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Biomedical subjects

M A Paul

Publications and source records attributed to M A Paul.

At least 19 recordsLinked to original sources

Reaching affects saccade trajectories.

The pre-motor theory suggests that, when attention is oriented to a location, the motor systems that are involved in achieving current behavioural goals are activated. For example, when a task requires accurate reaching, attention to a location activates the motor circuits controlling saccades and manual reaches. These actions involve separate neural systems for the control of eye and hand, but we believe that the selection processes acting on neural population codes within these systems are similar and can affect each other. The attentional effect can be revealed in the subsequent movement. The present study shows that the path the eye takes as it saccades to a target is affected by whether a reach to the target is also produced. This effect is interpreted as the influence of a hand-centred frame used in reaching on the spatial frame of reference required for the saccade.

Adolescent↗

CC130 pilot fatigue during re-supply missions to former Yugoslavia.

PURPOSE: Deployment of troops in foreign theaters requires a massive airlift capability. The fatigue encountered in such operations can be severe enough to pose a flight safety hazard. The current study documents sleep and the effect of fatigue on aircrew performance during re-supply missions in support of Canadian troops in Bosnia in 1996. METHODS: Ten routine re-supply missions from Trenton, Canada, to Zagreb, Croatia, were studied and involved 9 pilots and 9 co-pilots. To document their sleep hygiene, all pilots wore wrist actigraphs from approximately 5 d prior to the mission, until the mission was completed. Psychomotor performance was tested during the actual flights. Three psychomotor trials during the outbound transatlantic leg (Trenton to Lyneham, UK) were employed, one trial on the Lyneham-Zagreb-Lyneham leg, and three trials on the return transatlantic leg from Lyneham to Trenton. RESULTS: The amount of daily sleep during the 3-d period prior to the mission steadily decreased from an average of 8 h 40 min per day to 6 h 30 min (p < 0.001). During the missions, the worst night of sleep occurred during the second night overseas. During both transatlantic legs, there were significant decrements in the subjective ratings of alertness (p < 0.001), and increases in physical (p < 0.001) and mental fatigue (p < 0.001). Performance on the logical reasoning task as well as the multitask showed probable fatigue effects during the outbound leg of the missions. CONCLUSIONS: Our transport pilots showed a pattern of progressively decreasing sleep. Self-rated scores for alertness, mental and physical fatigue, indicate a deterioration of alertness, and an increase in fatigue throughout the long transatlantic flights.

Adult↗

Melatonin and zopiclone as pharmacologic aids to facilitate crew rest.

PURPOSE: In response to mission imperatives, transport aircrews must often sleep at inappropriate circadian times resulting in inadequate sleep. This study was undertaken to determine whether either melatonin or zopiclone could facilitate early circadian sleep, and to assess whether either of these medications would result in a psychomotor performance decrement which would preclude their use in aircrew. METHOD: Thirteen subjects from DCIEM completed a double-blind cross-over protocol. All subjects were assessed for psychomotor performance during 3 drug conditions (placebo, 10 mg melatonin, and 7.5 mg zopiclone), which were separated by one week. Each of these conditions involved 2 nights of sleep, back-to-back, with the first night being a normal circadian control sleep (23:00 h bedtime, arising at 06:45 h), and the second night being an early circadian drug sleep (drugs at 16:45 h, 17:00 h bedtime, arising at 23:45 h). All subjects were tested for psychomotor performance, on both nights of each of the 3 drug conditions, pre- and post-sleep. Further, during the early circadian drug night, all subjects were tested every hour after arising at 23:45 h (24:00 h until 07:00 h. At the beginning of each psychomotor test session, subjects were asked for their subjective levels of sleepiness and fatigue. RESULTS: Relative to placebo (339.5 min) the subjects slept more on melatonin (370.2 min, p < 0.01), and zopiclone (373.3 min, p < 0.01). Performance in serial reaction time (SRT) task (p < 0.001), logical reasoning task (LRT) (p < 0.001), serial subtraction task (SST) (p < 0.02), and Multitask (MT) (p < 0.03) were impaired for all 3 drug conditions immediately on awakening, compared with pre-sleep performance, as a result of a sleep-inertia effect. With respect to the subjective data, sleep inertia effects were evident for sleepiness (p < 0.001), mental fatigue (p < 0.002), and physical fatigue (p < 0.05). For SRT, LRT, and SST, performance recovered to pre-sleep levels within 1.25 h of awakening, and for MT recovery occurred 2.25 h after awakening. There were no differences in performance or subjective measures between placebo, melatonin and zopiclone. CONCLUSIONS: Both zopiclone and melatonin improved sleep relative to placebo. After sleep inertia, performance recovered to pre-sleep levels for all tasks and was sustained at that level throughout the balance of the testing period. There was no impact of melatonin or zopiclone on performance measures compared with placebo.

