Biomedical subjects
Publications and source records attributed to D L Morris.
Symptoms of pain, dyspepsia and nausea arising during the administration of intrahepatic chemotherapy should be investigated with endoscopy to exclude inadvertent perfusion of the stomach.
Neutropenia is a common and often dose limiting side effect of some chemotherapy regimens. The aim of this study was to investigate the ability of an immunomodulator, glycosaminylmuramyl dipeptide (GMDP, CAS 78113-36-7, romurtide) to reduce chemotherapy induced neutropenia. BALB/c mice were treated with 200 mg kg-1 cyclophosphamide (CY) to induce a reversible neutropenia lasting approximately 6-7 days. There was no change in the duration or depth of neutropenia in mice treated with GMDP for 3 consecutive days (2.5 or 25 mg kg-1) starting the day after CY injection. In addition, at the doses used, the time of administration of GMDP relative to CY did not alter this response. However, a marked neutrophilia compared to controls was consistently observed in all cases. Neutrophil counts of up to 14 times the baseline value were measured 6-7 days after the induction of neutropenia. GMDP had no effect in the absence of CY. Less variation was seen in white cell counts of older non-SPF mice treated with CY. When the activity of GMDP (5 mg kg-1) was compared with G-CSF (granulocyte colony stimulating factor, 100 micrograms kg-1) in these animals, GMDP showed a consistent trend to reduce the length of neutropenia, however, under the conditions tested only G-CSF treatment resulted in a significant reduction in the duration of neutropenia. In the 12-week-old mice, the neutrophilia seen with both G-CSF and GMDP was much smaller than in the 8-week-old mice, and was not significantly different from that in control mice treated with CY alone.
OBJECTIVE: To assess whether inflammatory bowel disease (IBD) is more prevalent in young Asians than Europeans living in Great Britain. DESIGN: Longitudinal birth cohort study of all those born 5-11 April 1970 in Great Britain--the 1970 British Cohort Study (BCS70). METHODS: The relationship of a diagnosis of ulcerative colitis or Crohn's disease by age 26 years with ethnic origin was investigated among 8,432 cohort members with complete data using multiple logistic regression. We adjusted for potential confounding factors, household crowding and sex, as well as for a family history of IBD. RESULTS: Young Asians born in Britain were significantly more likely than indigenous Europeans to have a diagnosis of IBD by age 26 years, with relative odds of 6.10 (95% CI 2.14-17.33). This group of cohort members had ethnic origins in India, Pakistan or Bangladesh (although none of those from Bangladesh had IBD). This relationship remained statistically significant after adjustment for the potential confounding factors and family history of IBD. CONCLUSION: Young Asians who were born in Britain are at a significantly higher risk of developing IBD than the indigenous European population. This may reflect a greater genetic predisposition to IBD that is uncovered by exposure to environmental factors.
OBJECTIVE: To delineate components of delay within the hospital ED for patients presenting with symptoms of stroke. METHODS: A prospective registry of patients presenting to the ED with signs or symptoms of stroke was established at a university hospital from July 1995 to March 1996. The ED arrival time, time to being seen by an emergency physician (EP), time to CT scan, and time to neurology consultation were obtained by medical record review. RESULTS: The median delay (interquartile range) from ED arrival to being seen by an EP for the 170 eligible subjects was 0.42 (0.20-0.75) hours. The median delay to CT scan was 1.88 hours (1.25-2.67) and the median delay to neurology consultation was 2.42 hours (1.50-3.48). Age, race, sex, and hospital discharge diagnosis had little influence on delay. Subjects arriving by emergency medical services (EMS) had a significantly shorter time to being seen by an EP (0.33 vs 0.50 hours) when compared with those who arrived by other means. Time to CT scan was shorter by 0.5 hours for patients arriving by EMS as well. These differences persisted when stratified by out-of-hospital delay times. CONCLUSIONS: These data suggest that arriving by EMS is associated with shorter times to being seen by an EP and receiving a CT scan. The influence of EMS on delays associated with rapid medical care of stroke patients reaches beyond the out-of-hospital transport phase.
We sought to determine the maternal serum levels of four tumor-associated antigens during the three trimesters of pregnancy in healthy women. CEA, CA 228, CA 15-3, and Her2/neu oncogene product p105 assay values were determined for 90 healthy pregnant women during the three trimesters of pregnancy at five participating evaluation sites. Results were compared to means and cut-off values determined for healthy nonpregnant women. Differences in assay values in the 1st and 3rd trimester were analyzed for statistical significance (Student's t-test). CEA, CA 228 and CA 15-3 assay values in general were found to be within the normal range. CA 15-3 and Her2/neu p105 serum assay values were above the cut-off (3.3% and 8.2%, respectively) and were significantly elevated in the 3rd trimester as compared to the 1st trimester of pregnancy (P < 0.05 and P < 0.001, respectively). CEA and CA 228 may be of potential value in monitoring pregnant women with malignant disease. Normal elevations in 3rd trimester serum Her2/neu p105 and CA 15-3 assay values should be considered when monitoring a pregnant patient with malignant disease.
