Biomedical subjects
S Ferry
Publications and source records attributed to S Ferry.
Cardiovascular sequelae of toxaemia of pregnancy.
OBJECTIVE: To determine whether the rate of cardiovascular disease is different among parous women with a general practitioner reported history of toxaemia of pregnancy than among those not reported to have experienced toxaemia, or among nulliparous women. DESIGN: Prospective cohort study. SETTING: 1400 general practitioners throughout the United Kingdom. SUBJECTS: Women who had never used oral contraceptives who were recruited to the Royal College of General Practitioners' oral contraception study (original cohort about 23000). MAIN OUTCOME MEASURES: Age, social class, and smoking standardised incidence rates for hypertensive disease, acute myocardial infarction, other acute ischaemic heart disease, other chronic ischaemic heart disease, angina pectoris, total ischaemic heart disease, total cerebrovascular disease, and total venous thromboembolic disease in the three groups. RESULTS: Compared with parous women with no history of toxaemia, those who had experienced toxaemia had a significantly increased risk of hypertensive disease (relative risk (RR) 2.35), acute myocardial infarction (RR 2.24), chronic ischaemic heart disease (RR 1.74), angina pectoris (RR 1.53), all ischaemic heart disease (RR 1.65), and venous thromboembolism (RR 1.62). The rates for all cerebrovascular disease and peripheral vascular disease were also increased but not significantly. Nulliparous women were more likely to develop hypertension or all cerebrovascular disease later in life than parous women without a history of toxaemia. CONCLUSIONS: A history of toxaemia of pregnancy increases the risk of several distinct cardiovascular conditions later in life. Although causality cannot be inferred (other characteristics of the women may account for both an increased risk of toxaemia and a risk of subsequent vascular disease), the findings merit further research because of their potential importance.
Influence of previous pain experience on the episode incidence of low back pain: results from the South Manchester Back Pain Study.
BACKGROUND: A pathological cause cannot be identified for most new episodes of low back pain (LBP) presenting to the general practitioner. One important potential influence on susceptibility is previous pain experience. To accurately investigate the contribution of this phenomenon to the onset of new episodes of LBP a prospective population study is required. AIMS: To determine the relationship of prior pain in the back and other musculoskeletal sites to risk of subsequent new episodes of LBP. METHODS: The population studied included all 2715 adults from the South Manchester Back Pain Study who were free of LBP during the month prior to the baseline survey. At baseline a detailed musculoskeletal pain history was obtained. New episodes of LBP over the subsequent 12 months were ascertained by: (i) prospectively monitoring all primary care consultations in the study cohort (consulting episodes) and (ii) a follow-up survey after 1 year to determine new episodes during that 12-month period not leading to consultation (non-consulting episodes). RESULTS: The 12-month cumulative incidence of new consulting episodes was 3% in males and 5% in females, and for new non-consulting episodes 31% in males and 32% in females. Those with a history of previous LBP had twice the rate of new episodes, both consulting and non-consulting, compared to those with no LBP in the past. Neck pain or pain in other musculoskeletal sites at baseline also doubled the risk of a subsequent new episode of LBP. Adjusting for psychological distress and the other pain variables had little influence on the findings. CONCLUSION: In those currently free of LBP a previous history of the symptom substantially increases the risk of a further episode, with pain in other sites an equally strong independent predictor of subsequent LBP.
Protein binding of methohexital. Study of parameters and modulating factors using the equilibrium dialysis technique.