Adult↗

Controlled introduction of the sentinel node biopsy in breast cancer in a multi-centre setting: the role of a coordinator for quality control.

AIMS: It is proposed that sentinel node biopsy should replace axillary lymph-node dissection. We analysed the role of a coordinator in the introduction of the sentinel node biopsy in breast cancer in a multi-centre setting to assure standardization and quality control. METHODS: We included 232 operable breast cancer patients. Part of the procedure was an ultrasound examination of the axilla with fine needle aspiration cytology. The sentinel node was identified with 99m-Technetium and Patent Blue. RESULTS: The results of the procedure, sensitivity and false negativity, were the same for the three participating hospitals. We think this is mostly due to the coordinator who supplied information about the technique, pitfalls and results to all teams. CONCLUSIONS: Our experience regarding the organization aspects of introducing the sentinel node procedure in a multi-centre setting now serves as a model in organizing its application in a much wider number of hospitals.

Axilla↗

Survival in early breast cancer patients is favorably influenced by a natural humoral immune response to polymorphic epithelial mucin.

PURPOSE: Polymorphic epithelial mucin (PEM or MUC1) is being studied as a vaccine substrate for the immunotherapy of patients with adenocarcinoma. The present study analyzes the incidence of naturally occurring MUC1 antibodies in early breast cancer patients and relates the presence of these antibodies in pretreatment serum to outcome of disease. MATERIALS AND METHODS: We measured immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies to MUC1 with an enzyme-linked immunoassay (PEM.CIg), which uses a MUC1 triple-tandem repeat peptide conjugated to bovine serum albumin, in pretreatment serum samples obtained from 154 breast cancer patients (52 with stage I disease and 102 with stage II) and 302 controls. The median disease-specific survival time of breast cancer patients was 74 months (range, 15 to 118 months). A positive test result was defined as MUC1 IgG or IgM antibody levels equal to or greater than the corresponding rounded-up median results obtained in the total breast cancer population. RESULTS: A positive test result for both MUC1 IgG and IgM antibodies in pretreatment serum was associated with a significant benefit in disease-specific survival in stage I and II (P =.0116) breast cancer patients. Positive IgG and IgM MUC1 antibody levels had significant additional prognostic value to stage (P =.0437) in multivariate analysis. Disease-free survival probability did not differ significantly. However, stage II patients who tested positive for MUC1 IgG and IgM antibody and who relapsed had predominantly local recurrences or contralateral disease, as opposed to recurrences at distant sites in the patients with a negative humoral response (P =.026). CONCLUSION: Early breast cancer patients with a natural humoral response to MUC1 have a higher probability of freedom from distant failure and a better disease-specific survival. MUC1 antibodies may control hematogenic tumor dissemination and outgrowth by aiding the destruction of circulating or seeded MUC1-expressing tumor cells. Vaccination of breast cancer patients with MUC1-derived (glyco)peptides in an adjuvant setting may favorably influence the outcome of disease.

Adolescent↗

Measurement of acute phase proteins in the rat brain: contribution of vascular contents.

A localized acute phase response occurs in the brain in Alzheimer's disease. Acute phase proteins have previously been measured in brain homogenates to quantify this response. The extent to which measurements of these proteins reflect brain parenchymal contents, as opposed to vascular contents, is unknown. In this study, the acute phase proteins ceruloplasmin (CP), complement factor 3 (C3), haptoglobin (HP), and albumin were measured in regional brain homogenates from phosphate buffered saline-perfused and sham-perfused rats (n = 7-9/group). Interleukin 1-beta (IL1-beta) and copper were also measured. Mean CP, C3, HP, and albumin concentrations in perfused specimens decreased by 94%, 88%, 90%, and 81% vs. sham-perfused specimens (all p < 0.001), while IL1-beta and copper were unchanged. These results suggest that acute phase protein measurements in brain homogenates reflect primarily vascular contents. However, IL1-beta and copper concentrations in brain homogenates are minimally influenced by vascular contents.

Acute-Phase Proteins↗

Multicentre study of ultrasonographically guided axillary node biopsy in patients with breast cancer.

