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Biomedical subjects

G A Kennedy

Publications and source records attributed to G A Kennedy.

At least 19 recordsLinked to original sources

Combination antithymocyte globulin and soluble TNFalpha inhibitor (etanercept) +/- mycophenolate mofetil for treatment of steroid refractory acute graft-versus-host disease.

Antitumor necrosis factor-alpha antibodies are increasingly being used for the treatment of steroid-refractory acute graft-versus-host disease (GVHD) complicating allogeneic stem cell transplantation. We retrospectively reviewed the outcomes of 16 patients with refractory acute predominantly visceral GVHD treated with combination antithymocyte globulin (ATG), tacrolimus and etanercept +/- mycophenolate mofetil (MMF) at our institution. Overall response rate (CR+PR) was 81%, with median survival post commencing salvage immunosuppression 224 days (range 20-1216 days). In total, eight patients (50%) died, including from progressive GVHD in two cases (13%), infection in five (31%) and relapse of underlying malignancy in one (6%). In comparison to our previous experience of ATG+tacrolimus as treatment for refractory visceral GVHD, both response rate and overall survival were improved with addition of etanercept, with no apparent increase in infectious complications. As such, use of etanercept in combination with ATG +/- MMF for treatment of steroid refractory acute GVHD appears to be associated with high response rates, significant survival and no unexpected toxicity. Further study of this immunosuppression combination in a larger cohort of patients in this setting is indicated.

Acute Disease↗

Myeloablative allogeneic stem cell transplantation for advanced stage multiple myeloma: very long-term follow up of a single center experience.

We aimed to review the long-term outcome of myeloablative allogeneic stem cell transplantation (SCT) performed for multiple myeloma (MM) at our institution. Records of all patients who received standard myeloablative allogeneic SCT for MM were retrospectively reviewed. Overall survival (OS), progression-free survival (PFS), and event-free survival (EFS) were calculated using the Kaplan-Meier method. In total 37 transplants had been performed. Median follow up post-SCT was 108 months (range: 33-148). The majority of patients suffered advanced stage disease and/or had received multiple prior therapies prior to SCT. Transplant-related mortality (TRM) at 100 days was 32%. Grades 2-4 acute graft-vs.-host disease (GVHD) occurred in 18 patients (49%), and extensive stage chronic GVHD in seven (28%) of 25 patients surviving greater than day 100. Median OS, PFS, and EFS were 28 months, 66 months and 13 months, respectively, with 5 year OS, PFS, and EFS 40%, 54% and 24%. Our results suggest that allogeneic SCT, even when performed in advanced stage, heavily pretreated MM, still results in long-term EFS in a significant minority of patients. Efforts should continue on alternative allogeneic SCT approaches to reduce the high early TRM rate associated with myeloablative conditioning.

Adult↗

An examination of the association between eating problems, negative mood, weight and sleeping quality in young women and men.

The aim of this study was to determine if low mood influenced the association between eating problem symptoms and self report sleeping quality in a large group of young women and men. A group of 381 female and male undergraduate students completed a set of self-report inventories in order to test a model developed for this study observing the association between eating problems, low mood, restricted dieting, weight and self-reported sleeping quality using a path analysis model. The model that best fit the data indicated that eating problem symptoms were associated with low mood and low mood was related to sleeping quality. There was also a direct association between eating problems and sleeping quality but this was reduced by the presence of low mood in the equation. There were no other direct relationships with sleeping quality but there was an association between low mood and low weight. There were also differences reported between men and women on sleeping quality suggesting that women in this sample reported more sleeping difficulties than men. In all this research demonstrates with a large non-clinical sample the links between eating problems, mood and sleeping difficulties.

Adolescent↗

Treatment of patients with advanced mycosis fungoides and Sézary syndrome with alemtuzumab.

