Bedside diagnosis of persistent post-sternotomy pain.

BACKGROUND: The prevalence of persistent post-sternotomy pain (PPSP) varies largely and has been mainly studied using questionnaires. We decided to perform a systematic qualitative and quantitative sensory examination study on a power-calculated sample of patients who had undergone sternotomy for cardiac surgery. Pain was diagnosed as PPSP if the patient complained of sternal pain that had developed after surgery together with corresponding sensory disturbances. PATIENTS AND METHODS: One hundred elective patients undergoing coronary artery bypass via sternotomy were recruited for dynamic sensory mapping 4-6 months after surgery. Sensory testing was performed using thermal rollers, a cotton stick and pinprick. The intensity of sensation was registered as a score on a numeric rating scale. The area of sensory dysfunction on the chest wall was traced onto paper and calculated with the help of a computer-based program. The patient also answered a validated pain questionnaire. RESULTS: Altogether 90 patients took part in the examination. Thirteen (15.4%) of the patients had pain and formed the PPSP group, while the remaining patients formed the non-PPSP group. Both groups had sensory abnormalities over the chest wall (69% of all patients). Sensory disturbances were more common, more profound and extended over a larger skin area in the PPSP group. Furthermore, daily activity performance in the PPSP group was poorer compared to the non-PPSP group. CONCLUSION: PPSP is a clinical diagnosis easily achieved using simple diagnostic tools and a medical history. Severity and extent of sensory abnormalities were found to be greater in the PPSP group.

Postoperative hyperalgesia does not predict persistent post-sternotomy pain; observational study based on clinical examination.

BACKGROUND: Persistent post-sternotomy pain is a common problem, but the risk of developing it varies among patients. We sought to find out whether the risk of persistent post-sternotomy pain could be predicted by measuring the area of acute sensory dysfunction around the sternotomy wound. The secondary aim was to determine risk factors for persistent post-sternotomy pain. PATIENTS AND METHODS: Hundred patients who were scheduled to undergo elective coronary artery bypass surgery were recruited to the study. Patients were excluded if they had undergone previous cardiac surgery or if they lacked co-operation. Preoperative pain scores were determined and the patients filled in questionnaires about depression, anxiety, and pain. The area of sensory dysfunction around the sternotomy wound was assessed by pin prick on postoperative day 4. The presence of persistent post-sternotomy pain was determined at a follow-up evaluation at 4-6 months after surgery. RESULTS: The sizes of the area of hyperalgesia or overall sensory dysfunction were not associated with persistent post-sternotomy pain. Independent risk factors for persistent post-sternotomy pain were found to be smoking and high pain score on postoperative day 1. The prevalence of persistent post-sternotomy pain in our study population was 38% analyzed by only the questionnaire and 15% according to the clinical examination. CONCLUSION: Measuring the area of hyperalgesia in the acute phase does not give any additional information on the risk of developing a persistent post-sternotomy pain. We do thus not recommend measuring the area in this particular group of patients. Evaluation of pain by only a questionnaire risks to overestimate the presence of persistent post-sternotomy pain as compared to clinical examination.

Preoperative levosimendan infusion in combined aortic valve and coronary bypass surgery.

BACKGROUND: Cardiopulmonary bypass may have detrimental effects on intestinal function and decrease the concentrations of the active, long-acting metabolites of levosimendan, an inodilator used to improve cardiac function. The aim of this study was to evaluate the haemodynamic effects of preoperative levosimendan in patients undergoing high-risk cardiac surgery. METHODS: Twenty-four patients were randomized to receive levosimendan (12 µg bolus followed by an infusion of 0.2 µg kg(-1) min(-1)) or a placebo 24 h before surgery. The inclusion criteria were left ventricular ejection fraction (LVEF) <50% or LV hypertrophy indicated by a wall thickness of >12 mm. Haemodynamics were recorded every hour for 24 h (pulmonary artery catheter) and daily until postoperative day 4 (whole-body impedance cardiography). Doppler echocardiography with tissue Doppler imaging was used to assess systolic and diastolic cardiac function. RESULTS: The cardiac index (CI) and stroke volume index (SI) were higher in the levosimendan group (LG) for the 4 day postoperative period (P<0.05); on the fourth postoperative day, the CI was 3.0 litre m(-2) min(-1) in the LG compared with 2.4 litre m(-2) min(-1) in the control group (CG) and the SI was 30 vs 25 ml m(-2), respectively. The LVEF measured at baseline and on the fourth postoperative morning decreased in the CG, but was maintained in the LG. CONCLUSIONS: Levosimendan improved haemodynamics compared with a placebo in patients undergoing high-risk cardiac surgery. The concentrations of levosimendan's metabolites were higher compared with earlier studies using perioperative dosing.

