Unemployment and prescribing.
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Drug Prescriptions↗
Biomedical subjects
C M Harris
Publications and source records attributed to C M Harris.
The replication fate of R- and S-styrene oxide adducts on adenine N6 is dependent on both the chirality of the lesion and the local sequence context.
In order to deduce the biological fate of adducts formed by the reaction of styrene oxide, a suspected carcinogen, with DNA, four oligodeoxynucleotides were synthesized which contained either R- or S-styrene oxide lesions on the N6 position of neighboring adenines within the human N-ras codon 61. When these adducted oligodeoxynucleotides were ligated into the single-stranded vector M13mp7L2 and the modified DNA used to transform repair-deficient Escherichia coli, the resultant plaque-forming abilities were found to vary as much as 300-fold, depending on the stereochemical configuration of the styrene oxide lesion and the sequence context in the vicinity of the damage. The frequency of mutations caused by the various styrene oxide adducts were similarly dependent on both their chirality and local sequence context. Oligodeoxynucleotide templates bearing these same four adducts were also constructed in order to evaluate their replication in vitro by the Klenow fragment. Three of the four styryl-modified templates yielded significant levels of fully extended primer upon polymerization. In contrast, the template containing R-styrene oxide at the second position of N-ras 61 was a very poor substrate for replication, a result which correlates well with the observed lethality of this lesion in vivo.
Adenine↗
Age, sex, and temporary resident originated prescribing units (ASTRO-PUs): new weightings for analysing prescribing of general practices in England.
OBJECTIVE: To derive demographic weightings to replace the existing system of prescribing units used in analysing prescribing by general practitioners in England. DESIGN: The prescribing data for one year from a sample of 90 practices in 80 family health service authority areas were used to calculate the relative frequency with which items were prescribed, for each sex, in nine age bands and for temporary residents. Data on the variation in cost per item by age and sex then allowed estimates to be made of the relative costs for these groups. Integer values for both the item based and cost based weightings were obtained by conversion to optimal integer scales. MAIN OUTCOME MEASURES: Item based and cost based weightings for each of the 18 age-sex groups and for temporary residents. The cost based weightings were considered more appropriate to the context in which the new system was to be used. RESULTS: Prescribing costs increased noticeably, for both sexes, in the middle years (ages 35-64). Compared with the existing system, the cost based weightings (ASTRO-PUs) gave greater weight to patients aged 45 and over, especially those in the 55-64 age band, at the expense of younger patients. Children under 5 received twice as many items as those aged 5-14, but the inexpensiveness of their drugs made the cost based weightings of the two groups equal. Similarly, women were generally given more items than men, but at a lower average cost per item, which reduced differences between the sexes in the cost based weightings. Costs for patients aged 75 and over, compared with those aged 65-74, were higher only for women. CONCLUSIONS: The cost based weightings proposed are believed to reflect the present distribution of prescribing costs, in relation to age and sex, in English general practice. They are intended for use in analyses at practice level.
Adolescent↗
Eye movements in a familial vestibulocerebellar disorder.
Eye movement abnormalities consisting of poor or absent smooth pursuit and vestibulo-ocular reflex suppression, gaze-paretic and rebound nystagmus, slow build-up of optokinetic nystagmus, mildly hyperactive vestibulo-ocular reflex, and a high incidence of strabismus were inherited in an autosomal dominant fashion in 10 members of a non-consanguineous English caucasian family. The onset was in early childhood, but was not congenital. In 7 cases there was no tremor, dizziness, consistent ataxia, or other cerebellar signs that are often associated with these ocular motor deficits, and apart from strabismus, patients were asymptomatic. Magnetic resonance imaging of the propositus was normal. After childhood there appears to be no progression, with the oldest affected member being 40 years. Two members had been prone to falling in childhood, and one admitted to dizziness when tired. This condition, which is probably benign, has not been previously described and may represent a very mild variant of episodic ataxia or a new vestibulocerebellar syndrome.
Adolescent↗
Eye movements in children with opsoclonus-polymyoclonus.
The anatomical localisation of the abnormality underlying opsoclonus-polymyoclonus-the "Dancing Eye Syndrome"-is uncertain and both the brainstem and cerebellum have been implicated. We used electrooculographic recordings to assess the eye movements in five children with this syndrome. Overshoot dysmetria was the consistent feature for the saccades of all five cases. One patient was also assessed after the main symptoms of ataxia and opsoclonus (saccadic oscillations, without an intersaccadic interval) had resolved and the saccades were found to remain hypermetric. Smooth pursuit and optokinetic nystagmus were normal, although the opsoclonus occurred throughout the recording session and were superimposed upon the normal eye movement waveforms. The vestibulo-ocular reflex was normal in four patients, but in one case, the time-constant was significantly prolonged: this has only been reported in experimental lesions of the nodulus in monkeys. The presence of saccadic overshoot dysmetria is highly suggestive of a cerebellar origin for the abnormal eye movements in these children. However, the preservation of normal smooth pursuit and the absence of gaze-paretic, rebound and downbeat nystagmus, implies the sparing of the flocculus and paraflocculus. We propose that the origin of these oculomotor deficits could be the cerebellar fastigial nuclei.
