Pulmonary endothelial permeability and circulating neutrophil-endothelial markers in patients undergoing esophagogastrectomy.

OBJECTIVE: Esophagogastrectomy is an established surgical treatment for esophageal malignancy. The postoperative period may be complicated by the development of acute lung injury syndromes and thus, may provide a useful model in which to study the early pathogenic mechanisms of inflammatory lung injury. DESIGN: Open, prospective study. SETTING: High dependency and intensive therapy units. PATIENTS: Eight healthy male volunteers and 20 patients in the early postoperative period INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The lung protein accumulation index (PAI) of radiolabeled transferrin was determined by using a portable, double-isotope system. The following circulating inflammatory markers-thought to reflect neutrophil-endothelial activation and injury including circulating neutrophil elastase-soluble L-, E-, and P-selectins and thrombomodulin and von Willebrand factor antigen were assayed from venous blood samples The PAI for healthy volunteers was median -0.5 (range, -1.73 to 0.27) x 10(-3)/min and for patients undergoing esophagogastrectomy -0.005 (range, -1.53 to 2.28) x 10(-3)/min. There was no statistical difference between the two groups. In the postesophagogastrectomy group, a significant elevation in circulating levels of neutrophil elastase, soluble P- and E-selectin, thrombomodulin, and von Willebrand factor antigen were observed relative to the control group but only circulating plasma elastase demonstrated a significant correlation with the PAI (r2 = .23, p =.03). CONCLUSIONS: The data suggest patients undergoing esophagogastrectomy develop a inflammatory response but this is not a surrogate of permeability and other factors are likely to determine persistent injury to the alveolar-capillary barrier function in this patient group.

Cerebral blood flow and metabolism in severe brain injury: the role of pressure autoregulation during cerebral perfusion pressure management.

OBJECTIVE: To ascertain if norepinephrine can be used as part of the cerebral perfusion pressure (CPP) management to increase arterial blood pressure (MAP) without causing cerebral hyperemia after severe head injury (HI). DESIGN: Prospective, interventional study. SETTING: Intensive care unit in a university hospital. PATIENTS: Twelve severely HI patients; median Glasgow Coma Scale was 6 (range 3-8). INTERVENTIONS: CPP management ( = 70 mmHg). Pressure autoregulation (assessed by norepinephrine infusion) was defined intact if % CPP/%CVR < or = 2. RESULTS: Cerebral blood flow (CBF: Xe133 inhalation technique), jugular bulb oxygen saturation (SjO2) and transcranial Doppler (TCD) were recorded during the test. Norepinephrine increased CPP by 33 % (+/- 4). Autoregulation was found to be intact in ten patients and defective in two. In the ten patients with preserved autoregulation, CBF decreased from 31 +/- 3 to 28 +/- 3 ml/ 100 g/min; in the two patients with impaired autoregulation CBF increased respectively from 16 to 35 and from 21 to 70 ml/100 g/min. SjO2 did not change significantly from baseline. TCD remained within the normal range. CONCLUSIONS: During CPP management norepinephrine can be used to increase MAP without potentiating hyperemia if pressure autoregulation is preserved. The assessment of pressure autoregulation should be considered as a guide for arterial pressure-oriented therapy after HI.

Serum 7 alpha-hydroxy-4-cholesten-3-one and selenohomocholyltaurine (SeHCAT) whole body retention in the assessment of bile acid induced diarrhoea.

