Biomedical subjects
Publications and source records attributed to A J Mackaay.
If there is an indication for sympathectomy in the case of severe hyperhidrosis or rubeosis, in our opinion the posterior approach is preferable because of the advantages in surgical technique and anesthesia. Bilateral treatment can be accomplished in a single admission, with all the concomitant advantages.
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BACKGROUND: A high plasma homocysteine concentration is associated with increased risk of atherothrombotic disease. We investigated the effects of homocysteine-lowering treatment (folic acid plus vitamin B6) on markers of subclinical atherosclerosis among healthy siblings of patients with premature atherothrombotic disease. METHODS: We did a randomised, placebo-controlled trial among 158 healthy siblings of 167 patients with premature atherothrombotic disease. 80 were assigned placebo and 78 were assigned 5 mg folic acid and 250 mg vitamin B6 daily for 2 years. The primary endpoint was the development or progression of subclinical atherosclerosis as estimated from exercise electrocardiography, the ankle-brachial pressure index, and carotid and femoral ultrasonography. FINDINGS: Ten participants in the treatment group, and 14 in the placebo group dropped out. Vitamin treatment, compared with placebo, was associated with a decrease in fasting homocysteine concentration (from 14.7 to 7.4 micromol/L vs from 14.7 to 12.0 micromol/L), and in postmethionine homocysteine concentration (from 64.9 to 34.9 micromol/L vs from 64.8 to 50.3 micromol/L). It was also associated with a decreased rate of abnormal exercise electrocardiography tests (odds ratio 0.40 [0.17-0.93]; p=0.035). There was no apparent effect of vitamin treatment on ankle-brachial pressure indices (0.87 [0.56-1.33]), or on carotid and peripheral-arterial outcome variables (1.02 [0.26-4.05] and 0.86 [0.47-1.59], respectively). INTERPRETATION: Homocysteine-lowering treatment with folic acid plus vitamin B6 in healthy siblings of patients with premature atherothrombotic disease is associated with a decreased occurrence of abnormal exercise electrocardiography tests, which is consistent with a decreased risk of atherosclerotic coronary events.
A high serum total homocysteine (tHcy) level is an independent risk factor for cardiovascular disease. Because it is not known whether the strength of the association between hyperhomocysteinemia and cardiovascular disease is similar for peripheral arterial, coronary artery, and cerebrovascular disease, we compared the three separate risk estimates in an age-, sex-, and glucose tolerance-stratified random sample (n=631) from a 50- to 75-year-old general white population. Furthermore, we investigated the combined effect of hyperhomocysteinemia and diabetes mellitus with regard to cardiovascular disease. The prevalence of fasting hyperhomocysteinemia (>14.0 micromol/L) was 25.8%. After adjustment for age, sex, hypertension, hypercholesterolemia, diabetes, and smoking, the odds ratios (ORs; 95% confidence intervals) per 5-micromol/L increment in tHcy were 1.44 (1.10 to 1.87) for peripheral arterial, 1.25 (1.03 to 1.51) for coronary artery, 1.24 (0.97 to 1.58) for cerebrovascular, and 1.39 (1.15 to 1.68) for any cardiovascular disease. After stratification by glucose tolerance category and adjustment for the classic risk factors and serum creatinine, the ORs per 5-micromol/L increment in tHcy for any cardiovascular disease were 1.38 (1.03 to 1.85) in normal glucose tolerance, 1.55 (1.01 to 2.38) in impaired glucose tolerance, and 2.33 (1.11 to 4.90) in non-insulin-dependent diabetes mellitus (P=.07 for interaction). We conclude that the magnitude of the association between hyperhomocysteinemia and cardiovascular disease is similar for peripheral arterial, coronary artery, and cerebrovascular disease in a 50- to 75-year-old general population. High serum tHcy may be a stronger (1.6-fold) risk factor for cardiovascular disease in subjects with non-insulin-dependent diabetes mellitus than in nondiabetic subjects.
