Studies of ara-C metabolism in acute leukemia.
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Acute Disease↗
Biomedical subjects
B W Thompson
Publications and source records attributed to B W Thompson.
A double beta-lactam combination versus an aminoglycoside-containing regimen as empiric antibiotic therapy for febrile granulocytopenic cancer patients.
The double beta-lactam combination of moxalactam plus piperacillin was compared with the aminoglycoside-containing regimen of moxalactam plus amikacin in a prospective, randomized trial of empiric therapy for 302 febrile episodes in granulocytopenic cancer patients. The moxalactam/piperacillin regimen was found to be as effective as the moxalactam/amikacin regimen (70 percent overall responses); responses with moxalactam/piperacillin and moxalactam/amikacin were similar for microbiologically documented infections (24 of 37, 65 percent, versus 20 of 35, 57 percent), for the subgroup with bacteremias (19 of 32 versus 14 of 28), and for clinically documented infections (41 of 58, 71 percent, versus 40 of 48, 83 percent). Responses were similar also for bacteremia in patients with persistent, profound (less than 100/microliter) granulocytopenia. Among profoundly (less than 100/microliter) granulocytopenic patients with gram-negative bacteremia, an increase in the granulocyte count to more than 100/microliter during therapy and a peak bactericidal activity of 1:16 or more (the latter noted in seven of nine moxalactam/piperacillin trials and six of nine moxalactam/amikacin trials) correlated with a favorable clinical response in 85 percent (p less than or equal to 0.00003) and 92 percent (p less than or equal to 0.044), respectively. Although serious side effects were minimal with either regimen, the double beta-lactam combination was associated with significantly less frequent nephrotoxicity (two of 145 versus 12 of 130; p less than or equal to 0.003) and ototoxicity (none of 34 versus seven of 34; p less than or equal to 0.006). The double beta-lactam combination of moxalactam plus piperacillin was found to be as effective as moxalactam plus amikacin but to have significantly less nephro- and ototoxicity.
Adolescent↗
111 In-labeled leukocytes in the detection of prosthetic vascular graft infections.
Making a clinical diagnosis of infection in prosthetic vascular grafts is difficult but when undiagnosed, this condition has a high mortality rate. Using Indium-111-labeled white-blood cells, 30 scans were performed in 21 patients suspected of having a prosthetic graft infection. The diagnosis of infected graft was confirmed by surgery in all cases, and lack of infection was established by resolution of symptoms with conservative therapy. Twenty-four hour scans of autologous Indium-111 leukocytes were obtained, and correlative CT studies were done in 11 cases. There were 13 infected grafts at surgery (purulent material present), and scans were positive in all (100% sensitivity); of 17 scans, there were 15 true negatives and two false positives (88% specificity). Using the criteria of gas or fluid around the graft, the sensitivity of CT was only 37% in a small subset of these patients. One-half of the cases in which infection was suspected clinically had no infection and had negative scans. Various types of grafts and graft materials were used, and there was no correlation with presence or absence of infection on the basis of the type of graft. Extragraft infection sites were found in five patients. In conclusion, use of Indium-111 leukocytes has been found to be an accurate and valuable diagnostic method for evaluation of suspected prosthetic vascular graft infection, and to have higher diagnostic accuracy than CT.
Aged↗
Metabolism of ara-C by blast cells from patients with ANLL.
