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Individual patient meta-analysis using information from clinically homogeneous acute pain trials with observations over 24h was used to investigate different ways trials can be analysed and reported. There were 13 third-molar extraction trials, with 1,330 patients using rofecoxib 50mg, 303 using ibuprofen 400mg, and 570 using placebo. Pain relief scores were available at individual time points, plus time to remedication. Many more patients remedicated with placebo than ibuprofen 400mg, and more with ibuprofen than rofecoxib 50mg. Median time to remedication, the proportion remedicated at various times, or survival curves would be useful outcomes. In dealing with missing data points when patients remedicated, baseline observation carried forward was more conservative than last observation carried forward, resulting in higher (worse) NNTs and lower average pain scores after 12 and 24h. Results based on both methods might be sensible for trials longer than eight hours. The distribution of pain relief was highly skewed, especially at later times, when almost no patient was average. Different cut points for pain relief (at least 25, 50 or 75% maxTOTPAR) and longer duration changed the NNT for ibuprofen compared with placebo, but less for rofecoxib, reflecting longer duration of action of rofecoxib. Reporting for each treatment group the percentage of patients with 25, 50 and 75% pain relief at various times after dose, and reporting the proportion of patients with good or complete pain relief, and inadequate pain relief, at each time point, would improve acute pain trial reporting.

Opioids are used increasingly for chronic non-cancer pain. Controversy exists about their effectiveness and safety with long-term use. We analysed available randomised, placebo-controlled trials of WHO step 3 opioids for efficacy and safety in chronic non-cancer pain. The Oxford Pain Relief Database (1950-1994) and Medline, EMBASE and the Cochrane Library were searched until September 2003. Inclusion criteria were randomised comparisons of WHO step 3 opioids with placebo in chronic non-cancer pain. Double-blind studies reporting on pain intensity outcomes using validated pain scales were included. Fifteen randomised placebo-controlled trials were included. Four investigations with 120 patients studied intravenous opioid testing. Eleven studies (1025 patients) compared oral opioids with placebo for four days to eight weeks. Six of the 15 included trials had an open label follow-up of 6-24 months. The mean decrease in pain intensity in most studies was at least 30% with opioids and was comparable in neuropathic and musculoskeletal pain. About 80% of patients experienced at least one adverse event, with constipation (41%), nausea (32%) and somnolence (29%) being most common. Only 44% of 388 patients on open label treatments were still on opioids after therapy for between 7 and 24 months. The short-term efficacy of opioids was good in both neuropathic and musculoskeletal pain conditions. However, only a minority of patients in these studies went on to long-term management with opioids. The small number of selected patients and the short follow-ups do not allow conclusions concerning problems such as tolerance and addiction.

Our objective was to determine the efficacy and safety of valdecoxib (a cyclo-oxygenase 2 inhibitor) in the treatment of arthritis. Randomised, controlled trials comparing 10 or 20mg valdecoxib with placebo or non-steroidal anti-inflammatory drugs (NSAIDs) in patients with active osteoarthritis or rheumatoid arthritis. The manufacturer provided clinical trial reports. Data were combined through meta-analysis. Main outcomes were patient global rating of arthritis, arthritis pain, Western Ontario and McMaster Universities indices for osteoarthritis, American College of Rheumatology indices for rheumatoid arthritis, discontinuation, endoscopic ulcers, clinically significant upper gastrointestinal or renal events. Nine trials (five in osteoarthritis, four in rheumatoid arthritis) were included with 5726 patients. Overall, valdecoxib 10 and 20mg were superior to placebo and equivalent in efficacy to maximum daily doses of NSAIDs. Significantly fewer discontinuations because of gastrointestinal adverse events (4% versus 8%), or endoscopic ulcers of 3mm or more (5% versus 13%) occurred with valdecoxib compared with NSAIDs. Clinically significant upper gastrointestinal events occurred in 2/2733 (0.1%) with valdecoxib compared with 8/1846 (0.4%) with NSAIDs. Rates of clinically significant renal events were the same (2-3%) for valdecoxib and NSAIDs. At an appropriate dose valdecoxib was as effective as NSAIDs in osteoarthritis and rheumatoid arthritis. There were fewer gastrointestinal adverse event withdrawals and endoscopically detected ulcers. Convincing evidence of reduced major gastrointestinal adverse events could not be addressed by the trials.