Cross-sectional associations between carotid artery stenosis (CAS) on the one hand, and parameters of glycaemia and specific insulin levels on the other, were investigated in an age, sex, and glucose tolerance stratified random sample from a 50-74-year-old Caucasian population. Subjects treated with insulin or oral hypoglycaemic agents were classified as having known diabetes mellitus (KDM) (n = 66). Using two oral glucose tolerance tests, and based on the World Health Organisation criteria, all other participants were classified as having a normal (NGT) (n = 287), an impaired (IGT) (n = 169) or a diabetic (NDM) (n = 106) glucose tolerance. CAS was defined haemodynamically using duplex scanning. The crude prevalences of only moderate (16-49%) CAS were 6.6%, 7.1%, 5.7% and 12.1% in NGT, IGT, NDM and KDM subjects, respectively. For any severe (> or = 50%) CAS, crude prevalences were 2.8%, 4.7%, 9.4% and 7.6%. The prevalence of any severe CAS was higher in NDM (p < 0.01) and KDM subjects (p = 0.07) than in NGT subjects. The prevalence of a history of stroke or transient ischaemic attack was 1.7%, 1.8%, 2.8% and 1.5% in NGT, IGT, NDM and KDM, respectively. In univariate logistic regression analysis, HbA1c, serum fructosamine, fasting and 2-h post-load glucose were significantly associated with any severe CAS. In multivariate analyses controlling for other risk factors, only HbA1c and 2-h post-load plasma glucose remained significantly associated (odds ratios: 1.29 per % and 1.09 per mmol/l, respectively) in separate models. No association could be shown between either fasting or 2-h post-load specific insulin and any severe CAS in either univariate or multivariate analyses. In conclusion, HbA1c and 2-h post-load plasma glucose are independently associated with any severe CAS, whereas specific insulin is not.
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OBJECTIVES: To study thrombin and plasmin activation during elective abdominal aortic aneurysm surgery. DESIGN: Prospective study. SETTING: University Hospital. MATERIALS: Nine consecutive patients undergoing elective surgery were included. The mean age was 72 years (range 60-79). Blood samples were drawn: (1) before induction of anaesthesia; (2) after induction and Swan Ganz catherisation; (3) just before cross-clamping; (4) before declamping; (5) 8 h postoperatively; (6) 18 h postoperatively. CHIEF OUTCOME MEASURES: Assays included: prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen, prothrombin fragments (F 1 + 2), anti-thrombin III (ATIII), plasminogen, alpha 2-antiplasmin, haematocrit, platelet and serum protein for correction of haemodilution. Data were expressed as mean (S.D.). Differences between mean values were tested by means of the ANOVA for repeated measures and the Wilcoxon signed rank test. MAIN RESULTS: The APTT and TT did not change until heparinisation. The F 1 + 2 were already elevated preoperatively. After correction for haemodilution the AT III and alpha 2-antiplasmin decreased in time (p = 0.009 and 0.0023, respectively) and the F1 + 2 increased (p < 0.0001). Postoperatively (t5 and 6) the values normalised again. CONCLUSIONS: The coagulation and fibrinolytic systems are activated during and after elective aortic replacement. Standard tests, like the prothrombin and partial thromboplastin time, are unreliable when assessing the coagulation status of the patient.
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Hyperhomocysteinemia (HHC) is associated with an increased risk of atherosclerotic vascular disease and may be inherited. Fasting and postmethionine HHC are independent risk factors that overlap to a limited extent. To study the familial occurrence of HHC, we investigated the prevalence of HHC (both fasting and after methionine) among 450 siblings of 167 consecutive young patients with vascular disease and postmethionine HHC. Furthermore, all subjects with postmethionine HHC (n = 125) were invited for noninvasive vascular testing; 101 (80.8%) agreed. Of those with a normal postmethionine plasma level (n = 325), we randomly selected 73 subjects for further studies; 53 agreed (72.6%). Thus, a total of 154 siblings underwent ultrasonography of the carotid arteries, measurement of ankle-brachial pressure indices at rest and after a treadmill exercise test, and exercise electrocardiographic stress testing. We observed HHC after methionine, fasting, or both, in 27.8% (95% CI, 23.7 to 31.9), 11.1% (CI, 8.2 to 14.0) and 8.7% (CI, 6.1 to 11.3) of the siblings. Abnormal peripheral, coronary, or carotid artery tests were observed in 35.7% (CI, 28.1 to 43.3), 7.1% (CI, 3.0 to 11.2), and 7.1% (CI, 3.0 to 11.2). Univariate and multivariate analyses revealed weak evidence of a relationship with homocysteine levels. In conclusion, we found a high prevalence of HHC and asymptomatic vascular disease in siblings of young patients with vascular (mainly peripheral arterial) disease and HHC. Our data raise the possibility that homocysteine does not play a major role in the early, asymptomatic phases of vascular disease, at least among siblings of young patients with vascular disease.