Adrenocorticotropic Hormone↗
Eye movement and electrophysiological findings in an infant with hemispheric pathology.
A visually unresponsive infant had a normal ophthalmological examination. Eye-movement studies using electro-oculography revealed asymmetrical binocular smooth pursuit, binocular optokinetic nystagmus and vestibulo-ocular reflex. Electrophysiological testing showed markedly asymmetrical occipital flash and pattern visual evoked potentials. Both investigations suggested a posterior right-hemispheric problem, which was confirmed with cranial ultrasound. This case study illustrates the usefulness of non-invasive techniques in neuro-ophthalmological investigations of young children.
Brain Diseases↗
Anxiogenic effect of disulfiram evaluated in an animal model.
The present experiment was designed to determine whether disulfiram produced an interoceptive discriminative stimulus (IDS) in rats similar to that exhibited by the anxiogenic drug pentylenetetrazol (PTZ). Rats were trained to discriminate PTZ (20 mg/kg IP) from saline, according to an FR10 schedule of food reinforcement. After training criteria had been met, discrimination testing revealed that disulfiram (100 mg/kg, IP) produced a PTZ-like IDS that fully substituted for PTZ 4 hours after injection, decaying to baseline values by the third day. The metabolite of disulfiram, diethyl dithiocarbamate (100 mg/kg, IP), followed much the same temporal pattern, but only showed partial substitution for PTZ. When ethanol (1 g/kg, gavage) or the monoamine oxidase inhibitor pargyline (50 mg/kg, IP) were administered in combination with disulfiram, no significant change of the PTZ-like stimulus was observed. Pargyline (100 mg/kg, IP) or acetaldehyde (200 mg/kg, IP), given alone, did not significantly substitute for PTZ. These data show that disulfiram produces an IDS in rats similar to that produced by other anxiogenic drugs. These data also suggest that the mechanism by which disulfiram produces its anxiogenic effect may not be entirely based upon the disulfiram metabolite diethyl dithiocarbamate, elevated acetaldehyde levels or stimulation of the catecholaminergic system.
Acetaldehyde↗
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↗
Forecasting the extent of the HIV/AIDS epidemic.
This paper has a dual objective: (1) to describe the current status of the structure of a newly developed model system to generate a wide span of U.S. HIV/AIDS estimates; and (2) to implement that system through the development of a dataset of HIV/AIDS incidence and prevalence, by stage, in the U.S. for a range of past and future years. There are many uncertainties regarding the anticipated effects of HIV/AIDS; examination of many of these effects indicates multiple societal difficulties. The characteristic of AIDS-growth is that of a long-delayed but inexorable disabling morbidity "taking off" in 1991-1992 from an HIV population widely thought to be 1.0-1.5 million spread throughout the Nation. Although widely dispersed, its impact, even at this early stage of growth, is to endanger the health and social support systems of our urban centers. The spread of AIDS cases into the smaller cities and rural counties indicates that those problems will not be limited to our major cities. This paper provides new and purposely pessimistic estimates of the levels of prevalence and incidence of HIV/AIDS for future years, based on U.S. AIDS cases reported. Although these numbers are essentially upper bounds, their values are consistent with the upper sides of some recent broad band projections released in early Summer 1989 by the U.S. Government Accounting Office (GAO). However, our estimation has generated data within a more proscribed range. A first set of forecasts has been provided to the State of Virginia's Department of Health for their use in statewide resource planning. The United States and the world face a severe HIV pandemic in the coming decade. The certainty of the threat is acknowledged by all of the major private and public medical authorities and institutions. Yet, to date, no official projection of the emergence, the level, and the sweep of the epidemic has been accepted by the medical community. And, there is certainly little agreement on the impact on the delivery of health care services in the United States and Canada, as well as throughout the world. On 26 June 1989, the U.S. GAO released a report that concluded, in part, that the Federal government's official data [e.g. from the Centers for Disease Control's (CDC) Morbidity and Mortality Weekly Report (MMWR) of 12 May 1989] were greatly understating the epidemic's extent. Specifically, the CDC's estimate of 185,000-320,000 (cumulative) cases of AIDS expected to be reported by the end of 1991 contrasted with GAO's estimate of 300,000-480,000.(ABSTRACT TRUNCATED AT 400 WORDS)
Acquired Immunodeficiency Syndrome↗
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↗