The dose-response relationship between extracellular concentration of cytosine arabinoside (ara-C) and intracellular formation of the putative active metabolites of ara-C [ara-C incorporation into DNA and intracellular pools of ara-C in triphosphate form (ara-CTP)] was investigated in blast cells obtained from patients with acute nonlymphocytic leukemia (ANLL) by exposing these cells in vitro to 10, 100, or 1,000 nmol/L of ara-C. We studied 23 untreated patients who subsequently achieved complete remission (CR) with a regimen using daunorubicin and conventional doses of ara-C (ara-C-sensitive group), and 30 patients judged to be ara-C-resistant either by failing initial induction therapy (16 patients) or by having relapsed on an ara-C-containing maintenance regimen (14 patients). In both patient groups, ara-C incorporation into DNA and intracellular ara-CTP both displayed statistically significant increases in response to increasing extracellular concentrations of ara-C (P = .0001 in both cases), with the rate of increase of ara-CTP greater than that of ara-C incorporation. Moreover, blast cells from all patients, even those who were most clinically resistant to ara-C, were able to form ara-CTP and to incorporate ara-C into DNA. Each tenfold increment in extracellular ara-C concentration caused an 8.5-fold increase in ara-CTP, but only a 3.6-fold increase in ara-C incorporation into DNA. Thus, the efficiency of incorporation of ara-C into DNA (defined as the ratio of ara-C incorporation to ara-CTP pools) decreased by 58% with each tenfold increment in the extracellular concentration of ara-C (P less than .0001), presumably as a result of the inhibitory effect of ara-CTP on DNA polymerase. Using an analysis of covariance, modest differences were found in the levels of the ara-C metabolite variables in the ara-C-sensitive group as compared with the resistant group. However, because there was considerable overlap in ara-C metabolite formation among the patient groups, it was not possible to predict clinical outcome by these in vitro assessments of ara-C metabolism.
Acute Disease↗
Angioscopically monitored saphenous vein valvulotomy.
Angioscopy was used during in situ saphenous vein bypass grafting in seven patients. We were able to visualize valve incision, immediately identify and correct incomplete valvulotomy, identify side branches as potential arteriovenous fistulas, and assess distal anastomotic integrity. We encountered no retained valve cusps after angioscopy, as verified by Doppler ultrasound and completion angiography. Angioscopy verified distal anastomotic integrity in all patients with distal vein grafts large enough to accept the angioscope. Angioscopy requires minimal time, is relatively easy to use, serves as an adjunct to Doppler ultrasound and completion angiography, and has future potential as a therapeutic tool.
Aged↗
Bronchial adenoma: a review of 51 patients.
The cases of 51 patients with bronchial adenomas were reviewed. There were 43 bronchial carcinoids, 5 adenoid cystic carcinomas, 2 mixed tumors, and 1 mucoepidermoid carcinoma. The carcinoid group was divided into typical (31, 72%) and atypical (12, 28%) subgroups. Nine carcinoids (20%) were categorized as metastasizing adenomas; in this group, 7 lesions were atypical and 2 were typical. Thirty-two lobectomies, 7 bilobectomies, 8 pneumonectomies, 2 sleeve resections, and 2 tracheal resections were performed. Ten-year survival was 88% for patients with typical carcinoids and 59% for those with atypical carcinoids. In the group with adenoid cystic carcinoma, 1 patient died postoperatively, 1 had recurrence of the tumor, 2 were alive and free from disease 16 and 23 years later, and 1 died of heart disease at 11 years. The patient with mucoepidermoid carcinoma was alive without recurrence 15 years after operation. In conclusion, bronchial adenomas of the carcinoid type are potentially malignant. Their prognosis depends on the histology of the tumor, and on the presence of metastasis to the regional lymph nodes and distant organs.
Adenoma↗
Thymectomy for myasthenia gravis: 14-year experience.
Forty-eight consecutive patients with myasthenia gravis (MG) attended by generalized weakness were treated by complete thymectomy, performed transsternally in 46 patients and through a left thoracotomy in two with thymomas. There were no operative deaths. A 12-year-old child with fulminating MG died of acute pneumonia shortly after hospital discharge. Of the remaining 47 evaluable patients, thymectomy resulted in complete remission in six, marked improvement with a reduced need for medication in 20, and mild improvement on the same dosage of medication in 18. Neither the age of the patient, nor the histopathology of the excised thymus, nor the postoperative change in acetylcholine receptor antibody titer were found to have a significant influence on the response to thymectomy. If the ten patients who were 20 years of age or younger were excluded, the patients with a shorter duration of MG achieved a better response to operation. The authors conclude that thymectomy is effective treatment for MG, regardless of the age of the patient or the type of thymic pathology.
