The Young Adult Human Brain: An MRI-based Morphometric Analysis

Morphometric analysis was performed on three-dimensional MRIscans of 10 male and 10 female young adults with four principalobjectives: (1) to characterize in vivo volumes of whole brainand substructures, (2) to explore volumetric symmetry in bilateralstructures, (3) to consider the extent to which volumetric measuresare dimorphic in the male and female brain, and (4) to providea normal volumetric database for the young adult brain. Totalbrain volumes ranged between 1173 and 1626 cm³. All bilateralstructures were symmetric or nearly symmetric in volume, withthe exception of a slightly larger right neocortex and amygdala,and larger left lateral ventricle. Male brains were larger involume than female brains, a difference that reached significancefor cerebellar but not for cerebral hemisphere volume. In females,there was less cerebral white matter while caudate volume waslarger than in the male brains. The proportions of caudate andhippocampus relative to total cerebral volumes were larger infemales than in males. These four measures accurately predictedgender in 85% of the subjects by discriminant analysis. No genderdifferences were noted in the structural symmetry analysis.These results represent the first step in establishing a comprehensivedatabase of morphometric parameters, with unexpected findingsrelative to brain symmetry and sexual dimorphism.     

Changes in bone mineral content during long-term CAPD. Indication of a sex-dependent bone mineral loss

Change in bone mineral content (BMC) was evaluated in a longitudinaltrial comprising 12 women and 11 men with chronic renal diseasetreated with CAPD and 1-alpha-OH-D3 for 2 years. The patientsserved as their own controls. No patients were treated withsteroids. Median age was 54 and 60 years for women and men respectively.No significant difference in 1-alpha-OH-D3 dosage or serum 1,25(OH)₂D3was found between the genders in the study period. Bone mineral content at the distal radius deteriorated significantlyin the females with a median decrease of 12% over 2 years, i.e.approximately 6% per year (P<0.001 and 95% confidence limits8–20%). No significant change was noted in the males.There was no correlation between age and BMC change. Serum total alkaline phosphatase decreased nonsignificantlyin both sexes. Total serum calcium increased significantly (P<0.05)and serum phosphate decreased significantly (P<0.05) in thewomen. Serum albumin and body weight decreased significantlyin the males (P<0.01 and P<0.05) while no change was seenin the females. The demonstrated decrease in BMC in the female patients of approximately6% per year exceeds the commonly observed loss of 1–2%per year in healthy women when measured with the same technique.Tentatively, the severe mineral loss in the women could indicatea sex-hormone-related disturbance in bone metabolism of uraemicfemales.     

Cerebrovascular reactivity during hypothermia and rewarming

Background: Experimental evidence from a murine model of traumatic braininjury (TBI) suggests that hypothermia followed by fast rewarmingmay damage cerebral microcirculation. The effects of hypothermiaand subsequent rewarming on cerebral vasoreactivity in humanTBI are unknown. Methods: This is a retrospective analysis of data acquired during a prospective,observational neuromonitoring and imaging data collection project.Brain temperature, intracranial pressure (ICP), and cerebrovascularpressure reactivity index (PRx) were continuously monitored. Results: Twenty-four TBI patients with refractory intracranial hypertensionwere cooled from 36.0 (0.9) to 34.2 (0.5)°C [mean (SD),P < 0.0001] in 3.9 (3.7) h. Induction of hypothermia [averageduration 40 (45) h] significantly reduced ICP from 23.1 (3.6)to 18.3 (4.8) mm Hg (P < 0.05). Hypothermia did not impaircerebral vasoreactivity as average PRx changed non-significantlyfrom 0.00 (0.21) to –0.01 (0.21). Slow rewarming up to37.0°C [rate of rewarming, 0.2 (0.2)°C h^–1] didnot increase ICP [18.6 (6.2) mm Hg] or PRx [0.06 (0.18)]. However,in 17 (70.1%) out of 24 patients, rewarming exceeded the braintemperature threshold of 37°C. In these patients, the averagebrain temperature was allowed to increase to 37.8 (0.3)°C(P < 0.0001), ICP remained stable at 18.3 (8.0) mm Hg (P= 0.74), but average PRx increased to 0.32 (0.24) (P < 0.0001),indicating significant derangement in cerebrovascular reactivity.After rewarming, PRx correlated independently with brain temperature(R = 0.53; P < 0.05) and brain tissue O₂ (R = 0.66; P <0.01). Conclusions: After moderate hypothermia, rewarming exceeding the 37°Cthreshold is associated with a significant increase in averagePRx, indicating temperature-dependent hyperaemic derangementof cerebrovascular reactivity.     

