Association of midlife obesity and cardiovascular risk with old age frailty: a 26-year follow-up of initially healthy men.

OBJECTIVE AND HYPOTHESIS: To investigate whether old age frailty is predicted by midlife overweight/obesity and cardiovascular disease (CVD) risk. DESIGN: Longitudinal observational study (the Helsinki Businessmen Study). SUBJECTS: In their midlife in 1974, 1815 initially healthy men (mean age 47 years) were clinically investigated, whereupon their weight status (normal weight < 25 kg m(-2), overweight 25 ≤ body mass index <30 kg m(-2) and obese ≥ 30 kg m(-2)), CVD risk factors and a composite risk score (%) of coronary artery disease (CAD) were assessed. After a 26-year follow-up in 2000, when 425 men had died, the frailty status of survivors (80.9%, n=1125, mean age 73 years) was assessed using a postal questionnaire including the RAND-36/SF-36 instrument. Phenotypic criteria were used to define frailty, and according to these criteria, 40.0% (n=450), 50.4% (n=567) and 9.6% (n=108) were classified as not frail, prefrail and frail, respectively. Risks are presented as odds ratios (OR) with 95% confidence intervals (CI). RESULTS: Compared with normal weight, the development of frailty was significantly higher among those men who were overweight or obese in midlife, with fully adjusted ORs (95% CI) of 2.06 (1.21-3.52) and 5.41 (1.94-15.1), respectively. Even the development of prefrailty was significantly increased with midlife overweight (OR 1.39; 95% CI, 1.03-1.87) and obesity (OR 2.96; 95% CI, 1.49-5.88). Age-adjusted composite CAD score in midlife predicted similarly 26-year total mortality (OR per 1% increase:1.16; 95% CI, 1.08-1.24) and development of frailty (OR 1.16; 95% CI, 1.02-1.33). CONCLUSION: Overweight/obesity and higher CAD risk in midlife were associated with frailty 26 years later. Preventing old age frailty should be recognized as an important goal of obesity and CVD risk control.

Chocolate, well-being and health among elderly men.

OBJECTIVE: We hypothesized that chocolate preference would be related to health and psychological well-being in old men. DESIGN, SETTING AND PARTICIPANTS: We have followed up a socio-economically homogenous group of men, born in 1919-1934, since the 1960s. In 2002-2003, a mailed questionnaire was used to assess the health and well-being (including questions related to positive life orientation, visual analogue scales and the Zung depression score) of survivors. In addition, candy preference was inquired. Those men who reported no candy consumption (n=108) were excluded from the analyses. OUTCOME MEASURES: Psychological well-being in old age. RESULTS: The response rate was 69% (1367 of 1991). Of the respondents, 860 and 399 preferred chocolate and other type of candy, respectively. The average age in both candy groups was 76 years. Of the respondents, 99% were home-dwelling, 96% were retired and 87% were presently married, without differences between the candy groups. Men preferring chocolate had lower body mass index and waist circumference, and they also reported more exercise and better subjective health (P=0.008) than other candy consumers. Variables related to psychological well-being were consistently better in those preferring chocolate. The differences were statistically significant in feeling of loneliness (P=0.01), feeling of happiness (P=0.01), having plans for the future (P=0.0002) and the Zung depression score (P=0.02). CONCLUSIONS: In this socioeconomically homogenous male cohort, chocolate preference in old age was associated with better health, optimism and better psychological well-being. SPONSORSHIP: The Academy of Finland, the Päivikki and Sakari Sohlberg Foundation, the Helsinki University Central Hospital and the Finnish Foundation for Cardiovascular Research.

Increased Mortality Despite Successful Multifactorial Cardiovascular Risk Reduction in Healthy Men: 40-Year Follow-Up of the Helsinki Businessmen Study Intervention Trial.

