Validation of a computerised logMAR visual acuity measurement system (COMPlog): comparison with ETDRS and the electronic ETDRS testing algorithm in adults and amblyopic children.

BACKGROUND/AIM: The COMPlog clinical visual acuity measuring system is being developed for both routine and research use. This study aimed to validate its performance in amblyopic children and both normal and diseased adults against the gold standard ETDRS chart and the E-ETDRS computerised acuity measurement algorithm. METHOD: Timed test and retest fully interpolated five letters per line logMAR visual acuity measurements were taken for 70 adults and 59 amblyopic children using the ETDRS chart and the COMPlog visual acuity measurement system. 39 of the adults also underwent computerised acuity testing using the E-ETDRS testing algorithm. The tested adults included normals as well as subjects with a range of ocular diseases. The methods of Bland and Altman were employed with test-retest variability (TRV) expressed as 95% confidence limits for agreement. RESULTS: No significant bias was observed between the gold standard ETDRS acuity measurements and those taken with either COMPlog or E-ETDRS. TRVs of +/-0.12 logMAR and +/-0.10 logMAR were respectively found for COMPlog measurements in the amblyopic children and adult groups compared with +/-0.12 logMAR for the ETDRS chart in both groups. The TRV of the E-ETDRS system was slightly greater at +/-0.16 logMAR. Median testing times for COMPlog and ETDRS were 95 and 85 s and 66 and 56 s respectively in the paediatric and adult groups and 120 s for the E-ETDRS measurements on adults. DISCUSSION: COMPlog measurements agree well with and are similarly reliable to the gold standard ETDRS chart with comparable test times. E-ETDRS algorithm measurements took approximately twice as long.

Epidural cooling for spinal cord protection during thoracoabdominal aneurysm repair: A five-year experience.

PURPOSE: We developed and applied a method for providing regional spinal cord hypothermia with epidural cooling (EC) during thoracoabdominal aneurysm (TAA) repair. Preliminary results indicated significant reduction in spinal cord ischemic complications (SCI), compared with historical controls, and a 5-year experience with EC was reviewed. METHODS: From July 1993 to September 1998, 170 patients with thoracic aneurysms (n = 14; 8.2%) or TAAs (types I and II, n = 83 [49%]; type III, n = 66 [39%]; type IV, n = 7 [4.1%]) were treated with EC. An earlier aneurysm resection was noted in 44% of patients, an emergent operation was noted in 20% of patients, and an aortic dissection was noted in 16% of patients. The EC was successful (mean cerebrospinal fluid [CSF] temperature at cross-clamp, 26.4 +/- 3 degrees C) in 97% of cases, with all 170 patients included in an intention-to-treat analysis. The operation was performed with a clamp/sew technique (98% patients) and selective (T(9) to L(1) region) reimplantation of intercostal vessels. Clinical and EC variables were examined for association with operative mortality and SCI by means of the Fischer exact test, and those variables with a P value less than.1 were included in multivariate logistic regression analysis. RESULTS: The operative mortality rate was 9.5% and was weakly associated (P =.07) with SCI; postoperative cardiac complications (odds ratio [OR], 35. 3; 95% CI, 5.3 to 233; P <.001) and renal failure (OR, 32.2; 95% CI, 6.6 to 157; P <.001) were the only independent predictors of postoperative death. SCI of any severity occurred in 7% of cases (type I/II, 10 of 83 [12%]; all other types, 2 of 87 [2.3%]), versus a predicted (Acher model) incidence of 18.5% for this cohort (P =. 003). Half the deficits were minor, with good functional recovery, and devastating paraplegia occurred in three patients (2.0%). Independent correlates of SCI included types I and II TAA (OR, 8.0; 95% CI, 1.4 to 46.3; P =.021), nonelective operation (OR, 8.3, 95% CI, 1.8 to 37.7; P =.006), oversewn T(9) to L(2) intercostal vessels (OR, 6.1; 95% CI, 1.3 to 28.8; P =.023), and postoperative renal failure (OR, 23.6; 95% CI, 4.4 to 126; P <.001). These same clinical variables of nonelective operations (OR, 7.7; 95% CI, 1.4 to 41.4; P =.017), oversewn T(9) to L(2) intercostal arteries (OR, 9.7; 95% CI, 1.5 to 61.2; P =.016), and postoperative renal failure (OR, 20.8; 95% CI, 3.0 to 142.1; P =.002) were independent predictors of SCI in the subgroup analysis of high-risk patients, ie, patients with type I/II TAA. CONCLUSION: EC has been effective in reducing immediate, devastating, total paraplegia after TAA repair. A strategy that combines the neuroprotective effect of regional cord hypothermia, avoiding the sacrifice of potential spinal cord blood supply, and postoperative adjuncts (eg, avoidance of hypotension, CSF drainage) appears necessary to minimize SCI after TAA repair.