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Cimetidine is known to have immunomodulatory effects and this study aimed to examine the effect of pre-operative cimetidine treatment on lymphocytic infiltration in n = 72 women with breast cancer randomised to 400 mg bd or placebo for five days presurgery. A combined index was devised by adding infiltrating lymphocyte percentage and lymphoid score. There were no significant differences in circumferential infiltrate and lymphoid follicles in cimetidine treated patients and control patients with breast cancer.
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BACKGROUND AND OBJECTIVES: Most patients with colorectal liver metastases are not eligible for resection because they have multiple lesions or because of anatomical constraints. We report the use of cryotherapy to destroy residual metastases following liver resection in patients with disease too widespread for treatment by resection alone. METHODS: Twenty patients with bilobar disease confined to the liver (median 3; range 2-8 lesions) were treated in this way. Seventeen patients also received regional chemotherapy postoperatively. RESULTS: Morbidity was high, but there were no procedure-related deaths and only one patient's hospital stay exceeded 24 days. Significant destruction of tumor, as evidenced by a decline in CEA levels, occurred within 3 months of surgery in all patients (P < 0.001). Median duration of follow-up was 15 (6-53) months. Survival rates at 1 and 2 years were 88% and 60%, respectively, and median survival was 32 months. Seven patients remain well and seven are alive with recurrent liver and/or other metastases. CONCLUSIONS: Although this is not a control study, it would appear that some patients with irresectable liver metastases benefit from this multimodality approach.
BACKGROUND AND OBJECTIVES: Hepatic cryotherapy is a method of in situ cytodestruction used for unresectable liver tumours that can be combined with regional cytotoxic administration. We have used intra-arterial chemotherapy with 5-fluorouracil (5-FU) after hepatic cryotherapy but changed to 5-fluorodeoxyuridine (FUDR) because of the arterial toxicity of 5-FU. A new complication was seen. METHODS: A retrospective case note study was performed of 130 patients who had undergone hepatic cryotherapy followed by regional chemotherapy at our centre. Seven patients received FUDR; 123 received 5-FU. RESULTS: Biloma at the cryotherapy sites was seen in three patients in the FUDR group; two other patients in this group had other types of hepatic collection. Our previous experience with intra-arterial 5-FU in 123 patients after hepatic cryotherapy showed no evidence of this syndrome. CONCLUSIONS: Intra-arterial FUDR should not be used after hepatic cryotherapy, at least during the immediate postoperative period.
While the prognosis for patients with untreated liver metastases from neuroendocrine primaries is rather good, they often suffer disabling symptoms due to syndromes of hormonal excess. Thirteen patients with metastatic neuroendocrine tumours were treated by hepatic cryotherapy; seven patients were symptomatic and five of these had elevated levels of hormonal tumour markers. Twelve patients are alive and mostly asymptomatic with a median follow up of 13.5 months; one patient died after 45 months of bronchopneumonia without evidence of tumour recurrence. All patients with elevated preoperative tumour markers have had a significant fall in markers postoperatively. Two patients were returned to the operating theatre for coagulopathy-associated bleeding: one patient each developed acute renal failure and pulmonary embolism, but there was no mortality. This study shows that hepatic cryotherapy offers a useful treatment option for this group of patients, alleviates symptoms and may have an impact on survival.
Cryoshock is a syndrome of coagulopathy, renal, and pulmonary injury following cryotherapy, and its etiology is unknown. The aim of this study was to assess the impact of hepatic cryotherapy on renal function, and whether this effect is related to volume of cryotherapy, and to identify any predictors of renal impairment in patients who undergo cryotherapy. A retrospective analysis of all patients with primary or secondary hepatic malignancy treated with cryotherapy from April 1990 to October 1996 was conducted. Ten of 204 patients with renal impairment (elevation in creatinine of greater than 0.02 mmol/L for more than 2 days postprocedure) were identified. One patient has postoperative pancreatitis with late renal impairment (20 days) and was excluded. The severity of renal impairment was usually modest (mean rise in creatinine of 0.31 mmol/L; SD, 0.19). Two patients required temporary hemodialysis. Only one patient, who had significant cardiac disease, had associated pulmonary injury and shock. Demographic data in both groups were comparable, except for a trend toward more noncolorectal cancer patients in the renal impairment group (4/9 vs 33/194). Patients in the renal impairment group had a greater number of lesions than those of the nonrenal impairment group (3.4 vs 2.1, p < 0.01), as well as larger lesion diameter (2.9 vs 1.9, p < 0.01), increased freezing time (74.7 vs 44.3, p < 0.01), and a higher aspartate transaminase (AST) (2254 vs 1157, p < 0.01). This study suggests that renal impairment is more likely to be seen in patients undergoing more extensive cryotherapy. The number and diameter of lesions together with AST data link renal injury with magnitude of liver injury--all renal impairment patients had an AST > 1000, compared with only 28% of patients who did not.
