Characterisation of collagen from normal and scoliotic human spinal ligament.

Acid-soluble and pepsin-soluble collagens have been isolated from spinal ligaments of normal and scoliotic individuals. Polyacrylamide gel electrophoresis of native and cyanogen bromide-treated collagens, and amino acid analysis, showed that the ligament collagen is almost all of the Type I variety with only trace amounts of Type III present. There was no evidence for abnormal ratios of collagen alpha-chains, or underhydroxylation of proline and lysine in the scoliotic ligament. These results indicate that collagen biochemistry is normal with respect to type, post-translational modification and cross-linking in spinal ligaments of patients with idiopathic scoliosis. Elastin and proteoglycan were only minor components of the ligaments. The nature of the non-collagenous part of the ligament is unknown, although it contains some proteins with a hydrophobic nature.

On the Lagrangian/Eulerian modeling of dispersed droplet inertia: internal circulation transition.

This article addresses a limitation of Lagrangian methods for droplet tracking, when approaching the transition point of internal circulation within droplets. Laminar multiphase flow with dispersed droplets in a co-flowing airstream is considered. Analytical and numerical formulations of droplet motion are developed based on a Lagrangian finite difference method of droplet tracking. Cases of both high and low relative Reynolds numbers are formulated. The role of interfacial drag in cross-phase momentum exchange increases at higher relative Reynolds numbers. A new transition criterion is developed to characterize conditions leading to shear-driven non-uniformities of velocity within a droplet. This criterion entails a momentum Biot number, in analogy with the Biot number criterion for conjugate heat transfer problems involving conduction and convection. At sufficiently high momentum Biot numbers, appreciable changes of velocity within a droplet imply that Lagrangian methods become unsuitable and transition to Eulerian volume averaging is needed. Predicted results of Lagrangian modeling of droplet motion in a co-flowing airstream are presented and discussed.

Delayed presentation of traumatic ventricular septal defect and mitral leaflet perforation.

A case of intracardiac stabbing is reported. The victim sustained injuries disproportionate to his initial presentation. These included a ventricular septal defect and mitral valve leaflet perforation. The need for immediate referral to a cardiothoracic unit and the importance of the use of echocardiography is stressed. This enables the safest and most appropriate management of potentially lethal injuries.

Elective femoro-femoral bypass for operations on the heart and great vessels.

Femoro-femoral bypass with "circulatory arrest" is no longer used in routine cardiac operations. Its use today is normally limited to operations wherein access to the arch of the aorta is required or the thoracic aorta is to be temporarily occluded. We have recently encountered three patients presenting with complications of previous operations. In all three, the use of this technique allowed us to approach the defect safely.

Malignant fibrous histiocytoma in thoracic surgical practice.

Malignant fibrous histiocytoma is a rare, although increasingly recognized, deep-seated pleomorphic sarcoma. A primitive tumor, it arises from tissue histiocytes and typically occurs in the extremities. Primary intrathoracic tumors have been reported rarely. The presentation of malignant fibrous histiocytoma in our series of seven patients has been varied. Two cases presented as solitary primary intrapulmonary tumors, two as primary chest wall tumors, one as an anterior mediastinal mass, one as a retroperitoneal tumor extending cephalad through the diaphragm, and one as a late metastasis from a primary pelvic site. Malignant fibrous histiocytoma is aggressive, with a propensity for early local and distant spread; three of the patients in our series died of progressive disease within 17 months of operation. The histologic nature of the tumor makes diagnosis on small biopsy specimens difficult and frequently misleading. We would suggest a policy of open biopsy to obtain adequate and representative specimens for histologic study and preoperative computed tomographic scanning to augment the clinical search for metastatic disease and to facilitate planning of subsequent radical, excisional operation. The preoperative use of deep x-ray therapy or the newer chemotherapeutic agents may reduce tumor bulk and thereby facilitate radical operation, which presently appears to be the most appropriate primary modality of treatment of malignant fibrous histiocytoma.

Alpha-stat acid-base regulation during cardiopulmonary bypass improves neuropsychologic outcome in patients undergoing coronary artery bypass grafting.