Initial experience with endovascular aneurysm repair: comparison of early results with outcome of conventional open repair.

PURPOSE: To determine the safety, effectiveness, and problems encountered with endovascular repair of abdominal aortic aneurysm (AAA). Initial experience with endoluminal stent grafts was examined and compared with outcome for a matched concurrent control group undergoing conventional operative repair of AAA. METHODS: Over a 3-year period, 30 patients underwent attempts at endovascular repair of infrarenal AAA. Of the 28 (93%) successfully implanted endografts, 8 were tube endografts, 8 bifurcated grafts, and 12 aortouniiliac grafts combined with femorofemoral bypass. Most of the procedures were performed in the past year because the availability of bifurcated and aortoiliac endografts markedly expanded the percentage of patients with AAA who might be treated with endoluminal methods. The follow-up period ranged from 1 to 44 months, with a mean value of 11 months. RESULTS: Endovascular procedures demonstrated significant advantages with respect to reduced blood loss (408 versus 1287 ml), use of an intensive care unit (0.1 versus 1.75 days), length of hospitalization (3.9 versus 10.3 days), and quicker recovery (11 versus 47 days). Although the total number of postoperative complications was identical for the two groups, the nature of the complications differed considerably. Local and vascular complications characteristic of endovascular repair could frequently be corrected at the time of the procedure and tended to be less severe than systemic or remote complications, which predominated among the open surgical repair group. On an intent-to-treat basis, 23 (77%) of the 30 AAAs were successfully managed with endoluminal repair. The seven (23%) failures were attributable to two immediate conversions caused by access problems, three persistent endoleaks, one late conversion caused by AAA expansion, and one late rupture. CONCLUSIONS: Although less definitive than those for conventional operations, these early results suggest that endovascular AAA repair offers considerable benefits for appropriate patients. The results justify continued application of this method of AAA repair, particularly in the treatment of older persons at high risk.

Thoracoabdominal aneurysm repair: perspectives over a decade with the clamp-and-sew technique.

OBJECTIVES: Experience over a decade with thoracoabdominal aortic aneurysm (TAA) repair using a clamp-sew technique was reviewed to compare overall results with alternative operative methods. SUMMARY BACKGROUND DATA: Controversy continues as to the optimal technique for TAA repair, with frequent contemporary emphasis on bypass-distal perfusion methods. Proponents of this technique claim improved results compared to those of historic control subjects in the parameters of operative mortality, postoperative renal failure, and lower extremity neurologic deficit. METHODS: Over the interval from 1987 to 1996, 160 TAA repairs (type I, 32%; type II, 15%; type III, 34%; and type IV, 19%) were performed in 157 patients with a mean age of 70 years and a male-to-female ratio of 1/1. Clinical features included ruptured TAA (10%), urgent operation (22.5%), and aortic dissection (18%). Operative management used a clamp-sew technique with regional hypothermia for spinal cord (epidural cooling, since 1993) and renal protection. Variables associated with the endpoints of operative mortality or major morbidity, particularly spinal cord injury, were assessed with Fisher exact test and logistic regression; late survival was estimated with the Kaplan-Meier method. RESULTS: In-hospital mortality was 9% and was associated with operation for rupture (p < 0.005) or other acute presentation (p < 0.001). After multivariate analysis, the postoperative complication renal failure (relative risk, 6.5 [95% confidence interval, 1.8-23.6, p = 0.004]) and significant spinal cord injury (relative risk, 16.5 [95% confidence interval, 3.2-83.2, p = 0.001]) were associated independently with operative mortality. Paraparesis-paraplegia occurred in 7%, an incidence significantly (p < 0.001) less than that (18.7%) predicted for this cohort from published models. Variables associated (univariate analysis) with this complication included TAA rupture (p < 0.0001), other acute presentation or dissection (p < 0.001), prolonged (>6 hours) operation (p < 0.04), and excessive (>3 L) transfusions (p < 0.02). Operation for acute presentation or dissection (relative risk, 7.9 [95% confidence interval, 1.7-37.7, p = 0.009]) and prolonged surgery [relative risk, 7.5 [95% confidence interval, 1.5-35.3, p = 0.01]) retained independent association with paraplegia-paraparesis after multivariate analysis. Dialysis was needed in 2.5%. Late survival at 1 and 5 years was 86 +/- 2.9% and 62 +/- 5.8%, respectively. CONCLUSIONS: These data compare favorably with those from contemporary reports using other operative strategies and do not support routine adoption of bypass-distal perfusion as the preferred technique for TAA repair.