Relationship of peak flow rate and peak velocity time during voluntarv couzhinc

The differences in phonation between men and women are thoughtto occur from anatomical differences in the larynx. However,it is not known if there are any differences in cough dynamicsbetween the sexes. We investigated this by asking 100 healthy,non-smoking adults (50 male) to perform a voluntary cough intoa tussometer. Each volunteer coughed at four different lungvolumes, ranging from total lung capacity to functional residualcapacity. There was a positive correlation between peak velocitytime and cough peak flow rate in both males (r = 0.73, P <0.001) and females (r = 0.78, P < 0.001). Multiple regressionanalysis showed that height (P < 0.05) and sex (P < 0.001)were significant determinants of the relationship between peakflow rate and peak velocity time. In a height-matched subgroup,sex differences remained significant (P<0.05). This may berelated to anatomical differences in laryngeal structure andmay have implications when using tussometry to assess laryngealfunction.     

Atrial remodelling is less pronounced in female endurance-trained athletes compared with that in male athletes

Objectives. Little data exists on atrial adaptation to training in women. Furthermore, data on right atrial (RA) volumes is lacking for both male and female athletes. The objective of this study was therefore to investigate atrial volumes in male and female athletes. Design. A total of 75 athletes (33 women) and 53 controls (21 women) underwent cardiovascular magnetic resonance imaging. Left atrial (LA) and RA volumes were measured by manual delineation. The atrial appendage was included in the volumes, and pulmonary veins were excluded. Results. Atrial volumes were larger in athletes compared with those in controls (males: LA 116 ± 19 ml versus 93 ± 19 ml, RA 166 ± 32 ml versus 133 ± 23 ml, p < 0.0001, females: LA 90 ± 15 ml versus 83 ± 17 ml, p < 0.05, RA 119 ± 24 ml versus 108 ± 18 ml, p = 0.07). When normalized for body surface area, atrial volumes remained larger in athletes. However, when normalized for total heart volume (THV) there were no differences between groups except for LA volumes in females where controls had higher LA/THV compared with those in athletes (p < 0.05). Conclusion. Atrial volumes were significantly larger in athletes. Atrial volumes normalized for THV did not differ between athletes and controls indicating a balanced enlargement. There was only a small difference between female controls and female athletes, suggesting that atrial adjustment to training is more modest in women.     

Factors predicting the diameter of the popliteal artery in healthy humans

Purpose: To determine the relevance of popliteal dilatations, knowledge of the normal popliteal artery diameter is essential. This study investigates the diameter of the popliteal artery in healthy males and females. Methods: We measured the diameter of the popliteal artery in 121 healthy volunteers (59 males and 62 females), ages 8 to 81, with echo-tracking B-mode ultrasonography. We analyzed the influence of age, sex, height, weight, body surface area (BSA) and systolic blood pressure with a multiple regression model. Results: The popliteal artery increased steadily in diameter throughout life. From 25 years on, the diameter was larger in males than in females. If corrected for BSA, this difference decreased from 17% to 7%. This study found a correlation between popliteal artery diameter and BSA (r = 0.47 and r = 0.61, respectively, p < 0.0001). Age, followed by BSA, was the most influencing factor on popliteal diameter in both males and females (r = 0.62 and r = 0.66, respectively, p < 0.0001). We used age and BSA in creating a model for prediction of popliteal artery diameter. Conclusions: The diameter of the popliteal artery increases with age, initially during growth, but also in adults. This is related to age, body size and sex, with males having larger arteries than females. It is now possible to predict the normal popliteal arterial diameter, and nomograms are presented for use in the study of aneurysmal arterial disease. (J Vasc Surg 1998;28:284-9.)     