Aim: To provide a colorectal cancer screening service for the general public, based on the detection of blood in faeces, that was effective, affordable and convenient., Methods: Kits for collecting faecal specimens were sold directly to the public and, after collecting three specimens, kits were transported to the laboratory for testing by an immunochemical procedure involving a positive cut-off value. Reports were sent to participants and their nominated doctors who were requested to provide information on participants testing positive., Results: Over a 10-year period, 35 139 kits were analysed and 5.63% were positive. After follow-up, 7.4% of positive testing participants were found to have colorectal cancer, 23.4% adenomas, 34.6% miscellaneous non-neoplastic pathology and in 25.0% no abnormality was found. Sixty-six per cent of cancers were early stage, Dukes stages A and B. There were 35 139 kits processed on 16 240 individuals, indicating that a number were repeat testing., Conclusions: The screening service was able to detect a high yield of colorectal pathology, especially early stage neoplasia which is curable, and encouraged repeat testing. Education of doctors about how to investigate a positive test, and of participants about symptoms, have been important lessons arising from this screening service.

Single-dose clinical trial methods for evaluating analgesics have been used successfully for over 50 years. The aims of this review were to examine which pain measurement scales have been used in high quality acute pain trials, to investigate other common measurements or characteristics, to confirm that different scales used by standard methods give the same estimate of analgesic effect, to investigate remedication methodologies and the potential of 'time to remedication' as a standard outcome. Published reports of randomised, double blind, placebo-controlled trials, investigating at least 20 adult patients (10 patients per treatment arm) experiencing moderate or severe pain using at least one standard pain intensity or pain relief scale were sought. Key design features, outputs and outcomes were catalogued for each report. The main outcomes reported were misleading, detailing only the mean values of data with a demonstrably skewed distribution. After 50 years, the reporting of results from acute pain trials warrants a fresh look. Possible improvements include reporting the number of patients with certain levels of pain relief, or the actual number (percentage) of patients with a certain level of pain relief at a certain time, or more useful information on remedication from trials of at least 12 h duration. Most useful would be all three. Further exploration would only be possible from analysis at the individual patient level.

There is uncertainty over whether the patient group in which acute pain studies are conducted (pain model) has any influence on the estimate of analgesic efficacy. Data from four recently updated systematic reviews of aspirin 600/650 mg, paracetamol 600/650 mg, paracetamol 1000 mg and ibuprofen 400 mg were used to investigate the influence of pain model. Area under the pain relief versus time curve equivalent to at least 50% maximum pain relief over 6 h was used as the outcome measure. Event rates with treatment and placebo, and relative benefit (RB) and number needed to treat (NNT) were used as outputs from the meta-analyses. The event rate with placebo was systematically statistically lower for dental than postsurgical pain for all four treatments. Event rates with analgesics, RB and NNT were infrequently different between the pain models. Systematic difference in the estimate of analgesic efficacy between dental and postsurgical pain models remains unproven, and, on balance, no major difference is likely.

Purpose: To examine changes in quadriceps and soleus MN pool activity resulting from knee joint effusion over a 4-h period and assess the relationship between the muscles., Methods: A repeated measures before-after trial design was used for this study. Eight, neurologically sound volunteers (age 23.3+/-2.1 yr, height 171.8+/-15.9 cm, mass 65.5+/-17.7 kg) participated in this study. An area superomedial to the patella was cleaned and anesthetized, and 30 mL of sterile saline was injected into the knee joint capsule to mimic mechanical joint effusion. The Hoffman reflex (H-reflex) was elicited by applying a percutaneous stimulus to the appropriate nerve and recording the response through surface electromyography. Soleus and vastus medialis H-reflex measures were collected from each volunteer before, at 30 min, 90 min, 150 min, and 210 min intervals over a 4-h period after knee effusion., Results: All soleus H-reflex measures after effusion (30 min 5.89+/-0.92 V; 90 min 6.16+/-0.48 V; 150 min 6.59+/-0.50 V; 210 min 6.70+/-0.56 V) were increased in relation to the preeffusion measure (5.01+/-0.79 V). All vastus medialis H-reflex measures after effusion (30 min 4.23+/-0.94 V; 90 min 4.15 +/-1.11 V; 150 min 4.16+/-0.57 V; and 210 min 4.99+/-1.23) were decreased in relation to the preeffusion measure (5.88+/-1.44 V; P < or = 0.05)., Conclusions: Afferent activity from the knee joint capsule resulted in an inhibitory effect on the vastus medialis and a facilitatory effect on the soleus. Facilitation of the soleus in cooperation with other lower extremity musculature could be a mechanism for compensation of the inhibited quadriceps to maintain lower kinetic chain function.