Magnetic resonance angiography in the management of lower extremity arterial occlusive disease: a prospective study.

PURPOSE: We conducted a prospective study to clarify the clinical utility of magnetic resonance angiography (MRA) in the treatment of patients with lower extremity arterial occlusive disease. METHODS: During the interval of September 1993 through March 1995, 79 patients (43% claudicants, 57% limb-threatening ischemia) were studied with both MRA and contrast arteriography (ANGIO) and underwent intervention with either balloon angioplasty (9%), surgical inflow (28%), or outflow (63%) procedures. MRA and ANGIO were interpreted by separate blinded vascular radiologists, and arterial segments from the pelvis to the foot were graded as normal or with increasing degrees of mild (25% to 50%), moderate (51% to 75%), or severe (75% to 99%) stenosis or occlusion. Treatment plans were formulated by the attending surgeon and were based initially on hemodynamic, clinical, and MRA data and thereafter with ANGIO. Additional study surgeons formulated independent and specific treatment plans based on MRA or ANGIO alone. Indexes of agreement (beyond chance) for arterial segments depicted by MRA and ANGIO were assessed (kappa value), and treatment plans formulated were compared (chi-square). RESULTS: Precise agreement (%) and the percent of major discrepancies (segment classified as normal/mild stenosis on one study and severe stenosis/occlusion on the other) between MRA and ANGIO for respective arterial segments was as follows: common and external iliacs (n = 256) 77/3.5; superficial femoral and above-knee popliteal (n = 255) 73/6.7; below-knee popliteal (n = 131) 84/3.8; infrapopliteal runoff vessels (n = 864) 74/12.4; pedal vessels (n = 111) 69/19.8 Kappa values indicated moderate agreement (between MRA and ANGIO) beyond chance for all arterial segments. Treatment plans formulated by the attending surgeon, the MRA surgeon, and the ANGIO surgeon agreed in more than 85% of cases. Inability of MRA to assess the significance of inflow disease and inadequate detail of tibial/pedal vessels were the principal deficiencies of MRA in those cases where it was considered an inadequate examination. CONCLUSION: These findings suggest MRA and ANGIO are nearly equivalent examinations in the demonstration of infrainguinal vascular anatomy. MRA is an adequate preoperative imaging study (and may replace ANGIO), particularly in those circumstances when the risk of ANGIO is increased or when clinical and hemodynamic evaluation predict the likelihood of straightforward aortofemoral or femoral-popliteal reconstruction.

Renal artery reconstruction for the preservation of renal function.

PURPOSE: We reviewed a 13-year experience with an emphasis on long-term survival and renal function response when renal artery reconstruction (RAR) was performed primarily for the preservation or restoration of renal function in patients who had atherosclerotic renovascular disease. METHODS: From January 1, 1980, to June 30, 1993, 139 patients underwent RAR for renal function salvage and were retrospectively reviewed. Inclusion criteria were either preoperative serum creatinine level > 2.0 mg/dl (67% of patients) or RAR to the entire functioning renal mass irrespective of baseline renal function. Patient survival was calculated by life-table methods. Cox regression analysis was used to determine relative risk (RR) estimates for the late outcomes of continued deterioration of renal function and late survival after RAR. A logistic regression model was used to evaluate variables associated with perioperative complications. RESULTS: Clinical characteristics of the cohort were notable for advanced cardiac (history of congestive heart failure, 27%; angina, 22%; previous myocardial infarction, 19%) and renal disease (serum creatinine level < 2.0 mg/dl, 33%; 2.0 mg/dl to 3.0 mg/dl, 40%, > 3.0 mg/dl, 27%). Cardiac disease was the principle cause of early (6 of 11 operative deaths) and late death. Operative management consisted of aortorenal bypass in 47%, extraanatomic bypass in 45%, and endarterectomy in 8%; 45% of patients required combined aortic and RAR. The operative mortality rate was 8%; significant perioperative renal dysfunction occurred in 10%. Major operative morbidity was associated with increasing azotemia (RR = 2.1; p = 0.001; 95% confidence interval [CI], 1.3 to 4.7 for each 1.0 mg/dl increase in baseline creatinine level). Of those patients who had a baseline creatinine level > or = 2.0 mg/dl, 54% had > or = 20% reduction in creatinine level after RAR. Late follow-up data were available for 87% of operative survivors at a mean duration of 4 years (range, 6 weeks to 12.6 years). Actuarial survival at 5 years was 52% +/- 5%. Continued deterioration in renal function occurred in 24% of patients who survived operation, and eventual dialysis was required in 15%. Deterioration of renal function after RAR was associated with increasing levels of preoperative creatinine (RR = 1.6; 95% CI, 1.2 to 1.8; p = 0.001 for each 1.0 mg/dl increment in baseline creatinine level), and inversely related to early postoperative improvement in creatinine level (RR = 0.41; 95% CI, 0.2 to 0.9; p = 0.04). CONCLUSIONS: Intervention before major deterioration in renal function and an aggressive posture toward the frequently associated coronary artery disease are necessary to improve long-term results when RAR is performed for renal function salvage.