Impetigo herpetiformis occurring during N-butyl-scopolammonium bromide therapy in pregnancy: case report.

Impetigo herpetiformis (IH) is a rare dermatosis arising during the third trimester of pregnancy which is generally considered as a form of pustular psoriasis of unknown aetiology. Clinically it is characterized by erythematous plaques surrounded by sterile pustules associated with fever, diarrhea, sweating and increasing risk of stillbirth for placental insufficiency. We describe a case of developed erythematous plaques surrounded by pustules localised initially to the trunk of a 35-year-old woman at the 34th week of gestation after 5 days of treatment with N-Butyl-Scopolammonium, and which later involved the upper and lower limbs. Skin histology confirmed the diagnosis of generalised pregnancy pustular psoriasis (impetigo herpetiformis). IH is reported to be associated with hypocalcemia, hypoparathyroidism, use of oral contraceptives and bacterial infections. This is the first report suggesting the potential role of drugs other than oral contraceptives in the pathogenetic mechanism of this disease. In this case an adverse cutaneous reaction to BB could be the cause of the development of Koebner isomorphism.

Pre-operative oral carbohydrate treatment before coronary artery bypass surgery.

BACKGROUND: Cardiac surgery is a stress that causes insulin resistance, which leads to an increase in insulin requirement. The aim of the present study was to evaluate the effect of a pre-operative oral carbohydrate drink vs. overnight fasting on perioperative insulin requirements in non-diabetic patients undergoing elective coronary artery bypass grafting (CABG) surgery. METHODS: One hundred and one patients scheduled for CABG were enrolled in the study. After fasting overnight, the patients were randomised into two groups. In the control group (C), no drink was given in the morning. In the treatment group (T), the patients ingested 400 ml of carbohydrate fluid 2 h before induction of anaesthesia. Blood glucose and insulin requirement was recorded. Gastric drainage was measured. Post-operative nausea and vomiting was recorded. RESULTS: Neither the number of patients requiring insulin nor the amount of insulin required to maintain normoglycaemia differed between the study groups. More patients in the treatment group experienced nausea post-operatively (26 vs. 16, P=0.044), but vomiting was equally common in the study groups (10 vs. 7). Intra-operative gastric drainage was 26.8+/-57.9 ml in the treatment group vs. 16+/-37.9 ml in the control group (NS). CONCLUSION: In this study patient population, a pre-operative oral carbohydrate drink did not reduce post-operative insulin resistance or post-operative nausea and vomiting. According to our findings, it is safe to allow cardiac surgery patients to drink clear fluids up to 2 h before induction of anaesthesia, because gastric emptying of the drink was almost total and no aspiration occurred.

Incidence of varicose veins in Finland.

BACKGROUND: Incidence of varicose veins in the population is unknown. The study aimed at estimating the incidence of varicose veins in complete cohorts of 40-60 year-olds in a general population. PATIENTS AND METHODS: The study was conducted in the city of Tampere, Finland. A validated questionnaire (with 93% sensitivity and 92% specificity) was used in a general population of 6874 individuals (aged 40, 50 or 60). Initially, 3065 of them had no varicose veins and 78% were followed-up for 5 years. RESULTS: 157 individuals reported new varicose veins during the follow-up. The overall incidence was 13.5 per 1000 person years (8.5 for men and 19.2 for women). Female sex was an independent and statistically significant risk indicator of varicose veins (adjusted odds ratio, OR 2.4). The incidence was significantly higher at the age of 50-55 years (OR 1.6). Higher body mass index seemed to be related to higher risk of new varicose veins (OR 1.2-1.8), but the association failed to reach statistical significance. The level of education did not affect the incidence. CONCLUSIONS: New varicose veins appear also in the middle-aged population, and the rate is linked with the female gender, especially at the beginning of the 6th decade.