The effects of age on cholecystokinin (CCK) release, pancreatic enzyme secretion, and growth of the pancreas mediated by dietary kidney beans or soya beans were evaluated in trials with 30-, 90-, 250-, and 400-day-old rats. Soya beans increased blood CCK and caused hypersecretion of digestive enzymes and rapid pancreatic growth in all rats. Kidney beans also elevated circulating CCK and stimulated enzyme secretion. However, with 90-, 250-, and 400-day-old rats, the secretory responses were attenuated. Furthermore, kidney beans did not induce pancreatic growth in 250- and 400-day-old rats.

The acute effects of kidney bean (Phaseolus vulgaris) E2L2 lectins (PHA) given orally to conscious rats or continually infused into the duodenum of anesthetized rats on blood cholecystokinin (CCK), secretin, and gastrin and on secretion of pancreatic digestive enzymes have been evaluated. PHA increased circulating levels of CCK and secretin but did not alter gastrin. In addition, PHA induced dose-dependent secretion of trypsinogen, chymotrypsinogen, and alpha-amylase by the pancreas in vivo. This pancreas output appeared to be modulated only in part through CCK. Thus pretreatment of rats with a CCK-A receptor antagonist (L-364718) attenuated the immediate (< or = 90 min) pancreas secretory response to PHA but could not prevent a PHA-associated increase in digestive enzyme output in the longer term (after 90 min). In contrast, treatment of rats with L-364718 abolished the stimulatory effects of soyabean trypsin inhibitors on digestive enzyme secretion in both the short and long term. Additional mechanisms or hormones, such as secretin, may play a role in modulating later exocrine pancreas responses to PHA.

Objectives: A systematic review of the analgesic efficacy and adverse effects of single-dose aspirin compared with placebo in postoperative pain., Design: Published studies were identified from systematic searching of bibliographic databases and reference lists of retrieved reports. Summed pain intensity and pain relief data were extracted and converted into dichotomous information to yield the number of patients with at least 50% pain relief. This was used to calculate the relative benefit and number-needed-to-treat for one patient to achieve at least 50% pain relief. For adverse effects, relative risk and number-needed-to-harm were calculated. Sensitivity analyses were planned to test the impact of different pain models, pain measurements, sample sizes, quality of study design, and study duration on the results., Results: Seventy-two randomized single-dose trials met our inclusion criteria, with 3253 patients given aspirin, and 3297 placebo. Significant benefit of aspirin over placebo was shown for aspirin 600/650 mg, 1000 mg and 1200 mg, with numbers-needed-to-treat for at least 50% pain relief of 4.4 (4.0-4.9), 4.0 (3.2-5.4) and 2.4 (1.9-3.2) respectively. Single-dose aspirin 600/650 mg produced significantly more drowsiness and gastric irritation than placebo, with numbers-needed-to-harm of 28 (19-52) and 38 (22-174) respectively. Type of pain model, pain measurement, sample size, quality of study design, and study duration had no significant impact on the results., Conclusions: There was a clear dose-response for pain relief with aspirin, even though these were single dose studies. Adverse effects, drowsiness and gastric irritation were also evident in the single dose studies. The pain relief achieved with aspirin was very similar milligram for milligram to that seen with paracetamol.

Anecdotal and scientific reports have suggested that some female endurance athletes may have an inexplicable imbalance between energy intake and energy expenditure. We compared energy intake (EI) from food diaries (FD) with assessment of free-living energy expenditure (EE) using doubly labeled water (DLW) and a food attitude survey for 7 d in nine female distance runners. Daily EE via DLW (2990 +/- 415 kcal) was greater (P < 0.01) than daily EI via FD (2037 +/- 298 kcal): a 32% imbalance. Body weight did not change during the 7 d (day 1, 55.3 +/- 6.2 kg; day 7, 55.1 +/- 5.6 kg). A positive relationship was observed between EE and body weight (r = 0.82) while a negative correlation existed between EE vs EI (r = -0.83) and between EI vs body weight (r = -0.74). A negative correlation was observed between body weight and food attitude/body image (r = -78), i.e., the heavier women self-reported lower EI and also reported lower body image scores. These female athletes had a significant imbalance between EI and EE by our measures. Since body image and EI were related to body weight, the estimates of EI may be low due to underreporting particularly by the heavier athletes.