Simultaneous aortic and renal artery reconstruction: evolution of an eighteen-year experience.

PURPOSE: We reviewed an 18-year experience with combined abdominal aortic and renal artery reconstruction (AOR) with a particular focus on patients' clinical risk profile and surgical results in contemporary practice as compared with earlier experience. METHODS: One hundred seventy patients underwent AOR during the interval January 1, 1976 to June 30, 1994. To examine parameters representative of current practice, the cohort was divided into group I patients (n = 110) treated before 1990 and group II (n = 60) treated between 1990 and 1994. Median follow-up duration for the entire cohort was 8.4 +/- 0.6 years. Renal artery reconstruction patency and patient survival rates were calculated by life-table methods. Logistic and Cox regression analysis were used to determine predictors of perioperative and long-term morbidity/mortality rates. RESULTS: Although demographic features changed little over the review period, the detection (56% vs 73%, p = 0.03) and treatment with percutaneous transluminal coronary angioplasty/coronary artery bypass grafting (11% vs 40%, p = 0.0001) of associated coronary artery disease were more frequent in group I patients. The operative mortality rate for the entire cohort was 6.5% (group I = 9% vs group II = 2%, p = 0.06). Changing trends of surgical techniques over the review period included (group I vs II, respectively) increased use of bilateral simultaneous renal artery repair (12% vs 25%, p < 0.005) and transaortic endarterectomy as the renal artery reconstruction technique (3% vs 25%, p < 0.0001). Favorable response in blood pressure control was noted in 68% of group II patients. The cumulative 5-year survival rate for all patients was 75% with an initial serum creatinine of 2.0 mg/dl or greater being the only negative predictor of late survival after regression analysis. CONCLUSION: The current operative mortality rate for AOR is in the range anticipated for aortic surgery alone, and this appears to be related to improved detection and treatment of associated coronary artery disease and intervention before major deterioration in renal function. These findings coupled with currently available natural history data relative to renovascular disease justify an aggressive approach with AOR when significant renal artery stenosis is detected during evaluation of aortic disease.

The durability of different reconstructive techniques for atherosclerotic renal artery disease.

PURPOSE: Among various surgical techniques for renal artery reconstruction (RAR), anatomic aortorenal bypass has been the preferred standard. Yet concern regarding origin of the bypass from a diseased aorta and desire to avoid a major aortic operation in these patients who are often at poor risk has led to increasing use of extraanatomic bypass grafting, particularly hepatorenal and splenorenal bypass. This study was conducted to compare the safety and long-term performance of these different techniques of renal artery reconstruction. METHODS: We reviewed a 15-year (1976 to 1991) experience with 323 surgical RAR performed in 285 patients with atherosclerotic renovascular disease. Long-term patency and survival rates were analyzed by life-table methods. Variables potentially affecting early failure of the RAR and perioperative and late mortality rates were examined by Cox proportional hazards models. RESULTS: Diffuse atherosclerosis characterized the patients' clinical profile. Clinically evident coronary artery disease was present in 54% of patients, and some degree of renal insufficiency was present in 60%. Ninety-five percent of patients had hypertension with poor control of hypertension seen in 50%. Aortic disease necessitated combined aortic grafting and RAR in 43% of the study group. Various techniques of RAR were used as follows: endarterectomy or patch angioplasty, 8.5%; extraanatomic bypass grafting, 37% (hepatorenal, 62; splenorenal, 52; iliorenal, 7); and aortorenal bypass grafting, 54% (native aorta, 34; combined aortic graft and RAR, 140). Early failure of the RAR occurred in 5% of cases, and the operative mortality rate for the entire cohort was 5.6%. Median follow-up duration was 9.4 years. A comparison of early and late patency for the major types of RAR revealed equivalent (p = 0.44) performance of aortorenal and extraanatomic bypass grafting. Perioperative complications occurred more frequently (p < 0.02) in patients undergoing combined operations. The cumulative 5-year survival rate for all patients was 75%. CONCLUSIONS: Because extraanatomic bypass grafting can provide long-term results equivalent to aortorenal bypass grafting, the choice among techniques for RAR in patients with diffuse atherosclerosis should be based on both technical and operative safety considerations, rather than adherence to aortorenal bypass grafting as an inherently superior technique.