Sex and oestrous cycle differences in visceromotor responses and vasopressin release in response to colonic distension in male and female rats anaesthetized with halothane{dagger}

Visceromotor responses and vasopressin release before and aftercolonic visceral distension were compared between male (n=5(n=4 for vasopressin)) and female rats and between females duringthe oestrous cycle (proestrus n=6, oestrus n=5, metestrus n=5,diestrus n=6) at a controlled depth of anaesthesia. Pre-stimulationvasopressin and blood pressures demonstrated oestrous cyclevariability. The mean (SEM) colonic balloon pressure triggeringvisceromotor responses was significantly higher in males (64(4) mm Hg) than females (41 (1) mm Hg), P=0.002 and within females,proestrus rats had the lowest thresholds, (29 (1) mm Hg, P<0.01).Post-stimulation, vasopressin concentrations increased significantlyin all groups (males 1.34 (0.39) to 2.24 (0.74) pmol litre^–1;females 1.54 (0.24) to 2.88 (0.58) pmol litre^–1; P=0.002).Within groups statistically significant differences were measuredin proestrus 2.06 (0.56) to 3.42 (1.12) and oestrus 1.16 (0.38)to 2.76 (0.60) pmol litre^–1 (P<0.05). High vasopressinconcentrations coupled with low-pressure stimulation duringproestrus shows sex-hormone dependent integration of the neuroendocrineresponse to noxious visceral stimulation. Br J Anaesth 2000; 85: 907–10     

Effects of age,sex steroids,and family relationships on volumes of prostate zones in men with and without prostate cancer

Benign prostatic hyperplasia (BPH) and prostate cancer commonly occur together. This suggests that common familial, hormonal, and environmental factors contribute to their development. In men at risk for the development of prostate cancer (at 40 men in 19 families) and aged-matched unrelated controls (n = 46), we have determined whether familial factors, age, and blood hormone concentrations are related to the transition zone (TZ), peripheral zone (PZ), or total volume of the prostate measured by transrectal ultrasound (TRUS). We determined that the influences of age, prostate cancer (n = 15), and familial status did not significantly affect the relationships reported. Therefore, data from all groups were combined for this study. TZ correlated positively with age (P = 0.003) after controlling for family status, but total prostate volume correlated insignificantly with age (P = 0.08). In addition, the ratio of TZ to PZ volumes also correlated significantly with age in the control group (r = 0.27, P = 0.014). Both TZ and PZ volumes correlated highly (r = 0.91, P < 0.0001, n = 86) with total volume. In addition, total volume correlated significantly (r = 0.71, P < 0.001) with the ratio of the TZ/PZ volumes, which also correlated significantly with each other (r = 0.61, P < 0.0001, n = 86). In contrast to the increase of TZ volume related to total prostate volume, PZ volume declined compared with total volume. Prostate volumes up to 50 ml are predominated by the PZ and above 50 ml by the TZ, which may compress and shrink the PZ. Both TZ and total prostate volume correlated positively with serum estrone concentrations (P = 0.04 and P = 0.003, respectively). These results suggest that the risk of prostate cancer does not contribute to generalized overgrowth of the prostate, including the TZ. However, estrogens and age strongly influence TZ but not PZ volume. Both PZ and TZ volumes rise together until the prostate exceeds 50 ml, when the growth of the TZ appears to exceed the PZ and then to compress it.     