Through a retrospective review, we identified 77 previously unreported cases of coccidioidomycosis during HIV infection. Patients were classified into 1 of 6 categories based on their primary clinical presentation: 20 had focal pulmonary disease (Group 1), 31 had diffuse pulmonary disease (Group 2), 4 had cutaneous coccidioidomycosis (Group 3), 9 had meningitis (Group 4), 7 had extrathoracic lymph node or liver involvement (Group 5), and 6 has positive coccidioidal serology without a clinical focus of infection (Group 6). Coccidioidal serologies were positive on initial testing in 83% of the patients in whom such serologic testing was performed. Sera from 39% of patients were positive for TP antibodies while 74% had CF antibodies. Eleven of 12 seronegative patients had pulmonary disease (Group 1 or 2). Serologic results of other patients sent to a single reference laboratory were similar, with 26% positive for immunodiffusion TP antibodies and 79% positive for immunodiffusion CF antibodies. For the 77 patients in this study, the CD4-lymphocyte count was below 0.250 X 10(9) cells/L in 46 of the 55 patients who had this test performed, and a low CD4 count was significantly associated with mortality (p less than 0.01). At the time of follow-up, 32 of the 77 patients (42%) had died. There were significantly more deaths in those with diffuse pulmonary disease (Group 2) than in other groups (p less than 0.001). Amphotericin B, ketoconazole, fluconazole, and itraconazole were all used as antifungal therapies. Outcome could not be related to the therapy used. Of note, 3 patients developed coccidioidomycosis while receiving ketoconazole for other conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

A case of vaginally delivered stillborn female thoracopagus conjoined twins is presented. Each twin had a cleft lip and cleft palate. They shared a common pericardial sac and a common abdominal cavity. The liver was conjoined, and the small bowel was common to both twins. One twin was asplenic. Although the twins were monozygotic, their viscera were neither identical nor mirror-image to each other, and the visceral anomalies were unique to each twin. The hearts were fused, and communications existed between the circulations at the atrial and ventricular levels. One twin had single atrium, solitary (right) ventricle, malposed great arteries, pulmonary valvular atresia and infundibular stenosis, right aortic arch with aberrant left subclavian artery and with left ductus arteriosus, and atresia of the common pulmonary vein. The other twin had two atrial septal defects of the fossa ovalis and sinus venosus types, partial anomalous pulmonary venous connection, persistent left superior vena cava to coronary sinus, solitary (left) ventricle, malposed great arteries, and left aortic arch with aberrant right subclavian artery and with left ductus arteriosus. There was atrial and ventricular fusion. On hypothetical grounds, and in a comparable anatomic situation, salvage of one twin might be possible by surgical means, while the other twin was sacrificed.

The pulmonary vascular bed was evaluated following a Blalock-Taussig shunt performed in 36 patients for decreased pulmonary blood flow. The time of follow-up ranged from one to 21 years after operation. No patients developed severe pulmonary changes in less than eight years after institution of the shunt. Ten of 20 patients having a shunt eight years or longer developed some degree of pulmonary vascular disease, mainly in the form of intimal fibrosis. This was severe in six of the 20 patients. As the duration of the shunt increased, so did the incidence of pulmonary vascular disease.

Two cases are described of sudden death resulting from rupture of small chronic false aneurysm of the left ventricle with secondary hemopericardium. The cases support the point that rupture of chronic false left ventricular aneurysm tends to occur. This appears to be contrary to the potential for chronic true aneurysms of the left ventricle which tend not to rupture. Rupture of true left ventriuclar aneurysm in its deveoping stahe may, however, occur.

In cardiac anomalies causing severe obstruction in the left side of the heart, such as aortic atresia, mitral atresia, or occasionally severe aortic stenosis, maintenance of circulation depends upon shunting of pulmonary venous blood into the right atrium. The usual pathway by which the shunt is achieved is across the atrial septum through the foramen ovale. When this route is closed or severely narrowed, alternate but less common pathways may exist. These involve either anomalous connections of pulmonary veins to systemic veins or communications with the coronary venous system. In the latter, as commonly occurs in aortic atresia, left ventricular myocardial sinusoids carry pulmonary venous blood from the left ventricular cavity and into the cardiac veins. In other instances of severe left-sided obstruction, a direct communication may exist between the left atrium and the coronary sinus.