Fever in pheochromocytoma.

BACKGROUND: Fever is an infrequently reported finding in patients with pheochromocytoma. Fever in patients with pheochromocytoma may be caused by the tumor, an infection or other factors, each of which will dictate different treatment strategies. METHODS: To determine the incidence, cause, and significance of fever in patients with pheochromocytoma, we reviewed the medical records of 50 hospitalizations of 48 patients. Patients were categorized by the presence or absence of fever. Body temperature elevation, duration of hospitalization in the period prior to surgery or death, age, sex, race, other conditions that could have been responsible for the febrile episode (comorbid events), location, gross and microscopic features of the tumors, and plasma and urine hormone levels were tabulated. The results were compared between the two groups of patients. RESULTS: Fever was present in 14 (28%) of 50 hospitalizations, seven patients (50%) of whom had pheochromocytoma multisystem crisis. Patients with fever and pheochromocytoma were significantly more likely to have a comorbid event, larger tumor, necrosis within the tumor, higher urinary metanephrine levels, longer duration of hospitalization prior to surgery, and to be non-white. Comorbid events included both infectious and noninfectious potential causes of fever. CONCLUSIONS: Fever is common in patients with pheochromocytoma. The causes may be multifactorial and often include an associated illness. A thorough search for coexisting disease is indicated. While fever may prolong hospitalization, it does not portend a disastrous outcome.

The diagnostic value of upper gastrointestinal radiography.

We reviewed the indications for and results of 788 consecutive upper gastrointestinal radiographs (UGIs) performed for ambulatory patients. Sixty-three percent of tests were ordered for the evaluation of abdominal pain, dyspepsia, or esophageal reflux. Of these tests, only 4.8% yielded results of major clinical importance to patient management. The yield for patients greater than 50 years of age was greater than for patients less than 50, 6.9 versus 3.0% (p = 0.04). There was a significant increase in yield with increasing age (chi trend = 11.6, p less than 0.001). Among patients with an indication of esophageal reflux alone (n = 62), there were no patients younger than age 60 with a test result that would significantly affect therapy or outcome. Among patients evaluated for fecal occult blood or weight loss (n = 120), 11.7% of tests ordered showed a finding of major clinical importance. In this group, the yield was higher in those greater than or equal to 50 years of age than in those less than 50, 14.7 versus 6.7%, (p = 0.2). These results indicate that UGIs ordered to evaluate pain or symptoms of esophageal reflux in the absence of bleeding or weight loss rarely yield results that significantly influence therapy. Such patients may be best served by an initial trial of empiric therapy or some other test. The UGI has greatest value when indications for it include bleeding or weight loss.

Is upper gastrointestinal radiography necessary in the initial management of uncomplicated dyspepsia? A randomized controlled trial comparing empiric antacid therapy plus patient reassurance with traditional care.

