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Biomedical subjects

J Kennedy

Publications and source records attributed to J Kennedy.

At least 145 records · Page 8Linked to original sources

Analysis of factors predicting speed of hematologic recovery after transplantation with 4-hydroperoxycyclophosphamide-purged autologous bone marrow grafts.

We previously described the predictive value of graft colony-forming units granulocyte macrophage (CFU-GM) content after 4-hydroperoxycyclophosphamide (4-HC) purging for the duration of aplasia after autologous bone marrow transplantation. Despite the uniform 4-HC concentration, we observed heterogeneity in CFU-GM survival and the kinetics of engraftment. We have now analysed patient and graft characteristics for 154 patients undergoing autologous transplantation with 4-HC purged grafts to further define this heterogeneity. Patients transplanted for the treatment of malignant lymphoma reached a peripheral blood granulocyte count of greater than 0.5 x 10(9)/l (median, 20 versus 40 days; p less than 0.001) and platelet transfusion independence (median, 30 versus 70 days; p less than 0.001) significantly faster than patients transplanted for acute non-lymphoblastic leukemia. Other diagnostic groups were intermediate. These differences were independent of graft CFU-GM content. Multiple other patient and graft factors including patient age, peripheral blood counts on day of harvest, and amounts of other hematopoietic progenitors also predicted the kinetics of engraftment in univariate and multivariate analysis. Cytomegalovirus infection during the aplastic period predicted a delay in granulocyte (p = 0.024) but not platelet recovery (p = 0.174). This analysis demonstrates that multiple patient, graft, and post-transplant factors predict the engraftment capacity of autografts, and the kinetics of engraftment with 4-HC purged grafts. The multiple predictive factors explain a significant portion of the variability in engraftment kinetics observed after transplantation with 4-HC purged autografts.

Adolescent↗

Actin and myosin isoforms in aneural and malformed chick hearts.

Although it is generally accepted that actin and myosin isoforms adapt to their functional requirements, the sequence of expression of these proteins in hearts developing abnormally is unknown. In the chick embryo it is possible to change various aspects of heart development without direct manipulation of the cardiovascular system, by removing various regions of the neural crest from early embryos. The neural crest provides both neural (sympathetic and parasympathetic) and ectomesenchymal components to the heart, and selective removal of various areas results in embryos with sympathetically aneural hearts, or persistent truncus arteriosus with or without parasympathetic denervation. Myosin isoform expression was studied in each of these types of hearts using an array of myosin antibodies specific for atrium, ventricle or the conduction system. Myosin expression in experimental hearts was found to follow the normal pattern of development using these antibodies. Actin expression was studied using cDNA probes for the 3' untranslated region of actin mRNA of the alpha-skeletal, alpha-cardiac and beta-actin isoforms. Using slot-blot hybridization analysis, the pattern of actin expression in atrium and ventricle was followed throughout the period of incubation in normal hearts. The pattern of actin expression was found to be abnormal in hearts which were sympathetically aneural and those which had persistent truncus arteriosus combined with parasympathetic denervation. ATPase activity was increased only in atria of hearts with persistent truncus arteriosus. It appears from these experiments that actin isoform expression is influenced in the chick heart by autonomic innervation.

Actins↗

The chest radiograph in acute bronchiolitis.

The relationship between clinical severity, as judged by a clinical scoring method, and the degree of radiological change on a chest X-ray, was assessed in 153 children with acute bronchiolitis. There was no statistical correlation between clinical severity and the degree of radiological change. The majority of radiographs were requested on the assumption that it was a useful routine investigation. We suggest that the request for a chest X-ray in acute bronchiolitis should be made only when the need for intensive care is being considered, where there has been an unexpected deterioration in the child's condition or the child has an underlying cardiac or pulmonary disorder.

Acute Disease↗

Risk factors in progression beyond stage 2 retinopathy of prematurity.