Among 119 cases of fatal dissecting aneurysm of the aorta, exclusive of those iatrogenically caused or associated with arachnodactyly or aortic stenosis, there were observed 11 cases of congenital bicuspid aortic valve (9%). The ages ranged from 17 to 69 years, five of the patients being 29 years old or younger. Among the latter, three had coarctation of the aorta and one had Turner's syndrome without coarctation. In one of the older patients, aortic insufficiency was present. Hypertension was either established or inferred from cardiac weight in 73% of the cases. In each case, cystic medial necrosis of the aorta was present. Prolapse of valves other than the aortic was observed in 45% of the cases with bicuspid aortic valve. Compared to an estimated incidence of bicuspid aortic valve of about 1 to 2% in the population, the high incidence among subjects with dissecting aneurysm suggests a causative relationship between bicuspid aortic valve and aortic dissecting aneurysm.

Echocardiographic and necropsy studies were performed in 304 patients with various cardiac diseases. The overall prevalence of disproportionate ventricular septal thickening (septal to free wall ratio greater than or equal to 1.3) was 10%. However, it was related to the type of cardiac lesion. Prevalence was high (greater than 20%) in pulmonary stenosis or primary pulmonary hypertension, lower (less than 15%) in Eisenmenger syndrome or aortic or mitral valvular disease and was not present in atrial or ventricular septal defect. In right ventricular overload, prevalence of disproportionate septal thickening correlated with increasing ventricular systolic pressure. None of 16 patients with disproportionate septal thickening studied at necropsy showed marked disorientation of cardiac muscle cells in the ventricular septum, characteristic of genetically transmitted asymmetric septal hypertrophy (ASH). Furthermore, disproportionate septal thickening was demonstrated by echocardiography in only one of 59 first degree relatives of patients with disproportionate septal thickening and associated cardiac diseases. Thus, disproportionate ventricular septal thickening associated with other cardiac diseases usually is due to secondary hypertrophy and is not a manifestation of genetically transmitted ASH.

Among 166 specimens with classical complete transposition, pulmonary or subpulmonary stenosis was present in 22 cases. The bases for obstruction were pulmonary valvular stenosis (one case), membranous subpulmonary stenosis (nine cases), anomalous attachment of the mitral valve to the ventricular septum (five cases) and combinations of causes (seven cases). Conditions contributing to combinations of causes included the above, in addition to accessory mitral or pulmonary valvular tissue and herniation of a tricuspid valvular pouch through a related ventricular septal defect. In addition to the 166 cases mentioned, our collection contained six cases of atypical complete transposition characterized by a conus being present in the each ventricel. In three of these six, subpulmonary stenosis was present and caused by a narrow inlet to the left ventricular conus.

Seven patients with Candida meningitis are reported. These 7, plus 21 previously cited cases, were reviewed. This infection arose by two distinct mechanisms: hematogenous dissemination and direct inoculation. Recent antibiotic therapy, corticosteroid administration and severe underlying diseases were important predisposing factors. Fever, meningismus, elevated CSF pressures and localizing neurologic signs were commonly noted. Organisms were seen on gram-stain of CSF in only 43% of cases. Mortality rate in patients receiving inadequate or no antifungal therapy was high (greater than 90%), while those patients given appropriate antifungal drugs, especially intravenous amphotericin B, had a significantly lower mortality rate (38%). Several factors associated with poor prognosis were delineated in this study: diagnostic interval after symptomatic onset longer than two weeks, CSF glucose levels below 35 mg/100 ml and presence of intracranial hypertension and focal neurologic deficits.

The clinical and pathological data from 46 patients who died during or shortly after coronary bypass surgery and one patient who died shortly after angiography were studied. Each patient was placed into one of three clinical categories of angina pectoris. Twelve were classified as having unstable angina pectoris, 20 as stable severe angina, and 15 as stable moderate angina. No significant difference was found between the three catagories whem age, sex, presence of hypertension, lipid abnormalities, diabetes, smoking, family history of myocardial infarction, or history of previous mycardial infarction were examined. Most patients in all classes of angina had extensive atherosclerotic coronary disease: 12 patients had triple vessel plus left main disease; 25, triple vessel disease; nine double vessel disease; and only one, single vessel disease. There was no difference in severity or distribution of coronary disease when the three catagories of angina were compared. Thirty-six of the 47 patients had evidence of scarring of one or more aspects of the left ventricular wall. There was likewise no significant difference between extent and distribution of myocardial scarring between the three clinical categories. Four of the 12 patients with unstable angina pectoris had pathologic evidence of preoperative myocardial infarction, whereas this was not found in any of the 35 patients with stable angina.

In an infant with patent ductus arteriosus and pulmonary hypertension, elevated pulmonary vascular resistance persisted following ligation of the ductus. Histologic examination of a pulmonary biopsy at two years of age and tissue obtained at autopsy at three years of age showed obstructive pulmonary vascular disease. The question as to whether the organic vascular lesions are secondary to the effects of the patent ductus or part of pulmonary hypertension cannot be resolved. The age of the patient favors a primary etiology.