STUDY OBJECTIVE: To compare two strategies for the evaluation and management of patients who have had acute dyspepsia for four days or more: empiric high-dose antacid therapy combined with patient reassurance (empiric care) versus therapy based on prompt upper gastrointestinal radiography (traditional care). DESIGN: Prospective, randomized trial. The patients in the empiric care group were reassured that upper gastrointestinal radiography was not necessary and were subsequently treated with high-dose empiric antacid therapy (15-30 ml of high-potency antacid one and three hours after meals and at bedtime). The traditional care group after meals and at bedtime). The traditional care group received upper gastrointestinal radiography as part of the initial evaluation. Subsequent treatment was determined by individual physicians based on test results. SETTINGS: Fee-for-service, hospital-based primary care practice and Veteran's Administration medical center outpatient clinic. PATIENTS: All patients were less than 70 years of age and without gastrointestinal bleeding, anemia, significant weight loss, or other specified symptoms of severe acid peptic disease. Fifty patients were randomized to traditional care, and 51 to empiric care. Pre-randomization clinical features were identical with the exception of sex distribution and baseline disability. MEASUREMENTS AND MAIN RESULTS: After six months of follow-up, there were no significant differences in symptom scores, disability, satisfaction, and quality of life measures (as measured by the Sickness Impact Profile scores) between the two groups. Findings were unchanged when adjusted for sex, study site, alcohol consumption, and cigarette smoking. Of the radiographs obtained in the traditional care group, 13 (27%) showed duodenal ulcer disease, gastritis, or duodenitis. There were no serious complications of ulcer disease or therapy noted in either group. The average costs per patient associated with traditional care at one study site were greater, $286 versus $116 (p less than 0.0001). CONCLUSIONS: Select patients with dyspepsia receiving a combination of reassurance and empiric antacid therapy do as well as patients whose initial management strategy includes upper gastrointestinal radiography, at a substantially lower cost.

The effect of a new branched chain--enriched amino acid solution on postoperative catabolism.

Branched-chain amino acids (BCAAs) may regulate muscle amino acid flux. Metabolic studies of both experimental animals and humans utilizing comparatively large amounts of BCAAs infused with hypocaloric glucose have shown that catabolism and proteolysis can be blunted. These studies suggested that the nitrogen-sparing properties of amino acid solutions used in postoperative trauma or sepsis might be improved by increasing the amount of BCAAs. This hypothesis was tested on ten patients undergoing operations of moderate severity utilizing a peripheral amino acid mixture with a branched-chain:non-branched-chain ratio of 45:55% given in 5% dextrose. The patients received 1.7 gm of protein equivalent/kg of ideal body weight in 5% dextrose-crystalloid solution with a concentration of 3.5% amino acids for the first 5 postoperative days. Nitrogen balance, 3-methylhistidine excretion, blood chemistries, and plasma amino acid profile tests were done daily. The results showed that nitrogen equilibrium was maintained for 5 postoperative days without any untoward effects on patients, their surgical wounds, or hepatic function. Plasma amino acids showed no significant changes from baseline with the exception of elevations of the BCAAs. We conclude that this 45% BCAA-enriched solution may be safely administered to patients with postoperative traumatic injury and results in nitrogen equilibrium over a 5-day period.

Infusion of branched-chain enriched amino acid solution in patients with hepatic encephalopathy.

Hospitalized patients with hepatic insufficiency often suffer from severe catabolic states and are in urgent need of nutritional support during their acute illness. Protein intolerence, however, remains a significant problem with respect to the provision of adequate nutrition, either enterally or parenterally. The following report is an anecdotal series of 63 consecutive patients in a large urban hospital treated prospectively with nutritional support using a prototype high branched-chain amino acid solution (FO80) given by technique of total parenteral nutrition by the subclavian or internal jugular route with hypertonic dextrose. Sixty-three patients, of which 42 had chronic liver disease (cirrhosis) with acute decompensation and 17 with acute hepatic injury as well as four with hepatorenal syndrome, are the subject of this report. All required intravenous nutritional support and were either intolerant to commercially available parenteral nutrition solutions or were in hepatic encephalopathy at the time they were initially seen. The cirrhotic patients had been hospitalized for a mean of 14.5 +/- 1.9 days before therapy, had a mean bilirubin of 13 mg/100 ml, and had been in coma for 4.8 +/- 0.7 days despite standard therapy. Patients with acute hepatitis had been in the hospital for 16.2 +/- 4.1 days before therapy, had a mean bilirubin of 25 mg/100 ml, and had been in coma 5.2 +/- 1.6 days before therapy. Routine tests of liver function, blood chemistries, amino acids, EEGs, and complex neurological testing including Reitan trailmaking tests were used in the evaluation of these patients. Up to 120 grams of synthetic amino acid solution with hypertonic dextrose was tolerated in these patients with improvement noted in encephalopathy of at least one grade in 87% of the patients with cirrhosis and 75% of the patients with hepatitis. Nitrogen balance was achieved when 75 to 80 grams of synthetic amino acids were administered. Survival was 45% in the cirrhotic group and 47% in the acute hepatitis group. Encephalopathy appeared to correlate with individual amino acids differentially in the various groups and with the ratio between the aromatic and the branched-chain amino acids. Ammonia did not correlate with either the degree of encephalopathy or improvement therefrom. In 24 Patients therapy for hepatic encephalopathy was limited to infusion of the branched-chain enriched amino acid solution only, with wake-up in 66% of this group. The results strongly suggest that in protein intolerant patients requiring nutritional support, infusion with branchedchain enriched amino acid solutions is well tolerated with either no worsening of or improvement in hepatic encephalopathy coincident with the achievement of nitrogen equilibrium and adequate nutritional support.