Association of chronic kidney disease with outcomes in chronic heart failure: a propensity-matched study

Background. Chronic kidney disease (CKD) is associated withincreased mortality in patients with heart failure (HF). However,its association with hospitalization in HF patients has notbeen well studied. Methods. Of 7788 patients in the Digitalis Investigation Grouptrial, 3527 had CKD, defined by an estimated glomerular filtrationrate (GFR) <60 ml/min/1.73 m² body surface area (BSA). Propensityscores for CKD were calculated using a multivariable logisticregression model and used to match 2399 pairs of patients withand without CKD. Matched Cox regression analyses were used toestimate association of CKD with outcomes. Results. All-cause hospitalization occurred in 1636 (rate, 4233/10 000person-years) and 1587 (rate, 3733/10 000 person-years)patients respectively, with and without CKD (matched hazardratio [HR] for CKD, 1.18, 95% confidence interval [CI], 1.08–1.29;P < 0.0001). Matched HR for cardiovascular and HF hospitalizationwere respectively 1.17 (95% CI, 1.06–1.28, P = 0.002)and 1.28 (95% CI, 1.13–1.45, P < 0.0001). Comparedto GFR 60 ml/min/1.73 m² BSA, HR for all-cause hospitalizationfor GFR 45–59 and <45 ml/min/1.73 m² BSA were respectively1.04 (95% CI, 0.94–1.16; P = 0.422) and 1.58 (95% CI,1.34–1.87; P < 0.0001). Similarly, HR for all-causedeath for GFR 45–59 and <45 ml/min/1.73 m² BSA wererespectively 1.03 (95% CI, 0.90–1.18; P = 0.651) and 1.70(95% CI, 1.40–2.07; P < 0.0001). Matched HR for deathdue to cardiovascular causes and progressive HF were respectively1.24 (95% CI, 1.09–1.40; P = 0.001) and 1.42 (95% CI,1.16–1.72; P = 0.001). Conclusion. CKD was associated with increased mortality andhospitalization in ambulatory patients with chronic HF, whichincreased progressively with worsening kidney function.     

Factor of Risk for Hip Fracture in Normal Chinese Men and Women in Taiwan

We have investigated the age-related change in factor of risk (Φ) for the proximal femoral load during free fall in 548 females and 240 males aged 21–79 years. These individuals were divided into either young (age <50 years) or old group (age ≥50 years). Another 26 females with hip fractures were included for comparison. The bone mineral density (BMD) of proximal femoral neck was measured by a Norland XR-26 dual-energy X-ray absorptiometer (DXA). The estimated fracture load (L) of femoral neck was calculated from the BMD with the regression equation derived by Courtney et al. [2,3] and estimated fall force (F) by body weight and height according to the regression equation derived by Nakamura et al. [6] respectively. Φ was defined as the quotient of F/L. The results showed an age-related decrease of BMD (P < 0.001) in both genders corrected for weight and height. By multiple linear regression analysis, the F decreased significantly with aging corrected for BMD in old males (partial r =−0.255, P < 0.01) and increased with aging in all females (young, partial r=0.287, p < 0.001; old, partial r = 0.252, P < 0.001). L decreased significantly with aging corrected for height and weight in males (young, partial r =−0.401, P < 0.01; old, partial r =−0.178, P < 0.05) and females (young, partial r =−0.168, P < 0.05; old, partial r =−0.459, P < 0.001). However Φ decreased with aging in young males (P < 0.01) and females (young: P < 0.001, old: P < 0.001). Φ increased in old women but not in old men, and was higher in old women compared with old men. The 26 patients with hip fractures had a significantly higher Φ value than 85 age-matched women. In conclusion, Φ may provide a comprehensive comparison of the risk of hip fracture in the elderly population. Received: 15 September 1997 / Accepted: 25 March 1999     