OBJECTIVES: In a 5-year multifactorial risk reduction intervention for healthy men with at least one cardiovascular disease (CVD) risk factor, mortality was unexpectedly higher in the intervention than the control group during the first 15-year follow-up. In order to find explanations for the adverse outcome, we have extended mortality follow-up and examined in greater detail baseline characteristics that contributed to total mortality. DESIGN: Long-term follow-up of a controlled intervention trial. SETTING: The Helsinki Businessmen Study Intervention Trial. PARTICIPANTS AND INTERVENTION: The prevention trial between 1974-1980 included 1,222 initially healthy men (born 1919-1934) at high CVD risk, who were randomly allocated into intervention (n=612) and control groups (n=610). The 5-year multifactorial intervention consisted of personal health education and contemporary drug treatments for dyslipidemia and hypertension. In the present analysis we used previously unpublished data on baseline risk factors and lifestyle characteristics. MAIN OUTCOME MEASURES: 40-year total and cause-specific mortality through linkage to nation-wide death registers. RESULTS: The study groups were practically identical at baseline in 1974, and the 5-year intervention significantly improved risk factors (body mass index, blood pressure, serum lipids and glucose), and total CVD risk by 46% in the intervention group. Despite this, total mortality has been consistently higher up to 25 years post-trial in the intervention group than the control group, and converging thereafter. Increased mortality risk was driven by CVD and accidental deaths. Of the newly-analysed baseline factors, there was a significant interaction for mortality between intervention group and yearly vacation time (P=0.027): shorter vacation was associated with excess 30-year mortality in the intervention (hazard ratio 1.37, 95% CI 1.03-1.83, P=0.03), but not in the control group (P=0.5). This finding was robust to multivariable adjustments. CONCLUSION: After a multifactorial intervention for healthy men with at least one CVD risk factor, there has been an unexpectedly increased mortality in the intervention group. This increase was especially observed in a subgroup characterised by shorter vacation time at baseline. Although this adverse response to personal preventive measures in vulnerable individuals may be characteristic to men of high social status with subclinical CVD, it clearly deserves further investigation.

Lercanidipine, enalapril and their combination in the treatment of elderly hypertensive patients: placebo-controlled, randomized, crossover study with four ABPM.

This double-blind, placebo-controlled, four-way balanced design crossover study included hypertensive patients aged 60-85 years with mean office-measured sitting systolic blood pressure (SBP) 160-179 mm Hg and daytime SBP > or =135 mm Hg. After a 2-week run-in period, during which previous medications were discontinued, each patient received the following four treatments in randomized order for 4 weeks each: lercanidipine 10 mg (L), enalapril 20 mg (E), lercanidipine 10 mg plus enalapril 20 mg (L/E) and placebo (P). At the end of each treatment period, office trough blood pressure (BP) was measured and a 24-h Ambulatory Blood Pressure Monitoring (ABPM) was performed. Seventy-five patients (mean age 66 years, office BP 168/92 mm Hg, daytime SBP 151 mm Hg) were randomized and 62 completed the study with four valid post-baseline ABPMs. The administration of P, L, E and L/E was associated with a mean 24-h SBP of 144, 137, 133 and 127 mm Hg, respectively. All active treatments significantly reduced the mean 24-h SBP in comparison with placebo, but L/E was significantly more effective than L and E alone. Similarly, office SBP was significantly more reduced with L/E (-16.9 mm Hg) than with L (-5.0 mm Hg) or E (-5.9 mm Hg). A BP <140/90 mm Hg was recorded in 18% of patients with L, 19% with E and 45% with L/E. Two patients on P and two on L/E were withdrawn from the study due to adverse events. In conclusion, combination therapy with L/E has additive antihypertensive effects on both ambulatory and office BP in elderly patients and is well tolerated.

Thoracoabdominal restriction in supine men: CT and lung function measurements.

Thoracoabdominal restriction was brought on by means of a corset, and the subsequent effects on thoracic dimensions and lung tissue were studied by computerized tomography (CT) and by various lung function tests in supine healthy volunteers (mean age 30 yr). Restriction caused reductions in total lung capacity (helium equilibration) from mean 6.84 to 4.80 liters, in functional residual capacity (FRC) from 2.65 to 2.08 liters, and in vital capacity from 5.16 to 3.45 liters. Closing capacity (single-breath N2 washout) fell from 2.42 to 1.88 liters, thus matching the reduction in FRC. The static pressure-lung volume curve was shifted to the right by 1.5 cmH2O at 50% of total lung capacity. However, no change in the slope of the curve was observed. The diaphragm was moved cranially by 1.2 cm, and the thoracic cross-sectional area was reduced by a mean 32 cm2 at a level just above the diaphragm. No changes in the lung tissue were seen on CT scanning. Gas exchange, as assessed by multiple inert gas elimination technique and arterial blood gas analysis, was unaffected by restriction. It is concluded that in supine subjects, thoracoabdominal restriction that reduces FRC by 0.6 liter is not accompanied by atelectasis (normal CT scan). In this respect the result differs from that found in anesthetized supine subjects who show the same fall in FRC and atelectasis in dependent lung regions.