Neuropsychologic impairment in patients undergoing cardiopulmonary bypass may be associated with cerebral blood flow changes arising from different management protocols for carbon dioxide tension during bypass. Seventy patients having coronary artery bypass grafting were randomized to either pH-stat or alpha-stat acid-base management during cardiopulmonary bypass with a membrane oxygenator. In each patient, cerebral blood flow (xenon 133 clearance), middle cerebral artery blood flow velocity (transcranial Doppler sonography), and cerebral oxygen metabolism (cerebral metabolic rate and cerebral extraction ratio) were measured during four phases of the operation: before bypass, during bypass (at hypothermia and at normothermia), and after bypass. A battery, of neuropsychologic tests were also conducted before and 6 weeks after the operation. During hypothermic (28 degrees C) bypass, cerebral blood flow was significantly (p < 0.001) greater in the pH-stat group (41 mlx100 gm(-1)xmin(-1); 95% confidence interval 39 to 43 mlx100 gm(-1)xmin(-1)) than in the alpha-stat group (24 mlx100 gm(-1)xmin(-1); confidence interval 22 to 26 mlx100 gm(-1)xmin(-1)) at constant pressure and How. Arterial carbon dioxide tensions were 41 mm Hg (40 to 41 mm Hg) and 26 mm Hg (25 to 27 mm Hg), respectively; pH was 7.36 (7.34 to 7.38) and 7.53 (7.51 to 7.55), respectively. Middle cerebral artery flow velocity was significantly (p < 0.05) reduced in the alpha-stat group to 87% (77% to 96%) of the prebypass value, whereas it was significantly (p < 0.05) increased (152%; 141% to 162%) in the pH-stat group. Cerebral extraction ratio for oxygen demonstrated relative cerebral hyperemia during hypothermic (28 degrees C) bypass in both the pH-stat and alpha-stat groups (0.12 [0.11 to 0.14] and 0.25 [0.22 to 0.28], respectively); however, hyperemia was significantly more pronounced in the pH-stat group, indicating greater disruption in cerebral autoregulation. Neuropsychologic impairment criteria of deterioration in results of three or more tests revealed that a significantly (Fisher's exact test, p = 0.02) higher proportion of patients in the pH-stat group fared poorly than in the alpha-stat group at 6 weeks (17/35, 48.6% [32% to 65.1%], and 7/35, 20% [6.7% to 33.2.2%], respectively). In conclusion, patients receiving alpha-stat management had less disruption of cerebral autoregulation during cardiopulmonary bypass, accompanied by a reduced incidence of postoperative cerebral dysfunction.

Cardiopulmonary bypass: perioperative cerebral blood flow and postoperative cognitive deficit.

Increased cerebral blood flow occurring during cardiopulmonary bypass as a result of changes in arterial carbon dioxide tension during acid-base regulation is thought to increase postoperative cognitive dysfunction. We studied 70 patients undergoing coronary artery bypass procedures who were randomized to two different acid-base protocols: pH-stat or alpha-stat regulation. Cerebral blood flow, cerebral blood flow velocity, and cerebral oxygen metabolism were measured before bypass, during bypass (hypothermic [28 degrees C] and normothermic phases), and after bypass. Detailed cognitive tests were conducted before operation and 6 weeks after operation. During 28 degrees C bypass, cerebral blood flow was significantly (p < 0.05) higher in the pH-stat group than in the alpha-stat group (41 +/- 2 versus 24 +/- 2 mL.100 g-1.min-1), and cerebral blood flow velocity was significantly increased in the pH-stat group and significantly decreased in the alpha-stat group (152% +/- 10% versus 78% +/- 7%). Cerebral extraction ratio of oxygen demonstrated a relatively greater disruption of autoregulation in the pH-stat group than in the alpha-stat group with relative hyperemia of 0.12 +/- 0.02 versus 0.26 +/- 0.03, respectively, during 28 degrees C bypass. Using the criterion of deterioration in three or more neuropsychologic tests, a significantly higher proportion of patients in the pH-stat group fared less well than in the alpha-stat group (49% +/- 17% versus 20% +/- 13%). Patients in the alpha-stat group experienced less disruption of cerebral autoregulation during hypothermic cardiopulmonary bypass, and this was accompanied by a reduction in postoperative cognitive dysfunction.