Adolescent↗
Pharmacokinetics and dosage reduction of cis-diammine(1,1-cyclobutanedicarboxylato)platinum in patients with impaired renal function.
cis-Diammine(1,1-cyclobutanedicarboxylato)platinum (CBDCA) is a nonnephrotoxic but myelosuppressive analogue of cisplatin (DDP) with greatly reduced protein binding and greatly increased renal excretion. Thus, CBDCA might produce undue toxicity in patients with decreased renal function. Twenty-two patients [14 females and 8 males; median age, 66 (range, 35 to 83); median Karnofsky performance status, 70 (range, 40 to 90)] with refractory tumors and renal dysfunction [creatinine clearance (CCr) 6 to 83 ml/min] were treated with 31 courses of i.v. bolus CBDCA every 4 to 5 weeks. Dosages were determined by pretreatment CCr. Patients with CCr greater than or equal to 40 ml/min received 400 mg/sq m; patients with CCr 20 to 39 ml/min received 250 mg/sq m; and patients with CCr 0 to 19 ml/min received 150 mg/sq m. Toxicities were assessed by weekly clinical and laboratory assessment. Responses were assessed in patients with measurable disease. Plasma pharmacokinetics and urinary excretion of total and ultrafilterable platinum were measured with flameless atomic absorption spectrometry. Observed toxicities were similar to those in patients with normal renal function. Myelosuppression, especially thrombocytopenia, was the major toxicity. Nausea and vomiting were mild to moderate. There was no ototoxicity, neurotoxicity, or nephrotoxicity or reduction in CCr due to CBDCA. Total body clearance of ultrafilterable platinum correlated highly with CCr. The percentage of reduction in platelet count correlated highly and linearly with the area under the curve (AUC) of plasma-ultrafilterable platinum. However, for any AUC, there was 17% greater platelet reduction in patients who had previously received extensive myelosuppressive chemotherapy than in nonpretreated patients. Since total body clearance is proportional to CCr, platelet reduction is proportional to AUC, and total body clearance = dosage/AUC, we have derived an equation to calculate a dosage that will produce a desired reduction in platelet count. Calculations for theoretical patients (both pretreated and nonpretreated) with CCr of 100 ml/min produce dosages very close to maximum tolerated dosages derived in actual Phase I trials. The actual clinical utility of these predictive equations must await validation in prospective studies with larger numbers of patients.
Adult↗
Nuclear cardiac ejection fraction and cardiac index in abdominal aortic surgery.
Since atherosclerotic heart disease results in more than half of the perioperative deaths that follow abdominal aortic surgery, a prospective protocol was designed for preoperative evaluation and intraoperative hemodynamic monitoring. Twenty men who were prepared to undergo elective operation for aortoiliac occlusive disease (12 patients) and abdominal aortic aneurysm (eight patients) were evaluated with a cardiac scan and right heart catheterization. The night prior to operation, each patient received volume loading with crystalloid based upon ventricular performance curves. At the time of the operation, all patients were anesthetized with narcotics and nitrous oxide, and hemodynamic parameters were recorded throughout the operation. Aortic crossclamping resulted in a marked depression in CI in all patients. CI remained depressed P less than 0.05 after unclamping in the majority of patients. There were two perioperative deaths, both from myocardial infarction or failure. Both patients had ejection fractions less than 30% and initial CIs less than 2 L/M2, while the survivors' mean ejection fraction was 63% +/- 1 and their mean CI was 3.2 L/M2 +/- 0.6. We conclude that preoperative evaluation of ejection fraction can select those patients at a high risk of cardiac death from abdominal aortic operation. These patients should receive intensive preoperative monitoring with enhancement of ventricular performance.
Aorta, Abdominal↗
Age and morbidity of vagotomy with antrectomy or pyloroplasty.