Serum matrix metalloproteinase-9 concentration in angiographically assessed coronary artery disease.

Expression of several matrix metalloproteinases (MMPs) in atherosclerotic plaques has been well documented, and there are findings to indicate that arterial inflammation is reflected in increased serum concentration of matrix metalloproteinase-9 (MMP-9). In coronary atherosclerosis, there is enhanced expression of this MMP, which may be predictive of the severity of the disease. We determined the concentrations of serum MMP-9 in 61 patients (47 males, 14 females) who had >50% obstruction in one or more coronary arteries as assessed by coronary angiography before bypass surgery. In a control group of 19 patients (9 males, 10 females) there were no pathological findings in coronary angiography. ANOVA showed that serum MMP-9 concentrations were highest in patients with 3-vessel coronary artery disease (CAD) (57.3+/-39.1 microg/L, p=0.011). The difference remained statistically significant after adjustment for age, diabetes and sex (p=0.025, ANCOVA). When the groups were compared with each other, serum MMP-9 concentration was higher in the patients with 3-vessel CAD than in those with 1- or 2-vessel CAD (40.4+/-25.1 microg/L, p=0.044) or in the controls (32.2+/- 16.1 microg/L, p=0.007). These results show that serum MMP-9 is elevated in patients with severe coronary stenosis compared with controls. Since MMP-9 has been suggested to reflect inflammation in atherosclerotic plaques, it may be useful in the evaluation of the severity of cardiovascular disease.

Methylenetetrahydrofolate reductase gene C677T mutation is related to the defects in the internal elastic lamina of the artery wall.

BACKGROUND: The C677T mutation of the methylenetetrahydrofolate reductase (MTHFR) gene leads to C/C, C/T and T/T genotypes, which affect the plasma homocysteine concentration in humans. In mini-pigs, high serum homocysteine levels are associated with defects in the internal elastic lamina (IEL) of the artery wall, which are apparently related to the migration of smooth muscle cells into the intima during atherogenesis. We studied the association between the MTHFR genotypes and the number of gaps in the IEL in the wall of the five major abdominal arteries. MATERIALS AND METHODS: The autopsy study included 123 subjects (90 males and 33 females) aged 18-93. For the light microscopy, a 0.5 cm circular segment of the coeliac, the superior mesenteric, the inferior mesenteric and the renal arteries were cut and embedded in paraffin blocks. The circumference of the IEL, the thickness of the intima and the number of the gaps per millimetre in the IEL were measured by MOP 3 image analysis. RESULTS: The T-allele carriers (C/T and T/T) of the MTHFR gene had significantly less gaps in the IEL than the subjects with the C/C genotype in the superior mesenteric and in the left renal arteries (2.02 +/- 2.25 vs. 2.53 +/- 1.89, P < 0.04 and 0.56 +/- 1.09 vs. 1.82 +/- 2.66, P < 0.02, respectively). The trend was similar for the coeliac and the right renal arteries. CONCLUSIONS: Our result suggests that MTHFR polymorphism may be involved in the fragmentation of the IEL.

Paraoxonase producing PON1 gene M/L55 polymorphism is related to autopsy-verified artery-wall atherosclerosis.

Paraoxonase (PON) is an antioxidative enzyme, which eliminates lipid peroxides. PON has two common polymorphisms (M/L55 and R/Q192) that influence PON concentration and activity. We studied whether the M/L55 or R/Q192 genotype relates with the severity of atherosclerosis of the abdominal aorta, and the mesenteric and common iliac arteries in 123 consecutive autopsy cases (90 males and 33 females, aged 18-93 years). The severity of atherosclerosis in the arteries was evaluated, and the percentage of stenosis was measured. The intimal thickness in the internal elastic lamina (IEL) of the coeliac (CA), superior mesenteric (SMA) and inferior mesenteric (IMA) arteries were measured by light-microscopy. The LL homozygous men had more atherosclerotic plaques and complicated lesions in the common iliac arteries (56.8%) than the M allele carriers (28.3%, P=0.007). In logistic regression analysis, age (P<0.001) and the PON M/L55 genotype (P=0.015) were associated significantly with the severity of atherosclerosis in the common iliac arteries independent of smoking status, R/Q192 genotype, hypertension, diabetes mellitus, BMI and sex. The mean intima of the IMA was significantly thicker (P=0.035) and the number of stenotic lesions in SMAs significantly higher (P=0.008) in the LL homozygous men than M allele carriers. In turn, the R/Q192 genotype was not statistically significantly associated with plaque type, intimal thickness in the IEL or with the number of stenotic lesions. This study demonstrates that PON L55 homozygosity is an independent risk factor for autopsy-verified atherosclerosis in Finns.

