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Biomedical subjects

J R Anderson

Publications and source records attributed to J R Anderson.

At least 19 recordsLinked to original sources

Bone marrow transplantation for peripheral T-cell lymphoma in children and adolescents.

We report nine children with relapsed (n = 8) or high-risk (n = 1) peripheral T-cell lymphoma (PTCL) who underwent autologous (n = 6) or allogeneic (n = 3) bone marrow transplantation (BMT). These children received transplants as part of a prospective phase I/II study of thioTEPA (TT) and total body irradiation (TBI) with escalating doses of VP-16. The median age of these patients at time of BMT was 6.5 years (range 2.5 years to 14 years). Three were transplanted with active disease after failing salvage chemotherapy. Of the other six, one was transplanted in first complete remission (CR) and five in second or subsequent CR. Of these nine patients, eight are free of disease a median of 25 months after BMT (range, 6 to 48 months), with an estimated 2-year relapse-free survival (RFS) of 89%. Six of these eight patients have been followed for 12 or more months after BMT, and in each their current remission exceeds their longest previous remission duration. The toxicity of the TT/TBI +/- VP-16 regimens was significant but manageable, predominantly consisting of severe mucositis. For a comparison, we reviewed retrospective data on the six additional children and adolescents with PTCL who underwent BMT during the 3-year period preceding this phase I/II study. The median age at BMT of these six patients was 19 years (range 15.5 years to 20 years). These patients were prepared for BMT with a variety of other regimens. One had no response to BMT and the other five relapsed at 1.5 to 5 months after BMT (median, 3 months) with an RFS of 0%. Our data suggest that thioTEPA plus TBI, with or without VP-16, is an effective preparative regimen for BMT for young patients with relapsed or high-stage PTCL and leads to prolonged RFS.

Adolescent

Chemotherapy of advanced Hodgkin's disease with MOPP, ABVD, or MOPP alternating with ABVD.

BACKGROUND AND METHODS: MOPP (mechlorethamine, vincristine, procarbazine, and prednisone) has been the standard treatment for Hodgkin's disease for almost 20 years. In a randomized, multicenter trial, we compared three regimens of primary systemic therapy for newly diagnosed advanced Hodgkin's disease in Stages IIIA2, IIIB, and IVA or IVB: (1) MOPP alone given for 6 to 8 cycles, (2) MOPP alternating with ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) for 12 cycles, and (3) ABVD alone for 6 to 8 cycles. Patients in a first relapse after radiation therapy were eligible. No additional radiation therapy was given. Patients who did not have a complete response or who had a relapse with either MOPP alone or ABVD alone were switched to the opposite regimen. RESULTS: Of 361 eligible patients, 123 received MOPP, 123 received MOPP alternating with ABVD, and 115 received ABVD alone. The patients were stratified according to age, stage, previous radiation, histologic features, and performance status. The overall response rate was 93 percent, with complete responses in 77 percent: 67 percent in the MOPP group, 82 percent in the ABVD group, and 83 percent in the MOPP-ABVD group (P = 0.006 for the comparison of MOPP with the other two regimens, both of which contained doxorubicin). The rates of failure-free survival at five years were 50 percent for MOPP, 61 percent for ABVD, and 65 percent for MOPP-ABVD. Age, stage (III vs. IV), and regimen influenced failure-free survival significantly. Overall survival at five years was 66 percent for MOPP, 73 percent for ABVD, and 75 percent for MOPP-ABVD (P = 0.28 for the comparison of MOPP with the doxorubicin regimens). MOPP had more severe toxic effects on bone marrow than ABVD and was associated with greater reductions in the prescribed dose. CONCLUSIONS: In this trial, ABVD therapy for 6 to 8 months was as effective as 12 months of MOPP alternating with ABVD, and both were superior to MOPP alone in the treatment of advanced Hodgkin's disease. ABVD was less myelotoxic than MOPP or ABVD alternating with MOPP.

Adult

Progressive disease after high-dose therapy and autologous transplantation for lymphoid malignancy: clinical course and patient follow-up.

