Biomedical subjects
Publications and source records attributed to L C Knight.
A lingual abscess is a great rarity. Only two cases have ever been reported from the United Kingdom, and only three cases have been recorded outside of India in the past fifty years. The third British case is reported and the previous literature reviewed, along with discussion of the aetiology, presentation, bacteriology and management of this rare condition.
A left anterior oblique image (LAO) and the geometric mean of anterior and posterior counts have both been proposed as methods for acquiring gastric emptying data. Both approaches are used to correct for the changes in attenuation that occur as the depth of radiolabeled solids changes during gastric emptying. These two methods were compared by using a power exponential curve fit to calculate a lag phase, an equilibrium emptying rate, and a half-time for gastric emptying in 20 patients. There were no significant differences (mean +/- 1 s.e.m.) in the measured half-emptying time (115 +/- 10 versus 104 +/- 7 min) (p = 0.08) or rate of gastric emptying (0.015 +/- 0.002 versus 0.015 +/- 0.002 min-1) (p = 0.56) for LAO imaging versus the geometric mean. However, the LAO measurements of the lag phase were significantly higher (69 +/- 7 min) than the geometric mean (53 +/- 6 min) measurements (p = 0.004). This resulted in 4/20 (20%) of patients with normal geometric mean lag phase measurements who would have been reclassified as abnormal using the LAO method.
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Most of the components of the thrombotic and fibrinolytic systems have at some time been evaluated as a means of carrying a radiolabel specifically to thrombi, although very few have been promising enough to emerge from investigational status to routine clinical use. New approaches are being explored, including improved methods of labeling platelets, chemically modified forms of previously tested plasma proteins, and new biomolecules, including monoclonal antibodies specific for fibrin and platelets. The current goal is to find one or more radiotracers that bind specifically and rapidly to thrombi, and that also have a rapid blood disappearance rate, permitting a clear diagnosis within a few hours after injection. Because this test may be needed to assess the course of therapy in an anticoagulated patient, the ideal radiopharmaceutical should be able to locate thrombi without interference by anticoagulants. Until a suitable thrombus-specific radiopharmaceutical becomes generally available, many hospitals will continue to attempt to make a diagnosis with nonspecific radiopharmaceuticals that can at best provide blood pool images to indicate filling defects. Several of the new approaches seem likely to provide the radiopharmaceutical sought, although clinical trials are at an early stage.
Ferric pyrophosphate (Fe-PyP) was investigated in an animal model of acute myocardial infarction for its potential to provide contrast enhancement of the peri-infarct zone using magnetic resonance (MR) imaging. Radiotracer studies compared the biodistribution of soluble 59Fe-PyP with 99mTc-PyP in excised tissue samples. Preferential localization of 59Fe-PyP in the peri-infarct zone was found to be similar to 99mTc-PyP. The ratio (percent dose/gram of tissue) at the edge of the infarct to normal tissue was 1.30 +/- 0.16 and 1.44 +/- 0.33 for 99mTc-PyP and 59Fe-PyP, respectively. In initial studies with high doses of the contrast agent, gated T1-weighted MR images of animals with 48-hour-old infarcts were obtained at 15-minute intervals after injection of Fe-PyP at a dose of 350 mg/kg. Contrast enhancement of the infarct zone was observed in all studies and was maximal 15-30 minutes after injection. Signal intensity ratios (infarct/normal) increased from a baseline 1.31 +/- 0.22 to a peak 1.90 +/- 0.57. Studies were then performed with smaller amounts of Fe-PyP. Images obtained with 50 mg/kg Fe-PyP showed contrast enhancement beginning at 60 minutes. Toxicology studies showed primarily respiratory effects, which became significant at doses of 190 mg/kg. These preliminary studies suggest that Fe-PyP potentially could serve as an MR contrast agent to localize and size acute myocardial infarcts; however, its clinical use may be limited by potential toxicity and dose limitations.
A prospective trial was carried out to assess whether mucociliary clearance (MCC) is either adversely affected or improved in the early weeks after nasal surgery. Three different subgroups of patients were studied: those having septoplasty, nasal polypectomy, or turbinectomy. MCC was assessed by the saccharine transport method. 40% of patients with deviated nasal septum, 59% of patients with nasal polyps, and 75% of patients with chronic rhinitis refractory to medical treatment (turbinectomy group) had abnormal MCC pre-operatively. At three weeks after operation there was no significant improvement or deterioration in MCC either in the whole patient population or in any of the three subgroups. Persisting mucociliary dysfunction may be an important factor in causing post-operative stasis of secretions, crusting, secondary infection, delayed healing, and patient discomfort.