OBJECTIVE: To assess the reliability of serum 7 alpha-hydroxy-4-cholesten-3-one (7 alpha-3ox-C) in the differential diagnosis of bile acid induced diarrhoea by comparison with 75selenohomocholyltaurine whole body retention (SeHCAT WBR). DESIGN: One hundred and sixty-four patients with chronic diarrhoea were investigated prospectively in two centres (Edinburgh and Sweden) by two different tests which measure bile acid loss or synthesis: the SeHCAT test which measures the 7-day SeHCAT WBR and serum 7 alpha-3ox-C which reflects the rate of bile acid synthesis. RESULTS: Forty-six patients had SeHCAT WBR of less than 10% (19 with ileal disease or resection, nine with idiopathic bile acid induced diarrhoea and 18 with miscellaneous causes for bile acid induced diarrhoea). All patients with ileal or idiopathic disease showed a favorable response to treatment as did 13 of the miscellaneous group. Serum 7 alpha-3ox-C was raised in all subjects with ileal disease/resection, seven patients with idiopathic disease and all subjects in the miscellaneous group who responded to treatment. Sixteen out of 118 patients with SeHCAT WBR greater than or equal to 10% had raised serum 7 alpha-3ox-C. CONCLUSION: The positive predictive value of serum 7 alpha-3ox-C was 74%. The high negative predictive value (98%) of serum 7 alpha-3ox-C indicates the possible use of this test for excluding bile acid malabsorption in this population. All but two subjects who responded to treatment had raised serum 7 alpha-3ox-C concentrations. The possibility that the sensitivity of the test can be improved by repeat testing needs to be further investigated. There was a significant correlation between fractional catabolic rate (FCR) SeHCAT and serum 7 alpha-3ox-C (r = 0.63, P < 0.0001). Further data are required to validate the reference range in women over 70 years of age.

Bone SPECT to assess mandibular invasion by intraoral squamous-cell carcinomas.

UNLABELLED: It is important for head and neck surgeons planning their operative approach to assess tumor infiltration to the mandible by intraoral squamous-cell carcinomas. Two- to 3-hr planar bone scintigraphy is sensitive but not specific in detecting mandibular invasion by tumor. We evaluated 3-hr SPECT bone scintigraphy, which provides better anatomical detail, to determine if it more accurately assesses tumor invasion. METHODS: Thirty consecutive patients with proven intraoral squamous-cell carcinomas were studied. Semiquantitative assessment of the mandible was performed with a three-level graded scoring system, based on comparisons of tracer uptake in the mandible to that in the upper cervical vertebrae and in an unaffected part of mandible. Lesion-to-cervical spine (L/S) count ratios and lesion-to-nonlesion (L/N) count ratios in the mandible on the 3-hr SPECT images were calculated. RESULTS: All patients with proven tumor invasion showed higher tracer uptake than those with normal mandible or other dental diseases. The L/S and L/N count ratios on the SPECT images were significantly higher in patients with tumor invasion than in those without (L/S, p < 0.001; L/N, p < 0.01). L/S ratios provided better differentiation than L/N ratios. CONCLUSIONS: Bone SPECT provides a reliable means of assessing tumor invasion to the mandible by intraoral squamous-cell carcinomas.

Idiopathic bile acid malabsorption: long-term outcome.

OBJECTIVE: Idiopathic bile acid malabsorption (IBAM) is a rare cause of diarrhoea. The natural history of this disorder has not previously been reported. The aim of our study was to determine the long-term outcome in a cohort of patients with severe IBAM using a subjective assessment and by measuring the proportion of 75Se-homocholic acid taurine (75SeHCAT) retained 7 days after its ingestion. PATIENTS AND METHODS: Twenty-three patients with IBAM were identified in 1989. All had responded well to treatment with a bile acid chelator (cholestyramine or aluminium hydroxide). Questionnaires relating to current clinical symptoms and prescriptions were sent to these patients and their general practitioners. 75SeHCAT tests were performed for objective assessment. RESULTS: Three patients were lost to follow-up, three had died owing to malignancy and three had been diagnosed as suffering from inflammatory bowel disease. The mean period of follow-up for the remaining fourteen patients was 99.2 (range 48-140) months. Seven of the patients showed an improvement in symptoms and no longer required treatment with cholestyramine. In the remaining seven symptomatic patients, diarrhoea was well controlled by continued treatment with cholestyramine (five patients) or standard anti-diarrhoeal treatment (two patients). All seven symptomatic patients and three asymptomatic patients underwent repeat 7 day 75SeHCAT tests. The test results in the asymptomatic group had all improved so that the retention of the tracer after 7 days was above 5%; all but two patients in the symptomatic group still had values under 5%. However, the small number of patients in both groups precluded statistical analysis. CONCLUSIONS: IBAM is a rare cause of diarrhoea and should be diagnosed only after malignancy and inflammatory bowel disease have been excluded by rigorous investigations. Patients should be followed up as some develop other serious gastrointestinal diseases. Fifty per cent of the patients in our survey have remitted spontaneously and no longer require medication with bile acid chelators or anti-diarrhoeal agents.