OBJECTIVE: To establish the minimum required temperature in cryoablation of human colorectal cancer cell lines grown as subcutaneous tumors in mice. METHODS: Male nu/nu nude mice were inoculated by a sc injection of 1 x 10(6) LoVo (n = 30) or C170 (n = 32) cells. After 2 weeks the tumors were frozen using a 3-mm cryotherapy probe (LCS 3000, Cryotech, UK) to temperatures ranging from -8 to -84 degreesC. RESULTS: (LoVo) Of 21 mice evaluable for analysis no tumors recurred in 3 mice which had their tumors frozen to less than -60 degreesC as measured at the presumed tumor/host boundary, whereas all but one tumor recurred in 18 mice which had their tumors frozen to >-60 degreesC. (C170) Of 18 mice evaluable for analysis 14 mice which had their tumors frozen to between -8 and -84 degreesC as measured at the presumed tumor/host boundary developed tumor recurrence. Four mice which had their tumors frozen to -11, -58, -62, and -81 degreesC did not develop tumor recurrence. CONCLUSION: Cryotherapy of subcutaneous human colon cancer xenografts in nude mice results in tumor recurrence if tumors are frozen to temperatures of as low as -60 degreesC (LoVo) or -84 degreesC (C170) with a single freeze-thaw cycle. A critical temperature for the effective cryoablation of human colorectal cancer cell lines grown as subcutaneous tumors in mice with a single freeze-thaw cycle was not defined.
Previous studies have demonstrated that repeated (14 day) administration of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) enhances the suppression of humoral immunity in DBA/2 (Ah-low responder) mice relative to the effect seen with identical cumulative doses after a single treatment (cumulative doses of 4.2, 14.0, and 42 mg/kg). In the present studies, we have explored this phenomenon further by determining the status of several specific parameters, which might account for the increase in antibody suppression in the DBA/2 strain following repeated TCDD exposures. Included in these studies was the induction of hepatic and splenic microsomal 7-ethoxyresorufin-o-deethylase (EROD; P4501A1) activity and biodistribution of the administered TCDD into various target organs and tissues. Changes in lymphocyte subpopulations within the spleen were also assessed by flow cytometry following both single and repeated dosing. All studies made use of direct comparisons between DBA/2 (Ah-low responder) and B6C3F1 (Ah-high responder) female mice. Results of these studies demonstrate that the enhanced suppression of humoral immunity in DBA/2 mice following repeated exposure to TCDD is not directly associated with increases in liver microsomal EROD activity and does not appear to be correlated with changes in the pattern of biodistribution or amount of TCDD within the liver or spleen of these animals. In contrast, the most significant changes that occurred following repeated dosing in either strain were observed in the levels of microsomal EROD activity and immune cell ratios within the spleen. This effect was characterized as an increase in microsomal EROD activity, and a corresponding reduction in the numbers of a non-B/non-T cell population in the spleen.
PURPOSE: Experts recommend left heart catheterization alone to evaluate uncomplicated ischemic heart disease, reserving right heart catheterization for specific indications. Yet some centers routinely perform combined cardiac catheterization (left heart catheterization and right heart catheterization together). SUBJECTS AND METHODS: Using 1992-1993 Pennsylvania Medicare claims for cardiac catheterizations (n = 41,180), we examined rates of combined cardiac catheterization for patients with uncomplicated ischemic heart disease for each hospital (n = 73) that performed catheterizations. We compared combined cardiac catheterization rates among hospitals and developed a multivariable model to identify hospital characteristics associated with high combined cardiac catheterization rates. A random sample of cases from the 10 hospitals with the highest combined cardiac catheterization rates were reviewed to determine justification, complications, and results of combined cardiac catheterization. RESULTS: Of the 41,180 cardiac catheterizations, 14,177 (34%) were combined procedures. Among hospitals, combined cardiac catheterization rates varied from 2% to 98%. Hospital characteristics associated with high combined cardiac catheterization rates included having a cardiology fellowship program (relative risk [RR] 1.7, 95% confidence interval [CI] 1.1-2.7), location in eastern Pennsylvania (RR 2.5, 95% CI: 1.8-3.5), and volume of catheterizations performed (RR 0.95, 95% CI: 0.91-0.99/100 procedures). For reviewed cases, the most common justification for combined cardiac catheterization was planned revascularization (44%), which is not a specific indication. Only 49% of cases had at least one specific indication for right heart catheterization (range by hospital, 30%-74%). The abnormal findings on the right heart catheterization rarely appeared to change management. CONCLUSION: There is wide variation in the practice of combined cardiac catheterization, which appears to be related to teaching status and geographic location. The most common justification for the procedure was planned revascularization, which is not one of the specific indications supported by current literature.