Incidence of deep venous thrombosis after thoracotomy.

BACKGROUND: Incidence of deep venous thrombosis (DVT) after thoracotomy has not been widely studied. DVT is a frequent complication in major surgery involving abdominal and pelvic areas and lower extremities. The aim of the present study was to evaluate the rate of postoperative DVTs after surgery of the lung. METHODS: In this prospective study with 25 patients undergoing thoracotomy both legs were studied with venous duplex imaging (VDI) preoperatively and on the second postoperative day. Clinically manifest thromboembolic events during one-month postoperative period were reviewed from the patients' records. DVT prophylaxis included compression stockings and early mobilization without low-molecular weight heparin. RESULTS: Frequency of postoperative DVTs was 4%. There were no clinically manifest thromboembolic events during one-month postoperative period. In 8% of the patients an old DVT was found preoperatively. CONCLUSIONS: Based on this material, incidence of DVT is low after thoracotomy. Early mobilization and the use of compression stockings may be a sufficient form of prophylaxis in these patients. The relatively small sample size and the use of ultrasound as a screening method should be noted in judging the results.

Apolipoprotein E polymorphism and atherosclerosis: association of the epsilon4 allele with defects in the internal elastic lamina.

The defects in the internal elastic lamina (IEL) have been proposed to be important for the migration of smooth muscle cells into the intima during atherosclerosis. We investigated the association of a genetic factor--apolipoprotein E (apoE) genotype--with the number of gaps in the IEL of the artery wall in 123 consecutive autopsy cases (90 male, 33 female) aged 18-93. At autopsy, the circumference of the IEL and the number of gaps in the IEL were measured in circular samples of the coeliac; (CA), superior mesenteric (SMA) and inferior mesenteric (IMA) arteries. In the series, the number of gaps per millimetre in the IEL of CA, SMA and IMA were associated with intimal thickening (P<0.0001, P=0.01 and P=0.005, respectively). In men, apoE genotype was significantly associated with the number of gaps in the IEL of the CA and IMA (P=0.033 and P=0.041, respectively). The carriers of epsilon4/3 or epsilon4/4 genotype had higher number of gaps in CA than the carriers of epsilon3/3 genotype (2.30+/-2.63 vs. 1.38+/-1.83 gaps/mm, P=0.035) and also higher number of gaps in IMA than the carriers of epsilon3/2 (2.18+/-1.71 vs. 0.66+/-0.60 gaps/mm, P=0.041). The results suggest that the apoE varepsilon4 allele may be involved with IEL fragmentation in men. This may be mediated through higher serum cholesterol associated with the varepsilon4 allele.

Allopurinol does not increase free radical scavenging capacity during reperfusion in coronary artery bypass graft patients.

OBJECTIVES: Allopurinol protects the heart against ischaemic events during coronary artery bypass grafting (CABG), possibly because of its antioxidant properties. This double-blind study was designed to investigate whether allopurinol (1 g), given before cardiopulmonary bypass and prior to the opening of cross-clamping, has an antioxidant effect in CABG patients by measuring plasma total peroxyl radical scavenging capacity. DESIGN: Twenty-seven patients with stabile angina were randomized into allopurinol (n = 14) or placebo (n = 13) groups. RESULTS: During 10 min reperfusion, plasma hypoxanthine and xanthine concentrations increased only in the allopurinol group, whereas uric acid concentrations decreased. Total peroxyl radical scavenging capacity (TRAP) decreased from the initial value at all measuring points in both groups. CONCLUSIONS: The reducing effect of allopurinol on free radical generation cannot be seen in TRAP values, obviously because the uric acid concentration of plasma decreases markedly. The positive clinical effects of allopurinol in CABG patients may arise from its direct oxygen free radical scavenging function.

The occurrence of the post-thrombotic changes after an acute deep venous thrombosis. A prospective two-year follow-up study.

