Health promotion in general practice.
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Biomedical subjects
Publications and source records attributed to D M Williams.
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The neurilemmoma is an uncommon tumour of the oral cavity. In this present series of soft tissue neurilemmomas the majority occurred within or around the mouth. Initially these were provisionally diagnosed on clinical appearances and behaviour as commoner benign lesions, including the fibro-epithelial polyp, mucocele and papilloma. On sampling they were found to have the histological features of a neurilemmoma. This suggests that the solitary neurilemmoma occurs more frequently than previously reported and should be included in the differential diagnosis of these more frequent benign lesions occurring in and around the mouth.
Acute traumatic aortic rupture is a lethal injury and requires immediate diagnosis and surgical repair. The standard of diagnosis for aortic rupture is aortography. In patients in whom the angiographic findings of rupture are subtle or uncertain, intravascular ultrasound (IVUS) imaging of the descending aorta has been useful in confirming or excluding mural injury. However, because IVUS is unable to provide a complete and expeditious survey of the aorta and brachiocephalic arteries, the diagnosis of rupture will continue to rely on aortography or current generation computed tomography.
PURPOSE: This report describes popliteal vein entrapment in three patients and demonstrates that it may present with manifestations of typical venous disease. METHODS: This report was compiled from a review of inpatient and outpatient records. RESULTS: In the first case, a 28-year-old woman was seen with left leg popliteal and calf deep vein thrombosis without obvious cause. She described long-standing calf discomfort, and passive dorsiflexion of the left foot caused disappearance of arterial pulsations at the pedal level. She was given the anticoagulants heparin and sodium warfarin (Coumadin) followed by surgical exploration. The popliteal vein and artery were entrapped by a fibrous extension of the medial head of the gastrocnemius muscle attaching to the lateral femoral condyle. After band lysis, the patient has been symptom free for 6 years. The second patient, a 37-year-old man, was seen with bilateral chronic venous insufficiency (CVI). Passive dorsiflexion and active plantar flexion of the feet did not diminish the pedal pulses; impedance plethysmography suggested mild outflow obstruction. Ascending venography demonstrated entrapment at the midportion of duplicated popliteal veins with no postthrombotic changes. He was treated with compression stockings and has done well during an 18-month follow-up. The third patient, a 17-year-old male, was seen with severe symptoms of right leg CVI and venous obstruction since 3 years of age. Air plethysmography revealed ambulatory venous hypertension, whereas venography demonstrated reflux down to the knee with an extrinsic narrowing at the midpopliteal vein. During operation, an abnormal origin of the lesser saphenous vein (LSV) from the popliteal vein was found; the LSV took a medial route, compressed the tibial nerve, and caused severe distortion and narrowing of the popliteal vein. Division of the LSV resulted in release of popliteal venous compression and immediate relief of symptoms. CONCLUSIONS: The three cases presented demonstrate that popliteal venous entrapment may begin with symptoms of deep vein thrombosis and CVI. Popliteal venous entrapment must be considered in the differential diagnosis of venous disease in younger patients in whom common predisposing factors are absent.
The magnitude of cubic intermodulation distortion generated when two tones are progressively separated in frequency reaches a broad maximum when the distortion frequency falls just over half an octave below the high-frequency stimulus (f2), when this distortion is measured with a microphone in the ear canal. For the component 2f1-f2, this peak occurs at an f2/f1 ratio of approximately 1.2. The tuning, magnitude, and mean group delay of this distortion peak was measured for a fixed f2 of 4 kHz at 40 dB SPL and a varied f1 at 55 dB SPL in eight human subjects with normal hearing. The distortion peak measures were compared with the frequency selectivity at 4 kHz of the same eight subjects derived using a forward-masking notched-noise paradigm. In the six subjects from whom good, repeatable levels of distortion were measured, a significant negative correlation was found between the tuning of the distortion peak and the psychophysical bandwidth at f2. It is concluded that the tuning of the distortion peak may provide an objective measure of frequency selectivity in the human cochlea.
The level of cubic distortion measured in the human ear canal reaches a peak when the distortion frequency falls approximately half-an-octave below that of the higher of two stimulus tones. The peak is thought to be indicative of a bandpass filter in the cochlea. The properties of the distortion peak have been measured during the administration of aspirin (3.84 g/day for 2 days) in eight human volunteers. In three of the subjects, there was a downward shift of the center frequency on the distortion peak by as much as 200 Hz during aspirin consumption, but no significant changes in Q3 dB of the peak. In two of these subjects, the shift in distortion peak was not associated with a change in psychophysical threshold. The mean group delay of the emitted distortion was reduced by approximately 0.5 ms in four of the eight subjects. The measurement of stimulus frequency emission (SFE) did not reveal any downward shift of features in the spectrum corresponding to those seen for the distortion peak. It is concluded (1) that aspirin affects the resonance frequency of the bandpass filter revealed by distortion measurement, but not its tuning; and (2) that the bandpass filter is dissociated from the mechanism responsible for the "fine structure" in the SFE spectrum.