Relative changes in cerebral blood flow during cardiac operations using xenon-133 clearance versus transcranial Doppler sonography.

BACKGROUND: Changes in cerebral blood flow (CBF) during cardiac operations have implications in terms of postoperative neurologic and neuropsychological dysfunction. Current techniques of CBF measurement are cumbersome and invasive. Transcranial Doppler sonography offers a noninvasive means of assessing changes in CBF. The aim of this study was validation of this technique with existing methods of CBF measurement during cardiac operations. METHODS: We compared the changes in CBF using xenon-133 clearance with changes in middle cerebral artery velocity by transcranial Doppler sonography (VMCA) using pH-stat and alpha-stat acid-base management during cardiopulmonary bypass. Measurements were taken (1) before bypass, (2) at 28 degrees C on bypass, (3) at 37 degrees C on bypass, and (4) after bypass. Relative changes in CBF and VMCA, calculated as the percent change from the prebypass baseline value normalized to 100%, were used in this analysis. RESULTS: During the hypothermic phase of cardiopulmonary bypass, CBF and VMCA increased by 45.9% and 51.8%, respectively (p < 0.001), during pH-stat acid-base management but decreased by only 26.4% and 22.4%, respectively (p < 0.0001), during alpha-stat acid-base management. Linear regression analysis of the absolute changes in CBF (mL . 100 g-1 . min-1) and VMCA (cm/s) showed a significant correlation (r = 0.60; r2 = 0.36; p < 0.0001), but a better correlation was obtained when relative changes in CBF and VMCA were compared (r = 0.89; r2 = 0.79; p < 0.0001). CONCLUSIONS: Measurements of VMCA, expressed as relative changes of a pre-cardiopulmonary bypass level (using the noninvasive transcranial Doppler sonographic technique), can be used to examine CBF changes during cardiopulmonary bypass.

St. Thomas' Hospital cardioplegia: enhanced protection with exogenous creatine phosphate.

BACKGROUND: Experimentally, creatine phosphate (CP) improves postischemic recovery of function and reduces postischemic arrhythmias. METHODS: We studied 50 patients undergoing valve replacement. They were randomized into either a control group, who received St. Thomas' Hospital cardioplegic solution No. 1, or a CP-treated group, receiving the same cardioplegic solution plus CP (10 mmol/L). There were no preoperative clinical differences between groups. Assessment was by electrocardiographic analysis, inotropic drug requirement, quantitative birefringence, myocardial high-energy phosphate content, function, and semiquantitative ultrastructural assessment. RESULTS: Direct-current shocks were reduced in the CP-treated group (0.88 +/- 0.15) compared with the control group (1.40 +/- 0.14; p < 0.02), as was the total number of joules (22.0 +/- 3.5 versus 34.4 +/- 3.7, respectively; p <0.02). The incidence of spontaneous sinus rhythm was higher in the CP-treated group (40% versus 8%; p < 0.05) and the incidence of postoperative arrhythmias, lower (8% versus 32%; p < 0.05). Prolonged inotropic administration (12 hours or longer) occurred in fewer patients in the CP-treated group (4% versus 28%; p < 0.05). Response to inotropic support (in the subset of patients requiring this treatment) was significantly greater in the CP-treated group than in the control group. There were no differences in recovery of function, birefringence changes, myocardial high-energy phosphate content, or ultrastructure between groups. CONCLUSIONS: St. Thomas' Hospital cardioplegic solution No. 1 plus CP enhanced myocardial protection and conferred a direct benefit to the patient by reducing postoperative arrhythmias and need of prolonged inotropic support.

Subjective reports of cognition in relation to assessed cognitive performance following coronary artery bypass surgery.

Evidence has accumulated to indicate that a proportion of patients who undergo coronary artery bypass surgery (CABS) do develop significant cognitive deficits. This study examines whether those patients who report cognitive deterioration after CABS do show cognitive changes as assessed by neuropsychological testing. The patients who considered that aspects of their cognitive function had deteriorated, were not found to have reduced functions as assessed on appropriate neuropsychological tests. When mood state was examined, it was found that those who report a deterioration in a particular cognitive function, tended to have significantly higher levels of depression as assessed by the Beck Depression Inventory and, to a lesser extent, have higher levels of state anxiety. These findings emphasise that subjective reports of cognitive function following CABS do not reflect actual changes in cognition but rather appear to be sensitive to mood state.

