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Biomedical subjects

M B Clarke

Publications and source records attributed to M B Clarke.

At least 19 recordsLinked to original sources

Length-tension recording system for strabismus surgery.

To meet the need for both scientific information and a clinical means for measurement of the mechanical parameters of the most difficult individual strabismus cases we present a technique for directly measuring and plotting the length-tension characteristics of the tissues supporting the eye. Semiconductor strain gauges mounted on the shanks of a custom machined eye forceps and an ultrasonic method of making continuous duction measurements of the eye have proved feasible. When the forceps are interfaced with a dedicated microcomputer, the system provides a permanent, quantitative, length-tension record displayed in real-time. The instrumented length-tension forceps system has provided a noninvasive means for quickly and simply assessing the mechanical underlying determinants of strabismus pathology in the office, the laboratory or in the operating room, and can aid in the planning and immediate intraoperative alteration of strabismus surgery. Under operator coordination, measurements can be made which precisely define the mechanical load which the eye muscles must move. The resulting objectively determined tissue stiffness asymmetries and muscle restrictions limiting ocular motion indicate the purely mechanical contributions to a patient's strabismus. Measurements of active force indicate the magnitudes and patterns of innervation over the entire range of gaze. By comparison of these active force and passive stiffness records, nerve signal imbalances may be quantitatively distinguished from mechanical imbalances in strabismus. It is the detailed interaction of these nonlinear muscle forces and mechanical elements which determines the position of each eye in strabismus and therefore the proper surgical treatment. A brief description of actual use and a few examples of clinical results are included from over 200 human records.

Calibration↗

Proportion of necrosis in transplanted murine adenocarcinomas and its relationship to tumor growth.

Percentage of necrosis has been measured in 30 murine adenocarcinoma transplants of known volume. It was found that changes in necrotic proportion during the growth of these particular tumors agree with the concept of a core of necrosis surrounded by a viable shell of constant thickness. This means that viable and necrotic fractions were proportional to the surface area of the tumor, which is consistent with the frequently observed superficial distribution of nutrient-supplying arteries. According to this model a plot of 1n tumor volume versus necrotic fraction is sigmoid and, if tumor growth is directly related to viable fraction, such a plot is not compatible with popular mathematical growth equations. However, the equation of von Bertalanffy gives a reasonable fit to the data here for total tumor growth, suggesting that growth too was proportional to surface area and in accord with a surface-related viable fraction and blood supply. An appropriate physiological explanation is given of necrosis development resulting from a superficial nutrient supply.

Adenocarcinoma↗

Ten minute radiopharmaceutical test in biliary atresia.

To provide an objective rapid means of excluding extrahepatic biliary atresia (atresia), a hepatic index was devised from the ratio of the net hepatic to cardiac distribution of 99mTc diisopropyl iminodiacetic acid or methylbrom iminodiacetic acid between 2.5 and 10 minutes after injection. The hepatic index was compared with subjective assessment of abdominal scintigraphy performed repeatedly over 24 hours. In 22 infants with hepatitis the hepatic index ranged from 5.03 to 14.9, one having no excretion on scintiscan. In 26 infants with atresia the index ranged from 0.49 to 4.26 and in two with paucity of intralobular bile ducts it was 1.85 and 3.69. None of these infants had excretion apparent on scintiscans. Similarly, low hepatic indices occurred in four infants with liver dysfunction but pigmented stools, three of whom had no excretion apparent on scintiscans. These preliminary studies suggest that a hepatic index of greater than 5 is much more rapid and as specific in excluding atresia as repeated abdominal scintigraphy.

Biliary Atresia↗

Measurement of blood supply to murine tumours using in vivo red cell labelling and dynamic scintigraphy.

Blood pool and flow were studied in transplanted adenocarcinomas on the legs of mice. The animals' red blood cells were labelled in vivo by consecutive injections of a stannous compound and 99mTc-pertechnetate. The distribution of radioactivity was then recorded continuously with a gamma camera. This method allows prolonged and repeated estimations of blood supply to undisturbed tumours in conscious mice. It was found that in small tumours (under 1 ml) circulating blood pool was usually high, often 2 or 3 times that in normal leg tissues. In tumours bigger than 1 ml blood pool per unit volume tended to be lower but was still about 1.5 times the normal tissue level. This relatively large blood volume would seem to be outweighed by a very slow rate of flow. Even in the small tumours blood perfusion was greatly reduced compared to that in the normal leg. The blood pool results here provide no evidence that in tumours larger than 1 ml blood supply decreased progressively with growth.

