Biomedical subjects
Publications and source records attributed to J M Ford.
This report describes a patient who underwent a subtotal hysterectomy 6 years ago for fibroids. She re-presented recently with lung metastases and a pelvic mass. Macroscopic appearances at laparotomy suggested a leiomyosarcoma of the uterine stump, but histological appearances suggested the patient was suffering from the rare condition 'metastasizing leiomyoma'. Subsequent response to hormone manipulation supported the latter diagnosis.
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To exploit possible different non-cross-resistant mechanisms of cytotoxicity, 25 patients with advanced breast cancer were given combination chemotherapy consisting of iv mitoxantrone (7 mg/m2) and doxorubicin (30 mg/m2) every 3-4 weeks. The patients had predominantly visceral disease and received a median of six (range, one to 12) cycles of therapy. There were no complete responders, but 13 patients (52%) achieved partial remission lasting a median of 8 months (range, 4-21+). Three patients (12%) had disease stabilization and nine (36%) had disease progression. Hematologic toxicity was generally mild, with median wbc count and platelet count nadirs of 1900/mm3 (range, 700-3100) and 160,000/mm3 (range, 49,000-406,000), respectively. One patient may have died from treatment-related sepsis (pneumonia), but lymphangitic lung disease was not excluded. Hair loss progressing to severe alopecia over several treatment cycles was relatively common, affecting seven of 16 evaluable patients (44%). Vomiting was mild or absent in 17 (71%) of 24 evaluable patients. Three of 15 patients in whom serial measurements of left ventricular ejection fraction were performed developed significant reductions compatible with anthracycline-induced cardiotoxicity. Two of these patients also had pericardial effusions and one developed congestive heart failure. In conclusion, mitoxantrone and doxorubicin is an active, well-tolerated drug combination for the treatment of advanced breast cancer but may have appreciable cardiotoxicity.
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Ten young women were tested with an ERP paradigm that used the words 'left,' 'right,' 'LEFT,' 'RIGHT' as stimuli. The stimulus sequence was presented as several separate runs with varying response instructions. Subjects were instructed to respond according to the meaning of the stimulus in the (WORD task), to the case in which the stimulus was written (CASE task), or to both the case and meaning of the stimulus (CASE/WORD) task. In each task, half the trials called for a response that was incompatible with the stimulus. For the WORD task, compatible and incompatible trials were presented as separate blocks of trials. For all 3 tasks an additional stimulus sequence was presented in which the words were degraded with superimposed visual random noise. Reaction time (RT) in the CASE/WORD task was more than 100 msec later than in the other tasks. In the WORD and CASE/WORD tasks, RT was delayed more than 100 msec when the response was incompatible with the stimulus. Degrading the stimulus additionally delayed RT by about 100 msec. In the WORD and CASE tasks, error RTs were earlier than correct RTs. P3 latency was measured with a single-trial latency adjustment algorithm. P3 latency was delayed in the CASE/WORD task compared to the other 2 tasks. P3 was delayed by degrading the stimuli. Contrary to some previous reports, P3 was delayed by about 70 msec when incompatible responses were required, but only in the WORD task. Taken together with error and RT data, these P3 latency data are consistent with the notion that the task causes subjects to adopt different strategies and hence different types of processing (i.e., serial vs. parallel). Depending on the type of processing, P3 may appear to be affected by response incompatibility.
Three experiments investigating the effects of response production and inhibition on the N2 and P3 components of the ERP are reported. In the first experiment, 12 young female volunteers were presented with the words "push' and "wait' (semantic stimuli). On a separate series of trials, they were presented with arbitrary symbols assigned the same meanings (symbolic stimuli). For each stimulus series half of the stimuli were degraded. To obtain an estimate of reliability of the data, each task was repeated. Data were collected from Fz, Cz and Pz electrode sites. The P3 amplitude had a parietal maximum when the stimuli instructed subjects to respond (Go). The P3 was equal at central and parietal sites when the stimuli instructed the subjects to withhold a response (No-Go). This topographic pattern was obtained for all stimulus manipulations, simple and degraded stimuli, words and symbols, and for the first and second runs. The N2 was a frontal maximum component that was larger to the No-Go than to the Go stimuli. This result was also robust to the manipulations. A second experiment investigated the dependency of these findings on an overt motor response. In this experiment, the symbolic and semantic stimulus series were each presented twice. The subjects counted the Go stimuli and did not count the No-Go stimuli for one presentation and pressed the reaction time button as in experiment 1 for the other presentation. While counting (compared to button pressing) delayed the N2 and P3 peaks, counting and pressing produced similar results, including the Go/No-Go P3 distribution effects. A third experiment investigated the sensitivity of these findings to the orientation of the symbols instructing the subjects to respond or withhold the response. Again the pattern of results was robust to this manipulation.