V/Q distribution and correlation to atelectasis in anesthetized paralyzed humans.

Regional ventilation and perfusion were studied in 10 anesthetized paralyzed supine patients by single-photon emission computerized tomography. Atelectasis was estimated from two transaxial computerized tomography scans. The ventilation-perfusion (V/Q) distribution was also evaluated by multiple inert gas elimination. While the patients were awake, inert gas V/Q ration was normal, and shunt did not exceed 1% in any patient. Computerized tomography showed no atelectasis. During anesthesia, shunt ranged from 0.4 to 12.2. Nine patients displayed atelectasis (0.6-7.2% of the intrathoracic area), and shunt correlated with the atelectasis (r = 0.91, P < 0.001). Shunt was located in dependent lung regions corresponding to the atelectatic area. There was considerable V/Q mismatch, with ventilation mainly of ventral lung regions and perfusion of dorsal regions. Little perfusion was seen in the most ventral parts (zone 1) of caudal (diaphragmatic) lung regions. In summary, shunt during anesthesia is due to atelectasis in dependent lung regions. The V/Q distributions differ from those shown earlier in awake subjects.

Atelectasis causes gas exchange impairment in the anaesthetised horse.

The anatomical basis of gas exchange impairment in the anaesthetised horse was studied by computerised tomography (CT; three shetland ponies) and morphological analysis (one pony and three horses). By means of CT, densities were seen in dependent lung regions early during anaesthesia, both with spontaneous breathing and with mechanical ventilation. The densities remained for some time where they had initially been created when the animal was turned from dorsal to sternal recumbency. Deep insufflation of the lungs reduced the dense area. Gas exchange was impaired roughly in proportion to the dense area. On histological analysis, the densities were atelectatic and congested with blood. Gravimetry showed no more extravascular water per unit lung tissue in the atelectatic than in the 'normal' regions, and the blood content was increased only slightly. It is concluded that the horse develops atelectasis in dependent lung regions early during anaesthesia in dorsal recumbency, and that atelectasis is the most likely explanation for the large shunt and impaired arterial oxygenation regularly seen during anaesthesia.

Stomach rupture following ingestion of sodium bicarbonate.

Spontaneous rupture of the stomach is an uncommon condition with a usually poor prognosis. The rupture occurs as a result of a closed loop obstruction with increased pressure against the stomach wall. A case of stomach rupture occurring after hyperdistention of the stomach following ingestion of sodium bicarbonate is described and the pathophysiological mechanism is discussed.

The significance of bacteriological findings at cholecystectomy.

The value of routine bacterial culture and gram staining of bile intraoperatively was investigated in 84 patients undergoing cholecystectomy. A positive bile culture was found in five of eight patients with an acute cholecystitis and in three of five patients with stones in the common bile duct, but in only nine of 66 patients with chronic cholecystitis without a common duct stone (14%). None of the patients with a normal gallbladder wall or cholesterolosis were bacteria-positive. Immediate microscopy of bile showed positive results in eight of 17 culture-positive bile specimens. As the majority of strains isolated from bile were aerobes sensitive to ampicillin and trimethoprim-sulphamethoxazole, any of these antibiotics can safely be administered intraoperatively to patients belonging to the risk group (acute cholecystitis, common bile duct stone). Immediate microscopy of bile is an unrealiable method of limited value and is not recommended for routine use.

Battered women: a diagnostic and therapeutic dilemma.