OBJECTIVES: Alemtuzumab (anti-CD52, Campath-1H) has recently been shown to be effective in the treatment of a range of hematological malignancies, including B-cell chronic lymphocytic leukemia and T-cell prolymphocytic leukemia. We undertook a phase II study to evaluate the safety, tolerability and efficacy of alemtuzumab in patients with relapsed or refractory advanced stage cutaneous T-cell lymphoma. PATIENTS AND METHODS: A total of eight patients were enrolled, seven with mycosis fungoides/Sézary syndrome (MF/SS) and one with large-cell transformation of MF. Seven patients had disease refractory to multiple previous therapies. Alemzumab (30 mg) was administered intravenously three times per week for 12 wk or until maximum response. RESULTS: The overall response rate was 38%, with three patients achieving partial remission, two patients with stable disease and three patients with progressive disease (PD) during treatment. The time to progression was short, with all patients developing PD within 4 months of starting alemtuzumab. Response duration in the three PR patients was also brief, with responses lasting less than 3 months in all three cases. Significant hematological and immunosuppressive toxicity was observed, with both grade 3-4 cytopenias and significant infectious complications occurring in a majority of cases. CONCLUSIONS: Our findings suggest that in heavily pretreated, refractory, advanced stage MF/SS, although alemtuzumab has biological activity, it is associated with significant toxicity and only modest clinical utility. As such, combination regimens incorporating alemtuzumab merit further investigation in this difficult to treat patient group.

Adult↗

Impact of stem cell donation modality on normal donor quality of life: a prospective randomized study.

As part of a previously reported trial comparing granulocyte-colony stimulating factor (G-CSF) stimulated bone marrow and peripheral blood stem cells (PBSCs) in allogeneic stem cell transplantation, we included a questionnaire to compare donor morbidity and long-term complications between the two donation procedures. Bone marrow donation was associated with significantly more donors experiencing localized pain at the donation site compared to PBSC collection. However, this was not associated with any increased delay in returning to normal activity. Although a minority of bone marrow donors suffered chronic pain at the donation site, no serious long-term side effects relating to G-CSF stimulated stem cell donation were identified.

Adolescent↗

Quantification of feto-maternal haemorrhage (FMH) by flow cytometry: anti-fetal haemoglobin labelling potentially underestimates massive FMH in comparison to labelling with anti-D.

Many centres now routinely use flow cytometry to quantify feto-maternal haemorrhage (FMH). However, which flow cytometric method is the most accurate in quantifying FMH is currently unknown. An audit of clinical results in which FMH had been estimated by both directly conjugated monoclonal anti-D and anti-fetal haemoglobin (HbF) labelling suggested that the anti-HbF labelling method may underestimate massive FMH in comparison to labelling with anti-D. Subsequent to this audit, 46 samples of adult D-negative blood were spiked with varying amounts of D-positive cord blood (0.05-10% fetal cells per sample), and the number of fetal cells present was quantified by both labelling methods. The percentage of fetal cells detected by anti-D was not significantly different to the estimated percentage of fetal cells added to each sample (P = 0.636). However, anti-HbF labelling significantly underestimated the percentage of fetal cells present (P = 0.0001). In comparison to anti-D, the percentage of fetal cells detected by anti-HbF was also significantly lower (P < 0.0001). The difference in fetal cell detection between anti-D and anti-HbF labelling was only apparent in the spiked samples containing > or =1% fetal cells per sample. In samples containing < or =0.6% fetal cells, no significant difference in the detection of fetal cells between anti-D and anti-HbF labelling was observed (P = 0.11). To allow adequate immunoprophylaxis in D-negative mothers with massive FMH, we recommend that anti-D labelling should be used in the routine flow cytometric estimation of FMH.

Adult↗

A novel method for preparing histology slides without a microtome.

A study was undertaken to determine if it might be possible to prepare tissue sections on slides without the use of paraffin embedding, microtome sectioning, or cryostat sectioning which involve equipment and training not always available to scholars or professionals wishing to examine tissue microscopically. After evaluating many different reagents, cutting instruments and solid supports, we developed a method involving application of super glue to a slide, adhering a section of tissue to it, cutting the tissue with a disposable microtome blade, staining the tissue and removing the superglue with a commercially available product. The sections are similar to those sectioned on a microtome, but do not at this time equal their quality. However, histoarchitecture is preserved and individual cell morphology is usually good. We conclude that this is a viable method for preparing histology sections without the use of a microtome or cryostat, something long thought impossible. We have dubbed the method 'RAMP' (Rapid Adhesive-Mediated Procedure).

Adhesives↗

Severe complication after administration of formalin for treatment of progressive ethmoidal hematoma in a horse.

Formalin was injected into an ethmoidal hematoma in an 18-year-old Arabian gelding. Abnormal neurologic signs were observed within minutes of the injection. The horse did not respond favorably to medical treatment of the neurologic signs and was euthanatized. Postmortem examination revealed erosion and necrosis of the ventral cribriform plate, which appeared to have allowed the injected formalin to reach the rostral portion of the frontal lobe of the brain. Endoscopy and radiography had been performed prior to euthanasia, but neither delineated the cribriform lesion. Before treating large progressive ethmoidal hematomas with formalin, it may be beneficial to perform computed tomography to assess the extent of damage caused by the lesion.