This paper describes the parameters that characterize methohexital-albumin binding and the influence of physiological or analytical factors on this binding. Two useful and reproducible methods for measuring the free concentration-equilibrium dialysis (ED) and ultrafiltration (UF)-are described and their performances are compared. Methohexital binds exclusively to albumin according to a two-class binding model. The first is a saturable class site of high affinity constant (KA = 11 200 M-1) and a number of sites per albumin molecule of 1. The second is a non-saturable site of poorer affinity (nKA = 810 M-1). The bound fraction of methohexital in the therapeutic range and at physiological albumin concentration is 86.7 +/- 0.9% in isolated albumin solution. In serum, it ranges from 80 to 84.5%, according to subjects (n = 6). Binding is inhibited by the presence of endogenous compounds of serum (for a given albumin concentration the bound fraction decreases from 90.3% in isolated albumin solution to 82.6% in serum), probably by free fatty acids. An increase in the bound fraction is observed when the pH is increased from 7 to 9. This phenomenon may be explained by a higher affinity of the drug towards the basic (B-form) conformation of the albumin molecule, in analogy with the close barbiturate thiopental. A decrease in the bound fraction against temperature is shown, as though binding forces diminished with increase in temperature. Indeed, the binding modification is less pronounced in the presence of serum endogenous compounds. As expected, there is no evidence of any effect of heparin anticoagulant on the bound fraction. Methohexital binding is strongly modified by the albumin concentration; the bound fractions change from 67 to 91% in the albumin range 150-900 microM.
Use of a postal questionnaire to estimate the likely under-diagnosis of asthma-like illness in adults.
BACKGROUND: Asthma is thought to be under-diagnosed. AIM: To estimate how many adults in two practices may have unknown asthma-like illness. METHOD: Results from a postal respiratory questionnaire, sent to 11,206 adults registered with two practices, were linked with practice records to identify patients who may have unknown asthma-like illness. RESULTS: The questionnaire replies were almost identical in both practices; 30.4% of respondents [95% confidence interval (CI) 29.4-31.4] reported wheezing and 14.1% (95% CI 13.3-14.9) had been woken by breathlessness during the previous year. Using a simple scoring system, 1112 (13.8%) of the respondents were judged possibly to have asthma-like illness; 529 (6.6%) had not previously been diagnosed as having asthma and had not received asthma treatments. CONCLUSION: The frequency of asthma-like symptoms was high. A large proportion of adults in the practices may have an unknown asthma-like illness which warrants further evaluation.
Psychologic distress and low back pain. Evidence from a prospective study in the general population.
STUDY DESIGN: The present is a prospective population-based cohort study. OBJECTIVES: To determine whether psychologic distress in patients free of low back pain predicts future new episodes of such pain. SUMMARY OF BACKGROUND DATA: An associating between symptoms of depression and anxiety and low back pain has been described in cross-sectional studies. It is unclear whether this represents cause or effect or whether it is found only in chronic pain sufferers attending specialist clinics. There is a need to investigate this prospectively in the general population. METHODS: The study population was 4501 adults aged 18-75 years who responded to a questionnaire survey mailed to all those registered with two family practices in the United Kingdom. The survey inquired about low back pain during the previous month and included the 12-item General Health Questionnaire, a validated schedule for measuring psychologic distress in the general population. New episodes of low back pain during the 12 months after the survey were identified by two methods--continuous monitoring of all primary care consulters and a second postal survey at the end of the 12-month period to determine occurrences for which consultation had not been sought. RESULTS: Among 1638 subjects free of current low back pain in the baseline survey, the likelihood of developing a new episode of nonconsulting low back pain was higher among those with General Health Questionnaire scores in the upper third of the range compared with the lower third (adjusted odds ratio, 1.8 [1.4, 2.4]). This could not be explained either by age and gender differences or by general physical health. The increased risk persisted when analysis was restricted to those who at baseline could not recall ever having had low back pain in the past and to those with full-time employment. CONCLUSION: Symptoms of psychologic distress in individuals without back pain predict the subsequent onset of new episodes of low back pain. We calculate from these data that the proportion of new episodes of low back pain that might be attributable to such psychologic factors in the general population is 16%.
Estimating the prevalence of low back pain in the general population. Evidence from the South Manchester Back Pain Survey.