Of 364 patients with lymphoid malignancy who underwent high-dose therapy with autologous bone marrow transplantation (ABMT) or peripheral stem cell transplantation (PSCT), 169 patients have had progressive disease after the procedure. The median survival from the time of relapse for patients with Hodgkin's disease (HD) who progressed after the transplant was 10.5 months. This compares with a median survival of 3 months for relapsed non-Hodgkin's lymphoma (NHL) patients (P = .0036). After failing transplantation, 56 patients were treated with further chemotherapy, 35 with involved field irradiation therapy, and 18 patients were treated with combination chemotherapy and irradiation. Seven patients received biologic therapy and seven patients underwent a second bone marrow transplant. The remainder of the patients were believed to be too ill for further therapy or chose not to receive further treatment for their recurrent lymphoid malignancy. Sixty of the 169 patients with progressive disease after the transplant are still alive; however, only 18 patients are alive off therapy without evidence of active disease after their relapse. Ten of the 18 patients are still less than 12 months past their posttransplant salvage therapy and are at high-risk for relapse. Five patients are progression free at 15 to 36 months after their posttransplant relapse. Only three patients (two NHL and one HD) treated with other modalities after autologous transplant failure are alive without evidence of disease and have been observed at least 4 years postrelapse. Although a few patients will have a durable response to subsequent therapy, the majority of patients who have progressive disease after an autologous transplant for lymphoid malignancy will succumb to recurrent disease within a short period of time.

Adult

Laser recanalization versus endoscopic intubation in the palliation of malignant dysphagia: a randomized prospective study.

Forty patients with histologically confirmed malignant dysphagia were randomized to either endoscopic intubation or laser recanalization. Age, sex, tumour histology and site were evenly distributed between the groups. Results were analysed on an 'intention to treat' basis. All patients treated by laser achieved patency; there was one failed intubation. The best swallowing grade achieved was significantly better with laser recanalization (median 4 (range 3-4)) than with intubation (median 3 (range 2-4)) (P < 0.001). The median survival was 21.5 (range 4-62) weeks in the group receiving laser treatment, compared with 14.5 (range 7-102) weeks in the intubated group (P = 0.09). The median inpatient stay as a proportion of survival time was 14 per cent in the group receiving laser treatment compared with 15 per cent in the intubated group (P > 0.05). The median weight loss was less in the laser-treated patients (2.0 (range 2-8) versus 3.0 (range 0-10) kg, P = 0.04). These results indicate that laser recanalization provides better palliation of dysphagia than does intubation, but this is not reflected in an improvement in survival time.

Adult

The effect of angiotensin II on tumor blood flow and the delivery of microparticulate cytotoxic drugs.

Colorectal hepatic metastases have a notoriously poor response to conventional systemic chemotherapy. We have synthesised cytotoxic drug (doxorubicin and mitomycin C) containing spheres 40 microns in diameter, using human albumin and ethyl cellulose as matrices. Introduction of these cytotoxic microspheres into the hepatic artery should embolise to the tumor and provide a controlled release depot for the anticancer agent. The vasoconstrictor, angiotensin II (AII) has been shown to increase tumor blood flow relative to normal tissue when administered via the hepatic artery, therefore we have investigated the effect of AII on targeting of cytotoxic microspheres to hepatic metastases. Patients with hepatic metastatic colorectal carcinoma had hepatic arterial catheters inserted at laparotomy and connected to subcutaneous injection ports. Peroperatively, 99mTc-labelled albumin microspheres were administered via the arterial catheter. Fifteen minutes later, AII was infused (10 micrograms per minuter for 4 min) via the catheter and 131I-labelled albumin microspheres were administered as a bolus at the midpoint of the AII infusion. Multiple biopsies were taken of normal liver and tumor metastasis and the tissue radioactivity counted for 99mTc and 131I. Further studies were performed postoperatively in which 99mTc-labelled microspheres were administered via the hepatic artery catheter and their distribution was followed using tomographic SPECT scanning. Combined results of this study suggested that AII can increase tumor SPECT scanning. Combined results of this study suggested that AII can increase tumor blood flow rates relative to normal hepatic tissue by approximately 3-fold.

Angiotensin II

Predicting genitourinary toxicity in patients receiving cisplatin-based combination chemotherapy: a Cancer and Leukemia Group B study.