Long-term follow up to determine the prognostic value of imaging after urinary tract infections. Part 1: Reflux.

In 3646 children with at least one confirmed urinary tract infection the prevalence of vesicoureteric reflux at presentation was correlated with progressive renal damage during follow up of not less than two and up to 16 years. Reflux was not demonstrated either at presentation or at any subsequent time in almost one half of the children who suffered progressive renal damage and was not a risk factor for progressive renal damage in boys under 1 year. It was an important risk factor in boys over 1 year and in girls of any age. The risk of progressive renal damage in children in whom micturating cystourethrography (MCU) did not reveal vesicoureteric reflux was substantially greater than in those who indirect isotope voiding study (IVS) did not show reflux. The risk of deterioration for those in whom reflux was demonstrated was similar for both techniques. This discrepancy indicates an appreciably higher false negative rate for the MCU than the IVS. Dilatation of the renal pelvis detected by ultrasound was associated with a significantly increased risk of progressive damage only when associated with reflux, but most children with progressive damage did not have a dilated collecting system at presentation.

Long-term follow up to determine the prognostic value of imaging after urinary tract infections. Part 2: Scarring.

Long term follow up of children with urinary tract infections, in whom imaging investigations were performed at presentation, has been used to identify features that distinguish those at greatest risk of progressive renal damage. No single investigation at presentation was able to predict subsequent deterioration but, by employing a combination of imaging investigations, it was possible to separate groups with high or low probability of progressive damage. In the low risk group the incidence of progressive damage was 0.2% (95% confidence interval (CI) 0 to 1.3%). The combination of both scarring and reflux at presentation, or one only of these but accompanied by subsequent documented urinary tract infection, was associated with a 17-fold (95% CI 2.5 to 118) increase in the relative risk of progressive renal damage compared with children without these features. The recommended combination of investigations at presentation for girls of any age and boys over 1 year is ultrasound and dimercaptosuccinic acid (DMSA) scintigraphy in all, to detect both scarring and significant structural abnormalities, renography in children with dilatation of any part of the urinary tract on ultrasound, to distinguish dilatation from obstruction, and an isotope voiding study in all who have acquired bladder control. This gives the best separation between those at high and those at low risk of progressive damage with least radiation dose and lowest rate of instrumentation. Micturating cystourethrography (MCU) should be restricted to girls who have not acquired bladder control, unless there is reason to suspect a significant structural abnormality such as urethral valves. A single non-febrile urinary tract infection that responds promptly to treatment is not a justification for performing MCU in boys under 1 year or in children of any age with bladder control. No case can be made for any abbreviated schedule of investigation. These risk factors should be taken into account when designing follow up protocols.

Isotope renography in childhood enuresis.

A retrospective review was performed of 100 enuretic children who underwent isotope renography during the period 1981-1989. Studies performed were Tc99mDMSA studies for renal size and to detect renal scarring and renography using Tc99mDTPA or MAG3 to evaluate excretion and detect vesicoureteric reflux. Fifty-five children had microbiological evidence of urinary tract infection (UTI), and 16 (29%) of these had abnormalities on their isotope studies. Forty-five had sterile urine and all had normal isotope studies. Thus despite recent reports of urodynamic abnormalities and increased incidence of reflux in patients with enuresis, our findings indicate that standard nuclear medicine renal studies show few abnormalities in patients with monosymptomatic enuresis. The 29% incidence of abnormal studies in patients with enuresis and UTIs suggests that the presence of infection should be an indication for further investigation in this subgroup of enuretic children.

Gall-bladder and colonic retention of SeHCAT: a re-evaluation.

A number of suggested alternatives and emendations to the 7-day SeHCAT retention test have been compared with whole-body counting. It was found that correction for colonic retention is an unnecessary complication in patients with diarrhoea and that imaging either of the gall-bladder or of the distribution of activity in the intestines at 24 h does not add useful information to the standard 7-day retention measurement. Neither could the patterns of colonic uptake identified in patients following extensive ideal resection or radiotherapy be reproduced in patients with idiopathic diarrhoea. Sadly it must be concluded that neither of these shortened techniques is of clinical value in patients with intact small bowel and that there remains no reliable alternative to the 7-day Se HCAT retention test. The simplest technique the best.