INFLUENCE OF AGE ON ATELECTASIS FORMATION AND GAS EXCHANGE IMPAIRMENT DURING GENERAL ANAESTHESIA

We have studied the effects of anaesthesia on atelectasis formationand gas exchange in 45 patients of both sexes, smokers and non-smokers,aged 23–69 yr. None of the patients showed clinical signsof pulmonary disease, and preoperative spirometry was normal.In the awake patient, partial pressure of arterial oxygen (Pa_O2)decreased with increasing age (P < 0.001) and the alveolar—arterialoxygen partial pressure difference (PA_O2 – Pa_O2) increasedwith age (P < 0.001). Shunt, assessed by the multiple inertgas elimination technique, was small (mean 0.5%) and uninfluencedby age. However, there was an increasing dispersion (log SDQ) of ventilation/perfusion ratios (VA/Q) and increasing perfusionof regions of low VA/Q (VA/Q <0.1) with increasing age (P< 0.001 and P < 0.05, respectively). No patient displayedany atelectasis as assessed by computed x-ray tomography ofthe chest. During inhalation anaesthesia (halothane or enflurane)with mechanical ventilation, 39 of 45 patients developed atelectasisand shunt. There was a strong correlation between the atelectaticarea and the magnitude of shunt (r = 0.81, P < 0.001). Atelectasisand shunt did not increase significantly with age, whereas logSD Q and perfusion of regions with low VA/Q ratios did (r =0.55, P < 0.001 and r = 0.35, P < 0.05, respectively).Awake, the major determinant of Pa_O2 was perfusion of regionsof low V;A/Q ratios, which increased with age, During anaesthesiashunt influenced Pa_O2 most low Va/Q being a secondary factorwhich, however, was increasingly important with increasing age,thus explaining the well-known age-dependent deterioration ofarterial oxygenation during anaesthesia.     

Postoperative nausea, vomiting, airway morbidity, and analgesic requirements are lower for the ProSeal laryngeal mask airway than the tracheal tube in females undergoing breast and gynaecological surgery

Background: We test the hypothesis that the frequency of postoperative nauseaand vomiting is similar for the ProSeal laryngeal mask airway(LMA) and the tracheal tube. Methods: Two hundred consecutive female patients (ASA I–II, 18–75yr) undergoing routine breast and gynaecological surgery weredivided into two equal-sized groups for airway management withthe ProSeal LMA or tracheal tube. Results: Ventilation was better and airway trauma less frequent for theProSeal LMA. For the ProSeal group, the time spent in the post-anaesthesiacare unit was shorter (69 vs 88 min, P < 0.0001); fewer dosesof tropisetron were required in the post-anaesthesia care unit(P 0.001) and ward (P = 0.004); morphine requirements werelower in the post-anaesthesia care unit (6.0 vs 8.1 mg, P =0.005) and ward (6.1 vs 8.9, P = 0.004); nausea was less frequentat all times (overall: 13% vs 53%, P < 0.0001); vomitingwas less frequent at 2 h (4% vs 18%, P = 0.003) and 24 h (5%vs 19%, P = 0.004); and sore throat was less frequent at alltimes (overall: 12% vs 38%, P < 0.0001). Conclusions: The ProSeal LMA reduced the absolute risk of postoperative nauseaand vomiting by 40% (53–13%). In patients without theneed for morphine, the ProSeal LMA reduced the absolute riskof postoperative nausea and vomiting by 23% (37–14%).We conclude that the frequency of postoperative nausea, vomiting,airway morbidity, and analgesic requirements is lower for theProSeal LMA than the tracheal tube in females undergoing breastand gynaecological surgery.     