BACKGROUND: The aim of the study is to investigate the development of subjective and objective findings during the first two years after DVT (deep venous thrombosis). METHODS: This prospective two-year follow-up study was established in Tampere University Hospital in Finland. Twenty-six patients with a two-year follow-up after a phlebographically confirmed DVT were followed. Patients were treated conventionally with heparin and warfarin. Phlebography was repeated 7 months after DVT. Color-flow duplex imaging (CFDI) was performed in both legs 7 and 20 months after DVT. The subjective symptoms in both legs were recorded at the beginning and at the end of the follow-up. The development of venous reflux, obstruction and subjective symptoms after DVT were studied. RESULTS: 50% of the legs with DVT had a pathological (deep reflux or obstructive change) CFDI-finding in the popliteal segment after a 20-month follow-up. The pathological findings in the control legs were rare. The rate of recanalisation was high. There was no difference between calf and more proximal DVTs. Pain (62%), oedema (46%) and pigmentation (35%) were common and only 27% of the legs with DVT were asymptomatic. CONCLUSIONS: The development of the post-thrombotic syndrome begins quite early. The frequency of the subjective symptoms is high. Calf DVT may lead to postthrombotic sequelae in the popliteal segment.

Effect of allopurinol on myocardial oxygen free radical production in coronary bypass surgery.

OBJECTIVES: Allopurinol protects the heart from reperfusion injury. The aim of this study was to investigate myocardial free radical production during reperfusion with and without allopurinol treatment in coronary artery bypass grafting patients randomized into allopurinol (n = 14) or placebo (n = 13) groups. DESIGN: Allopurinol (1 g) was given blind prior to cardiopulmonary bypass and prior to opening the aorta. Oxygen free radicals were measured before anesthesia in arterial blood, before cross-clamping and 1 and 10 min after reperfusion in arterial and coronary sinus blood. Levels were measured as relative concentrations by the electron spin resonance method. RESULTS: One minute after reperfusion the level of spin-trapped radicals in arterial blood was elevated significantly (p = 0.016) in the allopurinol group, from 7.7 (SE: 0.8) to 8.6 (1.4) and non-significantly (p = 0.074) in the placebo group, from 7.3 (0.7) to 8.3 (0.8). Ten minutes after reperfusion the arterial values were 8.6 (1.5) in the allopurinol and 7.6 (0.7) in the placebo group, the sinus values being 7.6 (1.3) and 8.3 (0.8), respectively. Myocardial free radical production was -0.94 (1.21) in the allopurinol and +0.79 (0.96) in the placebo group after 10 min reperfusion, the difference being significant (p = 0.043). CONCLUSIONS: All patients in both groups had an increasing tendency to free radical production during early reperfusion. Patients treated with allopurinol showed less myocardial production of free radicals, indicating that its protective effect may be due to its antioxidative properties.

The incidence and cardiovascular risk indicators of deep venous thrombosis.

BACKGROUND: To estimate the incidence and associated risk indicators of deep venous thrombosis (DVT) in the lower extremities. PATIENTS AND METHODS: A population-based 5-year follow-up study with self-administered questionnaire. The study included 5568 persons at the beginning, with a follow-up of 17,005 person-years. A questionnaire was sent to all residents in the city of Tampere, Finland, born in 1929, 1939 and 1949. In the first survey the number of participants was 5568 and in the second questionnaire 4903. The participation rates were 83% and 88%. RESULTS: The incidence of DVT was 140 per 100,000 person-years. The life-time prevalence of DVT was 3.1%. In a univariate analysis, the appearance of a new DVT during the follow-up time (incidence) was statistically significantly associated with pre-existing varicose veins, sex-steroid therapy, heart failure and arterial insufficiency in the lower limbs. In multivariate analysis varicose veins, arterial insufficiency in the lower limbs and sex-steroid therapy remained as significant risk factors associated with DVT. CONCLUSIONS: The study confirms that the incidence of DVT in Finland is close to the estimates in other Western populations. Pre-existing varicose veins, sex-steroid therapy and arterial insufficiency in the lower limbs are independent risk factors for DVT in our population-based study.

Accumulation of bisphosphonates in human artery and their effects on human and rat arterial function in vitro.