Seven hundred ninety-three vagotomies with either pyloroplasty (645 patients) or antrectomy (148 patients) were reviewed between 1970 and 1981. Mortality was lowest with elective pyloroplasty (0.4 percent) followed by elective antrectomy (0.7 percent), and emergency pyloroplasty (5.1 percent). The risk of death was significantly higher (p less than 0.05) for the older half of the population (older than 55 years of age). Major morbidity was lowest after elective pyloroplasty (6.3 percent) when compared with elective antrectomy (10.6 percent), and greatest after emergency pyloroplasty (18.1 percent). Proved ulcer recurrence was most frequently seen after pyloroplasty (4.5 percent) and least frequently seen after antrectomy of age) had a significantly decreased risk of ulcer recurrence (p less than 0.001). Disabling sequelae occurred in 3.6 percent of those who underwent pyloroplasty, in 5.6 percent of those who underwent antrectomy with Billroth I reconstruction, and in 8.5 percent of those who underwent antrectomy with Billroth II reconstruction. Significantly more patients who underwent antrectomy with Billroth II reconstruction required reoperation (p less than 0.01) than did those who underwent either pyloroplasty or antrectomy with Billroth I reconstruction. Although antrectomy has become a popular operation, vagotomy combined with pyloroplasty is still the procedure of choice in patients over the age of 55 years. In those requiring emergency operations for duodenal ulcer, and in those in whom antrectomy is technically difficult because of a badly scarred duodenum. Billroth II reconstruction should be avoided after vagotomy and antrectomy.
Adolescent↗
Posterior surgical approaches to the rectum.
This report summarizes experience with 19 posterior approaches to the rectum including nine trans-sacral (Kraske) and ten trans-sphincteric (Mason) procedures. This study included 12 men and 7 women, ranging in age from 18 to 89 years. Surgical indications included villous tumors in nine patients, various benign problems in four patients, primary carcinomas in three patients, and recurrent cancer in three patients. Eight complications developed in the 19 patients including: four fecal fistulae, two wound dehiscences, one rectal stricture, and one sacrococcygeal hernia. Spontaneous closure of the fecal fistulae occurred in two patients, and two patients required proximal colostomies. Fecal continence was achieved in 18 of the 19 patients. No patient died as a complication of the procedure. No recurrent tumors have developed. The conclusion is that a posterior approach to the rectum is a safe and effective procedure for various benign and for selected malignant conditions. It is particularly suitable for villous tumors that are too high for transanal resection and too low for transabdominal resection. It is an effective procedure for small, exophytic, mobile carcinomas of the lower 10 cm of the rectum in selected patients.
Adolescent↗
False aneurysm with arteriovenous fistula of the anterior tibial artery following fracture of the fibula.
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Adult↗
Energy usage for food service infrared heat processing of egg sandwich loaf.
Simulating volume demand within hospital food service departments, infrared heat processing conditions were used to heat two similar protein menu items to determine both energy consumption required for heat processing and energy/nutrient rations. A larger, conveyorized infrared oven (CTX-70) and a smaller, infrared unit (Krups 2002) were used to heat process varying sizes of oven loads which ranged from one to 36 slices. Although no significant differences were found for product yield after 12, 24 and 36 slices were heat processed in the CTX-70, the energy usage was significantly different: 637, 798 and 1005 watt hours/load were consumed, respectively. In the Krups 2002, a load of one slice had greater heat processing losses than either two or four slices. Energy consumption was 39, 47 and 50 watt hours/load to heat process one, two and four slices in the Krups 2002, respectively. Significantly more energy was used to heat process turkey-ham than egg sandwich loaf in the Krups 2002. The potential use of energy/nutrient rations by dietitians was discussed.
Conservation of Energy Resources↗
Arterial embolectomy in the leg. Results in a referral hospital.
The clinical characteristics and course of 90 patients in whom 121 arterial emboli occurred from 1968 to 1978 were reviewed. The factor that correlated most significantly with a favorable outcome was the interval from onset of symptoms until arterial embolectomy was performed. The results of embolectomy were excellent in the patients operated on within 6 hours of symptoms (amputation rate 4 percent, mortality rate 15 percent), but less favorable in the patients operated on within 6 to 12 hours of onset of symptoms (amputation rate 27 percent, mortality 40 percent). Mortality (48 percent) and amputation (52 percent) rates in the patients operated on 12 to 48 hours after onset of symptoms were excessive. It is recommended that immediate embolectomy be performed in all potentially viable extremities in patients who present within 12 hours of symptoms, but that after 12 hours only those limbs with obvious viability (not paralyzed or anesthetic) should be operated on. Alternatives for the remainder are high dose intravenous heparinization or expedient amputation. In patients who present greater than 60 hours after the onset of symptoms, embolectomy can be performed with low morbidity and mortality.