Animals↗

The hispid cotton rat (Sigmodon hispidus) as an experimental host for the bovine liver fluke (Fasciola hepatica).

The results of a study testing the susceptibility of the hispid cotton rat, Sigmodon hispidus, to infection with Fasciola hepatica are described. Ten cotton rats were placed into one of four test groups, one uninfected control or three animals each receiving two, five, or 10 F. hepatica metacercariae. Three of nine (33%) became infected, and two of these animals carried the infection to patency. At necropsy one animal had two mature F. hepatica within the common bile duct, and the other harbored a single fluke. Gross and microscopic changes, primarily of the liver, associated with infection are described, as are fecal egg counts throughout the duration of infection.

Animals↗

Molecular remission without blood product support using all-trans retinoic acid (ATRA) induction and combined arsenic trioxide/ATRA consolidation in a Jehovah's Witness with de novo acute promyelocytic leukaemia.

Arsenic trioxide has recently been used in the treatment of both relapsed and de novo acute promyelocytic leukaemia (APML). Molecular remissions have been attained using arsenic trioxide with minimal associated haematological toxicity, making protocols utilizing this drug an attractive option for Jehovah's Witnesses with APML. A 62-year-old female Jehovah's Witness with de novo APML was treated with all-trans retinoic acid induction followed by combined arsenic trioxide/ATRA consolidation, and achieved molecular remission with minimal haematological toxicity and no blood product support.

Antineoplastic Agents↗

Enzyme supplementation and particle size of wheat in diets for nursery and finishing pigs.

Three experiments were conducted to determine the effects of enzyme supplementation and particle size of wheat-based diets on growth performance and nutrient digestibility in nursery and finishing pigs. In Exp. 1, 180 weaned pigs (5.7 kg and 21 d of age) were fed diets in a 35-d growth assay without or with a Trichoderma longibrachiatium enzyme product (4,000 units of xylanase activity per gram of product) and with wheat ground to mean particle sizes of 1,300, 600, or 400 microm. Enzyme supplementation had no effect on ADG or gain/feed (P > 0.32), but there was a trend (P < 0.10) for greater digestibility of DM (d 6) in enzyme-supplemented diets. A particle size of 600 microm supported the greatest overall gain/feed (quadratic effect, P < 0.01). An interaction of enzyme supplementation with particle size occurred; gain/feed was improved (P < 0.01) with enzyme supplementation at the coarse (1,300 microm) particle size but not when the wheat was ground to 600 or 400 microm. In Exp. 2, 160 finishing pigs (67 kg) were fed a diet without or with the same enzyme used in Exp. 1 and wheat ground to 1,300 or 600 microm. No interactions occurred between enzyme supplementation and particle size of the wheat (P > 0.15). However, there were trends for greater gain/feed (P < 0.10) during the 67- to 93-kg phase of the experiment and for greater digestibility of DM (P < 0.10) and N (P < 0.07) with enzyme supplementation. When particle size was reduced from 1,300 to 600 microm, gain/feed was improved (P < 0.03) for the 93- to 114-kg phase of the growth assay, and digestibilities of DM (P < 0.02) and N (P < 0.04) were greater. In Exp. 3, 160 finishing pigs (63 kg) were given diets without or with the enzyme product and wheat ground to 600 or 400 microm. Enzyme supplementation improved ADG (P < 0.04) in the 90- to 115-kg phase but otherwise did not affect growth performance, carcass measurements, or stomach lesions. A particle size of 400 microm increased overall gain/feed (P < 0.04), digestibilities of DM and N (P < 0.01), and development of stomach lesions (P < 0.01). In conclusion, pigs did not benefit consistently from enzyme supplementation. However, wheat particle sizes of 600 and 400 microm supported the best overall performance in nursery and finishing pigs, respectively.

Animal Feed↗

Brucellosis induced by RB51 vaccine in a pregnant heifer.

Brucellosis developed in a 14.5-month-old Gelbvieh heifer after the animal was vaccinated with the calfhood dose of strain RB51 Brucella abortus vaccine s.c. during the fourth month of its first pregnancy. The heifer experienced dystocia and was euthanatized during cesarean section because of a large uterine tear. The fetus was dead at delivery. Suppurative placentitis and fetal pneumonia were evident at necropsy. Brucella abortus strain RB51 was isolated from the placenta and the fetus' lung.

Agglutination Tests↗