Adenocarcinoma↗

Normal volunteer studies with modified 99Tcm tin colloid.

99Tcm tin colloid, modified by the addition of various amounts of the surfactant Pluronic F68 was evaluated as a new liver imaging agent in normal adult male volunteers. The relative amounts taken up in the liver and spleen were measured by two quantitative methods with a view to establishing the most useful technique. The changes in biodistribution resulting from mechanical shaking during preparation of the colloids and in vitro ageing of the preparations were assessed. The pharmacokinetics of uptake into liver and spleen of the various formulations tested were independent of Pluronic F68 content. However, at low levels of Pluronic F68 the liver:spleen ratio decreased as the colloid preparation was aged before use. At high levels of Pluronic F68 there was increased background activity. An optimum formulation was identified combining low background activity with a stable pattern of biodistribution independent of preparation age.

Adult↗

Increased uptake of bone radiopharmaceutical in diabetic neuropathy.

Uptake of radiopharmaceutical was markedly abnormal in all phases of the bone scan in the feet of patients with diabetic neuropathy. Bone scans were performed in three groups of patients; diabetics with neuropathic osteoarthropathy (Charcot joints); diabetics with neuropathy but no evidence of osteoarthropathy and non-diabetic controls. Uptake was monitored in three phases; during the first 2 min after injection, then at 4 min and finally at 4 h. Uptake in all three phases was markedly increased in the neuropathic subjects, not only in those with osteoarthropathy but also in those with no radiological abnormalities. Increased uptake at 2 and 4 min indicates increased blood flow which can also result in increased uptake at 4 h. Increased blood flow secondary to peripheral neuropathy may lead to excessive bone resorption, susceptibility to fracture and finally the development of neuropathic osteoarthropathy of the diabetic foot.

Adult↗

Thrombocytopenia in renal transplantation. Diagnostic use of homologous platelet labelling with 111In oxine.

We have used homologous platelet labelling with 111In oxine in the diagnosis of thrombocytopenia occurring in a patient who had received two renal transplants. The technique enabled us to prove that platelet destruction was occurring in the right-sided, non-functioning transplant. In the presence of moderately impaired bone marrow function, this destructive process was sufficient to cause thrombocytopenia. Transplant nephrectomy relieved the thrombocytopenia.

Blood Platelets↗

Hepatobiliary imaging: a comparison of 99Tcm-dihydrothioctic acid and 99Tcm-pyridoxylidene glutamate in the non-jaundiced patient.

A comparison of two hepatobiliary imaging agents, 99Tcm-dihydrothioctic acid (99Tcm-DHT) and (99Tcm-pyridoxylidene glutamate (99Tcm-PG) has been carried out in 44 non-jaundiced patients. Thirty-one patients were admitted for investigation of upper abdominal pain and 13 patients were volunteers who were undergoing treatment for unrelated conditions. Satisfactory liver images were obtained with both agents in patients without liver disease, but they were inferior to those seen after 99Tcm-sulphur colloid. 99Tcm-PG produced clearer images of the gall-bladder and bile ducts than 99Tcm-DHT. Non-visualization of the gall-bladder was interpreted as gall-bladder disease; in patients with inflammatory gall-bladder disease no gall-bladder image was seen (nine 99Tcm-DHT, nine 99Tcm-PG). The gall-bladder was also not demonstrated in two of the volunteers' group (one 99Tcm-DHT, one 99Tcm-PG), nor was a gall-bladder seen in five patients whose abdominal pain was not due to acute cholecystitis. Despite this, there was agreement between the results of imaging and oral cholecystography in 21 out of 22 subjects. 99Tcm-PG is non-toxic, cheap and rapidly excreted by the liver into the bile. A 99Tcm-PG scan would be useful when rapid diagnosis is required in suspected acute cholecystitis when conventional contrast radiology is unlikely to be of value.

Adult↗

Hepatobiliary imaging: the use of 99Tcm-pyridoxylidene glutamate scanning in jaundiced adults and infants.