Clodronate, etidronate and pamidronate are bisphosphonates introduced in the treatment of hypercalcaemia and osteoporosis. Interestingly, they also inhibit development of experimental atherosclerosis and affect smooth muscle tone of isolated rat tail artery. We have studied in vitro whether these hydrophilic compounds 1) accumulate in the wall of the human artery, 2) influence human arterial tone, and 3) interfere with the vascular action of L-type Ca2+ antagonists. Human internal mammary artery rings were incubated with 14C-labelled bisphosphonates. After a 2-hr incubation, the ratios of artery-to-incubate concentrations with 4 and 40 mumol/l of clodronate were, respectively, 3.0 +/- 0.5 (mean +/- S.E.M.) and 1.3 +/- 0.2, with 4 and 40 mumol/l of etidronate 7.4 +/- 0.9, and 3.2 +/- 0.4, and with 0.4 and 4 mumol/l of pamidronate 4.7 +/- 0.7 and 3.9 +/- 0.8. Both tested bisphosphonates, clodronate and pamidronate, reduced the arterial contractile force induced by alpha-adrenergic stimulation with noradrenaline and membrane depolarization with high concentration of KCl. Clodronate also decreased the arterial contraction induced by cumulative addition of Ca2+ with KCl as the agonist, and had an additive inhibitory effect on this response with the L-type Ca2(+)-channel blocker nifedipine. The results demonstrate that 1) bisphosphonates accumulate markedly in human artery, 2) clodronate and pamidronate reduce human arterial contactile force to alpha-adrenergic and depolarizing stimuli, and 3) as shown with clodronate, bisphosphonates may exert an additive inhibitory effect on human arterial contractions with an L-type Ca2(+)-channel blocker.

Postoperative hyperamylasaemia in cardiac surgery.

The mechanism of postoperative hyperamylasaemia was studied in 48 patients undergoing coronary artery bypass grafting (CABG). Mild hyperamylasaemia developed in 87% of the patients, and in 10% the serum amylase activity was > 1000 U/l. Serial measurements of serum salivary (S-) and pancreatic (P-) isoamylases indicated that hyperamylasaemia was highest 24 hours after CABG and consisted mainly of P-amylase component. Serum creatinine, creatinine clearance and urinary albumin concentration remained normal after CABG, excluding severe renal damage. The fractional clearance (i.e. relative to creatinine clearance) of P-amylase decreased more than of S-amylase (from 3.6 to 0.9% vs 1.3 to 0.8%). Decreased rate of excretion into urine, rather than pancreatic cellular damage, is the main source of hyperamylasaemia after CABG.

Effect of antioxidants on postoperative hyperamylasemia in coronary bypass surgery.

Antioxidants may reduce pancreatic cellular injury after coronary artery bypass grafting (CABG) Twenty patients (Group A) received vitamin E (600 mg/ day) for 28 days and vitamin C (2 g/day) and allopurinol (600 mg/day) 2 days before and 1 day after CABG. Seventeen patients (Group C) received all drugs for 3 days, and 25 (Group B) and 19 (Group D) patients served as corresponding controls. The pre- and postoperative pancreatic isoamylase (P-amylase), creatinine, and antioxidant concentrations were measured. Serum hyperamylasemia was highest on the first postoperative day and occurred in 73% of the patients. After surgery serum P-amylase increased in all study groups and urine P-amylase decreased. Postoperative serum hyperamylasemia, whether primarily renal or pancreatic, cannot be decreased by pretreatment with allopurinol, vitamin C, and vitamin E.

Intimal thickening and fragmentation of the internal elastic lamina in the mesenteric arteries.

To evaluate the intimal thickness and continuity of the internal elastic lamina (IEL) in the mesenteric arteries, proximal segments of the coeliac artery (CA), superior mesenteric artery (SMA) and inferior mesenteric artery (IMA) were studied light microscopically in 123 consecutive postmortem examinations. The mean age of the subjects was 62 years. Arterial segments were fixed in formalin, embedded in paraffin blocks, sectioned, and stained with Masson's trichrome. Fifty-one per cent of the samples examined showed at least minimal intimal thickening. The occurrence of significant luminal narrowing increased with age. We found a positive correlation between defects in the IEL and thickness of the intima in the mesenteric arteries, which is in harmony with previous observations showing marked fragmentation of the IEL in atherogenesis.