A prospective study of women attending a surgical emergency department in an 8-month period showed that 117 (9%) had been battered. Offered in-patient treatment was accepted and completed by 58 women (the index group), while 59 declined or did not complete treatment (the drop-out group). Both groups were compared with age-matched controls. In the battered group there were more foreign-born women and more divorces than in the control group. The drop-out group differed from the index group either in being less severely injured and seeking only certification of injury for legal purposes, or in having more previous psychiatric morbidity. The consumption of somatic and psychiatric care during the preceding 10 years was significantly greater in the battered group than in the controls, probably due to the maltreatment and reluctance to report it spontaneously. Breaking of a battering pattern at an early stage requires awareness by surgeons, general practitioners and psychiatrists that recurrent injuries of unclear origin may be due to such violence.

A comparison of methods for estimating the transition:transversion ratio from DNA sequences.

Estimation of the ratio of the rates of transitions to transversions (TI:TV ratio) for a collection of aligned nucleotide sequences is important because it provides insight into the process of molecular evolution and because such estimates may be used to further model the evolutionary process for the sequences under consideration. In this paper, we compare several methods for estimating the TI:TV ratio, including the pairwise method [TREE 11 (1996) 158], a modification of the pairwise method due to Ina [J. Mol. Evol. 46 (1998) 521], a method based on parsimony (TREE 11 (1996) 158), a method due to Purvis and Bromham [J. Mol. Evol. 44 (1997) 112] that uses phylogenetically independent pairs of sequences, the maximum likelihood method, and a Bayesian method [Bioinformatics 17 (2001) 754]. We examine the performance of each estimator under several conditions using both simulated and real data.

Separate lung blood flow in anesthetized dogs: a comparative study between electromagnetometry and SF6 and CO2 elimination.

Anesthetized, prone dogs were intubated with a double-lumen endobronchial tube, and the lungs were ventilated independently. Three methods of recording differential blood flow were compared during unilateral lung hypoxia: electromagnetic flow measurement, flow probes being fitted onto each main pulmonary artery after thoracotomy (QPr); SF6 elimination from each lung, the inert gas being continuously infused into a central vein (QSF6); and CO2 elimination (QCO2). During control conditions (100% O2 to both lungs), the test lung QPr was 54% of cardiac output, and corresponding QSF6 and QCO2 were 56% and 52%, respectively. Hypoxic challenge with 8% O2 to the test lung reduced QPR, QSF6, and QCO2 by 25%, 27%, and 7%, respectively. Ventilation of the test lung with pure nitrogen reduced its blood flow further, QPr, QSF6, and QCO2 being reduced by 39%, 42%, and 23%, respectively, from initial control. A strong correlation between test lung QPr and QSF6 was seen with a slope of 0.90 (r:0.89, P less than 0.001). Only 60% of the reduction in test lung blood flow was detected by CO2 elimination, as compared to electromagnetic flow measurement or SF6 elimination. The poor results obtained with CO2 elimination can be explained by its dependence on the ventilation-perfusion ratio and the effect of oxygen tension on the CO2 binding capacity of blood (Haldane effect). The findings emphasize the necessity of using an inert, poorly soluble gas for the measurement of separate lung blood flow.

The influence of body position and differential ventilation on lung dimensions and atelectasis formation in anaesthetized man.

The effects of body position and anaesthesia with mechanical ventilation on thoracic dimensions and atelectasis formation were studied by means of computerized tomography in 14 patients. Induction of anaesthesia in the supine position reduced the cross-sectional area for both lungs and caused atelectasis formation in dependent lung regions in 4/5 patients. Conventional ventilation with positive end-expiratory pressure (PEEP) increased thoracic dimensions and reduced, but did not eliminate, the atelectatic areas. The vertical diameters of both lungs were smaller in the lateral position as compared to the supine position (16.7 vs 10.4 cm in the left lung and 17.3 vs 12.8 cm in the right lung). The lateral positioning also caused a large reduction of the atelectatic area in the non-dependent lung. Differential ventilation with selective PEEP to the dependent lung eliminated (3/8 patients) or reduced (5/8 patients) dependent lung atelectasis. It can be concluded that lung geometry is altered in the lateral position: the shape of the lung makes the vertical diameter of each lung less in the lateral position, compared to the supine position. The atelectatic areas are mainly located in the dependent lung in the lateral position, and these atelectatic areas could be further reduced by selective PEEP to this lung.