Of the 96 babies born at less than 30 weeks gestation at Westmead Hospital between January 1986 and December 1987, 91 were studied. Of these 37 developed some form of retinopathy of prematurity (ROP), with eight babies having stage 3 or worse. We compared the clinical features of these eight babies to a control group of eight babies with stage 2 ROP, having matched for gestational age. Factors of statistical significance in progression beyond stage 2 were male sex and number of days of assisted ventilation. The presence of a patent ductus arteriosus, although not statistically significant, is a factor which we consider to be clinically important. The development of Plus disease is associated with a poor prognosis.

Australia↗

Carpe diem!

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Attitude↗

Regulation of gluconeogenesis in swine kidney proximal tubule cells.

Proximal tubule cells were isolated from swine kidney and cultured for periods of more than 30 days. The cells formed confluent monolayers after plating on a collagen surface and they were passaged more than 5 times on this matrix. The cells maintain several metabolic functions of proximal tubule cells, including gluconeogenesis and the ability to respond to epinephrine and parathyroid hormone. Gluconeogenesis, a principal metabolic pathway in proximal tubule cells, was examined as a function of days in culture. The isolated cells showed a nearly constant rate of gluconeogenesis from 14C-lactate, 14C-alanine and 14C-glycerol with no significant loss of activity for at least 30 days in culture. Likewise, the activities of several cytosolic and membrane associated enzymes including, alkaline phosphatase, delta-glutamyltransferase, fructose-1,6-bisphosphatase and phosphofructokinase were nearly constant over the same time period. The cells responded to treatment with epinephrine and parathyroid hormone, and the rate of gluconeogenesis from 14C-lactate doubled in the presence of these hormones. The morphological and biochemical evidence obtained in these studies show that the proximal tubule cells isolated from swine kidney provide an excellent well defined system for studying the hormonal regulation of carbohydrate metabolism in this tissue.

Amino Acids↗

A controlled clinical trial of baclofen as protective therapy in early Huntington's disease.

We carried out a controlled clinical trial to examine the potential of baclofen to slow the functional decline of patients with early Huntington's disease (HD). The basis of the trial was: (1) the hypothesis that excitatory amino acid neurotransmission mediates the neuronal degeneration of HD, (2) preclinical evidence that baclofen retards corticostriatal release of glutamate and aspartate, and (3) reports that baclofen produces short-term clinical benefits in some HD patients. Sixty patients with early HD were randomized to chronic baclofen, 60 mg/day, or placebo treatments and followed systematically for up to 42 months. Total functional capacity was not favorably influenced by baclofen treatment. Factors that contributed, although nonsignificantly, to a more rapid rate of total functional capacity decline included younger age (less than 35 years), earlier stage (stage I) of illness, paternal inheritance of the HD gene, and baclofen treatment. Our patients declined at a pace slower than that observed in other prospective studies, a finding likely due to selection criteria, avoidance of neuroleptic therapy, and strong psychosocial support.

Adolescent↗

Toxicity of IL-2 and Corynebacterium parvum following direct intracranial injection.

The toxicity of IL-2 and/or C. Parvum when injected directly into the mouse brain was examined by survival and histopathology using different numbers of injections, different doses of IL-2, different solvents for the IL-2, and different doses and routes of administration of C. Parvum. Two injections was found significantly to increase mortality (19%) over a single injection (4%). Mortality from two injections of 30,000 U (23%) or 60,000 U (20%) was higher than from two injections of 15,000 U (12%). The mortality from two injections with normal saline as solvent was much higher (29%) than from two injections with sterile water (19%) or D5W (9%). Two injections of IL-2 given simultaneously with C. Parvum showed a much higher mortality (26%) than other doses and routes of C. Parvum administration. Mice dying acutely (6-24 days) of toxicity showed an extensive mononuclear infiltrate at the site of injection. The brains of surviving mice (sacrificed at 30 days) showed a mild residual mononuclear cell infiltrate with the exception of mice which had received IL-2 and C. Parvum simultaneously. Brains from this latter group had an extensive residual mononuclear cell infiltrate.

Animals↗

Prospective, randomized, placebo-controlled trial of norfloxacin for the prophylaxis of recurrent urinary tract infection in women.