Incidence and patterns of depression following coronary artery bypass graft surgery.

A number of studies have examined the impact of coronary artery bypass graft surgery (CABG) on mood by means of cross-sectional analyses. These studies have provided a "snapshot" view of the numbers of patients showing psychological disturbance. To examine both the incidence and patterns of depression, 121 patients undergoing routine elective CABG were assessed preoperatively and postoperatively at 8 days, 8 weeks, and 12 months on the Beck Depression Inventory (BDI). The incidence findings suggested a small, transient increase in the number of patients with depression shortly after surgery. The preoperative score on the BDI was the best predictor of postoperative depression at all times of measurement. Discriminant function analysis on the patterns of depression indicated that trait anxiety maximally separated those patients who were depressed pre- and postoperatively from those only depressed shortly after the operation. The findings emphasize the value of examining patients' levels of anxiety and depression prior to surgery.

Collagen stability and cross-linking in normal and kyphoscoliotic mouse intervertebral discs.

Intervertebral discs of the cervical-thoracic region of the spine of BDL mice which are homozygous for the ky gene mutation undergo degeneration. Discs from these mice have a normal collagen content and undergo normal collagen cross linking prior to the appearance of degenerative changes. The major reducible collagen cross-link formed in discs of these mice and in normal CBA strain mice is hydroxylysino-5-ketonorleucine. These results and other previous results indicate that the discs in the ky mouse develop degenerative disease due to an extrinsic factor rather than to an intrinsic abnormality of their extracellular matrix. The extrinsic factor has been identified as spinal muscle atrophy.

Disc failure in a Björk-Shiley mitral prosthesis.

The case of a 50-year-old man is presented who underwent reoperation for a malfunctioning Björk-Shiley spherical valve which had been inserted 14 years previously. The patient made a satisfactory recovery after surgery. Examination of the explanted valve revealed that a segment of the pyrolytic carbon disc was missing. There was no evidence of embolization.

Survival following pulmonary metastasectomy.

One hundred and fifty-six thoracic operations have been performed over an 8-year period, from 1980 to 1987, for 118 patients with pulmonary metastases. In 27 instances, the disease has been bilateral requiring a midline approach or sequential lateral thoracotomies. Resection was achieved by wedge excision in 74%, lobectomy in 16%, pneumonectomy in 4%, lobectomy plus wedge excision in 2%, bilobectomy in 1%, segmentectomy in 2% and segmentectomy plus wedge excision in 1%. The operative mortality for the group as a whole was 1.6% per patient (70% confidence limits CL. 0.6%-4.2%) and 1.2% per operation (70% CL. 0.5-3.2%). Actuarial survival for the histological subgroups at 2 and 5 years were: carcinoma 50% (+/- 11% standard error) and 35% (+/- 12%), sarcoma 59% (+/- 10%) and 51% (+/- 12%), teratoma 89% (+/- 5%) and 84% (+/- 7%) respectively. No patient following resection for metastatic melanoma was alive at 2 years. The survival in the teratoma group was significantly higher than in the other groups (P less than 0.001 carcinoma; P less than 0.01 sarcoma; P less than 0.001 melanoma). Survival in all groups was significantly greater than for the melanoma group. Metastasectomy is well tolerated by the patient. Worthwhile longterm survival is obtained in those patients in whom the primary disease has been controlled and all secondary disease is encompassed by the proposed surgery.

Cerebral blood flow during cardiopulmonary bypass.