Rectally administered suspensions of 5-aminosalicylic acid (5-ASA) are topically effective in treating left-sided ulcerative colitis. The extent to which the contents of these enemas are distributed to inflamed mucosal linings has not previously been determined. This study was undertaken to validate a technique for labeling 5-ASA with 99mTc and to quantitate the distribution of [99mTc]5-ASA in eight patients with left-sided ulcerative colitis. Eight patients underwent three colonic scintigraphic exams within five days, receiving a 60-ml radiolabeled 5-ASA enema into the unprepared rectum for each study, with sequential anterior abdominal images obtained for 4 hr. Activity within the rectum, sigmoid, descending, transverse, and ascending colon was quantitated. Over 50% of the labeled enema had advanced beyond the rectum in five of eight patients and in six of eight patients by 30 min and 60 min, respectively. The distribution of [99mTc]5-ASA was quantitatively reproducible when repeated in the same patient on different days, despite apparent visual differences. By 2 hr, the amount of the enema present within the rectum decreased significantly (P less than 0.05) compared to the initial distribution. The amount of enema present within the descending colon was increased significantly at 0.5 hr (P less than 0.05) and at 2 hr (P less than 0.01). There were no significant changes in the distribution from initial values for the sigmoid, transverse, or ascending colon at any time. In each of these cases the spread of the enema to or beyond the extent of disease was documented. In patients with left-sided ulcerative colitis, small volume [99mTc]5-ASA enemas reliably reach the area of inflammation.
Middle ear adenomas are rare epithelial tumours. Reports indicate that neuroendocrine (carcinoid) tumours may also occur at this site, often in association with an adenomatous component. The clinico-pathological findings (including C.T. scan appearances) of such a 'mixed' neoplasm are presented together with a brief review of the few previously described cases. The importance of immuno-histochemistry and electron microscopy for accurate pathological diagnosis of these neoplasms is confirmed.
This study presents the results of a 20 year review of maxillary sinus wash-outs performed on children. The results show a decreasing incidence of purulent sinusitis over the study period. Only 17 per cent of antral wash-outs undertaken yielded pus, indicating that surgical practice has failed to adequately take account of the changing disease incidence.
Patients presenting with sharp pain in their throat after eating fish were studied to determine the site and frequency of impacted fish bones. In 79% no fish bone was demonstrated despite careful follow up. In those proven to have a fish bone 93% were in the oropharynx. The role of X-rays and the indications for referral for endoscopy are discussed.
An antifibrin antibody (T2G1s) Fab' fragment labeled with technetium-99m was tested for its ability to produce images of fresh thrombi in dogs. In gamma camera images, all thrombi were evident by 2-4 hours after injection. Mean thrombus-to-blood and thrombus-to-muscle ratios averaged 4.0 and 69 at four hours after injection and increased to 24 and 270, respectively, by 24 hours after injection. When compared with I-125 fibrinogen injected into the same dogs, Tc-99m-antifibrin Fab' had lower absolute uptake in thrombus but higher thrombus-to-blood ratios due to a faster rate of disappearance from the blood. The primary route of excretion was through the kidneys. Tc-99m-antifibrin Fab' was highly stable in vivo, with an average of 82% of the circulating radioactivity able to bind to fibrin at 4 hours after injection. When compared with an In-111-labeled Fab fragment of antifibrin antibody 59D8, thrombus-to-blood and thrombus-to-muscle ratios were slightly higher for the Tc-99m-labeled antibody, and the blood disappearance rate was slightly faster. The absolute uptake in thrombus, however, was not significantly different, and the thrombus was visualized at about the same time after injection. These studies suggest that Tc-99m T2G1s Fab' is a potential agent for detecting thrombi in a clinical setting.
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Mixtures of alginic acid and antacid, when given orally, react with gastric acid to form a viscous barrier (raft) which floats on the surface of the gastric contents. 111In was used to label magnesium alginate in order to study the effect of gastric acidity on the extent of formation of the raft. In vitro, acid concentrations less than 0.05 N diminished raft formation. In vivo, raft formation was significantly better in normal subjects who ingested dilute acid with the labeled alginate/antacid than in subjects who ingested the labeled alginate/antacid with plain water. Gastric emptying of the labeled alginate was also slowed by the presence of acidified gastric contents. These results suggest that the formation of an effective alginic acid antireflux barrier requires acidic gastric contents.
Monoclonal antibodies which recognize fibrin but not fibrinogen can be used to detect deposits of fibrin in vivo. Recently, two monoclonal antibodies with such specificity have been created: 59D8 (raised against a synthetic heptapeptide by Hui et al.) and T2G1s (raised against a fibrin fragment by Kudryk et al.). These two antibodies appear to share the same epitope in the N-terminus of the beta chain of fibrin, a site which is not exposed in fibrinogen. In the form of radioiodinated IgG, both antibodies have been shown to bind to deposits of fibrin and induce fresh thrombi in animal models. Use of antibody fragments which retain immunoreactivity could enhance thrombus detection by (1) increasing the rate of blood disappearance and thus increasing target/background contrast, and (2) favouring renal excretion over liver uptake. Antibody fragments which have been derivatized to contain diethylenetriaminepropyleneamineoxime (DTPA) groups have been labelled with 111In and used to produce images of fresh thrombi in animal models with thrombus-to-blood ratios of greater than 7:1 and thrombus-to-muscle ratios of greater than 200:1 by 24 h post injection. Initial clinical trials of these antibodies suggest that thrombi may be visualized within the first few hours after injection, although the image quality improves with time. Shorter-lived radiolabels (such as 99Tcm) may be useful for anti-fibrin antibody fragments if adequate thrombus/background contrast can be achieved within a few hours post injection.