Concurrent ketamine and alfentanil administration: pharmacokinetic considerations

Background. A ketamine–alfentanil combination has beensuggested for total i.v. anaesthesia. We determined the pharmacokineticsof ketamine and alfentanil, alone and together, in three groupsof adult male rats, to assess any pharmacokinetic interaction. Methods. Group 1 animals were infused with i.v. ketamine for5 min; in group 2, constant low plasma concentrations of alfentanilwere maintained by computer-controlled infusion; in group 3,the treatments were combined. Serial plasma and terminal tissueconcentrations were measured by high performance liquid chromatographyor gas chromatography-mass spectrometry. Results. In the presence of alfentanil, the mean plasma ketamineconcentration–time area under the curve (AUC) value wassignificantly lower (by 13%, P<0.05), while clearance (Cl_T)and volume of distribution (V_SS) were significantly higher (by16 and 28%, respectively, both P<0.05). Tissue:plasma distributioncoefficients for ketamine in the presence of alfentanil weresignificantly higher in forebrain (by 128%, P<0.005), hindbrain(by 207%, P<0.01), gut (by 254%, P<0.005), and fat (by344%, P<0.0001). Mean AUC values for alfentanil did not differsignificantly in the presence of ketamine, but alfentanil tissueconcentrations were significantly lower in forebrain (by 77%,P<0.0001), hindbrain (by 28%, P<0.01), heart (by 33%,P<0.01), lung (30%, P<0.05), and gut (by 21%, P<0.05).Corresponding tissue:plasma distribution coefficients were significantlylower for forebrain (by 69%, P<0.0001) alone. Conclusions. The finding that the distribution of ketamine intothe brain was increased by low plasma concentrations of alfentanilcould have important clinical applications for pain management. Br J Anaesth 2002; 88: 94–100     

Fluid recruitment from shell tissues of the body during haemodialysis

Patients with kidney failure are prone to accumulate fluidswithin the superficial tissues, leading to a puffiness of theface, hands, and feet. After dialysis these symptoms disappear.It was the aim of this study to quantify these changes. Withthe help of A-mode ultrasound in 49 patients (20 females, 29males) the tissue thickness in the forehead and tibia was measuredduring dialysis. In the forehead the tissue thickness beforedialysis was 4.01 mm (females) and 3.87 mm in the males, decreasingcontinuously during dialysis by 13.6% and 12.8% respectively(P<0.001). In the tibia the tissue thickness was 3.87 mm(females) and 3.07 mm (males) and decreased by 12.8% and 23.9%respectively. The sex difference was significant (P<0.05).From these values it was calculated that 45% of fluid withdrawncame from the superficial shell tissues of the body. It wasconcluded that these tissues serve as water stores in the interdialyticphase.     

Bone mass as referent for urinary hydroxyproline excretion: Age and sex-related changes in 125 normals and in primary hyperparathyroidism

Summary Fasting urinary hydroxyproline:creatinine ratio (OHPr:Cr) and bone mineral content of the forearm (BMC) were measured in 125 normals, 67 females and 58 males, aged 20–79 years, and in 15 patients with primary hyperparathyroidism. In normals, both variables were significantly correlated to age and sex. The interrelation of OHPr:Cr and BMC was studied in subgroups of normals who were supposedly in metabolic balance, that is, females aged 20–39 years (n=24) and males aged 20–49 years (n=29). In both sexes OHPr:Cr and BMC were positively correlated: r=0.60 and 0.58, respectively (P<0.001). On this basis, BMC correction of all OHPr:Cr values was undertaken now revealing a stable increased level of bone resorption per unit of bone mass in post-menopausal females. In males OHPr:Cr per unit of BMC remained unaltered throughout life. In primary hyperparathyroidism, in which increased bone resorption is inherent, the discriminatory power of OHPr:Cr was significantly improved when calculated per unit of BMC (P<0.001). These observations suggest that estimation of bone resorption by use of OHPr:Cr requires adjustment for differences in bone mass.     