Obstructive defaecation and slow transit constipation: the proctographic parameters.

Twenty-two patients with functional obstructive defaecation were compared with seven patients with slow transit constipation using isotope proctography. The obstructive defaecation patients were unable to perform a complete rectal evacuation (% of the activity evacuated: 54%). The defaecation time in this group was prolonged (120 s) with a lower defaecation rate (0.5%/s) compared with the slow transit constipation subjects (32 s and 1.8%/s). The anorectal angle (ARA) on straining did not change in the obstructive defaecation patients but became more obtuse in the slow transit constipation subjects (P < 0.02). The pelvic floor (PF) descent on straining and evacuation was greater in obstructive defaecation patients compared with the slow transit constipation ones (P < 0.01). Obstructive defaecation is characterised by prolonged defaecation and reduced defaecation rate compared with slow transit constipation. Obstructive defaecation patients present with more acute ARAs on straining, and abnormal perineal descent in contrast to the slow transit constipation ones.

Cholelithiasis and bile acid absorption after truncal vagotomy and gastroenterostomy.

Gallbladder disease in the form of gallstones demonstrated by ultrasonography or previous cholecystectomy was found in 15 of 26 women of median age 69 (range 52-82) years who had had truncal vagotomy and gastroenterostomy performed a median of 27 (range 11-30) years previously, compared with eight of 31 healthy age- and sex-matched controls drawn from the community (P < 0.02). Bile acid malabsorption identified by retention of 23-selena, 25-homotaurocholate (75SeHCAT) occurred in only two of the 26 patients after vagotomy and there was no relationship between retention and the presence or absence of gallbladder disease. The serum concentration of 7 alpha-hydroxycholestenone, an indicator of bile acid turnover, was significantly lower in patients with gallbladder disease after vagotomy than in controls (mean(s.e.m.) 19.1(3.7) versus 31.4(4.4) ng/ml, P < 0.05). Bile acid malabsorption does not play a significant role in the pathogenesis of gallstones after vagotomy but decreased bile acid synthesis may be important. There is no correlation between retention of 75SeHCAT and 7 alpha-hydroxycholestenone levels in patients after vagotomy, indicating that bile acid synthesis and absorption are uncoupled in this situation.

Symptomatology of metastatic prostate cancer: prognostic significance.

OBJECTIVE: To identify the various presenting symptoms in patients with metastatic prostate cancer, quantify the metastatic load for each symptom group and compare their case-specific survival. PATIENTS AND METHODS: A prospective and consecutive series of 279 men with metastatic cancer of the prostate was analysed. Based on the symptom at presentation, six different groups were identified: bladder outflow obstruction, bone pain, anaemia, weight loss, paraplegia and alteration of bowel habit. RESULTS: Significant variations were observed in their metastatic load (Kruskal-Wallis test, P = 0.0035) and in case-specific survival (log-rank test, P = 0.0038). CONCLUSION: Bladder outflow obstruction, bone pain and anaemia not only dictate treatment selection but we provide evidence that each of these symptoms has considerable prognostic significance in patients with metastatic cancer of the prostate.

Evidence for a reflex provoking contraction of the renal pelvis (with some comments on its clinical implications).

The effect of swallowing a small quantity of water or of solid food (biscuit) on the renogram curve was observed in 177 patients. Swallowing provoked contraction of the renal pelvis in 63% of the kidneys with a pelvicalyceal system which was neither obstructed nor dilated, with expulsion of a substantial fraction of the contents within 30 s. This did not occur in obstructed or denervated kidneys, nor in patients with a high transection of the spinal cord. Evidence is adduced that this contraction is mediated reflexly. This effect may be used diagnostically to distinguish physiological dilatation from obstruction. The implications when performing and interpreting renography are discussed.

Prevalence of impaired cerebrovascular reserve in patients with symptomatic carotid artery disease.

