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Biomedical subjects

M A MacKenzie

Publications and source records attributed to M A MacKenzie.

At least 19 recordsLinked to original sources
PubMed2005

Short intensive sequential therapy followed by autologous stem cell transplantation in adult Burkitt, Burkitt-like and lymphoblastic lymphoma.

The feasibility and efficacy of up-front high-dose sequential chemotherapy followed by autologous stem cell transplantation (ASCT) in previously untreated adults (median age 33 years; range 15-64) with Burkitt lymphoma (BL), Burkitt-like lymphoma (BLL) or lymphoblastic lymphoma (LyLy), both without central nervous system or extensive bone marrow involvement was investigated in a multicenter phase II study. Treatment consisted of two sequential high-dose chemotherapy induction courses incorporating prednisone, cyclophosphamide, doxorubicin, etoposide and mitoxantrone, without high-dose methotrexate or high-dose cytarabine. Patients with at least PR went on with BEAM and ASCT. Protocol treatment was completed by 23/27 (85%) BL/BLL and 13/15 (87%) LyLy patients. Median treatment duration until BEAM was 70 (range: 50-116) days. No toxic deaths occurred. Response to treatment was complete response (CR) 81% and partial response (PR) 11% for BL/BLL, CR 73% and PR 20% for LyLy. At a median follow-up of 61 months of patients still alive, six BL/BLL and eight LyLy patients have died. The actuarial 5-year overall and event-free survival estimates are 81 and 73% for BL/BLL vs 46 and 40% for LyLy patients. In conclusion, this short up-front high-dose sequential chemotherapy regimen, followed by ASCT is highly effective in adults with BL/BLL with limited bone marrow involvement, but less so in patients with LyLy.

Adolescent↗
PubMed2004

Prognostic significance of activated cytotoxic T-lymphocytes in primary nodal diffuse large B-cell lymphomas.

Clinical outcome in diffuse large B-cell lymphoma (DLBCL) remains unpredictable, despite the identification of clinical prognostic parameters. Here, we investigated in pretreatment biopsies of 70 patients with DLBCL whether numbers of activated cytotoxic T-lymphocytes (CTLs), as determined by the percentage of CD3-positive lymphocytes with granzyme B (GrB) expression, have similar prognostic value as found earlier in Hodgkin's lymphoma and anaplastic large-cell lymphoma and whether loss of major histocompatibility complex (MHC)-I molecules or expression of the GrB antagonist protease inhibitor 9 (PI9) may explain immune escape from CTL-mediated cell death. Independent of the International Prognostic Index (IPI), the presence of >/=15% activated CTLs was strongly associated with failure to reach complete remission, with a poor progression-free and overall survival time. Downregulation of MHC-I light- and/or heavy-chain expression was found in 41% of interpretable cases and in 19 of 56 interpretable cases PI9 expression was detected. We conclude that a high percentage of activated CTLs is a strong, IPI independent, indicator for an unfavorable clinical outcome in patients with primary nodal DLBCL. Although in part of DLBCL expression of PI9 and loss of MHC-I expression was found, providing a possible immune-escape mechanism in these cases, no correlation with clinical outcome was found.

Adolescent↗
PubMed2003

Pseudoplatelets: a retrospective study of their incidence and interference with platelet counting.

AIMS: Spurious platelet counts can be found in acute leukaemias, as a result of the fragmentation of blood cells. Microscopic examination of a blood smear should be performed to detect the presence of these so called pseudoplatelets. When present, the platelet count should be corrected because of the important clinical consequences that a lower platelet count may have in these patients. METHODS: K(3)EDTA anticoagulated blood was measured on an automated blood cell counter, and a blood smear was made and stained according the May Grünwald-Giemsa method for microscopic observation. A 500 cell/particle differentiation was performed and the automated platelet count was corrected. RESULTS: The incidence of pseudoplatelets in 169 patients with acute leukaemia was studied. Pseudoplatelets were detected in 43 patients (25.4%), and seven patients (4.1%) were re-classified as having a major bleeding risk (platelet count, < 15 x 10(9)/litre). CONCLUSIONS: Platelets should be determined morphologically in patients with acute leukaemia and a routine screening method for the detection of pseudoplatelets should be developed.

Acute Disease↗
PubMed2002

Dosimetric verification of inverse planned step and shoot multileaf collimator fields from a commercial treatment planning system.