We investigated the cross-sectional association between peripheral arterial disease and glycaemic level in an age, sex, and glucose tolerance stratified random sample from a 50-74-year-old Caucasian population. Subjects treated with oral hypoglycaemic agents or insulin were classified as having known diabetes mellitus (KDM) (n = 67). Using two oral glucose tolerance tests, and based on World Health Organisation criteria, all other participants were categorized as having a normal (NGT) (n = 288), an impaired (IGT) (n = 170), or a diabetic (NDM) (n = 106) glucose tolerance. Prevalence rates of ankle-brachial pressure index less than 0.90 were 7.0%, 9.5%, 15.1% and 20.9% in NGT, IGT, NDM and KDM subjects, respectively (chi-square test for linear trend: p < 0.01). Prevalence rates of any peripheral arterial disease (ankle-brachial pressure index < 0.90, at least one monophasic or absent Doppler flow curve or vascular surgery) were 18.1%, 22.4%, 29.2% and 41.8% in these categories (chi-square test for linear trend: p < 0.0001). The prevalence of any peripheral arterial disease was higher in KDM and NDM than in NGT (p < 0.03, p < 0.0001, respectively), whereas no statistically significant difference was demonstrated between IGT and NGT. The same applied when using the ankle-brachial pressure index criterion. Logistic regression analyses showed that any arterial disease was significantly associated with HbA1c, fasting and 2-h post-load plasma glucose after correction for cardiovascular risk factors (odds ratios and 95% confidence intervals 1.35; 1.10-1.65 per %, 1.20; 1.06-1.36 and 1.06; 1.01-1.12 per mmol/l, respectively), whereas it was not associated with fasting and 2-h post-load specific insulin. Ankle-brachial pressure indices were not associated with either plasma glucose parameters or insulin in univariate or multivariate analyses. In conclusion, parameters of glucose tolerance are independently associated with any peripheral arterial disease, whereas insulin is not.
OBJECTIVES: To study the distribution of peripheral vascular disease and the relationship to diabetes. DESIGN: Prospective population based study of Dutch caucasian inhabitants. METHODS: From a total of 10,500 subjects aged between 50 and 75 years, 2484 Caucasian inhabitants were screened with respect to their glucose tolerance. Subjects using oral antidiabetic agents or insulin were classified directly as having diabetes mellitus. The other participants were screened using two oral glucose tolerance tests and classified using WHO criteria. A group of 173 people with diabetes and a representative age/sex stratified sample of 288 non-diabetic subjects were seen in the vascular laboratory. Carotid artery disease was investigated with Duplex scanning, arm and leg artery obstructions with real time frequency analysis of continuous wave Doppler signals and indirect blood pressure measurements. RESULTS: Comparing diabetic with non-diabetic subjects, we found significantly more obstructions of the carotid arteries (8.7 vs 2.8%), arm arteries (2.3 vs 0%), as well as leg arteries (31.8 vs. 18.4%). The same holds if only the crural artery obstructions were compared (23.7 vs 16.0%). Two of the four diabetic subjects with arm artery obstructions had retrograde vertebral flow, three of them had carotid artery obstructions as well, and three also had leg artery obstructions. More than half of the subjects with a carotid artery obstruction, also had leg artery obstructions. CONCLUSIONS: Peripheral vascular disease is common in diabetes, but most are asymptomatic.
The records of 28 patients who underwent free jejunal graft reconstruction after resection for cancer involving the pharynx were analysed. Seven patients had a T3 carcinoma, 15 patients T4 and six patients recurrence after laryngectomy. Ten patients had received radiotherapy in the past. Post-operatively, 15 patients (54%) had complications and two patients (7%) died. No significant difference was observed in the complication rate between the group that received radiotherapy in the past and those who did not. Nineteen patients received post-operative radiotherapy. Nine patients had no radiotherapy on the basis of complete resection or because of serious complications. For the whole group the 2-year recurrence free period and survival were 42% and 51% respectively. The post-operative radiotherapy group had a significantly better survival (73%) and recurrence free period (63%) than the group without post-operative radiotherapy (0%). Thus, post-operative radiotherapy seems indicated irrespective of resection margins.