Apparent diffusion coefficient mapping predicts mortality and outcome in rats with intracerebral haemodynamic disturbance: potential role of intraoperative diffusion and perfusion weighted magnetic resonance imaging to detect cerebral ischaemia

Background. Usefulness and ability of diffusion and perfusionweighted magnetic resonance images (DWI and PWI) to detect intracerebralhaemodynamic disturbance have not been fully evaluated. Methods. After the right common carotid artery had been ligated,rats were exsanguinated to maintain a mean arterial pressureof 35, 42, or 50 mm Hg (n=6, each group). Apparent diffusioncoefficient (ADC) maps were calculated from DWIs and lesionvolume (area) was defined based on ADC values (ADC lesion volume(area)). Results. ADC lesion volume during exsanguination in the 35 mmHg group (417 (111) mm³, P<0.01) was significantly largerthan in the 42 mm Hg group (87 (84) mm³) and 50 mm Hg group(42 (58) mm³). The low relative cerebral blood flow area, calculatedfrom PWI, was significantly larger during exsanguination inthe 35 mm Hg group than in the other groups. ADC lesion volumein the six rats that died within 3 days of the MRI study wassignificantly larger (median 421 mm³, range 205–476 mm³,P<0.005) than in the 12 rats that survived for 3 days (median26 mm³, range 3–517 mm³). Rats with an ADC lesion areaover 14 mm² on the coronal slice including the caudate putamenduring exsanguination died within 3 days or revealed a moresevere histopathological outcome than those that survived for3 days. Conclusions. Incomplete cerebral ischaemia created by the combinationof common carotid artery occlusion and exsanguination couldbe detected by DWI and PWI both qualitatively and quantitatively.The size of the lesion on ADC mapping was found to correlatewith mortality and outcome. Br J Anaesth 2002; 89: 605–13     

Positron emission tomography study of regional cerebral blood flow and flow-metabolism coupling during general anaesthesia with xenon in humans

Background: The effects of xenon on regional cerebral blood flow (rCBF)are controversial. Moreover, the precise sites of action atwhich xenon exerts its effects in the human brain remain tobe established. Methods: rCBF was sequentially assessed by H₂¹⁵O positron emission tomographyin six volunteers. rCBF was determined at baseline and duringgeneral anaesthesia induced with propofol and maintained withone minimum alveolar concentration xenon. rCBF measurementswere started after the calculated plasma concentration of propofolhad decreased to subanaesthetic levels (<1.0 µg ml^–1).Changes in rCBF were calculated for 13 cerebral volumes of interestby measurement of a semi-quantitative perfusion index (PI).In addition, voxel-wise changes in rCBF were analysed usingstatistical parametric mapping. Results: Xenon had only minor effects on PI in grey matter volumes ofinterest. In contrast, PI was increased in white matter [from1.01 (0.11) to 1.24 (0.15) kcnt ml^–1 MBq^–1, P=0.05,mean (SD)]. Voxel-based analysis showed an increase of rCBFin white matter and a relative decrease of rCBF during xenonanaesthesia in distinct grey matter regions, particularly theorbito- and mesiofrontal cortex, cingulate gyrus, thalamus,hippocampus and bilateral cerebellum (P<0.05 corrected).When correlating PI with cerebral metabolic rate of glucose(previously obtained in another group of six volunteers using¹⁸F-fluorodeoxyglucose as tracer), the flow–metabolismcoupling was preserved during xenon anaesthesia. Conclusions: Xenon exerted distinct regional effects on CBF: relative decreasesin several cortical, subcortical, and cerebellar areas wereaccompanied by an increase in white matter. Flow–metabolismcoupling was not impaired during xenon anaesthesia.     

What is the natural history of internal rectal prolapse?