STUDY DESIGN: This report gives the results of a population-based cross-sectional mailed questionnaire, with prospective follow-up of survey responders and nonresponders. OBJECTIVE: To determine the 1-month period prevalence of low back pain in an adult population in the United Kingdom and to estimate the effect of nonresponse bias. SUMMARY OF BACKGROUND DATA: Previous United Kingdom population studies have reported a 1-year period prevalence of low back pain of 37%. However, the definitions of low back pain have varied, and the influence of nonresponse rarely has been reported. METHODS: The study population was made up of all 7669 adults (18 to 75 years old) registered with two family practices in a sociodemographically mixed suburban area. The questionnaire, including a pain drawing to identify the site of any pain, was mailed to the entire study population. Two repeat mailings were sent to nonresponders. Family practice consultations about low back pain by individuals from the study population were monitored over the following 12 months using computerized records of all surgery contacts. RESULTS: Of the study population, 4501 (59%) responded. The 1-month period prevalence of low back pain was 39% (35% in males, 42% in females). The age distribution was unimodal, with peak prevalence in those aged 45 to 59 years old. Responders to the first mailing had a small but nonsignificant increase in prevalence compared with those who responded to the second or third mailing. Nonresponders had a subsequent consultation rate for low back pain that was 22% lower than that for the survey responders. CONCLUSIONS: After considering potential differences in nonresponders, the estimated 1-month prevalence of low back pain was between 35% and 37%. Prevalence figures in survey responders may overestimate the true population prevalence by a modest amount.
Number of children as a risk factor for low back pain in men and women.
OBJECTIVE: To estimate the influence of the number of liveborn children on the risk of low back pain. METHODS: The study design was a cross-sectional population-based survey. The 4,501 respondents to a postal survey were asked to provide data on the occurrence of low back pain and on any children they had. Data on some potential confounding variables were also obtained. RESULTS: There was an increased risk of low back pain in those who were married compared with those who were unmarried, among both men (odds ratio 1.7) and women (odds ratio 1.6). Among married individuals, there was a linear trend of increasing risk with increasing numbers of children. CONCLUSION: The risk of low back pain is related more to childrearing than to childbearing, although this effect might be partially mediated by unknown confounders associated with increasing family size.
Assessment of the practicality and safety of thrombolysis with anistreplase given by general practitioners.
BACKGROUND: Recent guidelines recommend that patients with obvious acute myocardial infarction receive thrombolysis, unless contraindicated, within 60-90 minutes of summoning assistance. If this target is to be achieved, an increasing number of general practitioners are likely to be involved in the administration of thrombolytic agents. AIM: This study aimed to assess the practicality and safety of thrombolysis with anistreplase when given by general practitioners. METHOD: An observational study was conducted in 805 general practices throughout the United Kingdom. Between March 1991 and September 1992, a total of 3383 patients with a clinical diagnosis of myocardial infarction were recruited--888 by 344 general practitioners who wished to include anistreplase in their management of myocardial infarction ('user' group) and 2495 by 776 general practitioners who did not wish to use anistreplase but who were willing to provide information about their cases ('comparison' group). RESULTS: More than half the patients were seen within two hours of onset of symptoms. A high frequency of contra-indications to thrombolysis, diagnostic uncertainty, and other, mainly practical, reasons limited the number of occasions on which anistreplase was administered. Thus, only 310 patients were given anistreplase in the community. The general practitioners in the study used anistreplase safely. Their diagnostic accuracy was high (of the 310 patients given anistreplase 69% had a definite, possible or probably myocardial infarction, 4% a definite non-cardiac diagnosis), the number of patients given anistreplase in spite of a documented contraindication was small (seven patients), and the doctors appeared to be aware of potential bleeding problems associated with thrombolysis. In all cases, the complications of acute myocardial infarction appeared to be managed appropriately. CONCLUSION: General practitioners can use anistreplase both appropriately and safely in the early management of acute myocardial infarction. Recognized contraindications to thrombolysis and practicalities of diagnosis and drug administration may, however, limit the number of occasions on which anistreplase is used.
Agism as explanation for sexism in provision of thrombolysis.
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Effect of cardiopulmonary bypass on plasma concentrations of diltiazem and its two active metabolites.