We recently speculated that mitral-aortic separation (MAS) might be increased in discrete subaortic stenosis (DSS). We have examined this hypothesis in 22 heart specimens in which the subaortic obstruction originated on the muscular ventricular septum below the right aortic sinus, either as a discrete band, an accumulation of several bands or a diffuse ridge, and extended posteriorly into the MAS or anterior leaflet of the mitral valve or both, with a variable relationship to the aortic cusps and sinuses. No specimen had ventricular septal defect, supravalvular aortic stenosis or other features of Shone syndrome. The mean MAS was nearly twice that of 80 normal specimens (4.9 vs 2.5 mm), the range of MAS was increased from normal (0.11 vs 0.7 mm) and the mean diameter of the aortic annulus was decreased compared with the normal specimens, data that will be of interest to echo- and angiocardiographers in the clinical description of DSS, and to the surgeon who must resect these lesions.

Clinically, there is a group of patients with elevated pulmonary arterial pressure in whom the underlying cause is not apparent. The pulmonary arterial wedge pressure is not elevated. For such cases, the designation of primary pulmonary hypertension may be made clinically. From the clinical categorization of primary pulmonary hypertension, three distinct pathologic entities emerge, namely 1) plexogenic pulmonary arteriopathy, 2) recurrent pulmonary thromboembolism, and 3) pulmonary veno-occlusive disease. The plexogenic type is characterized initially by pulmonary arterial vasoconstriction with medial hypertrophy. Secondary proliferative intimal lesions, including the plexiform lesion, develop. Recurrent pulmonary thromboembolism is characterized by the presence of arterial thrombi of varying ages involving the microscopic-sized pulmonary arteries. Thrombi may be embolic in nature or may develop in situ. Pulmonary veno-occlusive disease is characterized by obstructive lesions of pulmonary veins and venules. The clinical presentation of the three pathologic types may be so similar that definitive diagnosis depends upon histologic examination of the lung from tissue obtained either by biopsy or at necropsy.

Two cases of rupture of the right ventricle following closed chest cardiac massage are presented. This is believed to result from trapping of blood in the right ventricle at levels of systemic arterial pressure. In one case there was massive pulmonary embolism which interfered with egress of blood from the right ventricle. In the other case, application of pressure during a closed chest resuscitative attempt might have closed the right ventricular outflow tract.

Specimens of heart from 30 subjects with persistent truncus arteriosus were studied for the nature and sites of coronary arterial origin. These factors were related to the sinuses of the truncus valve. Bicuspid truncal valve was observed in six cases (20%) and tricuspid in 21 cases (70%). Single coronary artery was observed in four cases (three with tricuspid and one with quadricuspid truncal valves). In three other cases the coronary arteries arose separately but near one another. There was a strong tendency for the left coronary artery to arise from a more posterior level than it does normally from the aorta. It was common for the posterior descending artery to arise from the left circumflex artery. This arrangement was noted in eight of 25 cases (32%) with single posterior descending coronary artery. In five other cases, two posterior descending arteries were present, one arising from the left circumflex and the other from the right coronary artery.

The pathologic appearance of pulmonary arteries subjected to balloon dilation was studied in four subjects with stenosis of pulmonary arteries. Nine vessels were dilated. Successful dilation in seven vessels was accompanied by intimal disruption and tearing of the media. In one vessel, at the site of a previous surgical procedure, dilation could not be accomplished. Histologically, this vessel was encased by reactive fibrous tissue, which may have precluded successful dilation. In one case, simultaneous rupture of the dilating balloon and the left pulmonary artery occurred. Morphologic examination could not adequately explain the cause of vessel rupture. Among the six vessels successfully dilated and studied 4 to 14 months after the dilation, the postdilation luminal diamter had been maintained. Tears in the intima and media as seen histologically had been filled in by scar tissue. In one artery a dilated segment distal to a residual obstruction revealed marked intimal proliferation.