In a study of the cerebral consequences of cardiopulmonary bypass (CPB), we have assessed cerebral blood flow (CBF) by intra-arterial Xenon 133 clearance, utilising a Novocerebrograph 10a, before, during and immediately following CPB. All patients (n = 51), under the care of a single surgical team underwent elective coronary revascularisation using a standardised anaesthetic and surgical protocol. CBF, measured as the initial slope index (ISI), fell significantly from before (median 22.5) to on bypass (median 20) (Wilcoxon P less than 0.005) and was significantly increased in the immediate post-bypass period (median 28) compared with pre-bypass (Wilcoxon P less than 0.001). Scattergrams reveal CBF to be independent of arterial pressure (BP) but show an important relationship between arterial PaCO2 and CBF. The correlations between PaCO2 and CBF prior to bypass (r = 0.46 P less than 0.005) and post-bypass (r = 0.46 P less than 0.001) are very similar, whilst on bypass, the correlation, although remaining significant, is reduced (r = 0.31 P less than 0.02). The median values for arterial PaCO2 are low throughout the study (pre-bypass median 33 mmHg, on bypass median 28 mm Hg and post-bypass median 36 mm Hg). The maintenance of PaCO2 within the normal range of 35-45 mm Hg may minimise the risk of low CBF due to hypocarbia which could theoretically be harmful in patients known to be at risk of both short term and long term cerebral dysfunction.

Hyperperfusion and cerebral dysfunction. Effect of differing acid-base management during cardiopulmonary bypass.

Alterations in cerebral blood flow (CBF) occurring during cardiopulmonary bypass (CPB), which are thought to be responsible for increased morbidity, are probably related to changes in arterial carbon dioxide during acid-base management. In this study, 70 patients undergoing elective coronary artery bypass surgery (CABS) were randomised to one of two differing, but widely practised, cardiopulmonary bypass acid-base protocols; pH-stat and alpha-stat. Cerebral blood flow was measured during surgery using the xenon-133 isotope clearance technique. Cerebral oxygen metabolism was measured as the cerebral metabolic rate for oxygen (CMRO2) and matching of the cerebral blood flow to oxygen demand as the cerebral extraction ratio for oxygen (CERO2). Detailed neuropsychological tests were conducted in all patients before surgery and repeated at 6 weeks after surgery for assessment of changes in cognitive function. During hypothermic (28 degrees C) CPB, CBF was significantly greater (P < 0.001) in the pH-stat group (41 ml/100 g per min; 95% confidence intervals (CI), 39-43) than in the alpha-stat group (24 ml/100 g per min; 95% CI, 22-26). The cerebral extraction ratio for oxygen indicated a degree of mismatch of cerebral perfusion and demand during CPB in both pH-stat and alpha-stat groups (0.12; 95% CI, 0.11-0.14 and 0.25; 95% CI, 0.22-0.28, respectively). This mismatch was far more pronounced in the pH-stat group than in the alpha-stat group, indicating greater disruption in cerebral autoregulation in the former group.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of differing acid-base regulation on cerebral blood flow autoregulation during cardiopulmonary bypass.

Cerebral dysfunction following cardiopulmonary bypass may be aggravated by altered autoregulation of cerebral blood flow. We have used trans-cranial Doppler to measure middle cerebral artery blood flow velocity during cardiopulmonary bypass managed by either pH-stat or alpha-stat acid-base protocols. Fourteen patients were studied, 7 in each group. During bypass at 28 degrees C, patients underwent incremental alterations in mean arterial pressure from 20-90 mmHg, maintaining systemic perfusion flow at 1.75 L/min per m2. The cerebral extraction ratio of oxygen was measured to indicate matching of cerebral blood flow to demand. The pH-stat group showed a pressure passive cerebral circulation with significant (r = 0.999, P less than 0.05) increase in blood flow velocity with increasing arterial pressure. This also occurred in alpha-stat group during the pressure range of 20-50 mmHg (r = 0.951, P less than 0.05). During the pressure range of 50-90 mmHg in alpha-stat group the change in flow velocity (0.16 cm/sec per mmHg) was significantly (P less than 0.05) less than that in pH-stat group (0.58 cm/second per mmHg). The cerebral extraction ratio of oxygen was less depressed in the alpha-stat group than in the pH-stat group, indicating more appropriate matching of cerebral blood flow and tissue demand. These results suggest that, during alpha-stat managed cardiopulmonary bypass, cerebral blood flow velocity is less subject to wide pressure alteration than pH-stat.

A clinical comparative study between crystalloid and blood-based St Thomas' hospital cardioplegic solution.