Diltiazem is often used to prevent myocardial ischaemia during the perioperative period of coronary artery bypass surgery. The purpose of this study was to investigate the effect of cardiopulmonary bypass (CPB) on plasma concentrations of diltiazem and of its two main and active metabolites (N-monodemethyldiltiazem (N-desmethyldiltiazem) and desacetyldiltiazem). The patients were administered their usual treatment during the preoperative days. The last dose was administered immediately before anaesthesia. At the onset of CPB, a significant decrease in the plasma concentrations of diltiazem and its metabolites was observed, whereas the variation was slight and not significant when the plasma concentrations were corrected for haemodilution. These results confirm that the decrease observed at the initiation of the bypass procedure can be ascribed to the haemodilution induced by the CPB. During CPB, the concentrations of diltiazem and its metabolites remained constant suggesting that the rate of metabolism and excretion of the drug was altered during the bypass procedure. At the end of CPB, there was no increase of drug plasma concentrations suggesting that no redistribution of diltiazem from tissues to plasma occurred. Furthermore, this study shows that only 33% of subjects have therapeutic levels of diltiazem before anaesthesia, and that all subjects have subtherapeutic levels during and after the CPB. These results suggest that a higher chronic oral dose of the drug should be given in patients undergoing cardiac surgery with CPB.
[Staph saprophyticus urinary tract infection. Spontaneous remission is rare but pivmecillinam is effective].
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Comparison of the pharmacokinetics of methohexital during cardiac surgery with cardiopulmonary bypass and vascular surgery.
The aim of this study was to assess the pharmacokinetics of methohexital (ME) in major vascular surgery (VASC) and to compare these data with the pharmacokinetics of ME during hypothermic cardiopulmonary bypass (HCPB) (temperature: 28 degrees C) and normothermic cardiopulmonary bypass (NCPB) (temperature: 37 degrees C). An ME bolus (2 mg/kg) was administered to 8 VASC patients at the start of surgery and to 11 HCPB patients and 11 NCPB patients at the start of cardiopulmonary bypass (CPB). Twenty-one arterial blood samples were withdrawn over the following 24 hours for ME assays. All of the patients were given similar anesthesia (fentanyl, diazepam) and muscle relaxation (pancuronium). In the VASC group, ME total body clearance (TBC) was 6 +/- 2 mL/kg/min (mean +/- SD), which is less than in previous studies. When comparing HCPB and NCPB groups, elimination half-life (T1/2), TBC, volume of distribution (VD), area under the curve (AUC), and mean residence time (MRT) were similar. When comparing VASC and CPB patients, TBC and VD were greater in CPB patients than in VASC patients; thus, T1/2 (equal to 0.693 x VD/TBC) was similar. AUC was smaller in CPB patients because of hemodilution, but MRT was similar. It is concluded that ME clearance is lower in patients undergoing major vascular surgery than in healthy patients. The temperature and the duration of CPB do not seem to substantially influence the pharmacokinetics of ME when a bolus is administered. Parameters such as AUC, TBC, and VD appear modified by hemodilution during CPB; however, T1/2 and MRT, which allow comparisons between CPB and non-CPB patients, were similar in these patients.
[Plasma concentrations of diltiazem and its metabolites in coronary surgery: relation with preoperative treatment].