Fragment E1 is a fragment of human fibrin, produced by controlled plasmin digestion of cross-linked fibrin. It comprises the N-terminal regions of all six polypeptide chains of fibrin. It has been shown to contain a pair of dimeric binding sites which are complementary in binding to sites in the D domains of fibrin which are formed when fibrin polymerizes, so fragment E1 binds to fibrin dimers and polymers but not fibrin monomer or fibrinogen. Radioiodinated fragment E1 has been shown to localize in venous thrombi in a pig model. Thrombus/blood ratios of up to 100: 1 were obtained at 24 h post injection, in thrombi up to 5 days old at the time of tracer injection. In humans, deep-venous thrombi were visualized within 30 min of 123I-labelled fragment E1. Fragment E1 exhibits very rapid blood disappearance, which enhances its ability to produce high thrombus/blood ratios at early times. The thrombus uptake of labelled fragment E1 is not affected by heparin. Fragment E1 has been derivatized with metal chelating groups [diethylene-triaminepentaacetic acid (DTPA) and deferoxamine], to facilitate labelling with 111In and 67Ga. Although these labels appeared promising in animal models, they have not yet achieved success in man. Clinical trials are continuing with 123I-labelled fragment E1, which is felt to be a most promising radiopharmaceutical for thrombus localization.
The existence of a lag phase during the gastric emptying of solid foods is controversial. It has been hypothesised that among other early events, the stomach requires a period of time to process solid food to particles small enough to be handled as a liquid. At present no standardised curve fitting techniques exist for the characterisation and quantification of the lag phase or the emptying rate of solids and liquids. We have evaluated the ability of a modified power exponential function to define the emptying parameters of two different solid meals. Dual labelled meals were administered to 24 normal volunteers. The subjects received meals consisting of either Tc-99m in vivo labelled chicken liver or Tc-99m-egg, which have different densities, and In-111-DTPA in water. The emptying curves were biphasic in nature. For solids, this represented an initial delay in emptying or lag phase followed by an equilibrium emptying phase characterised by a constant rate of emptying. The curves were analysed using a modified power exponential function of the form y(t) = 1-(1-e-kt)beta, where y(t) is the fractional meal retention at time t, k is the gastric emptying rate in min-1, and beta is the extrapolated y-intercept from the terminal portion of the curve. The length of the lag phase and half-emptying time increased with solid food density (31 +/- 8 min and 77.6 +/- 11.2 min for egg and 62 +/- 16 min and 94.1 +/- 14.2 min for chicken liver, respectively). After the lag phase, both solids had similar emptying rates, and these rates were identical to those of the liquids. In vitro experiments indicated that the egg meal disintegrated much more rapidly than the chicken liver under mechanical agitation in gastric juice, lending further support to the hypothesis that the initial lag in emptying of solid food is due to the processing of food into particles small enough to pass the pylorus. We conclude that the modified power exponential model permits characterisation of the biphasic nature of gastric emptying allowing for quantification of the lag phase and the rate of emptying for both solids and liquids.
Colonic transit scintigraphy, a method for quantitatively evaluating the movement of the fecal stream in vivo, was employed to evaluate colonic transit in the cat. Scintigraphy was performed in duplicate in five cats and repeated four times in one cat. After instillation of an 111In marker into the cecum through a surgically implanted silicone cecostomy tube, colonic movement of the instillate was quantitated for 24 h using gamma scintigraphy. Antegrade and retrograde motion of radionuclide was observed. The cecum and ascending colon emptied rapidly, with a half-emptying time of 1.68 +/- 0.56 h (mean +/- SE). After 24 h, 25.1 +/- 5.2% of the activity remained in the transverse colon. The progression of the geometric center was initially rapid, followed later by a delayed phase. Geometric center reproducibility was found to be high when analyzed using simple linear regression (slope = 0.92; r = 0.73; P less than 0.01). Atropine (0.1 mg/kg im) was found to delay cecum and ascending colon emptying and delay progression of the geometric center. These results demonstrate both 1) the ability of colonic transit scintigraphy to detect changes in transit induced by pharmacological manipulation and 2) the fact that muscarinic blockade inhibits antegrade transit of the fecal stream. We conclude that feline colonic transit may be studied in a quantitative and reproducible manner with colonic transit scintigraphy.
Monoclonal antibody 59D8 developed by Hui et al., binds to fibrin but not fibrinogen. An 111In-labeled Fab fragment of 59D8 was studied in vitro and in animal models to evaluate its potential for imaging thrombi and emboli in man. Rabbits and dogs were used as models for studying thrombus uptake in vivo. Thrombi and emboli up to 4 days old were successfully visualized at 4-24 hr postinjection in five of eight rabbits. In dogs, 0.5-hr-old and 24-hr-old thrombi were successfully imaged at 24 hr in six of eight animals, and 3/6 of these were positive at 3-4 hr postinjection. Thrombus-to-blood ratios in the dogs averaged 7.1 +/- 1.3. The findings suggest this antibody may be useful for imaging thrombi in man.