Thirty women were randomized in a double-blind, placebo-controlled study to receive either norfloxacin, 200 mg orally daily at bedtime, or placebo for the prevention of recurrent bladder infection. Subjects were followed monthly to monitor compliance and symptoms, for urine culture and periurethral and anal canal swabs to monitor colonization, and for blood specimens for hematologic and biochemical studies to monitor safety. During 1 year of follow-up, 10 of 15 placebo subjects and none of 15 norfloxacin subjects developed infection (P less than 0.001). Adverse effects occurred with equal frequencies in the two groups. For norfloxacin subjects, only 2 (1.6%) of 129 periurethral and 4 (3.1%) of 129 anal canal swabs showed colonization with aerobic gram-negative organisms, while 16 (22%) of 73 periurethral and 47 (64%) of 73 anal canal swabs from placebo subjects showed colonization. Daily therapy with norfloxacin at bedtime is effective in preventing recurrent cystitis. During 1 year of norfloxacin therapy, colonization was infrequent and superinfection with norfloxacin-resistant organisms did not occur.

Adult↗

Pseudodementia.

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Aged↗

Isolation of a complementary DNA clone encoding a precursor to human eosinophil major basic protein.

A 14-kD protein was purified from human PMNs and its NH2-terminal sequence was determined. Comparison of a portion of the NH2-terminal sequence of this protein to the recently reported NH2-terminal sequence of eosinophil major basic protein (MBP) showed them to be identical. To aid further characterization of the structural and functional properties of this molecule, we isolated from an HL-60 cDNA library a single class of cDNA clones whose sequence matched exactly the NH2-terminal amino acid sequence of the 14-kD polypeptide. Northern analysis of HL-60 cells suggests that MBP is constitutively expressed in HL-60 cells and is highly transcribed from a single copy gene. The sequence of the full-length cDNA clones predicts that MBP is synthesized as a 23-kD precursor form (pro-MBP) which is subsequently cleaved to release the mature 14-kD MBP. The putative pro-MBP has a predicted pI of 6.0, but both the charged and the hydrophobic residues are asymmetrically distributed, creating a bipolar molecule. The NH2-terminal half has a predicted pI of 3.7 and is hydrophilic, while the COOH-terminal half (corresponding to mature MBP) has a predicted pI of 11.1 and is hydrophobic.

Base Sequence↗

The nature of the chromophore responsible for naturally occurring fluorescence in mouse skin.

Normal mouse skin has a prominent fluorescence peak at 674 nm. Fluorescence emission and fluorescence excitation spectroscopy, carried out both in vitro and in vivo, led to the conclusion that the chromophore(s) responsible for this naturally occurring fluorescence is/are pheophorbide a and/or pheophytin a, degradation products of chlorophyll a that are derived from the mouse food.

Animals↗

A pilot study of carboplatin (JM8, CBDCA) and chlorambucil in combination for advanced ovarian cancer.

Forty-six patients with previously untreated, advanced ovarian cancer received carboplatin (JM8, CBDCA) and chlorambucil (CLB) to assess the efficacy and toxicity of this combination. Carboplatin 300 mg m-2 was given on day 1 with CLB 10 mg daily for 7, 10 or 14 days; 6 treatment courses were given at 4-6 weekly intervals in the absence of disease progression. Tumour response was assessed, where possible, by restaging laparotomy after 6 treatment cycles. Five complete and 16 partial remission were seen in 37 evaluable patients giving an overall response rate of 57%. The median survival of all patients was 15 months. The major toxicity was myelosuppression. Nausea and vomiting were generally minor (WHO, grades I or II) and most courses were given on an outpatient basis. Leucopenia was the major factor causing treatment delays, particularly with the 10 and 14 day CLB regimens. Thrombocytopenia was minimal in the early chemotherapy cycles but the data suggest that cumulative toxicity may occur. This combination may provide a satisfactory degree of efficacy with less toxicity than cisplatin-based regimens.

Adult↗