Cerebrovascular reserve (CVR) was studied in 104 consecutive patients with symptomatic carotid territory disease and ipsilateral internal carotid artery stenosis. Overall, 30 of 104 patients (29 per cent) had impaired CVR. The frequency of CVR impairment increased with the severity of internal carotid artery stenosis: impairment was present in none of 11 patients with stenosis of less than 50 per cent, four of 24 with stenosis of 50-69 per cent, 14 of 41 with stenosis of 70-89 per cent and 12 of 28 with stenosis of 90-99 per cent. Patients presenting with a stroke were significantly more likely to have impaired CVR than those with transient ischaemic attacks and/or amaurosis fugax (odds ratio 3.7 (95 per cent confidence interval (c.i.) 1.5-9.0)), as were those with a residual neurological deficit (odds ratio 4.3 (95 per cent c.i. 1.6-11.5)) and evidence of infarction from computed tomography (odds ratio 3.8 (95 per cent c.i. 1.6-9.4)).

Bile acid malabsorption in Crohn's disease and indications for its assessment using SeHCAT.

Patients with Crohn's disease who suffer from longstanding diarrhoea that does not respond to conventional treatment pose a common clinical problem. Bile acid malabsorption is a possible cause, although its prevalence and clinical importance is unclear. This paper explores the clinical indications for referring patients with Crohn's disease for bile acid assessment and the extent of bile acid malabsorption in this selected group of patients. The selenium labelled bile acid SeHCAT was used to assess the effect of disease on the integrity of the enterohepatic circulation. Altogether 76% of the patients referred for bile acid assessment had longstanding diarrhoea that had not responded to conventional anti-diarrhoeal treatment or an increase in steroid therapy as their sole or predominant symptom. Ninety per cent of patients with bowel resections, almost exclusively ileocaecal, had abnormal SeHCAT retention (< 5% at seven days). Twenty eight per cent of patients with Crohn's disease who had not undergone resection 28% had a SeHCAT retention < 5%, signifying bile acid malabsorption. Nineteen of 22 patients given cholestyramine treatment subsequent to the SeHCAT test had a good symptomatic response. In conclusion, the prevalence of bile acid malabsorption in this selected group with Crohn's disease is sufficiently high to justify performing the SeHCAT test in order to separate the various differential diagnoses.

99mTc-MDP scintigraphy in ankylosing spondylitis.

99mTechnetium-MDP bone scintigrams in 11 patients with ankylosing spondylitis were reviewed. Increased activity in sacroiliac joints was present in five of 11 cases, all of whom had symptoms of less than 5 years duration. Patients with longstanding disease had normal or low sacroiliac joint activity. In the spine, appearances included diffuse symmetrical, unifocal or multifocal asymmetrical increased uptake involving the costovertebral, costotransverse and facet joints as well as the spinous processes. In advanced disease with extensive ankylosis, the lumbar spine was featureless on scintigraphy, except for focal increased activity at the site of previous fracture in one patient. Of six available views of the sternum, increased uptake was present in five at the manubriosternal joint and five at the sternoclavicular joints. Increased peripheral uptake was mainly in the hips and knees in advanced cases. Plain radiographic changes correlated poorly with scintigraphic changes, scintigraphy detecting considerably more lesions than radiography. Awareness of the scintigraphic appearances of ankylosing spondylitis may lead to diagnosis before the development of radiographic changes and avoid confusion with other pathology. Clinical indications for bone scintigraphy in ankylosing spondylitis are suggested.

Patterns of bone metastasis and their prognostic significance in patients with carcinoma of the prostate.

The different patterns of bone metastasis, metastatic load and their prognostic significance were examined in a consecutive series of 169 men with prostatic cancer and bone metastasis at presentation. Patients with an isolated metastasis in the pelvis or dorsal vertebrae had a better prognosis than those whose metastases were either diffuse or involved more distal sites such as the skull or the sternum, although all of these patients were classified as having M1 disease. Bone metastasis involving an area equivalent to 1 vertebral body equalled a metastatic load of 2. Based on their total metastatic load, 3 prognostic groups were identified with significant differences in case-specific survival despite receiving the same hormonal treatment. When comparing the potential efficacy of various treatments one must stratify the metastatic load, which is a powerful prognostic indicator of the outcome in patients with metastatic carcinoma of the prostate.

