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Biomedical subjects

C M Harris

Publications and source records attributed to C M Harris.

At least 19 recordsLinked to original sources

Reduction-driven polypeptide folding by the delta Tt mechanism.

Poly(Gly-Val-Gly-Val-Pro), i.e., poly(GVGVP), exhibits composition and solute dependence of Tt, the temperature of the inverse temperature transition at which hydrophobic folding and assembly occur on raising the temperature. Importantly, a means whereby the value of Tt is lowered from above to below the working temperature becomes an isothermal means of driving folding and assembly, i.e., of achieving free energy transduction. Using poly[0.73(GVGVP),0.27(GK[NMeN]GVP)] where [NMeN] indicates N-methyl nicotinamide attached to the epsilon-NH2 of the Lys(K) residue, chemical and electrochemical reductions are found to remarkably lower the value of Tt; reduction can drive hydrophobic folding and assembly as effectively as decreasing ionization. Changing the redox state of a protein becomes yet another means of achieving free energy transduction by the delta Tt mechanism.

Amino Acid Sequence

Comparison of warfarin and external pneumatic compression in prevention of venous thrombosis after total hip replacement.

OBJECTIVE: To compare the effectiveness and safety of warfarin and external pneumatic compression (EPC) in prevention of venous thrombosis after total hip replacement. DESIGN: Prospective, randomized trial in consecutive patients, with blinded assessment of the primary end point. SETTING: University medical center and large community hospital. PATIENTS: Patients over age 18 years scheduled for elective primary total hip replacement were eligible. Of 254 patients interviewed, 232 were randomized, 220 patients had surgery and received prophylaxis, and 201 had venography. INTERVENTIONS: Patients were randomly assigned to prophylaxis with a device providing bilateral sequential EPC to both the calf and thigh or to receive warfarin in a low-intensity regimen beginning 10 to 14 days preoperatively. Prophylaxis was continued until venography. MAIN OUTCOME MEASURES: Venous thrombosis was diagnosed by venography between postoperative days 6 and 8. Bleeding was assessed by surgical blood loss, transfusion requirements, changes in hematocrit, and clinically identified bleeding complications. RESULTS: The total incidence of venous thrombosis was virtually the same in the warfarin and EPC groups (31% vs 27%), but the distribution of thrombi was different. Proximal thrombosis occurred in 12% of patients in the EPC group compared with only 3% in the warfarin group (P = .012, 95% confidence interval for difference, 2% to 18%). In contrast, calf vein thrombosis was more frequent in the warfarin group (21%) than in the EPC group (12%) (P = .021, 95% confidence interval for difference, 0% to 18%). Most proximal thrombi in EPC-treated patients were located within 15 cm of the femoral head and were not continuous with thrombi in deep calf veins. The high incidence of proximal thrombosis in the EPC group resulted in termination of the study by the safety monitoring committee. Blood loss and bleeding complications were similar in the two groups. CONCLUSION: Warfarin therapy is significantly more effective than EPC in preventing serious proximal vein thrombosis after total hip replacement. The greater effectiveness of warfarin therapy in preventing proximal vein thrombi and of EPC in preventing thrombosis in the calf suggests that there are differences in the pathogenesis of thrombosis in these two locations.

Aged

Hydrophobicity scale for proteins based on inverse temperature transitions.

In general, proteins fold with hydrophobic residues buried, away from water. Reversible protein folding due to hydrophobic interactions results from inverse temperature transitions where folding occurs on raising the temperature. Because homoiothermic animals constitute an infinite heat reservoir, it is the transition temperature, Tt, not the endothermic heat of the transition, that determines the hydrophobically folded state of polypeptides at body temperature. Reported here is a new hydrophobicity scale based on the values of Tt for each amino acid residue as a guest in a natural repeating peptide sequence, the high polymers of which exhibit reversible inverse temperature transitions. Significantly, a number of ways have been demonstrated for changing Tt such that reversibly lowering Tt from above to below physiological temperature becomes a means of isothermally and reversibly driving hydrophobic folding. Accordingly, controlling Tt becomes a mechanism whereby proteins can be induced to carry out isothermal free energy transduction.

Amino Acid Sequence

A community study of bladder cancer screening by the detection of occult urinary bleeding.

A possible method of improving the prognosis of bladder cancer may be the widespread introduction of screening. We investigated the ability of urine dipsticks to detect early bladder cancer in a group of men in the community. In 2,356 men more than 60 years old the urine was tested with a dipstick for the presence of blood. The subjects then tested their own urine on 10 subsequent occasions. Of the men 474 (20%) had dipstick hematuria and 319 agreed to undergo urological investigation. An asymptomatic bladder tumor was found in 17 men, associated in 10 with abnormal urine cytological findings. Urine dipsticks for the detection of red cells provided an inexpensive, simple and acceptable screening test for bladder cancer. However, introduction of generalized population screening by this method would produce large numbers requiring investigation. Combining urine cytology with dipstick hematuria results may provide a realistic alternative and further evaluation of the effectiveness of screening for bladder cancer in the community is required.