Amputation, Surgical↗
Activated clotting time monitoring of intraoperative heparinization: our experience and comparison of two techniques.
The activated clotting time (ACT) has been used clinically for 41/2 years to monitor the adequacy of intraoperative heparinization in both cardiopulmonary bypass (CPBP) and peripheral vascular surgery (PVS) patients. Since January, 1976, we have operated on 440 PVS patients in our institutions, of whom 255 had intraoperative monitoring of heparinization by means of the ACT test; an additional 185 patients received heparin according to an empiric protocol. An automated machine for determining the ACT (Hemochron) had been used on the last 28 patients in the ACT group. We conclude that: (1) the ACT is an acurate method of monitoring anticoagulation during PVS, (2) the Hemochron is a simple and effective machine to perform the ACT, (3) values obtained by the Hemochron generally exceed those of the ACT done by hand by approximately 20 seconds at lower levels of heparin and are equal at higher levels of heparin, (4) supplemental heparin was required in 22% of our patients to maintain their ACT values at twice control values, (5) the response to heparin is twofold: an initial sensitivity or resistance followed by an independent and variable rate of consumption, and (6) the ACT is a useful method for predicting inadequate heparin reversal or heparin rebound at the conclusion of the operation.
Autoanalysis↗
Infected prosthetic grafts.
An experience with 20 infected prosthetic grafts in a series of 652 prosthetic arterial reconstructions has been reviewed. There was 13 aortofemoral, one straight aortic, three femoropopliteal, one carotid subclavian, one axilloaxillary, and an axillocarotid graft. The most common site of infection was the groin. All patients had received preoperative and postoperative broad-spectrum antibiotic coverage, perhaps contributing to a high incidence of Gram-negative bacterial cultures. Early procrastination contributed to morbidity and mortality. Attempts at local wound management with drainage and irrigation generally failed, especially if the suture line was involved. Graft excision without revascularization resulted in a number of amputations and a high mortality. Excision of the entire aortofemoral graft combined with extra-anatomical revascularization was uniformly fatal. Our experience suggests that the first objective should be to establish operatively the extent of the infection. If very localized, antibiotic irrigation may cure. Involvement of one side can be treated in one stage by extra-anatomical bypass using the obturator foramen coupled with excision of the infected portion. If the entire graft is involved, we recommend extra-anatomical bypass as the initial procedure. High-dose antibiotic for systemic effect are then administered and two to three days later the infected graft is removed.
Aorta, Abdominal↗
Identification of heparin resistance during cardiac and vascular surgery.
An investigation of the response of the activated clotting time to systemic heparinization during cardiopulmonary bypass and peripheral vascular surgery was prompted by the death from clotting of a patient with endocarditis while undergoing valve replacement. The activated clotting time during cardiopulmonary bypass was thereafter maintained at 300 to 400 seconds. Consumption of heparin sodium, derived from an individual dose-response curve, was 0.01 to 3.86 units/kg/min. There was no correlation between initial heparin resistance and the subsequent rate of consumption. Some patients undergoing peripheral vascular surgery required additional heparin after an initial standard dose of 8,000 units so as to maintain their activated clotting time at twice the control values. These data are discussed in relation to previous articles, and recommendations are made for adequate intraoperative heparinization.
Adolescent↗
Acute perforations of the sigmoid colon secondary to diverticulitis.
Diverticulitis is a complex disease and demands careful cooperation between physician and surgeons, because although it is a benign disease, the presence of complications makes it potentially lethal. For successful management, knowledge of the treatment in past decades should be integrated with current surgical technics. A retrospective review of forty-one patients with perforated diverticulitis revealed a significant decrease in morbidity and hospital stay for the group of patients undergoing the Hartmann procedure versus the group undergoing the classic three stage approach. In addition, the Hartmann group required fewer additional surgical procedures for drainage of abscesses. In view of these results as well as those of others, we believe that resection is the primary goal of therapy. The two stage approach therefore offers significant decrease in morbidity with acceptable mortality.
Abscess↗