Comparison of distal and proximal splenorenal shunts: a randomized prospective trial.

Controversy still surrounds the place of portalsystemic shunting in the therapy of bleeding esophageal varices. Recently, a selective shunt, the distal splenorenal shunt, has achieved some degree of popularity and, apparently, is associated with less chronic encephalopathy. Because of this, a trial was initiated at the Massachusetts General Hospital and continued at the University of Cincinnati Medical Center, prospectively randomizing central and distal splenorenal shunts in consecutive elective cases of patients with established variceal bleeding. Preoperative evaluation included endoscopic examination at the time of hemorrhage, angiography and upper gastrointestinal series, emphasis on mental function including EEG, amino acids, neurologic examination, as well as standard liver chemistries. Nineteen patients underwent central splenorenal shunts and 23 distal splenorenal shunt. There was one operative death from hemorrhagic pancreatitis in a Child's Class A patient with distal splenorenal shunt. Four late deaths, from gunshot wound, auto accident, overwhelming pneumonitis similar to postsplenectomy syndrome, and metastatic carcinoma (2.5 years after operation), have been recorded in the distal splenorenal shunt group, and none in the central splenorenal shunt group. On follow-up angiographic examination, six shunts have clotted, with three patients requiring reoperation, generally mesocaval shunt. There has been no chronic encephalopathy, three individual episodes of encephalopathy, two in the central splenorenal shunt group and one in the distal splenorenal shunt group, two associated with gastrointestinal bleeding and one with intercurrent infection and overdiuresis. Follow-up liver chemistries and amino acids which may be useful as an indicator of hepatic function suggest that although the distal shunt group had a better amino acid pattern before operation, branched-chain amino acids tend to become lower in the distal group while remaining the same in the central group. Aromatic amino acids increase post shunt, equally in the two groups. The results do not support the contention that distal splenorenal shunt is associated either with greater survival or freedom from encephalopathy than central splenorenal shunt, a small side-to-side shunt. Ascites seems better controlled by the central splenorenal shunt.

Comparative study of parenteral nutrition in renal failure using essential and nonessential amino acid containing solutions.

One of the controversies in the nutritional therapy of patients with renal failure is the respective role of either the essential amino acids alone or both essential and nonessential amino acids in the treatment of these patients. During a period when essential amino acids were unavailable, a large number of patients with acute renal failure was treated with a modified solution consisting of both essential and nonessential amino acids. The solution consisted of 3.8 grams of nitrogen in 46 per cent dextrose in units of 750 milliliters. A mean of 2,322 +/- 151 calories was administered to this group of patients. Over-all, the survival rate was 9 per cent as opposed to 75 per cent in the previous group treated with essential amino acids only and hypertonic dextrose, 40 per cent, in the group of historical controls treated with hypertonic dextrose. The groups are not strictly comparable because the group treated with both essential and nonessential amino acids may not have been strictly comparable, particularly with a slightly longer duration of renal failure, higher initial blood urea nitrogen level and lower urine volume than either of the other two groups previously treated. While adequate stabilization, but not a decrease in the blood urea nitrogen level, may be achieved from the use of both essential and nonessential amino acids, the excessive mortality seen may be related to differential effects of essential amino acids in supporting host resistance, while nonessential amino acids do not. The results of this study suggest that, until the safety and efficacy of a mixture of essential and nonessential amino acids in renal failure can be demonstrated, essential amino acids remain the treatment of choice as the nutritional support of patients with acute tubular necrosis.

Plasma amino acids as predictors of the severity and outcome of sepsis.