Ventilation-perfusion relationships and atelectasis formation in the supine and lateral positions during conventional mechanical and differential ventilation.

Patients without respiratory symptoms were studied awake and during general anesthesia with mechanical ventilation prior to elective surgery. Ventilation-perfusion (VA/Q) relationships, gas exchange and atelectasis formation were studied during five different conditions: 1) supine, awake; 2) supine during anesthesia with conventional mechanical ventilation (CV); 3) in the left lateral position during CV; 4) as 3) but with 10 cm of positive end-expiratory pressure (PEEP) and 5) as 3) but using differential ventilation with selective PEEP (DV + SPEEP) to the dependent lung. Atelectatic areas and increases of shunt blood flow and blood flow to regions with low VA/Q ratios appeared after induction of anesthesia and CV. With the patients in the lateral position, further VA/Q mismatch with a fall in PaO2 and increased dead space ventilation was observed. Atelectatic lung areas were still present, although the total atelectatic area was slightly decreased. Some of the effects caused by the lateral position could be counteracted by adding PEEP. Perfusion of regions with low VA/Q ratios and venous admixture were then diminished, while PaO2 was slightly increased; shunt blood flow and dead space ventilation were essentially unchanged. During CV + PEEP, there was a decrease in cardiac output, compared to CV in the lateral position. DV + SPEEP was more effective than CV + PEEP in decreasing shunt flow and increasing PaO2 in the lateral position; in addition to this, cardiac output was not affected.

Lung collapse and gas exchange during general anesthesia: effects of spontaneous breathing, muscle paralysis, and positive end-expiratory pressure.

Lung densities (atelectasis) and pulmonary gas exchange were studied in 13 supine patients with no apparent lung disease, the former by transverse computerized tomography (CT) and the latter by a multiple inert gas elimination technique for assessment of the distribution of ventilation/perfusion ratios. In the awake state no patient had clear signs of atelectasis on the CT scan. Lung ventilation and perfusion were well matched in most of the patients. Three patients had shunts corresponding to 2-5% of cardiac output, and in one patient there was low perfusion of poorly ventilated regions. CT scans after 15 min of halothane anesthesia and mechanical ventilation showed densities in dependent lung regions in 11 patients. A shunt was present in all patients, ranging from 1% in two patients (unchanged from the awake state) to 17%. Ventilation of poorly perfused regions was noted in nine patients, ranging from 1-19% of total ventilation. The magnitude of the shunt significantly correlated to the size of dependent densities (r = 0.84, P less than 0.001). Five patients studied during spontaneous breathing under anesthesia displayed both densities in dependent regions and a shunt, although of fairly small magnitude (1.8% and 3.7%, respectively). Both the density area and the shunt increased after muscle paralysis. PEEP reduced the density area in all patients but did not consistently alter the shunt. It is concluded that the development of atelectasis in dependent lung regions is a major cause of gas exchange impairment during halothane anesthesia, during both spontaneous breathing and mechanical ventilation, and that PEEP diminishes the atelectasis, but not necessarily the shunt.

Constitutional factors promoting development of atelectasis during anaesthesia.

The extent of atelectasis was correlated to constitutional factors in 38 patients who underwent computed tomography prior to and during general anaesthesia with halothane. All patients but two developed atelectasis in dependent regions of both lungs immediately after induction of anaesthesia prior to surgery. The transverse area of the densities ranged from 0 to 27 cm2, and there were no significant differences between patients of different age or sex, or with different smoking habits. A significant linear regression was found between Broca's index weight (kg)/height (cm)-100 and the area of the densities, and also between an index describing the shape of the thorax and the density area. Thus, patients who were overweight and/or had a low and wide thorax tended to develop more extensive atelectasis during anaesthesia. This finding might partly explain why overweight patients develop postoperative pulmonary complications more often than non-obese patients.

Pulmonary densities during anesthesia with muscular relaxation--a proposal of atelectasis.