OBJECTIVES: Prostate-specific antigen (PSA) is the most useful of all tumor markers. Although the sensitivity is impressive, low specificity results in a lack of cancer detection in a significant proportion of patients undergoing prostate biopsy. Several recent studies have addressed the need for improved specificity. Of all these approaches, the free/total PSA ratio appears to be the most promising. Given that most circulating PSA is complexed to alpha1-antichymotrypsin, and that this moiety represents a greater proportion of the total PSA in those men with carcinoma, we set out to determine whether complexed PSA would improve specificity in the detection of men with prostate cancer. METHODS: Archival sera were obtained from 300 men, 75 of whom had biopsy-proved prostate cancer. All sera had been previously stored at -70 degrees C for variable periods. An investigative assay for complexed PSA (Bayer) was used. The Tandem-R free and total PSA assays (Hybritech) were used according to the manufacturer's recommendations. RESULTS: Among all patients, specificities for the total PSA, free/total PSA, and complexed PSA alone were 21.8%, 15.6%, and 26.7%, respectively, at cutoffs yielding 95% sensitivity. Similar equivalence or superior performance, in terms of specificity relative to the free/total PSA ratio, was seen at other sensitivity thresholds and other total PSA ranges. CONCLUSIONS: Complexed PSA alone performs better than total PSA or the free/total PSA ratio and obviates the need for a second analyte determination. We believe this marker may offer significant enhancement in PSA testing with significant economic advantages.
STUDY OBJECTIVE: To evaluate intramuscular dihydroergotamine in direct comparison with opioid analgesia in the treatment of acute migraine headache. METHODS: This was a prospective, multicenter, double-blind trial performed in the emergency departments of 11 general hospitals in the United States. One hundred seventy-one patients between the ages of 18 and 60 years who presented to the ED with acute migraine headache were enrolled. Patients were randomly assigned to receive either 1 mg dihydroergotamine (DHE) or 1.5 mg/kg meperidine (MEP) by intramuscular injection. The anti-nauseant hydroxyzine (H) was coadministered in both treatment groups. RESULTS: One hundred fifty-six patients were evaluable. Treatment groups were comparable in sample size, demographics, and baseline measurements of headache pain. Reduction of headache pain as measured on a 100-mm visual analog scale was 41+/-33 mm (53.5% reduction) for the DHE group, and 45+/-30 mm (55.7% reduction) for the MEP group at 60 minutes after treatment (difference=2.2%; 95% confidence interval [CI] -10%, 14.5%; P=.81). Reduction in the severity of nausea and improvement in functional ability were similar between treatment groups. Central nervous system adverse events were less common in the DHE group (DHE 23.5% versus MEP 37.6%, difference-14.1%: 95% CI -28%, 0%). In particular, dizziness was reported less commonly with DHE than MEP (2% versus 15%, difference=-13%: 95% CI -21%, -5%). CONCLUSION: In this prospective, double-blind trial of a convenience sample of ED patients randomly assigned to one of two treatment regimens, DHE and MEP were comparable therapies for acute migraine. The use of DHE avoids several problems associated with opioid analgesia, including dizziness.
Research on elders' health behavior has largely ignored the stage between experiencing a bodily change and defining it as an illness. This paper addresses the question of what explains such definitions of bodily complaints as illness symptoms. The issue is examined in a longitudinal study with a random sample of 350 community dwelling persons aged 65 and over. Multiple regression was used to analyze the effects of external stresses, psychological factors and health attitudes as well as contextual variables, on three types of illness representations. These consisted of giving the bodily changes an illness label, initiating contact with a physician, and/or using some form of self care. These illness representations were treated as outcome variables singularly and in combination. The findings revealed that the overall frequency of a person's bodily changes was the best predictor of an illness designation. Other significant predictors at Time 4 of the study included belief in the seriousness of a complaint, the occurrence of prior illness representations and self-assessed health. This research study on the elderly is unique in that it seeks to explain, within a longitudinal design, the intermediate step between the experience of a bodily change and the definition of the change as an illness.