Asymmetric septal hypertrophy, or ASH, is a genetically determined myocardial disorder that is transmitted as an autosomal dominant trait. ASH is characterized by a disproportionately thickened ventricular septum that contains numerous hypertrophied, bizarrely-shaped and disorganized cardiac muscle cells. Disproportionate hypertrophy of the ventricular septum has also been observed in association with certain congenital cardiac malformations. To determine whether such congenital cardiac malformations are part of the disease spectrum of genetically determined ASH, cardiac pathologic observations were made in eight patients with disproportionate septal thickening (ventricular septal to posterobasal left ventricular free wall thickness ratios of 1.5 to 2.5) and the following three categories of associated lesions: 1) parachute deformity of the mitral valve (occurring either as an isolated lesion or with ventricular septal defect, coarctation of the aorta, supravalvular ring of the left atrium, or double outlet right ventricle); 2) complete interruption of the aortic arch; and 3) ventricular septal defect. The arrangement of cardiac muscle cells in the disproportionately thickened ventricular septum was normal in six of the eight patients; in the other two patients (one with parachute deformity of the mitral valve and one with ventricular septal defect) numerous bundles of hypertrophied cardiac muscle cells were interlaced in a disorganized fashion among more normally arranged bundles of cells. First degree relatives of six of the eight patients were studied by echocardiography and found to have normal ventricular wall thicknesses and septal-free wall ratios. It is concluded that disproportionate ventricular septal thickening may occur in patients with a variety of congenital heart malformations, but that such a finding is not necessarily a manifestation of the disease spectrum of genetically determined ASH.

From ten patients aged 15 to 40 years with chronic rheumatic valvular disease and histologically proved Aschoff bodies of active rheumatic myocarditis, the valves were evaluated for incidence, distribution and degree of severity of active inflammation. Prior to death, there had been clinical evidence of active rheumatic fever. In each case, active rheumatic valvulitis was present in at least one valve. Of the individual valves studied, 83% were involved by active inflammation of the leaflets or the anulus or both. The aortic valves was involved in 100% of cases, the mitral valve in 86%, the tricuspid valve in 78% and the pulmonary valve in 70%. The mitral and aortic valves were most frequently involved, but the mitral and tricuspid valves were most severely involved when affected. In every case, active rheumatic lesions of the left atrial appendage were present, but these tended to be less widely distributed than the myocardial Aschoff bodies. The high incidence of active valvulitis supports the concept that chronic fibrosing rheumatic valvular disease results from recurrent active inflammation. Such inflammation may occur without clinical suspicion of active rheumatic fever.

Six cases of classical dissecting aneurysm of the aorta complicating aortic valvular disease in which aortic stenosis was dominant are described. In three of the cases the aortic complication occurred after the natural aortic valve had been replaced by a prosthetic valve. The longest postoperative period was four months. The factor common to all reported cases in our series was cystic medial necrosis of the aorta. The authors agree with the concept of McKusick and associates that aortic dissecting aneurysm complicating aortic valvular disease is an association other than chance and is related to cystic medial necrosis of the aorta. The latter, in turn, is a consequence of the altered hemodynamics of aortic valvular disease, particularly stenosis.

A variant of double-outlet right ventricle (DORV) associated with common atrioventricular (A-V) canal was identified. As yet, this syndrome has not been successfully repaired. Of 16 patients with this diagnosis, 14 had the diagnosis confirmed at postmortem examination and two had the diagnosis confirmed by exploratory cardiotomy. The 16 patients were divided into two groups according to the position of the cardiac apex: group 1, ten patients with levocardia, and group 2, six patients with dextrocardia and ventricular inverson. When pulmonary stenosis was present, the clinical presentation was similar to that in tetralogy of Fallot, and when such stenosis was not, the presentation was similar to that in ventricular septal defect with bidirectional shunting. The electrocardiogram had the typical feature of common A-V canal. The right ventricular angiocardiogram had features typical of DORV. The left ventricular angiocardiogram revealed left ventricular outflow deformity typical of A-V canal in patients with levocardia but not in those with dextrocardia. Splenic anomalies were commonly seen (nine of the 16 patients). Asplenia was present in seven, and polysplenia in two. Ten patients had persistent left superior vena cava, seven had common atricum, six had anomalous pulmonary venous connection, and three had subaortic stenosis. Twelve of the 16 patients had pulmonary stenosis. Of the 16, 14 had common A-V canal (Rastelli type C) and two had a ventricular septal defect of the persistent common A-V type.