Aim The nature and clinical significance of internal rectal prolapse is controversial. Its natural history is unclear. Longitudinal cohort studies show rare progression to external prolapse but lack adequate follow‐up. We aimed to study the relationship of age to various stages of internal rectal prolapse using the Oxford Rectal Prolapse Grade (ORPG) and evaluate the influence of sex and vaginal delivery on this relationship. Method Internal rectal prolapsed (IRP) diagnosed at proctography and external rectal prolapse were graded using the ORPG. Age, sex and obstetric history were documented. Mean age of each prolapse grade (1–5) was analysed and regression analysis performed for age and prolapse. Subgroup analyses were made for males, and females with (V+) and without (V0) history of vaginal delivery. Results Sixty males (11%) and 471 females (89%) were studied. The difference in the mean ages of each group was statistically significant (grade 1,38.6; grade 2, 52.1; grade 3, 56.0; grade 4, 60.3 and grade 5, 66.5, P < 0.0001). On average male (8.7 years) and V0‐group (8.0 years) were younger than V+ group (95% CI difference 4.5–12.9 years, P < 0.0001, and 3.8–12.2 years, P < 0.0001, respectively). Males and V0‐group had weaker correlation between age and prolapse grade (r = 0.16 and r = 0.17, respectively, vs 0.41), and a faster prolapse progression rate than the V+ group. Conclusion These data demonstrate a strong relationship between age and prolapse grade, supporting the view of internal rectal prolapse as a precursor to external prolapse in the spectrum of rectal prolapse disease.     

INFLUENCE OF AGE AND SEX ON THE PHARMACOKINETICS OF THIOPENTONE

Thiopentone was given to eight women and eight men (60–79yr). The disappearance of thiopentone from the venous bloodwas described by a three-compartment open model. The only significantdifference between the sexes was a higher initial venous concentrationin males. The dose (mg kg ^–1) for induction was 70% ofthe value (P<0.05) previously reported for a comparable groupof younger men and women (20–40 yr). The volumes of distributionV₂ and V₃ were larger in the elderly (P<0.05). The terminalhalf-lives were increased with advancing age (from 75% to 100%on average) (P0.01). The clearance value was 50% greater inthe older women than in a group of young women. For all groupsa significant correlation between initial drug concentrationand k₁₂ supported the hypothesis that the redistribution rateconstant k₁₂ is the predominant factor in the pharmacokineticprofile of a dose of thiopentone sufficient to obtund the eyelashreflex.     

Gallbladder Pathology in Morbid Obesity

Background: Obese patients are at increased risk for biliary disease. The prevalence and type of gallbladder pathology in morbidly obese patients was evaluated, and compared with a non-obese control group. Methods: A consecutive series of obese patients (n=478) who had undergone bariatric surgery with concurrent routine cholecystectomy and a consecutive group of organ donors (n=481) were compared. Gallbladder pathology was defined as: cholelithiasis, cholecystitis, cholesterolosis, or normal pathology. Results: Mean age of obese patients and of donors was 42 ± 9 and 43 ± 17 years respectively and mean BMI was 52 ± 10 and 27 ± 7 kg/m² respectively, P<0.05. There were more females in the obesity group (88% vs 47%, P<0.0001). 31% of obese patients and 7% of controls had a previous cholecystectomy (P<0.0001). 21% of the obese and 72% of the controls had normal gallbladder pathology (P<0.0001). Overall, obese patients had a higher incidence of cholelithiasis (25% vs 5%, P<0.0001), cholecystitis (50% vs 17%, P<0.0001), and cholesterolosis (38% vs 6%, P<0.0001) compared with controls. Obese patients with BMI <50 were more likely than those with BMI ≥50 to have normal gallbladder pathology (27% vs 14%, P<0.001). Female patients were more likely to have undergone previous cholecystectomy than males in both the obese group (34% vs 11%, P<0.001) and the control group (12% vs 2%, P<0.0001). Normal pathology was more common in male patients (80% vs 63%, P<0.0001) and patients <50 years (76% vs 66%, P<0.05) in the control group. Conclusions: Obese patients have an increased incidence of benign gallbladder disease than a group of controls, and the relative risk appears to be positively correlated with the level of increase in the BMI. Obesity appears to change the effect of age and gender on gallbladder pathology.