Factors influencing the hyperaemic response after carotid endarterectomy.

Transcranial Doppler ultrasonography was used to evaluate serially the changes in middle cerebral artery blood flow velocity (MCAV) in 37 consecutive patients during the first 72 h after carotid endarterectomy to identify factors that may predispose towards postoperative hyperaemia. Within 6 h of endarterectomy, median MCAV in the operated hemisphere was 48 per cent (95 per cent confidence interval 37-60 per cent) above that on admission and remained 27 per cent (95 per cent confidence interval 19-37 per cent) higher at 72 h. There was a similar, but less marked, increase in MCAV in the contralateral middle cerebral artery during the same time period. There was no association between the postoperative increase in MCAV and clinical presentation, admission MCAV, the presence or absence of a residual neurological deficit or infarction on computed tomography before operation, carotid clamp time, shunt usage, internal carotid artery stump pressure or MCAV during clamping. The greatest increase in MCAV was observed in patients with internal carotid artery stenosis > or = 50 per cent and, more particularly, in those with preoperative evidence of impaired cerebrovascular reserve. In the latter patients, MCAV was 100 per cent above the admission level within 12 h of operation and was still 50 per cent raised at 72 h.

Serial imaging of the carotid bifurcation and cerebrovascular reserve after carotid endarterectomy.

A radioisotopic method of quantifying mean cerebral transit time was used to assess the immediate effects of carotid endarterectomy on cerebrovascular reserve (CVR) in 69 patients. In addition, serial postoperative data were acquired on CVR, clinical status and non-invasive imaging of the internal carotid arteries in 56 patients over a period of 6-48 (median 24) months. Twenty-one patients (30 per cent) had preoperative evidence of impaired CVR in the symptomatic hemisphere. Within 4 days of surgery, however, reserve had returned to normal in 17 of the 21 patients. During follow-up, four of the 56 patients developed recurrent stenosis (> 50 per cent) or occlusion of the artery operated on but only two of these had impairment of CVR and none was symptomatic. Three patients suffered recurrent transient ischaemic attacks (TIAs) but none had recurrent internal carotid artery disease or impaired CVR. One patient suffered a TIA in the territory of the non-operated artery during follow-up in association with disease progression and CVR impairment. However, the TIA preceded recognition of either of these changes. Twelve other patients had (or developed) stenosis (> 50 per cent) in the non-operated artery during follow-up but none was symptomatic or developed impairment of CVR. Although assessment of CVR provided useful information on the frequency of haemodynamic compromise before carotid endarterectomy and on the natural history of disease progression, neither serial assessment of reserve nor non-invasive imaging of the carotid bifurcation influenced clinical practice during follow-up.

Immediate effects of carotid clamp release on middle cerebral artery blood flow velocity during carotid endarterectomy.

Transcranial Doppler ultrasound was employed in 44 patients undergoing carotid endarterectomy in order to identify factors associated with the greatest increases in middle cerebral artery blood flow velocity (MCAV) immediately after carotid clamp release and restoration of flow. Previous reports have suggested that such increases might reflect post-ischemic hyperaemia. Overall, the median increase in MCAV on restoration of flow [58 cm/s (95% Cl 44-68)] was greater than the median decrease in MCAV after initial carotid clamping [36 cm/s (95% Cl 26-43), p < 0.0001]. However, the immediate increase in MCAV tended to be transient and, in one patient, may have represented a hyperaemic response to a haemodynamically induced intraoperative neurological deficit. There was no association between the magnitude of MCAV increase and clinical presentation, degree of carotid stenosis, computed tomography scan findings, type of anaesthesia, nor the presence or absence of impaired cerebral vascular reserve, nor the occurrence of intraoperative air embolisation. The greatest increases in MCAV on clamp release were observed in patients with the greatest decreases in MCAV at clamping and those with the lowest internal carotid artery stump pressures. The most likely explanation for the findings is that they represent a transient hyperaemic response to carotid occlusion. It remains unclear whether this phenomenon is mediated by some degree of ischaemic injury or simply by the effect of a sudden surge of blood through low resistance arterioles that have dilated in order to maintain the collateral circulation during carotid clamping.