BACKGROUND: Axillary lymph node dissection is still performed as a staging procedure since lymph node status is the most important prognostic factor in patients with breast cancer. Sentinel node biopsy may replace routine axillary lymphadenectomy, especially in patients with small breast cancers. This study investigated whether ultrasonographically guided fine-needle aspiration cytology (FNAC) of the axillary lymph nodes in clinically node-negative patients was an accurate staging procedure to select patients for sentinel node biopsy. METHODS: One hundred and eighty-five consecutive patients were included. All had axillary ultrasonography and detected nodes were categorized according to their dimensions and echo patterns. Ultrasonographically guided FNAC was carried out if technically possible. These results were compared with the results of the sentinel node biopsy and subsequent axillary dissection. RESULTS: In 116 patients no lymph nodes were detected by ultrasonographic imaging. Of 69 patients with visible nodes, 31 had malignant cells on FNAC. There were no false-positive results. Some 87 of 185 patients had axillary metastases on definitive histological examination. Ultrasonography was sensitive in patients with extensive nodal involvement. Failure of the examination was caused by problems learning the method, difficulty in puncturing small lymph nodes and sampling error. CONCLUSION: In patients without palpable axillary nodes, a sentinel node biopsy could be avoided in 17 per cent since ultrasonography combined with FNAC had already diagnosed axillary metastases. The method is particularly valuable in larger breast cancers.

Adult↗

Medical and psychosocial effects of early discharge after surgery for breast cancer: randomised trial.

OBJECTIVE: To assess the medical and psychosocial effects of early hospital discharge after surgery for breast cancer on complication rate, patient satisfaction, and psychosocial outcomes. DESIGN: Randomised trial comparing discharge from hospital 4 days after surgery (with drain in situ) with discharge after drain removal (mean 9 days in hospital). Psychosocial measurements performed before surgery and 1 and 4 months after. SETTING: General hospital and cancer clinic in Rotterdam with a socioeconomically diverse population. SUBJECTS: 125 women with operable breast cancer. MAIN OUTCOME MEASURES: Incidence of complications after surgery for breast cancer, patient satisfaction with treatment, and psychosocial effects of short stay or long stay in hospital. RESULTS: Patient satisfaction with the short stay in hospital was high; only 4% (2/56 at 1 month after surgery and 2/52 at 4 months after surgery) of patients indicated that they would have preferred a longer stay. There were no significant differences in duration of drainage from the axilla between the short stay and long stay groups (median 8 v 9 days respectively, P=0.45) or the incidence of wound complications (10 patients v 9 patients). The median number of seroma aspirations per patient was higher for the long stay group (1 v 3.5, P=0.04). Leakage along the drain occurred more frequently in short stay patients (21 v 10 patients, P=0.04). The two groups did not differ in scores for psychosocial problems (uncertainty, anxiety, loneliness, disturbed sleep, loss of control, threat to self esteem), physical or psychological complaints, or in the coping strategies used. Before surgery, short stay patients scored higher on scales of depression (P=0.03) and after surgery they were more likely to discuss their disease with their families (at 1 month P=0.004, at 4 months P=0.04). CONCLUSIONS: Early discharge from hospital after surgery for breast cancer is safe and is well received by patients. Early discharge seems to enhance the opportunity for social support within the family.

Breast Neoplasms↗

An enzyme-linked immunosorbent assay for the measurement of circulating antibodies to polymorphic epithelial mucin (MUC1).

INTRODUCTION: About one-third of breast and ovarian carcinoma patients have circulating antibodies reactive with polymorphic epithelial mucin (MUC1), either free or bound to immune complexes. While the presence of these immune complexes has prognostic significance in breast cancer patients, the significance of free MUC1 antibodies is less clear. The objective of this study was to develop a reliable assay for the accurate determination of circulating free antibodies to MUC1. MATERIAL AND METHODS: We developed an enzyme-linked immunosorbent assay (ELISA) (PEM.CIg) employing a 60 mer peptide (a triple tandem repeat sequence of the MUC1 peptide core) conjugated to bovine serum albumin and peroxidase-labeled antihuman immunoglobulin G or M antibodies. The assay was standardized and its analytical performance evaluated. A total of 492 serum samples were obtained from 40 healthy men, from 201 healthy women (including 55 women without a history of pregnancy and 45 pregnant women), and (before primary treatment) from 62 benign breast tumor patients and 190 breast cancer patients. MUC1 serum levels were determined with commercial CA 15-3 tests. RESULTS: Circulating antibodies to MUC1 are present both in healthy subjects and in breast cancer patients. The within- and between-assay coefficients of variation were, respectively, 2 and 12% for the IgG determinations and 1.2 and 3% for the IgM determinations. Correlation coefficients for serially diluted serum samples ranged from 0.9998 to 0.9920 for IgG and from 0.9996 to 0.9818 for IgM determinations. The reactivity of serum samples was partially blocked by the addition of various MUC1 peptides and by MUC1 mucin. The inhibiting effect of modified 60 mer peptides suggests the presence of antibodies directed to more than one epitope. CONCLUSIONS: The PEM. CIg assay is a reliable ELISA for measuring free MUC1 antibodies in serum. We are in the process of relating the results obtained in the breast cancer group to disease outcome to evaluate its prognostic significance. In addition, the assay may become a useful tool for vaccine therapy monitoring.