Normal adult volunteer subjects ranging in age from 18 to 90 years participated in a study in which analogous auditory and visual paradigms, with infrequently occurring target and non-target events, were used to elicit event-related potentials (ERPs) with a prominent P3 component. Of the 135 subjects participating, 66 completed both auditory and visual paradigms. The amplitude and latency of P3 were analyzed using average ERPs, single trials (adaptive filter) and principal components analysis (PCA). Age regressions were calculated using measures derived from average ERPs and single trials. Single trial measures were better than average ERP measures in demonstrating age-related changes in P3 latency. There was a significant increase in P3 latency with age of 1-1.5 msec/year. The range of normal P3 latency for a given age (1 S.E. of the regression = 40 msec for the visual target stimuli) was much larger than obtained by other investigators. The visual paradigm produced higher P3 latency/age correlations than the auditory paradigm (visual target r = 0.52, non-target r = 0.42; auditory target r = 0.32, non-target r = 0.33). Within individuals, the amplitude and latency of P3 generated by auditory and visual stimuli were highly correlated, though the visual paradigm produced larger and later P3s than the auditory paradigm. There is an apparent change in the scalp topography of P3 with age. In young adults, P3s to target stimuli have a markedly parietal distribution. The distribution of P3 becomes more uniformly distributed from Pz to Fz with age. This may be due to changes in overlapping components such as the slow wave (SW) rather than to changes in the amplitude of P3 per se.
Patients with dementia, schizophrenia and depression were tested with analogous auditory and visual event-related potential (ERP) paradigms designed to elicit a large P3. The patient groups were compared to age normative predictions derived from a large control sample for a number of ERP and behavioral variables. The results were similar for the auditory and visual paradigms. P3 latency was prolonged two or more S.D.s beyond that predicted by age for less than one-half of the demented patients. This latency prolongation was significant for the group as a whole but would result in too many false negatives if used diagnostically for individuals. Furthermore, increased P3 latency was not specific, as the schizophrenic patients also had later P3s. The amplitude of P3 was reduced in the demented patients, but it was also smaller in other patient groups. The only variable which distinguished the demented patients from both controls and from the other patients was the single trial P3 latency/RT correlation. The demented patients, as a group, had significantly lower P3 latency/RT correlations, but this effect also was not sensitive enough to be diagnostic for individuals. The data from these two paradigms suggest that the P3 amplitude and latency abnormalities observed reflect a common, rather than a diagnostically specific deficit. This study is in contrast to some others which report much more sensitivity and specificity in the use of P3 latency in the diagnosis of dementia. Differences in task demands, patient samples and ERP analysis techniques might explain some of the discrepancy.
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191 combined collections of granulocytes (PMN) and platelets (PLT) obtained by discontinuous cytapheresis were given to 23 patients with acute myeloid leukaemia (AML). The circulation in recipients of the concomitantly transfused cells was compared by measuring the % recovery of PMN at 1 h, and of PLT at 1 and 20 h. The recovery of both cells was greatly reduced in transfusions accompanied by a transfusion reaction. Fever in recipients had no effect on the recovery of either cell, but PMN recovery was significantly higher in patients receiving oral prednisolone. Alloimmunization to PLT, defined as recovery levels less than 15% at 1 h and/or less than 10% at 20 h, was recorded in 42 transfusions, and PMN recovery was significantly reduced in this group. In transfusions where PMN recovery was 'low' (less than 5%); the recovery of the coincidentally transfused PLT was significantly reduced only in transfusions accompanied by a reaction. These results emphasize the deleterious effects of transfusion reactions and suggest that donor PMN frequently circulate less well in recipients alloimmunized to PLT from the same donor.
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In a case-control study of 36 men with cancer of the ureter and 307 male controls with the same age distribution tobacco smoking conferred a relative risk for this cancer of 2.9, whereas consumption of analgesics of any kind did not increase the risk. The relative risk for cancer of the renal pelvis, determined for 29 men, was 2.4 for tobacco and 6.0 for phenacetin-containing analgesics. Analgesics containing no phenacetin conferred no increased risk for cancer at this site. Data for 13 women with ureteral cancer, 5 of whom had taken phenacetin, are presented but not analyzed.
In a case-control investigation of 154 women with cancer of the bladder and 440 female population controls spanning the same age range, the relative risk for this cancer was 2.6 in consumers of phenacetin-containing analgesics and 2.7 in tobacco smokers. The relative risks for cancer of the renal pelvis, determined for 31 cases, were 5.4 with phenacetin and 4.7 with tobacco. Increasing consumption of either agent increased the risk for cancer at each of the two sites, while a synergistic rather than purely additive effect was apparent when both phenacetin-containing analgesics and tobacco had been taken. Consumption of analgesic preparations which contained no phenacetin did not increase the risk of developing cancer at either site. The evidence indicates that phenacetin is a clinically important carcinogen for the lower as well as for the upper urinary tract.
A dye reduction method for determining a definitive endpoint with agar dilution susceptibility testing has been developed. Bacterial growth was determined by applying to the inoculum spot a dye solution containing 2-(p-iodophenyl)-3-(p-nitrophenyl)-5-phenyltetrazolium chloride and phenazine methosulfate. Viable colonies reduced the tetrazolium salt to a visible red color within 3 to 5 min. The minimum inhibitory concentrations of six antimicrobial agents tested against 167 clinical streptococcal isolates were recorded before and after the addition of the tetrazolium-phenazine methosulfate solution. A total of 252 discrepancies (25%) were observed, and of these, 30 (12%) differed by more than one tested antibiotic concentration. Endpoint reproducibility of the dye procedure was assessed by four technologists in a double-blind study. A 2.7-fold reduction in disagreement was observed when the dye was used. Use of the tetrazolium-phenazine methosulfate solution involves little deviation from standard antimicrobial susceptibility test procedures and yields more accurate, as well as reproducible, susceptibility results.