An inverse treatment planning (ITP) module on a commercial treatment planning system (TPS) (Helax AB, Uppsala, Sweden) is being used for an in-house clinical trial for treatment of nasopharyngeal cancer with contralateral parotid sparing. Intensity modulated radiation therapy (IMRT) fields are delivered by step and shoot multileaf collimator (MLC) with a DMLC enabled Varian 2300 CD (Varian Associates, Palo Alto, CA). A series of testing procedures have been devised to quantify the modeling and delivery accuracy of routine clinical inverse planned IMRT using Helax TMS and the Varian step and shoot MLC delivery option. Testing was done on specific aspects of the TPS modeling germane to DMLC. Measured relative dose factors (head scatter plus phantom scatter) for small MLC fields, normalized to a 10x10 cm2 non-MLC field, were found to differ by 2-3% from the TPS values for the smallest of the fields tested. Relative distributions for small off axis fields were found to be in good agreement. A process for the routine clinical verification of IMRT fields has been implemented. Each IMRT field in an inverse plan is imported into a flat water tank plan and a "beam's eye view" (BEV) dose distribution is generated. This is compared to the corresponding measured BEV dose distribution. The IMRT verification process has also been performed using an anthropomorphic phantom. Large clinical fields (i.e., greater than 14.5 cm in the leaf direction) caused difficulties due to a vendor specific machine restriction, and several techniques for dealing with these were examined. These techniques were (i) the use of static stepping of closed junctions, (ii) the use of two separate IMRT fields for a given gantry angle, and (iii) restricting the overall maximum field size used. The overall process has allowed implementation of an in-house protocol for IMRT use on an initial clinical site. Results of the verification measurements for the first ten patients treated at this center reveal an average maximum dose per IMRT field delivered of 71.0 cGy, with a mean local deviation from the planned dose of -1.2 cGy, and a standard deviation of 2.4 cGy.

Algorithms↗
PubMed2001

[Patient with refractory celiac disease and secondary lymphoma].

A 50-year-old woman who had suffered from well-regulated coeliac disease for 16 years, presented with weight loss, soft stools and abdominal cramps. She had ulcers in the oesophagus and stomach, and in biopsies localisations of so-called enteropathy-associated T-cell lymphoma (EATL) were detected. During a staging investigation she suffered an enteric perforation and later on repeated haemorrhages, from which she eventually died. Patients with coeliac disease who do not respond to a gluten free diet or who relapse after an initial response should be investigated for the presence of a gastrointestinal malignancy. Weight loss is an important symptom. The most frequently occurring malignant complication is an EATL. This is often difficult to diagnose and the prognosis is poor, with frequent complications such as haemorrhages and perforations.

Biopsy↗
PubMed2000

A case of anaplastic lymphoma kinase-positive anaplastic large cell lymphoma presenting with spontaneous splenic rupture: an extremely unusual presentation.

In a 22-year-old male with a 10-day history of fever, painful swelling in the left groin, and abdominal complaints, emergency surgery was performed because of spontaneous splenic rupture. At histology, a cellular infiltrate of intermediate-sized atypical lymphocytes was seen in the splenic white pulp, staining for T-cell markers. In addition, CD30 and anaplastic lymphoma kinase 1 (ALK) were diffusely positive, thus, representing a case of anaplastic large cell lymphoma (ALCL), T-cell, ALK-positive, small cell monomorphic variant. ALK-positive ALCL patients generally bear a much better prognosis than patients with T-cell lymphomas, unspecified, or ALK-negative ALCL. Therefore, besides the very unusual clinical presentation, this case highlights the importance of immunostaining for CD30 and ALK in all T-cell lymphomas. This report is the first extensive description of ALK-positive ALCL involvement of the spleen.

Adult↗
PubMed2000

A polymorphic tetranucleotide repeat in the CYP19 gene and male breast cancer.

The CYP19 gene codes for the aromatase enzyme that is involved in the synthesis of oestrogens. This case-control study examines the relationship between a tetranucleotide repeat sequence in the CYP19 gene and the development of male breast cancer. No significant differences were found between male breast cancer cases and controls.

Aromatase↗
PubMed1997

[Clinical thermometry. I. Historical developments].

Determination of human core temperature has a long history. Since Antiquity, the significance of normal and abnormal body temperatures has been the subject of various interpretations. In this respect, theories based on humoral pathology were replaced by more scientific concepts in the 19th and 20th centuries. Objective measurement and comparison could be performed only after the invention of the thermometer and the introduction of temperature scales. Sanctorius and subsequently Boerhaave and others emphasized the use of measurement of body temperature in the clinic, but its importance was not accepted generally until the late 19th century. Many physicians and scientists have contributed to the progress of thermometry; however, the creation of a firmer scientific basis for clinical thermometry is usually attributed to Wunderlich.

Body Temperature↗
PubMed1997

[Clinical thermometry. II. Current dilemmas].