Autoantibodies↗

Neurokinin receptor mRNA localization in human midbrain dopamine neurons.

The structurally related neurokinin peptides, substance P and neurokinin A, are found in abundance within the substantia nigra of a variety of mammalian species. Although it has been established recently that the neurokinin-3 (NK3) receptor is the predominant neurokinin receptor found in rat substantia nigra and adjacent midbrain nuclei, the nature of the neurokinin receptor expressed in human midbrain has not been elucidated. In the present study, neurokinin receptor messenger RNA (mRNA) content within rat and human midbrain were directly compared by using quantitative in situ hybridization histochemistry. In contrast to the high abundance of NK3 receptor mRNA within dopamine (DA) cells of the rat midbrain, neurokinin-1 (NK1), but not NK3, receptor mRNA was localized to human midbrain DA cells. Within the human midbrain, the abundance of NK1 receptor mRNA differed significantly among the distinct DA cell-containing nuclei, with the highest level of expression seen in several subdivisions of the substantia nigra. Thus different neurokinin receptor subtypes apparently mediate the effects of substance P and neurokinin A on human versus rat DA neurons.

Adolescent↗

The use of biliary CEA measurements in the diagnosis of recurrent colorectal cancer.

To assess the usefulness of biliary CEA determinations in the diagnosis of recurrent tumour, gallbladder bile was sampled in patients who underwent laparotomy for proven or suspected recurrent colorectal cancer and in control patients. Biliary CEA concentrations in controls were < 5 ng/ml, whereas significantly elevated CEA concentrations were found in the bile of all patients with tumour recurrence. Serum concentrations in these patients were elevated in 77% only. In a series of 12 patients with (a) suspicious lesion(s) on liver imaging but normal serum CEA concentration during follow-up, biliary CEA determination differentiated clearly between metastases and benign lesions. Biliary CEA determination seems to aid detection of tumour recurrence at an early stage and may preclude unnecessary surgery in patients with undefined liver lesions.

Bile↗

Prognostic value of negative intraoperative ultrasonography in primary colorectal cancer.

The risk of developing recurrent tumour was assessed in a group of 85 patients with primary colorectal cancer who had a negative intraoperative ultrasonographic examination at the time of primary tumour resection. At a median follow-up of 40 months liver metastases had developed in 14 patients (16 per cent). Dukes classification of the primary tumours was stage A, B and C in one, three and ten patients respectively. The interval between primary tumour resection and detection of metastases varied from 6 to 24 months but all became evident within 2 years. Sixteen patients (19 per cent) presented with extrahepatic recurrence, one of whom also developed liver metastases. A negative intraoperative ultrasonographic examination did not prove to be a favourable prognostic factor which allowed exclusion from follow-up or adjuvant chemotherapy.

Adult↗

Extended-coverage-bladder G-suits can provide improved G-tolerance and high Gz foot pain.