99Tcm-pyridoxylidene glutamate (99Tcm-PG) scans have been carried out in 24 jaundiced adults (mean total bilirubin 255 mumol/l and 11 infants with prolonged obstructive jaundice (mean total bilirubin 165 mumol/l). Absence of radioactivity in the gut was interpreted as complete biliary obstruction which was the cause of jaundice in ten adults and six infants. Using this criterion occlusion or patency of the bile ducts was correctly determined in 21 adults and eight infants. False-negative gut images were found in one adult and two infants, and three scans were inconclusive (two adults, one infant). The scan was unable to show details of the site of obstruction or pathology but the technique was simple and atraumatic and was safely performed in patients with serious complications, e.g. renal failure, coagulation defects, septicaemia. In infants the 99Tcm-PG scan compared well with the 131I rose bengal faecal excretion test and with liver biopsy in the investigation of prolonged obstructive jaundice. Repeat scans in infants with biliary atresia were used to assess postoperative bile drainage. It is suggested that 99Tcm-PG scanning is useful screening test in difficult cases of jaundice. It is especially useful in frail patients, and patients with complications.

Adult↗

Physical characteristics and ventilatory function of 404 commercial divers working in the North Sea.

The physical characteristics and simple lung ventilatory indices (FVC, FEV 1, FEV 1/FVC) of 404 commercial divers employed by companies operating in the North Sea were analysed. These findings were correlated with the diving experience and maximum operating depth of each diver. All the divers were men of average height 176-9 cm, and weight 77-1 kg which is greater than average for active Western males, but only 6% were more than 120% of their predicted weight. The average duration of commercial diving was 7-1 years, 11% of divers having less than one year's experience. Sixty-seven per cent had worked at a maximum depth of 200 ft (61 m) and only 6% had worked deeper than 500 ft (153 m). The mean forced vital capacity (FVC) was 120-4% of the predicted value which indicated that they could voluntarily move large amounts of gas in and out of their lungs. This was greatest in the divers who when deepest. The mean forced expired volume in one second (FEV 1) was 117% of the predicted value showing that expiratory airflow capacity was also increased, but to a lesser extent than the FVC. Thper and activated by zinc. Plasma protein protected the enzyme from both inhibition and activation. ALAD activity was found to be an indicator of the total metal ion concentration in the blood and was therfore considered to be of doubtful value in screening large population for increased lead absorption.

Adolescent↗

Factors involved in the detection of pulmonary emboli by labelling techniques.

Experiments were set up to assess quantitatively the problem of detecting, by scanning and gamma-camera, labelled pulmonary emboli in the presence of background radioactivity. In vitro, a relative concentration of radioactivity of 2:1 was required to detect a 1-1 cm diameter "hot spot". The results in vivo suggest that the level of radioactivity of a pulmonary embolus situated in the centre of the lung field should be at least six times that of the circulating blood.

Animals↗

Liver and gall-bladder imaging with technetium-99m dihydorthioctic acid and technetium-99m pyridoxylidene glutamate-a study in the young pig.

Seventeen scans on ten young pigs were performed after injection of Technetium-99m labelled dihydrothioctic acid (99Tcm-DHT) and Technetium-99m labelled pyridoxylidene glutamate (99Tcm-PG) using a gamma-camera. Sequential images of the liver, gall-bladder and intestine were observed in all healthy animals. 99Tcm-DHT produced the clearer liver images, whereas 99Tcm-PG produced more rapid and intense gall-bladder images. Analysis of hepatic bile in three animals also suggested a more rapid and higher concentration of 99Tcm-PG than 99Tcm-DHT (36% vs. 4% of the injected dose over two hours). Bowel images were not seen in an animal that had undergone exicision of the extrahepatic biliary tract, but scans performed after hepaticojejunostomy demonstrated intestinal transit of isotope. This study shows that the hepatobiliary system can be easily imaged using Technetium-99m labelled compounds which are excreted into bile. These agents may be useful in the diagnosis of obstructive lesions of the extrahepatic biliary tract of adults and infants.

Animals↗

Myocardial infarction and deep-vein thrombosis.

In a study of 52 patients admitted into the coronary intensive care unit the incidence of deep-vein thrombosis was measured with the (125)I-fibrinogen test. Of these patients 31 were eventually confirmed to be suffering from acute myocardial infarction. This preliminary study showed that in patients with a confirmed infarct who were not treated with anticoagulants the incidence of deep-vein thrombosis was 38% and in those treated it was 5.5%. In patients who were "severely ill" from whatever the cause there was a high incidence of deep-vein thrombosis (68%).

Anticoagulants↗