest a conflict between microbial and lysosomal hydrolases in infected phagocytes. The outcome of this conflict depends on the number and hydrolytic activity of the ingested yeasts and may be decisive in the progress of infection.
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