Aged

Eye movement tics.

An 8-year-old girl presented with opsoclonus-like eye movement and an 18 month history of intermittent facial tics. Investigations were all normal. Electro-oculography showed the eye movements to be of variable amplitude (10-40 degrees), with no intersaccadic interval, and with a frequency of 3-4 Hz. Saccades, smooth pursuit, optokinetic, and vestibular reflexes were all normal. These abnormal eye movements eventually disappeared. It is thought that they were a form of ocular tics.

Child

Measure of satisfaction of general practitioners with the chemical pathology services in Leeds Western Health District.

The satisfaction of general practitioners with the District Chemical Pathology Services in Leeds Western Health District was assessed by means of a postal questionnaire. The areas of interest covered included communication, test turn-round times, format of reports, advice about tests undertaken in the practice and chemical pathology information services. Communication with the laboratory was the major area of dissatisfaction (21% GPs), followed by test turn-round times (14%) and format of reports (10%). More than half the respondents were interested in an offer of help in selecting equipment for their surgeries and subsequent quality control. Customer satisfaction will become an important issue as a result of the NHS reforms and laboratories may find this exercise useful.

England

Aspects of albinism.

Genetic, clinical and electrophysiological aspects of albinism are described. Emphasis is placed on electrophysiological features which help to distinguish albinism from other clinical conditions, and on stimulating and recording factors which can affect the clarity of VEP results.

Albinism, Ocular

The use of video in assessing and illustrating abnormal eye movements in young children.

Eye movement studies can be useful in neuro-ophthalmological investigations of infants and young children. In our laboratory we use a combination of an electro-oculogram and video to record eye movements. A composite video image is created consisting of an image of the electro-oculographic eye movement trace superimposed on an image of the patient's eyes and face. This permits the qualitative clinical appearance of the case to be illustrated simultaneously with the quantitative eye movement trace.

Electrooculography

Descriptive research.

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Attitude of Health Personnel

Ankle arthrodesis with vertical Steinmann's pins in rheumatoid arthritis.

Many techniques for ankle arthrodesis have been described but some of them are not applicable in patients with severe rheumatoid arthritis (RA) who have also developed osteopenia and decreased bone density. A technique utilizing two longitudinally placed Steinmann's pins to fixate and align the joint was used in five patients with severe RA and is described here. Results showed a 100% fusion rate and patient satisfaction over an average follow-up time of six years. This ankle arthrodesis technique was found to be applicable in arthritic patients with osteopenia and decreased bone density caused by RA.

Ankle Joint

Pipecolic acid biosynthesis in Rhizoctonia leguminicola. I. The lysine saccharopine, delta 1-piperideine-6-carboxylic acid pathway.

The biosynthesis of pipecolic acid from L-lysine in the fungal parasite, Rhizoctonia leguminicola has been reinvestigated. Pipecolate is then utilized to form the toxic octahydroindolizine alkaloids, slaframine and swainsonine. Incorporation studies of L-versus D-[U-14C]lysine into R. leguminicola metabolites confirmed earlier findings that L-lysine is the predominant substrate for pipecolate formation and D-lysine for alpha-N-acetyllysine (concerned in lysine catabolism). However [alpha-15N]lysine, not [epsilon-15N]lysine as previously reported, labeled pipecolate. Such findings implied that delta 1-piperideine-6-carboxylate, not delta 1-piperideine-2-carboxylate, was formed from lysine and was the immediate precursor of pipecolate. Evidence from cell-free enzyme systems established the following biosynthetic events: L-lysine A----saccharopine B----delta 1-piperideine-6-carboxylate C----pipecolate. Products of reactions A and C were identified from biological and chemical considerations. Reaction B was carried out by a previously undescribed flavin enzyme termed saccharopine oxidase. The product of reaction B, which reacted with p-dimethylaminobenzaldehyde, was reduced with Na-CNB2H3. Its NMR spectrum was identical with that of deuteriated pipecolate prepared from authentic delta 1-piperideine-6-carboxylate, but not from authentic delta 1-piperideine-2-carboxylate. Reaction B represents a branching of primary lysine metabolism from saccharopine to a secondary pathway leading to pipecolate and to octahydroindolizine alkaloids in R. leguminicola.

Lysine

Fourier analysis of saccades in monkeys and humans.