Host defense against murine Chlamydia trachomatis (mouse pneumonitis agent [MoPn]) in a murine model was investigated. Gamma interferon (IFN-gamma) was produced in the lungs by both MoPn-susceptible nude athymic (nu/nu) and MoPn-resistant heterozygous (nu/+) mice. In vivo depletion of IFN-gamma in nu/nu mice led to exacerbation of infection. Fluorescence-activated cell sorter analysis disclosed induction of GL3 antibody-positive cells (putatively gamma/delta+ T cells) in nu/nu mouse lung during infection with MoPn. Treatment of nu/nu mice in vivo with antibody to NK cells (anti-asialo GM1 antibody) or to gamma/delta cells (UC7-13D5) did not significantly decrease IFN-gamma production in the lung. However, treatment of severe combined immunodeficiency mice (which lack gamma/delta cells) with antibody to NK cells significantly reduced lung IFN-gamma levels.
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The rapid and accurate diagnosis of childhood malignancy is important both in the planning of appropriate treatment and in relieving the inevitable family anxiety. The use of flow cytometry to analyse monoclonal antibody coated single cell suspensions is widely accepted as having increased the speed and accuracy of diagnosis in leukaemias, though its use in solid tumour diagnosis is not widely reported. Ten cases of childhood malignancy in whom the diagnosis was initially made by flow cytometry and subsequently confirmed histologically are described. The technique has a number of advantages. Only a small sample is required as the analysis is carried out on a single cell suspension, the method is rapid, a diagnosis being reached within three hours of receipt of the sample, and information is obtained on cell lineage and stage of differentiation. Diagnostic accuracy is good when compared with histological results.
Several lines of evidence suggest that the Wilms's tumour susceptibility gene, WT1, has an important role in genital as well as kidney development. WT1 is expressed in developing kidney and genital tissues. Furthermore, mutations in WT1 have been detected in patients with the Denys-Drash syndrome (DDS), which is characterised by nephropathy, genital abnormalities, and Wilms's tumour. It is possible that WT1 mutations may cause genital abnormalities in the absence of kidney dysfunction. We tested this hypothesis by screening the WT1 gene for mutation in 12 46,XY patients with various forms of genital abnormality. Using single strand conformation polymorphism (SSCP) we did not detect any WT1 mutations in these patients. However, in addition to the 12 patients, three DDS patients were also analysed using SSCP, and in all three cases heterozygous WT1 mutations were found which would be predicted to disrupt the DNA binding activity of WT1 protein. These results support the notion that DDS results from a dominant WT1 mutation. However, WT1 mutations are unlikely to be a common cause of male genital abnormalities when these are not associated with kidney abnormalities.
A significant proportion of the non-infectious diseases of oral mucosa are either auto-immune in nature or have lesions which are the result of immunologically-mediated events. These include pemphigus, benign mucous membrane pemphigoid, linear IgA bullous dermatosis, dermatitis herpetiformis, epidermolysis bullosa acquisita, erythema multiforme, and lichen planus. Although each of these has certain specific characteristics, all may produce bullae, erosions, and ulcers on the oral mucosa, resulting in confusingly similar clinical presentations. With careful clinical, histological, and immunofluorescence examination, it is possible to establish a definitive diagnosis in a high proportion of cases. However, one of the most exciting developments which has emerged from recent research into these diseases is their precise molecular characterization. This raises the prospect of accurate, highly specific diagnostic tests which would provide the basis for sound clinical management, with original approaches replacing the somewhat unsatisfactory symptomatic treatment which is often all that is available.
PURPOSE: Massive pulmonary embolism (PE), defined by systemic hypotension and need for inotropic support, has a high mortality rate. Transvenous catheter pulmonary embolectomy performed with the patient receiving local anesthetic provides an expeditious alternative to lytic therapy or open embolectomy on cardiopulmonary bypass. METHODS: The indication for embolectomy in this series of 46 patients was hypotension despite inotropic support in all but four patients (91%); the latter sustained major embolism and were respirator dependent. In the first 10 patients treated from 1970 to 1974, a metal cup attached to a straight catheter was used. RESULTS: Hemodynamic improvement occurred in nine of 10 initial patients, but recurrent PE and a mortality rate of 50% prompted addition of a vena caval filter and directional control to the catheter. Subsequently 36 patients were treated with this combination from 1975 to 1992. Emboli were extracted in 76% (35 of 46) of the total series with a 30-day survival rate of 70% (32 of 46). Hemodynamic data showed an average reduction in mean pulmonary artery pressure of 8 mm Hg and a significant increase in mean cardiac output from 2.59 L/min to 4.47 L/min (p = 0.003) after embolectomy. Complications included wound hematoma (15%), pulmonary infarct (11%), recurrent deep venous thrombosis (6%), pleural effusion (4%), and myocardial infarction (4%). CONCLUSIONS: Successful embolectomy was most likely for categories of major PE (4 of 4, 100%) and massive PE (27 of 33, 82%) and least likely for chronic PE (5 of 9, 56%) (p < 0.03). Successful embolectomy also predicted long-term survival (p < 0.01), which was 89 months for the series (range 1 to 237 months). Catheter pulmonary embolectomy by surgeon and radiologist is of maximal benefit for major or massive PE but less likely to benefit patients with chronic recurrent PE.