METHOD: An extended coverage bladder (ECB) G-suit was evaluated on the DCIEM centrifuge against the current service G-suit (CSU-15/P) in two separate series of experiments. The ECB G-suit covered approximately 85% of the lower body measuring from the umbilicus and all five bladders completely encircled each leg and the lower trunk. The CSU-15/P G-suit covered approximately 30% of the lower body and its five bladders were located only over the frontal aspect of each leg and the lower trunk. The first series of experiments involved five subjects from the highly experienced DCIEM A-team. A standard gradual onset rate (GOR) run was used and suit testing order was counterbalanced across subjects. RESULTS: The test condition G-tolerances are listed as mean +/- SEM; relaxed uninflated tolerances were 4.0 +/- 0.14 for the CSU-15/P suit vs. 4.1 +/- 0.09 for the ECB suit (ns, single tailed, paired t-test) while relaxed inflated tolerances were 4.7 +/- 0.19 for the CSU-15/P suit and 5.5 +/- 0.37 for the ECB suit (p = 0.02, single tailed, paired t-test). The straining tolerances were 8.1 +/- 0.44 for the CSU-15/P suit and 9.0 +/- 0.56 for the ECB suit (p = 0.01, single tailed, paired t-test). The second series involved nine subjects for the following three G-suit conditions; CSU-15/P, ECB with inflation limiters, and ECB with inflation limiters and foot bladders. Relaxed uninflated tolerances were 4.0 +/- 0.13, 4.0 +/- 0.08, and 3.9 +/- 0.10 (ns) while straining inflated tolerances were 9.4 +/- 0.48, 10.1 +/- 0.38 and 10.6 +/- 0.42, respectively (p = 0.01 between all three straining conditions, ANOVA with Scheffé F-test). The ECB G-suit with inflation limiters eliminated abdominal pain and discomfort. CONCLUSION: The ECB G-suit provides improved G-tolerance for both inflated relaxed and straining exposures. Foot bladders eliminated high Gz foot pain and improved straining G-tolerance by about half a Gz. The efficacy of ECB G-suits should be evaluated when used in conjunction with positive pressure breathing. While the ultimate G-suit has yet to be conceived and will no doubt be part of an integrated life support system, ECB G-suits are a step in the right direction in the evolution of life support garmentry.

Abdominal Pain↗

Detection of occult liver metastases by measurement of biliary carcinoembryonic antigen concentrations.

OBJECTIVE: To assess whether biliary CEA concentrations can be used as early markers of occult liver metastases in patients with colorectal cancer. DESIGN: Consecutive open study. SETTING: University hospital, The Netherlands. SUBJECTS: 76 patients with a primary colorectal carcinoma (group 1) and 19 patients who had recently undergone a curative resection of a locally advanced carcinoma (group 2). INTERVENTIONS: Bile sampling by transhepatic puncture of the gallbladder. MAIN OUTCOME MEASURE: Recurrence of tumour. RESULTS: Twenty-one of the 76 patients (28%) with primary colorectal carcinoma had liver metastases; all had a raised biliary CEA concentration. Of the remaining 55 patients 39 (71%) also had raised CEA concentrations. At a median follow-up of 30 months, only seven patients had developed liver metastases, indicating a high number of false-positive results. In Group 2 7/19 patients (37%) had a CEA concentration above the cut-off point. Six of them developed recurrent tumour; 2 patients had liver metastases and 4 others had extrahepatic recurrences. None of the 12 patients with biliary CEA concentrations within the reference range has developed recurrent tumour. CONCLUSION: Biliary CEA concentrations do not predict the presence of occult liver metastases if bile samples are taken during resection of the primary tumour. If samples are taken some time afterwards, a raised CEA concentration seems to predict recurrence at an early stage, either in or outside the liver.

Adult↗

Instrument flying performance after G-induced loss of consciousness.

INTRODUCTION: While both the USAF and the USN have characterized the immediate sequelae of G-induced loss of consciousness (G-LOC) as resulting in approximately 24 s of incapacitation, very little is known about the effect of a G-LOC immediately after this incapacitation period. This study is an attempt to determine the effect of G-LOC on instrument flying performance immediately after G-LOC. METHOD: In order to establish their flying performance baselines, 29 Canadian Forces (CF) pilots attending the high sustained G (HSG) course flew 3 iterations of a 15-min instrument flying task on the day prior to their HSG course. All 29 pilots performed this same task the next day within 5 min of completing the centrifuge training. In addition, the pilots who experienced G-LOC flew the task again 45 min after G-LOC. Flying performance was assessed by calculating Root Mean Square (RMS) error on 11 flight parameters. These RMS values were submitted to a multivariate analysis of variance. RESULTS: Of the 29 pilots, 12 experienced G-LOC during the centrifuge training. The flying performance of the 17 non-G-LOC pilots was not affected by their exposure to HSG. Of the 12 G-LOC pilots, 11 had no measurable performance decrement while 1 pilot, after a severe G-LOC, stalled and "spun-in" on take-off and then (after being re-established on the outbound radial) could not complete the task. This same pilot flew the task very well 45 min later. This study did not identify a degradation in flying performance after HSG nor after G-LOC except in the 1 pilot. CONCLUSIONS: Whether or not a pilot's flying performance is affected after G-LOC may be related to the severity of the G-LOC. Some pilots may experience seizure activity relating to the G-LOC with a resulting sustained performance decrement that appears to resolve by 45 min. It is possible that some of the other G-LOC pilots in the study might have had measurable performance decrements if we had been able to have them fly the task while they were still in the gondola (i.e., immediately after the G-LOC).

Adult↗