Twenty patients (23-76 yr) were studied with regard to lung tissue changes prior to and following induction of general anesthesia with muscular relaxation, and another four subjects were studied for a longer period awake. The transverse thoracic area and the structure of the lung tissue were determined by computerized tomography. No abnormalities in the lung tissue were noted before anesthesia. Within 5 min after induction, including muscular relaxation, all subjects had developed crest-shaped changes of increased density in the dependent regions of both lungs. They were largest in the most caudal segment (4.8 +/- 0.8% of the transverse lung area, mean +/- SE) and smaller in the cephalad exposures (3.4 +/- 0.7% of the transverse area). The size of the densities showed no correlation to age. The densities did not increase after a further 20 min of anesthesia and were not affected by the inspiratory oxygen fraction. When the subjects were moved from the supine to the lateral position, the crest-shaped densities disappeared in the nondependent lung and remained in the dorsal part of the dependent lung. The application of positive end-expiratory pressure of 10 cmH2O eliminated or reduced the densities. The four awake subjects showed no lung densities after 90 min in the supine position. It is suggested that these crest-shaped densities represent atelectases, which develop by compression of lung tissue rather than by resorption of gas.

New aspects on atelectasis during anaesthesia.

Sixteen subjects were studied with regard to lung tissue changes during general anaesthesia. The transverse area and the structure of the lung tissue were studied by computerized tomography. No abnormalities were noted in the lung tissue before anaesthesia, but within five minutes after induction, all subjects had developed crest-shaped dependent changes of an increased density in both lungs. They correspond to 4 - 5 per cent of the total transverse area. The size of the densities could not be correlated to the age of the subjects, or time of the anaesthesia, and they were not affected by the inspiratory oxygen fraction. They could be rotated by turning the patient, and the application of a positive end-expiratory pressure eliminated or reduced the densities. It is suggested that the densities are atelectases, which develop by compression of lung tissue, and not by gas resorption.

What causes the lowered FRC during anaesthesia?

Functional residual capacity (FRC) by means of body plethysmography chest-abdomen dimensions by whole body computerized tomography, central blood volume (CBV) by double-indicator dilution technique and extremity (peripheral) blood volume (PBV) by segmental thigh and upper arm plethysmography, were assessed in lung-healthy patients who were to undergo general anaesthesia and elective surgery. Anaesthesia was induced by thiopentone and was maintained either by a continuous drip of thiopentone or by inhalation of halothane. Muscle relaxation was obtained by pancuronium bromide. Anaesthesia caused a reduction of the total thoracic volume by an average of 0.75 1. This followed from a cranial shift of the diaphragm and to less extent by a reduced transversal chest area. FRC was concomitantly reduced by an average of 0.5 1 and the CBV, mainly thoracic blood, was reduced by 0.25 - 0.3 1. PBV was slightly reduced by 0.1 1, and it is concluded that these fractions of CBV and TBV must have been pooled in the abdomen. This pooling resulted in more or less maintained transversal abdomen area despite the cranial shift of the diaphragm.

Functional residual capacity, thoracoabdominal dimensions, and central blood volume during general anesthesia with muscle paralysis and mechanical ventilation.

Functional residual capacity (FRC), rib cage and abdominal dimensions (rc-ab), central blood volume (CBV), and extra vascular lung water (EVLW) were measured in six lung-healthy subjects awake and during halothane anesthesia, muscle paralysis, and mechanical ventilation. FRC was assessed by multiple breath nitrogen washout, rc-ab dimensions by computerized tomography, and CBV and EVLW by a double-indicator dilution technique (thermo-dye). During anesthesia, FRC decreased by 0.5 1 (17%). The cross-sectional chest area was reduced by 12-20 cm2, causing an approximate reduction in thoracic volume by 0.3 1. Concomitantly, the diaphragm was moved cranially by an average of 1.9 cm, diminishing the thoracic volume a further 0.5 1. The abdominal cross-sectional area did not alter significantly, despite the shift of the diaphragm. CBV decreased by 0.3 1. EVLW did not change significantly. It is concluded that the thoracic volume is reduced during halothane anesthesia, muscle paralysis, and mechanical ventilation as a result of cranial shift of the diaphragm and reduction in transverse area. The decrease in thoracic volume is accompanied by a reduction in FRC and a displacement of blood from the thorax to the abdomen, the transverse area of the latter thus being maintained despite the shift of the diaphragm.