Assessment of renal function prior to cisplatin chemotherapy has long been based on measurement of creatinine clearance by 24-hour urine collection (CrCmeas). Estimated creatinine clearance (CrCest) as calculated from the patient's age, weight, and serum creatinine level has been suggested as an adequate surrogate for CrCmeas, as it provides advantages of improved convenience, decreased cost, and possibly increased accuracy. We studied 847 patients receiving cisplatin-based chemotherapy on Cancer and Leukemia Group B (CALGB) protocols to determine whether the CrCmeas, CrCest, or serum creatinine value or the age of the patient would predict the subsequent genitourinary (GU) toxicity. Both CrCmeas (P = 0.001) and CrCest (P = 0.02) were predictive of subsequent grade 2+ GU toxicity, with CrCmeas being a slightly better predictor. Patient age also influenced subsequent GU toxicity, with the risk increasing with age (P = 0.0008). When patients were classified by age group and by CrCmeas, distinct subgroups were identified, with differences in the risk for grade 2+ GU toxicity ranging from 14% to 32%. Using a logistic model to assess the probability of grade 2+ GU toxicity, we found that an age of greater than or equal to 60 years (P = 0.005), a CrCmeas value of less than 75 ml/min (P = 0.004), and the risk characteristics of the individual cisplatin trial were important, whereas CrCest was not. Furthermore, CrCest proved to be a poor predictor of a CrCmeas value of less than 75 ml/min, "misclassifying" nearly half of the patients to a "lower-risk" subgroup. In summary, both CrCmeas and the patient's age independently provided predictive information concerning cisplatin GU toxicity. Our data support the continued clinical usefulness of determining the CrCmeas value prior to the administration of cisplatin-based chemotherapy to most patients.

Adult

Development of self-recognition in chimpanzees (Pan troglodytes).

Chimpanzees (Pan troglodytes) demonstrate the ability to recognize themselves in mirrors, yet investigations of the development of self-recognition in chimpanzees are sparse. Twelve young chimpanzees, grouped by age, were given mirror exposure and tested for self-recognition and contingent movement. All 6 juveniles, 4 and 5 years old, exhibited mirror-guided, mark-directed behavior and clear evidence of self-recognition. In contrast, among the infants, only the oldest group of 2 1/2-year-olds exhibited clear evidence of self-recognition. All chimpanzees exhibited both self-directed behaviors and contingent movements. These results suggest that self-recognition occurs at a slightly older age in chimpanzees than in human infants. In humans, self-recognition is linked with other cognitive abilities. The results conform to the general pattern that great apes exhibit many cognitive skills comparable to those of 2-year-old humans.

Affect

Self-recognition in Alzheimer's disease: a mirror and video study.

Twenty-nine subjects with Senile Dementia of the Alzheimer Type (SDAT) were tested for self-recognition when confronted with their reflection in a mirror and with a noncontingent video image. All subjects at stage 5 (moderately severe cognitive decline) on the Global Deterioration Scale (GDS) showed self-recognition in the mirror condition, whereas 25% of GDS stage 6 subjects (severe cognitive decline) did not self-recognize. Only seven subjects showed signs of self-recognition on video (six at GDS 5, one at GDS 6). The results confirm two hypotheses: the first, based on studies with infants, is that contingency cues in the mirror condition facilitate self-recognition; the second is that SDAT patients may show "regression" of at least some cognitive functions.

Aged

A phase II study of recombinant interleukin-2 with or without recombinant interferon-beta in non-Hodgkin's lymphoma. A study of the Cancer and Leukemia Group B.

Interleukin-2 (IL-2) and interferon-beta (IFN-beta) have demonstrated activity against lymphoid malignancies, presumably mediated by the augmentation of lymphokine-activated killer (LAK) cell and natural killer (NK) cell activity. There is in vitro and in vivo evidence to suggest that the combination of IL-2 and IFN-beta is synergistic. The Cancer and Leukemia Group B (CALGB) conducted a randomized phase II trial of IL-2 with or without IFN-beta in 49 patients with relapsed or refractory non-Hodgkin's lymphoma (NHL). Overall toxicity was severe, with 17 patients experiencing life-threatening toxicity. Three patients had treatment-related deaths. Responses were noted in seven patients (17%). There were no meaningful differences between treatment arms in toxicity profile, response rate, or modulation of in vivo NK and LAK activity. We conclude that IL-2 with or without IFN-beta is not effective therapy for NHL in the doses and schedule used in this study.

Adult

Abiotic factors influencing embryonic development, egg hatching, and larval orientation in the reindeer warble fly, Hypoderma tarandi.

Wild-caught, tethered females of the reindeer warble fly, Hypoderma tarandi (L.) (= Oedemagena tarandi (L.)), (Diptera, Oestridae) were stimulated to oviposit on hairs of a reindeer hide. Newly laid eggs incubated at constant temperatures and relative humidities hatched within 3 days to 2 weeks, depending on the experimental conditions. Over a range of 7-40 degrees C, hatching only occurred between 20 and 37 degrees C. Eggs held at 100% relative humidity had lower hatchability and longer time to hatch relative to eggs held at 77% relative humidity. The average number of degree-days for hatching was 50.35. Between 20 and 33 degrees C there was a temperature-dependent linear trend in developmental rate, and the proportion of eggs hatching was highest, and least variable, at the mid-temperature ranges. The temperature range found in the natural host micro-habitat where H. tarandi commonly affix their eggs (close to the skin at the base of a host hair) was consistent with the experimental temperature treatments that produced the highest hatching rate. Newly emerged larvae displayed positive thermotaxis, while showing no phototaxic or geotaxic behaviour. Results indicate that constraints of the host environment, coupled with temperature-dependent hatching success, may impose a selective pressure on oviposition behaviour.