Ascending phlebothrombosis of the lower extremities can have serious consequences if not identified at an early stage. In the Academic Hospital of the Free University, Amsterdam, 18 patients with this disease were seen in the period 1980-1991. Treatment should be aimed at preventing progression of the disease to the deep venous system. This may necessitate ligation and dissection of the V. saphena magna in the groin. Usually conservative treatment will do, provided regular follow-up is performed to see whether progression has taken place to the hiatus saphenus or the popliteal fossa. As the disease has usually progressed further than the clinical signs indicate, duplex scanning should be used in case of doubt. Progression to the deep system should immediately be treated surgically.
The kinetics of systemically and locally administered cefuroxime or ceftazidime in wound fluid were investigated in the period after vascular prosthetic implantation. Cefuroxime or ceftazidime was administered intravenously in patients. Simultaneously 250 mg ceftazidime or cefuroxime was added to preclotted blood. Locally administered antibiotics could not be detected in our samples. In groin fluid samples 24-48 h after the operation the average concentration of cefuroxime was 8.3 and of ceftazidime 5.0 mg/l. The decline of the concentration of cefuroxime or ceftazidime in groin fluid seems to be much slower than one would expect from the half-lives of the antibiotics. We conclude that cefuroxime and to a lesser extent ceftazidime are suitable as prophylactic agents in arterial reconstruction.
The primary pacemaker, i.e. the group of pacemaker cells discharging the sinoatrial node comprises less than 1000 cells in the guinea-pig and about 5000 cells in the rabbit. These primary pacemaker cells are described as 'central nodal' cells in light microscopy and as 'typical nodal' cells in electron microscopy. The action potential of the leading cells has a higher upstroke velocity in the guinea-pig than in the rabbit (6.2 v. 1.9 V/s). Gap junctions have been observed even in the very center of the node in both species. A zone of double-component action potentials at the septal margin of the node was observed in the rabbit, but not in the guinea-pig. Evidence is presented for abrupt transitions in electrophysiological as well as in ultrastructural characteristics in the guinea-pig sinoatrial node. The differences in intrinsic cycle length between both species but also between individuals of the same species are discussed.
Under the influence of adrenaline (Adr) and acetylcholine (Ach), pacemaker dominance in the sinoatrial node moves from one site to another. The Adr-center is located in the inferior part of the sinoatrial node. The Ach-center, an elongated cell group in the periphery of the sinoatrial node, is located nearer to the crista terminalis and is often more caudally located than the leading center under standard conditions. Under the combined influence of Ach and Adr, the Ach-center is dominant. The sinoatrial node preparation shows a cycle length-dependent chronotropic response to Adr. A greater shortening of cycle length is related to a longer basic cycle length. This agrees with previously reported findings concerning the positive chronotropic action of high calcium. The chronotropic response to Ach is not cycle length-dependent. In the presence of Ach, the effect of Adr remains cycle length dependent, although no shift of the pacemaker occurs. This demonstrates that cycle length dependence of chronotropic responses can be the property of one and the same cell group, and is not necessarily caused by different chronotropic responses of different cell groups.
The rabbit sinoatrial node is functionally inhomogeneous with respect to its response to changes in Mg concentration (0.6 to 6.0 mmol X litre-1) and in Ca concentration (1.1 to 2.2 mmol X litre-1) and to changes in experimental temperature (30 to 38 degrees C). High Mg (6.0 mmol X litre-1) stabilises the position of the leading pacemaker. This pacemaker decelerates under high Mg, but the subsidiary ones decelerate even more. Consequently when a subsidiary pacemaker turns dominant--eg under low Ca or at low temperature--an enhanced chronotropic response to high Mg is observed. The superior (cranial) part of the rabbit sinoatrial node is more responsive to changes in Ca concentration than the inferior (caudal) part. The same holds true for changes in temperature.
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