Sepsis is a major catabolic insult resulting in a peripheral energy deficit which is made up in part by increased breakdown of lean body mass and oxidation of amino acids, principally the branched chain amino acids. The prognosis in any given case of sepsis is difficult to predict, but should theoretically be related to the degree of disturbance in peripheral energy deficit, which may in turn, be related to plasma amino acid pattern. In order to study whether this hypothesis was correct, plasma amino acids and some of their metabolic byproducts, the beta-hydroxyphenylethanolamines, were studied in 25 septic patients, and were used as discriminant variables in a series of computer performed discriminant analyses and multiple regressions. The two functions tested were the degree of metabolic septic encephalopathy as a determinant of the severity of sepsis and the final outcome in the septic patient. Plasma amino acid patterns exhibited elevated levels of the aromatic and sulfur containing amino acids, phenylalanine, tryosine, tryptophan, methionine, cysteine, and taurine, normal concentrations of alanine, and low normal concentrations of the branched chain amino acids, valine, leucine and isoleucine. Arginine levels, as previously noted, were very low. Patients not surviving the septic episode exhibited higher concentrations of aromatic and sulfur containing amino acids, while patients surviving sepsis had higher concentrations of the branched chain amino acids and arginine. When the degree of encephalopathy as a determinant of the severity of sepsis and step wise discriminant analysis with multiple crescent techniques were used, the best discriminant function between patients with and without encephalopathy was found to result from the interaction of cysteine, methionine, phenylalanine, isoleucine, leucine, and valine. These amino acids gave a correct classification in 82% of patients with no encephalopathy, and 80% of patients with septic encephalopathy. When the same amino acids were used for the discriminant analysis for patients dying of sepsis and patients surviving, the best discriminant function was achieved by using plasma concentrations of alanine, cysteine, methionine, isoleucine, arginine, tyrosine and phenylalanine resulting in 91% of the nonsurvivors, and 79% of the survivors correctly classified. The results suggest a close and significant relationship between the deranged energy metabolism and muscle protein breakdown in sepsis, and the outcome. This further suggests a central role for certain amino acids in perhaps predicting the severity of sepsis and its outcome.

Infusion of the branched chain amino acids in postoperative patients. Anticatabolic properties.

Postinjury metabolism is characterized by breakdown of muscle protein as substrate for energy production and gluconeogenesis and by the resultant loss of lean body mass and weight loss. The branched chain amino acids (BCAAs) which are principally oxidized by the skeletal muscle have been implicated in recent in vitro and in vivo studies as having special anticatabolic and regulating effects in skeletal muscle. We studied the anticatabolic effects of the BCAAs in 35 patients undergoing operative injury of moderate severity. In a prospective randomized and blinded manner patients were infused for five days starting immediately after surgery with either 5% dextrose or 5% dextrose with an amino acid solution containing 22, 35 or 100% BCAAs. All patients survived and there were no major postoperative complications. Mean hospital stay was 17 days for patients receiving amino acids and 19 days for patients receiving 5% dextrose only (p = ns). All three groups receiving amino acid solutions were in nitrogen equilibrium or in a slight positive nitrogen balance, while the group receiving 5% dextrose only was in a mean negative nitrogen balance of 6.6 +/- 0.6 gN/day. The differences between the three groups receiving amino acids were slight and not significant. Weight loss was 2 +/- 0.7 kg in the 5% dextrose group, 1 +/- 0.7 kg in the 22% BCAAs group, 0.5 +/- 0.5 kg in the 35% BCAAs group and the 100% BCAAs group gained 0.4 +/- 1.8 kg. Blood chemistries in the different groups and during the study period remained within normal limits except for ammonia levels rising significantly in the 5% dextrose group and SGOT levels rising in the 22% and 35% BCAA groups. With mild variations the plasma amino acid patterns in all groups were similar to the normal pattern, even in the 100% BCAAs group receiving an unbalanced amino acid solution, suggesting the complete cessation of amino acid efflux from muscle, the muscle depending solely on the exogenous supply of BCAAs to satisfy its metabolic requirements. The results suggest that early nutritional suppport in the postoperative period will result in nitrogen equilibrium and that the infusion of the three BCAAs only in the postoperative state is as effective in preventing muscle catabolism as other more balanced amino acid solutions. In the postinjury state balanced amino acid solutions rich in BCAA may prove beneficial.

Chromium deficiency during total parenteral nutrition.

Chromium is required for maintenance of normal glucose tolerance. After complete bowel resection and five months of total parenteral nutrition, severe glucose intolerance, weight loss, and a metabolic encephalopathy-like confusional state developed in a patient. Serum chromium levels were at the lowest normal level. Supplementation of 150 microgram of chromium per day reversed the glucose intolerance, reduced insulin requirements, and resulted in weight gain and the disappearance of encephalopathy. The low levels of chromium and response to chromium supplementation suggest that chromium deficiency can arise in long-term total parenteral nutrition.