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We have studied the distortion generated by the cochlea to gain insight into the mechanisms responsible for the sharp tuning or 'frequency selectivity' of the inner ear. We used two stimulating tones of moderate intensity which are progressively separated in frequency, and measured the ear canal cubic distortion components which are generated as a consequence of the stimulus interaction in the cochlea. We inferred that the distortion is generated from the frequency region of the higher of the two stimulus tones and that it is then band-pass filtered by a structure which is tuned to a frequency just over half an octave below that of the high-frequency tone. We suggest that the structure responsible for this band-pass filtering is the tectorial membrane, and we conclude that our results support theories of cochlear mechanics in which resonances due to the tectorial membrane interact with those of the basilar membrane to enhance the frequency selectivity of the inner ear.
2'-Fluoro- and 2'-amino-2'-deoxynucleoside 5'-triphosphates have been investigated as substrates for T7 RNA polymerase. Michaelis-Menten kinetic parameters are reported for the incorporation of 2'-fluoro-2'-deoxyuridine, 2'-fluoro-2'-deoxycytidine, and 2'-amino-2'-deoxyuridine into runoff transcripts. The 2'-amino derivative of uridine is a better substrate than the 2'-fluoro derivative. Gel electrophoretic analysis shows that full-length transcripts with a length of 2500 nucleotides can be obtained with the analogues, although a considerable amount of shorter fragments accompanies the full-length product. In keeping with the kinetic analysis, the 2'-aminouridine triphosphate gives a cleaner product than the 2'-fluoro analogue. Transcription of two tRNA genes shows that such shorter templates can be transcribed to full-length products essentially without premature termination with any of the analogues.
The importance of the 2'-hydroxyl group of several guanosine residues for the catalytic efficiency of a hammerhead ribozyme has been investigated. Five ribozymes in which single guanosine residues were substituted with 2'-amino-, 2'-fluoro-, or 2'-deoxyguanosine were chemically synthesized. The comparison of the catalytic activity of the three 2' modifications at a specific position allows conclusions about the functional role of the parent 2'-hydroxyl group. Substitutions of nonconserved nucleotides within the ribozyme caused little alteration in the catalytic activity relative to that obtained with the unmodified ribozyme. In contrast, when either of the guanosines within the single-stranded loop between stem I and stem II of the ribozyme was replaced by 2'-deoxyguanosine or 2'-fluoro-2'-deoxyguanosine, the catalytic activities of the resulting ribozymes were reduced by factors of at least 150. The catalytic activities of the corresponding ribozymes containing 2'-amino-2'-deoxyguanosine substitutions at these positions, however, were both reduced by factors of 15. These effects resulted from decreases in the respective kcat values, whereas variations in the Km values were comparatively small. A different pattern of reactivity of the three 2' modifications was observed at the guanosine immediately 3' to stem II of the ribozyme. Whereas both 2'-deoxyguanosine and 2'-amino-2'-deoxyguanosine at this position showed catalytic activity similar to that of the unmodified ribozyme, the activity of the corresponding 2'-fluoro-2'-deoxyguanosine-containing ribozyme was reduced by a factor of 15. The implications of these substitution-specific reactivities on the functional role of the native 2'-hydroxyl groups are discussed.
An autoperfusion catheter is similar to an angioplasty balloon catheter with side holes in the guide-wire lumen proximal to the balloon. When the balloon of the autoperfusion catheter is deployed and inflated in an artery, the guide wire is removed, and the hub of the guide-wire lumen is capped. The catheter then allows passive distal perfusion by using ambient pressure to drive blood into the guide-wire lumen, through the balloon, and out the end hole. This article discusses the requirements and constraints of a high-flow autoperfusion catheter, summarizes attempts to modify standard angioplasty catheters for use as an autoperfusion catheter, and describes the design and testing of a custom autoperfusion catheter capable of delivering approximately 3 mL/sec at physiologic pressures. In a model of canine acute renal artery occlusion lasting 90 minutes, the custom autoperfusion catheter provided marked protection from acute tubular necrosis compared with conventional percutaneous transluminal angioplasty catheters. The authors conclude that the high-flow autoperfusion catheter may be useful as a temporary stent in cases of rupture, dissection, or penetrating wounds involving large arteries.