The relevance of measuring core temperature for diagnosis and treatment of various diseases is generally acknowledged nowadays. Despite introduction of new techniques and markedly improved understanding of body temperature regulation and the pathophysiology of fever, several dilemmas remain to be elucidated in clinical thermometry. In the measurement and interpretation of body temperature, the many variables that influence core temperature, the site of temperature registration and the significance of an elevated or decreased core temperature should be taken into account. With every type of thermometer, good calibration and an adequate recording technique remain pivotal to obtain reliable and reproducible results.

Body Temperature↗
PubMed1996

Skin blood flow and autonomic reactivity in human poikilothermia.

Autonomic reactivity is pivotal in maintaining a constant body core temperature. Skin vasomotor reflexes and cardiovascular reactivity were investigated in four women (aged 28-37 years) with acquired poikilothermia, during steady-state spontaneous hypothermia (rectal temperature (Tr) = 33.7 +/- 1.0 degrees C [mean +/- SD]) and steady-state normothermia (Tr = 36.7 +/- 0.3 degrees C), as well as in 12 normothermic control subjects. Baseline finger temperature (Tf) during hypothermia was significantly lower than during normothermia (Tf = 32.4 +/- 1.2 compared with 36.2 +/- 0.3 degrees C, respectively), and than in the controls (Tf = 34.8 +/- 0.8 degrees C). No significant differences in baseline skin blood flow and forearm blood flow were found between subjects during hypothermia or normothermia and controls, suggesting a failure of sympathetic drive to counter-regulate hypothermia in the subjects. Skin vasoconstrictor responses to the contralateral cooling test and neck cooling test were markedly attenuated in three subjects, and to the finger cooling test in two subjects, during normothermia compared with hypothermia. Blood pressure responses to the Valsalva manoeuvre and head-up tilting were normal in all subjects, whereas the heart rate response to head-up tilting was blunted in three subjects during hypothermia. The responses of blood pressure and forearm blood flow to the cold pressor test in the subjects during both thermal conditions were comparable with the controls. We conclude that in our subjects, without generalized autonomic failure, poikilothermia has to be attributed predominantly to disorders of the central thermoregulatory pathways. Our findings during hypothermia and normothermia indicate that variations in core and skin temperature significantly affect skin vasomotor reactivity.

Adult↗
PubMed1995

Effect of steady hypothermia and normothermia on multimodality evoked potentials in human poikilothermia.

OBJECTIVE: To assess the effects of steady-state spontaneous hypothermia on multimodality evoked potentials and on peripheral nerve conduction in human poikilothermia. DESIGN AND SETTING: Case series at a university hospital. PATIENTS: Four patients (four women, aged 28 to 37 years) with acquired poikilothermia. MAIN OUTCOME MEASURES: Short-latency somatosensory, brain-stem auditory, and visual evoked potentials as well as motor and sensory peripheral nerve conduction velocity during steady-state spontaneous hypothermia and normothermia. RESULTS: The marked latency prolongation of all evoked potentials and decreased peripheral nerve conduction velocity observed during steady-state spontaneous hypothermia (mean +/- SD core temperature, 33.5 +/- 0.3 degrees C) compared with normothermia (36.9 +/- 0.4 degrees C) agrees with previous findings during short-term induced hypothermia. CONCLUSIONS: The unequivocal effect of sustained mild spontaneous hypothermia on evoked potentials and peripheral nerve conduction velocity underlines the importance of meticulous attention to even small alterations in core temperature in interpreting neurophysiological investigations.

Adult↗
PubMed1995

Sudomotor function in human poikilothermia.

Hypohidrosis predisposes to hyperthermia and may indicate generalized thermoregulatory failure. To assess the sweating capacity in human poikilothermia, we performed a quantitative analysis of the central and peripheral sudomotor pathways in four women with acquired poikilothermia (aged 29 to 38 years) and nine controls. Heat challenge in a climatic chamber (ambient temperature 40 degrees C, 50% relative humidity) for 180 minutes revealed that both sweat secretion and evaporative weight loss were significantly lower in the patients than in the controls (p < 0.01). Temperature thresholds for thermal sweating were markedly elevated in at least two patients, whereas a third patient showed no sweating response. Stimulation of the eccrine sweat glands by intradermally injected acetylcholine during reduced core temperature (34.9 +/- 0.7 degrees C) revealed a significantly reduced sweating response in all patients (p < 0.01); the sudomotor response to pilocarpine iontophoresis was reduced or absent in three patients. We conclude that the generalized thermoregulatory sudomotor failure in these patients was attributable primarily to disorders of the central sudomotor drive; the impaired postganglionic sudomotor response is temperature related and possibly secondary to (long-standing) poikilothermia. Quantification of heat-dissipating capacity is pivotal for diagnosing severe thermolability and may help to prevent serious heat illness.

Acetylcholine↗