Preoperative oral administration of calcium channel blocking agents has been found ineffective to prevent perioperative myocardial ischaemia. Our hypothesis was that low plasma concentrations may account for this inefficiency. Twenty-three male patients, scheduled for surgical myocardial revascularisation, were administered their usual anti-anginal treatment, including 180 to 360 mg of diltiazem since more than one week. The usual dosage was given at 8.00 p.m. on the day before surgery. On the morning of surgery, after withdrawal of a first blood sample, 60 mg of diltiazem were administered per month before the induction of anaesthesia. The anaesthesia was obtained with fentanyl, midazolam or flunitrazepam, pancuronium and isoflurane as required. The cardiopulmonary bypass (CPB) was associated with total haemodilution with Ringer's Lactate and a membrane oxygenator. A second blood sample was withdrawn after CPB. Plasma concentrations of diltiazem and its two active metabolites, N-monodemethyldiltiazem (MA) and desacetyldiltiazem (M1), were assessed by HPLC. Plasma diltiazem concentrations decreased from 78 +/- 66 (mean +/- SD) to 51 +/- 42 micrograms.l-1 (p < 0.05) with wide individual variations. These concentrations were under therapeutic levels in 18 out of 23 patients before (p < 0.05) with wide individual variations. These concentrations were under therapeutic levels in 18 out of 23 patients before induction and in 22 patients after CPB. The metabolite/diltiazem ratios remained constant. A dosage-plasma concentration relationship was observed preoperatively with diltiazem and MA. It is concluded that plasma concentrations of diltiazem should be optimized preoperatively in order to prevent myocardial ischaemia.
Electrophysiologic effects of a potassium channel activator (pinacidil) on repolarization parameters in healthy volunteers: a surface ECG study.
About a quarter to a third of patients receiving pinacidil, a new cyanoguanidine vasodilator, show ECG changes, in particular T-wave modifications that sometimes mimic myocardial ischemia. To investigate these changes, we performed a randomized placebo-controlled trial in 10 carefully selected, healthy subjects who received single oral doses of either pinacidil (25 mg), quinidine (330 mg), and placebo. Quinidine, which induces specific modifications to the surface ECG signal, was used as an internal control. The complete experimental design involved five consecutive administrations of the drugs in random order: pinacidil (twice), quinidine (twice), and placebo (once), separated by a week-long washout period. Electrophysiologic data acquisition and signal analysis were performed with the Lyon vectocardiographic processing system. Pinacidil decreased T-wave amplitude (-0.26 +/- 0.1 mV) significantly as compared with placebo (-0.14 +/- 0.06 mV), but did not change the duration of the T-wave. Although the cardiac rate increased with pinacidil, the QTc interval remained constant. Conversely, quinidine did not modify the RR interval but significantly increased duration of the T-wave (+67 +/- 20 ms) and QTc interval (+53 +/- 13 ms) as compared with placebo (+17 +/- 13 and +18 +/- 11 ms). In addition, no specific ischemic changes to the T-loop were observed with pinacidil. The modifications to the surface ECG signal caused by pinacidil appear to be drug-specific and related to its electrophysiologic properties rather than involving any ischemic mechanism. Such an approach may be useful for describing morphologic ECG changes caused by new drugs and identifying possible underlying electrophysiologic mechanism(s), which should then be confirmed in further studies.
Factors associated with consultation length and characteristics of short and long consultations.
Consultation length illustrates how general practitioners balance contradictory concerns such as productivity and quality, listening to patients, and handling their own stress. Important factors for consultation length are list size, characteristics of doctors and patients, and character of the problem. The purpose of this study of 463 consultations was to describe factors that are associated with short and long consultations and to examine the relative influence on the consultation length of patients' age and sex, character of the problem, continuity, and the 'doctor's speed'. A questionnaire was used for both doctors and patients. Short consultations were often made by younger male patients about physical problems, while long consultations often were made by older patients about problems with both psychological and physical dimensions. The 'doctor's speed' explained 22.5%, character of the problem 11.6%, and patient's age 2.9% of the variation in consultation length.
[Substantial lowering of the limit for bacteriuria in lower urinary tract infections is unethical without sufficient documentation].
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Modified high-performance liquid chromatographic method for the determination of ganciclovir in plasma from patients with severe renal impairment.
Using the rapid and sensitive high-performance liquid chromatographic (HPLC) method previously described for the analysis of ganciclovir in plasma, we have observed an interfering peak which co-elutes with the peak of ganciclovir in plasma samples from heart-transplant patients with severe renal insufficiency. A slight modification of this method allows the separation of the two peaks. The modified HPLC method, presented in this paper, is suitable for the accurate determination of ganciclovir in plasma from patients with severe renal impairment.