1. By recording eye movements with the search coil technique and subjecting them to an accurate infinite Fourier transform algorithm, we describe the Fourier spectra of human and monkey saccades. In both species we find heretofore undescribed features consisting of a regular pattern of local minima in the power plot, which cannot be attributed to noise. The frequency of these minima is well correlated with saccade duration. 2. Computer simulation shows that if the pulse component of the saccade is considered to be rectangular, then the first of these minima (called M1) occurs at a frequency that is the reciprocal of the duration of the pulse. 3. Comparing the position of this component during individual monkey saccades with electrophysiological recordings of motoneurons during the same saccades leads to the conclusion that these minima are related to the burst components in ocular motoneuron discharges. Specifically, the reciprocals of the frequencies of these minima are correlated with the duration of the burst component in the motoneuron discharge. 4. In the Fourier spectra of human saccades, the relationship of the frequency of M1 to saccadic duration is a function similar to that in the monkey. This adds to the evidence that the human saccade also is driven by a pulse-step signal. 5. In both monkeys and humans, T1, the reciprocal of the frequency of M1, is shorter than both the saccade duration and the burst duration of individual motoneurons, even though neurophysiological studies in monkeys generally report the saccadic burst duration to be equal to the saccade duration. This probably arises because the saccadic pulse is not rectangular, with the extremes contributing very little energy to the Fourier spectrum. By further computer modeling we show these shape effects explicitly: as the rise- and falltime increase, making the pulse less rectangular, T1 becomes shorter; in addition, as the asymmetry of rise and fall increases, the depth of the minima is reduced. We conclude that T1 measures the "effective pulse" duration of the motoneuron. 6. There is a difference in the relationship of effective pulse duration to the saccade duration between short and long saccades. For saccades shorter than approximately 40 ms in the human and 50 ms in the monkey, the pulse width as measured by this technique varies little with saccade duration. For longer saccades, effective pulse width increases linearly with duration. We agree with others that for short saccades the pulse is both height- and width-modulated; but for longer saccades, height modulation saturates and only width modulation remains.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult

The relationship of physician assistants to an orthopedic residency program.

In 1979, coincident with a planned decrease in the size of the general surgery training program, the orthopedic department of the senior author's university-affiliated teaching hospital began to employ physician assistants. The intent of using physician assistants was to relieve the two orthopedic residents assigned to the hospital of many service responsibilities and patient care that previously had been rendered by the general surgical residents and interns. The non-M.D. physician assistants record a comprehensive past and present medical history, carry out physical exams, and assist at surgery. They are directly under the supervision of and responsible to the attending surgeon. It was hoped the addition of these individuals will help maintain a quality educational experience for the orthopedic residents. The general response to the use of physician assistants in this affiliated hospital has been favorable.

Hospital Bed Capacity, 300 to 499

Bilateral hip and bilateral knee arthroplasties in a patient with ochronotic arthropathy.

Alkaptonuria is a rare, autosomal-recessive, inborn, metabolic disease that causes ochronotic arthropathy leading to disabling arthritis. Few reports of arthroplasty in patients with this disease have been published, and none documents four total joint replacements in the same patient. This case report describes the history and findings in a 70-year-old man who underwent bilateral hip and knee total joint arthroplasties with significant improvement in pain and exercise tolerance. The metabolic and clinical aspects of alkaptonuria are also discussed.

Aged

Antithrombin III prophylaxis of venous thromboembolic disease after total hip or total knee replacement.

The use of antithrombin III (ATIII) replacement in combination with low-dose heparin therapy in prevention of postoperative venous thrombosis in patients following total hip replacement or total knee replacement was evaluated. A randomized prospective venographically controlled trial in hip replacement compared treatment with dextran 40 with a regimen of ATIII (1,500 units preoperatively and 1,000 units daily for five days) and low-dose heparin. Patients receiving ATIII/heparin had significantly higher postoperative ATIII concentrations than dextran-treated patients and also had a low incidence of venous thromboembolic disease (7 percent). The ATIII/heparin regimen was well tolerated with no increase in bleeding or significant prolongation of the activated partial thromboplastin time. Two cohorts of patients undergoing total knee replacement were studied using different doses of ATIII in combination with heparin. An initial 10 patients were treated with the same ATIII dose used for patients undergoing total hip replacement, with a 50 percent incidence of venous thrombosis. A second group of 11 patients was treated with twice the dose of ATIII, and an incidence of venous thrombosis of 27 percent was found. The higher ATIII dose resulted in significantly higher ATIII concentrations and maintained the postoperative ATIII concentration above normal. Among patients receiving prophylaxis with either warfarin. dextran, or ATIII/heparin, no clear association was found between reduced ATIII concentrations and occurrence of venous thrombosis. It is concluded that ATIII replacement following total hip or knee replacement corrects the postoperative ATIII deficiency and that the combination of ATIII and low-dose heparin is an effective prophylactic regimen following total hip replacement.

Antithrombin III

The ethology of saccades: a non-cognitive model.

It is proposed that there is a low-level automatic component of visual scanning in which saccades are triggered probabilistically in time by non-foveal stimulus features. By ignoring cognitive factors and memory, a first-order Markov approach is taken, which is tractable for spatially homogeneous stimuli. The predicted distributions of saccade magnitude, fixation duration, fixation position, and how they are related to stimulus size are in good agreement with empirical observations by Bahill et al. (1975), Enoch (1959), and Harris et al. (1988). Ways in which this low-level process could be modulated by cognitive factors are discussed.

Eye Movements