Abnormalities of cardiac rhythm have been reported by others in patients with a persistent left superior vena cava. We present the histological findings from postmortem examination of the cardiac conduction system of two such patients. The first patient was a schoolboy who died suddenly and unexpectedly. His sinus node was abnormally small, his A-V node contained numerous venous lacunae and was stretched out beneath the enlarged coronary sinus, both A-V node and His bundle were dispersed in the central fibrous body in a fetal pattern, and isolated fragments of A-V nodal tissue were connected to the myocardium at the crest of the interventricular septum. The second patient complained of palpitations many months prior to surgical correction of an interventricular septal defect; his postoperative course included multiple arrhythmias and he died suddenly on the 16th postoperative day. Although his sinus node was histologically normal, the nutrient artery contained a polypoid fibromuscular mass virtually occluding its lumen; his A-V node and His bundle were also dispersed in the central fibrous body in the fetal pattern, and the A-V node contained numerous venous lacunae as well as being histologically disorganized in its cytological pattern. These anatomical findings may indicate a basis for various forms of cardiac electrical instability, and deserve consideration in the future evaluation of any patient found to have a persistent left superior vene cava, but particularly if there is clinical evidence suggesting an arrhythmia or conduction disturbance.

The clincopathologic features of 14 cases of sudden death attributable to dysrhythmias associated with the myxomatous mitral valve are described. The patients were 14-59 years old (mean 27 +/- 11 years). Eleven were female and three male. Of the seven ECGs available, none showed prolongation of the QT interval, but two showed repolarization abnormalities. The material was classified according to the degree of prolapse in the pathologic specimen. When obvious prolapse was found, the expected auscultatory findings had been documented. In three cases there was minimal prolapse, casting some doubt on the hypothesis that traction on the papillary muscles or diastolic dumping of the leaflets may be implicated in the pathogenesis of the dysrhythmias. In one of the cases with minimal prolapse there was a strong family history of sudden death. Endocardial friction lesions were present in 11 cases, including two of the three with minimal prolapse. In five cases there was a thrombotic lesion in the angle between the posterior leaflet and the left atrial wall containing fibrin and platelets. These abnormalities may be important in the pathogenesis of the ventricular dysrhythmias.

The coronary arteries were examined in 60 specimens from patients with mitral stenosis. In three, localized obstruction was nonatherosclerotic in nature (in one, arterial dysplasia; in two, embolic). In 18 of the remaining 57 cases (31.5%), significantly obstructive atherosclerosis in one or more segments of the coronary arterial system was found. This represented 46% of the males and 27% of the females. The incidence of involvement of three or more arteries by significantly obstructive atherosclerosis was 39%, while in a cited series of subjects with angina pectoris three or more vessels were involved in 79% of the cases. It may be concluded that, on the average, the distribution of lesions in patients with mitral stenosis and significant coronary atherosclerosis is less wide than in subjects with clinical coronary disease.

Absence of continuity between the heart and the pulmonary arteries has the potential for total correction. When the pulmonary arteries are narrow, a palliative first stage systemic-pulmonary arterial anastomosis serves to enlarge the pulmonary arteries so that, with time, they become of adequate caliber for total correction. In a case with bilateral ductal origin of pulmonary arteries, palliative anastomosis between the aorta and right pulmonary artery was performed as the first stage in a program planned for ultimate total correction.

Uremic pericarditis may complicate either acute or, more commonly, chronic renal failure. When dialysis is not employed, uremic pericarditis is usually a preterminal event and is characterized by a serofibrinous exudation of an amount inadequate to cause cardiac tamponade. Nevertheless, cardiac tamponade may uncommonly be observed in nondialyzed patients. Cardiac tamponade, which may be life-threatening, is more common in dialyzed than in nondialyzed patients with chronic renal failure. The primary causes of cardiac tamponade in uremic pericarditis in order of decreasing frequency are (1) pericardial effusion, usually of the serosanguineous type, (2) massive hemorrhage into the pericardial sac and (3) collagenization of pericardial exudate. From pathologic evidence, the following forms of therapy appear appropriate to manage uremic pericarditis that has reached the stage of causing cardiac tamponade. For effusion, pericardiocentesis or parietal pericardiectomy are logical procedures. Massive hemorrhage into the pericardial sac is usually attended by clotting and requires pericardiotomy and evacuation of clot. Collagenization of exudate yields an encasing, fibrous shell over the heart and requires decortication, as is practised in classical constrictive pericarditis.

In a 45-year-old man with hypereosinophilic syndrome, cardiac disease, mainly endocardial thickening and extensive mural thrombosis of both ventricles, was confirmed at autopsy. Early in the course of the disease, right ventricular endocardial biopsy had demonstrated the basic process. Restriction in filling and contraction of the right ventricle were demonstrated by functional studies. By echocardiographic study, progressive reduction in size of the right ventricular cavity and premature opening of the pulmonary valve were demonstrated, while this method was less adequate in identifying the process in the left ventricle.