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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
PubMed2006

Multicenter phase II trial of accelerated cisplatin and high-dose epirubicin followed by surgery or radiotherapy in patients with stage IIIa non-small-cell lung cancer with mediastinal lymph node involvement (N2-disease).

To assess the therapeutic activity of accelerated cisplatin and high-dose epirubicin with erythropoietin and G-CSF support as induction therapy for patients with stage IIIa-N2 non-small-cell lung cancer (NSCLC). Patients with stage IIIa-N2 NSCLC were enrolled in a phase II trial. They received cisplatin 60 mg m(-2) and epirubicin 135 mg m(-2) every 2 weeks for three courses combined with erythropoietin and G-CSF. Depending on results of clinical response to induction therapy and restaging, patients were treated with surgery or radiotherapy. In total, 61 patients entered from March 2001 to April 2004. During 169 courses of induction chemotherapy, National Cancer Institute of Canada (NCI-C) grade III/IV leucocytopenia was reported in 35 courses (20.7%), NCI-C grade III/IV thrombocytopenia in 26 courses (15.4%) and NCI-C grade III/IV anaemia in six courses (3.6%). Main cause of cisplatin dose reduction was nephrotoxicity (12 courses). Most patients received three courses. There were no chemotherapy-related deaths. Three patients were not evaluable for clinical response. Twenty-eight patients had a partial response (48.3%, 95% CI: 36-61.1%), 24 stable disease and six progressive disease. After induction therapy, 30 patients underwent surgery; complete resection was achieved in 19 procedures (31.1%). Radical radiotherapy was delivered to 25 patients (41%). Six patients were considered unfit for further treatment. Median survival for all patients was 18 months. Response rate of accelerated cisplatin and high-dose epirubicin as induction chemotherapy for stage IIIa-N2 NSCLC patients is not different from more commonly used cisplatin-based regimen.

Adult↗
PubMed2006

Isolated lung perfusion with melphalan: pharmacokinetics and toxicity in a pig model.

BACKGROUND: In patients with unresectable lung cancer or pulmonary metastases, isolated lung perfusion (ILP) has been described as an alternative method to deliver high-dose chemotherapy to the lungs, thereby minimizing systemic toxicity. Pharmacokinetics of ILP have not been extensively investigated. Therefore, we studied the feasibility of ILP with melphalan in a pig model with emphasis on pharmacokinetics and acute lung damage. METHODS: Five pigs underwent ILP with melphalan. Blood and tissue samples were obtained for determination of melphalan levels. Tissue biopsies were taken for microscopic evaluation of lung damage. RESULTS: During ILP, no hemodynamic effects of importance were noted. No systemic leakage of melphalan was observed in any of the animals. Compared with normal lung tissue, microscopic examination of lung tissue after perfusion without melphalan showed pulmonary edema. Directly after melphalan perfusion additional hemorrhagic areas were seen; however, electron microscopy displayed no irreversible endothelial damage. CONCLUSION: This study on pigs proved to be a well reproducible model for ILP with melphalan. Pharmacokinetics show a safety profile with no systemic toxicity, which could justify further patient studies, necessary to determine its effect on pulmonary metastases in humans, especially in case of adjuvant therapy after surgical resection or in unresectable disease.

Animals↗
PubMed2004

[Sternal pain: not always harmless].

In two patients, men aged 39 and 66 years, a sternal mass in combination with pain developed. One patient was diagnosed with a non-Hodgkin lymphoma located in the sternum and the other one with a primary chondrosarcoma of the sternum. They both recovered after treatment. The differential diagnosis of disorders of the chest wall is troublesome and includes haematologic, rheumatologic and infectious processes. Tietze's syndrome is a rare cause of pain and non-suppurative swelling of the costosternal joints. However, tumours of the anterior chest wall can also cause these symptoms and these must therefore be excluded if the complaints persist or the swelling progresses. The most common malignant tumours of the chest wall are non-Hodgkin lymphoma, primary chondrosarcoma and metastases. Diagnostics should consist of blood tests and X-rays. CT and MRI scans are more helpful in establishing the diagnosis. A definitive diagnosis can only be determined by biopsy.

Adult↗
PubMed2004

['Palm reading' as a diagnostic aid].

In four patients, a man aged 53, a woman aged 63 and two men aged 67 and 53 years, respectively, inspection of the hand led to the final diagnosis. In the first patient who presented with clubbing of the fingers and pulmonary hypertension, a small atrial septal defect was detected. The second patient had thick curved yellow nails and recurrent pleural effusions as part of this yellow nail syndrome. The third patient presented with clubbing and hypertrophic osteoarthropathy, a secondary complaint to adenocarcinoma of the lung. The fourth patient had increasing pulmonary hypertension as a secondary complaint to recurrent multiple pulmonary embolism from deep venous malformations of his right hand, arm and shoulder as a part of the Klippel-Trenaunay syndrome. These cases show that inspection of the hand may give a clue to the diagnosis.

Adenocarcinoma↗
PubMed2001

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↗
PubMed2001

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↗
PubMed2001

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed1999

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↗
PubMed1999

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1997

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↗