Animals

Continuous coeliac plexus blockade plus intermittent wound infiltration with bupivacaine following upper abdominal surgery: a double-blind randomised study.

In this double-blind trial, we observed the effect of intermittent wound infiltration with local anaesthetic plus continuous coeliac plexus blockade on postoperative pain relief, pulmonary function, the neuroendocrine and acute phase protein response following upper abdominal surgery. In Group A (n = 10) patients received bupivacaine intermittently into the wound and continuously into the coeliac plexus following an initial bolus. A total of 862.5 mg of bupivacaine was used over 12 h with no observed toxicity. Group B (n = 10) received equal volumes of saline. Although pain relief was poor in both groups, the bupivacaine group used less morphine postoperatively and had lower pain scores than the saline group 4 h after operation (P less than 0.05). Pulmonary function was significantly reduced in both groups with no statistical difference between the two. Significant reductions in serum glucose and cortisol were achieved (P less than 0.05), suggesting that afferent neural blockade was partially effective in attenuating the neuroendocrine response. However, the postoperative rise in interleukin-6 was not affected by this technique. It is concluded that total afferent neural blockade cannot be achieved with peripheral wound and coeliac plexus administration of relatively large doses of local anaesthetic during upper abdominal surgery.

Abdomen

A prospective trial of endoscopic sclerotherapy v oesophageal transection and gastric devascularisation in the long term management of bleeding oesophageal varices.

In a prospective three centre study oesophageal transection and gastric devascularisation have been compared with endoscopic sclerotherapy in the long term management of bleeding oesophageal varices. Cirrhotic patients (Child's A or B grade) with documented bleeding oesophageal varices were treated initially with emergency sclerotherapy, and after five days stability, were allocated to one of the two treatment regimes. The endoscopic sclerotherapy group underwent regular sclerotherapy until variceal obliteration while those undergoing surgery were not endoscoped unless bleeding recurred, when they were treated by sclerotherapy if appropriate. Ninety two patients were eligible for analysis (68% alcoholic cirrhosis; mean age 50.1 years) and follow up was achieved for a mean of 52.5 months (range 17-83). Mortality in the first three months was greater in the oesophageal transection and gastric devascularisation group (20% v 1%) but by two years the survival curves were the same and thereafter there was no difference in mortality. Rebleeding occurred in 13/41 (31%) patients, undergoing oesophageal transection and gastric devascularisation. The costs incurred during the first year of oesophageal transection and gastric devascularisation treatment were significantly greater than with endoscopic sclerotherapy (4369 pounds v 1067 pounds, p < 0.0001) and the high rate of rebleeding in the surgical group meant that no cost savings occurred in subsequent years. It is concluded that oesophageal transection and gastric devascularisation confers no benefit over endoscopic sclerotherapy in terms of long term survival and that it is not cost effective as judged by the current health care costs in the United Kingdom.

Adult

A comparison of SMS 201-995 and oesophageal tamponade in the control of acute variceal haemorrhage.

Forty endoscopically proven active variceal bleeds were entered in a prospective trial comparing oesophageal tamponade with SMS 201-995 infusion. Oesophageal tamponade controlled 19 of 20 bleeds over the first four hours and 14 of 18 bleeds over 48 hours. SMS 201-995 infusion controlled 18 of 20 bleeds over the first four hours and 10 of 20 bleeds over 48 hours (p = 0.15). No significant differences between the groups were seen in time to control of bleeding, amount of blood transfused or number of patients crossed over to the opposite treatment. Complications in the oesophageal tamponade group were discomfort due to the tube (17 patients) and chest infection (10 patients), while in the SMS 201-995 group 7 chest infections and one episode of hyperglycaemia occurred, with no symptomatic complaints. The patient survived the admission in 15 of the oesophageal tamponade bleeds and all of the SMS 201-995 bleeds (p = 0.047). An intravenous infusion of SMS 201-995 appears to have comparable efficacy to oesophageal tamponade in variceal bleeding.