OBJECTIVE: Myocardial protection with blood cardioplegia during cardiac surgery is increasingly preferred, but few studies have compared the protective effects of crystalloid cardioplegia to the same solution with blood as the only variable. This clinical study compared the protective effects of crystalloid or blood-based St. Thomas' Hospital cardioplegic solution No. 1. METHODS: Fifty higher risk patients undergoing elective coronary artery bypass surgery, with an ejection fraction less than 40%, were randomly allocated to receive cold (4 degrees C) intermittent crystalloid St. Thomas' No. 1 cardioplegia (n = 25), or a similar blood-based solution (n = 25) with a haematocrit of 10-12%. We determined (1) peri-operative and post-operative arrhythmias, (2) left and right ventricular function (24 h) using the thermodilution technique, (3) left ventricular high-energy phosphate content sampled before ischaemia, the end of ischaemia and the end of bypass. RESULTS: Pre-operative haemodynamic data, aortic cross-clamp and bypass times were similar in both groups of patients; there was no mortality. At the end of ischaemia there were no differences in ATP content between groups but creatine phosphate was maintained at a significantly (P < 0.007) higher level in the blood-based St. Thomas' cardioplegia group than the crystalloid St. Thomas' cardioplegia group (20+/-2 (SE) vs. 13+/-1 micromol/g dry wt, respectively). Return to spontaneous sinus rhythm was significantly (P = 0.002) increased in the blood-based St. Thomas' cardioplegia group (96%) compared to the crystalloid St. Thomas' cardioplegia group (60%). Early post-operative ventricular dysfunction occurred in both groups, but normal LV function (stroke work index) recovered significantly (P = 0.043) more rapidly (by 2 h) in the blood-based St. Thomas' cardioplegia group of patients. CONCLUSIONS: In a higher risk (EF < 40%) group of patients undergoing elective cardiac surgery, addition of blood to an established crystalloid cardioplegic solution significantly enhanced myocardial protection by reducing arrhythmias, improving rate of recovery of function and maintaining myocardial high-energy phosphate content during ischaemia.

Paraprosthetic leak: a complication of cardiac valve replacement.

Paraprosthetic leak (PPL) is a rare but potentially serious complication of cardiac valve replacement. Between 1974 and 1988, 1175 prosthetic valves were implanted in 1026 patients by one cardiac surgeon at St. Thomas' Hospital, London. Of these 539 (52.5%) were aortic (AVR), 334 (32.6%) mitral (MVR), 7 (0.7%) tricuspid, and 144 (14%) AV and MV double valve replacements (DVR). There were only 2 triple valve replacements. The prosthetic valves implanted were the Starr-Edwards (7%), Bjork Shiley (11.8%), Lillehei-Kaster (23%), Carpentier-Edwards bioprosthesis (35.2%), Duromedics bileaflet (16.4%) and a variety of other mechanical and bioprosthetic valves (6.6%). Over the 15 year period there were a total of 82 (7%) valve failures of which PPL was diagnosed in 29 (2.5%) valves in 24 patients. Presenting features included cardiac decompensation in 72%, bacterial endocarditis in 12% and haemolytic anaemia in 12%. One patient (4%) had no symptoms. Nineteen patients underwent re-operation. Median time to re-operation was 15 months (range 1-65 months) with a re-operative mortality of 22%. Clinical evidence of prosthetic valve infection was found in 79% of MVR and 67% of AVR. A heavily calcified aortic annulus, found in 47% of patients, may also have contributed to PPL after AVR.

Is the undeniably palpable liver ever 'normal'?

A study of whether the lower border of the normal liver, if it extended below the costal margin, could be reliably identified by clinical examination was undertaken in 42 patients in whom there was no clinical, biochemical or scintographic evidence of liver disease. Two clinical observers independently agreed that in 10 of these patients the liver extended infracostally. However, scintiscanning demonstrated that 30 patients had livers extending below the costal margin and that 2 of the 10 livers clinically identified did not in fact lie infracostally. Thus whilst the normal liver commonly extended below the costal margin, recognition of this extension by clinical methods occurred no more frequently than would be expected by chance. It is concluded that the confident clinical finding of a liver projecting below the costal margin should suggest that the organ is abnormal.