Acute Disease

Airway inflammation predicts diffuse alveolar hemorrhage during bone marrow transplantation in patients with Hodgkin disease.

We determined risk factors present in patients with Hodgkin disease that predicted the development of diffuse alveolar hemorrhage syndrome (DAH) during autologous bone marrow transplantation (BMT). One hundred twenty-three patients with Hodgkin disease prospectively underwent bronchoscopy with bronchoalveolar lavage (BAL) before receiving BMT. The bronchitis index (BI) of the airways and bronchial and alveolar cell counts and differentials were determined in all patients and compared with 20 normal nonsmoking volunteers. Logistic regression analysis was used to determine factors that predicted for the development of DAH. Visual evidence of bronchial injury was observed regardless of smoking history (BI = 7.8 +/- 0.5 for BMT versus 2.3 +/- 0.5 for volunteers, p = 0.001). BMT patients who developed DAH (n = 14) had significantly greater numbers of bronchial neutrophils and eosinophils compared with DAH-negative (n = 109) patients (bronchial polymorphonuclear leukocytes (PMN), 33 +/- 7% versus 14 +/- 2%, p = 0.006; bronchial eosinophils, 0.9 +/- 0.3% versus 0.4% +/- 0.07%, p = 0.02). Logistic regression analysis revealed that the presence of bronchial PMN > 20% or bronchial eosinophils > zero% were predictive of DAH (p = 0.005 and 0.05, respectively). When both predictors were positive, the rate of DAH was 10 times greater than when both predictors were negative (43% versus 4% DAH occurrence). Survival was also significantly reduced when these predictors were positive. This study demonstrates that bronchial inflammation is present with or without intraluminal inflammatory cells in the majority of patients with Hodgkin disease before BMT. The subgroup of these patients with increased bronchial inflammatory cells are at greatly increased risk for development of DAH and death.

Academic Medical Centers

Adolescents and human immunodeficiency virus infection.

As of March 31, 1992, individuals 13 to 19 years of age had been diagnosed with acquired immunodeficiency syndrome; over one third were diagnosed in the past 2 years alone. Because of the long incubation period from initial infection to acquired immunodeficiency syndrome diagnosis, the majority of young adults with acquired immunodeficiency syndrome were probably initially infected as adolescents. In 1991, 34% of adolescents with acquired immunodeficiency syndrome were female, and their predominant mode of transmission was heterosexual contact. Human immunodeficiency virus seroprevalence studies of adolescents show a male-to-female ratio approaching 1:1, with many human immunodeficiency virus-infected adolescent women identifying none of the standard risk. Factors such as sexual and drug experimentation, risk taking, and sense of invulnerability so characteristic of adolescence put adolescents at special risk for human immunodeficiency virus. There is no published information on if or how clinical manifestations of human immunodeficiency virus disease in adolescents might differ from those seen in adults. Medical care should be broad-based and should include access to clinical trials for new drug treatments. General knowledge levels about acquired immunodeficiency syndrome are high among US adolescents, but behavioral changes have lagged behind. All adolescents should be targeted for intensive education about human immunodeficiency virus along with interventions designed to enhance their general coping, communication, and decision-making skills.

Adolescent

Correlation of Aedes sierrensis captures at human sentinels with CO2-baited Fay-Prince and duplex cone traps.

The efficiency of the duplex cone and Fay-Prince traps for monitoring adult male and female Aedes sierrensis was evaluated at 3 field sites in California. The numbers of females captured by both types of traps were significantly correlated with human sentinel collections. The Fay-Prince trap captured more Ae. sierrensis females than the duplex cone trap and was a better tool for estimating female activity levels. There was no significant correlation between the number of males captured in Fay-Prince traps and at humans. Male numbers in duplex cone trap collections explained only 27% of the variation in the number of males collected at sentinels, suggesting that neither trap is a robust tool for estimating male activity around humans.

Aedes

Automaticity and the ACT* theory.

An explanation of automaticity within the framework of the Adaptive Control of Thought (ACT*) production system theory (Anderson, 1983, 1987) is presented. There is no automaticity mechanism per se in ACT*. This is as we would expect it to be. It would be the exception rather than the rule that we would find in a scientific theory mechanisms that directly correspond to natural language concepts. The critical question is whether ACT* can give an account of the phenomena associated with the term automaticity. This article is structured as follows: First, I will try to identify the phenomena of automaticity to be explained, then give a brief overview of the ACT* theory, and finally explain how these phenomena of automaticity are to be understood in terms of the theory.

Attention