PubMed Health⌕ Search

Biomedical subjects

H MacDonald

Publications and source records attributed to H MacDonald.

At least 19 recordsLinked to original sources
PubMed2004

Different meanings of respite: a study of parents, nurses and social workers caring for children with complex needs.

AIM: To examine the meaning of respite care to parents of children with complex conditions and providers. METHODS: In-depth interviews, participant observation and document review were used to collect data from nineteen mothers and seven fathers of children between the ages of 8 and 16 years who required complex care and from their respite providers, including thirteen nurses, and four social workers from three counties in North-west England. RESULTS: Parents described three categories of respite: short breaks provided by the extended family or friends, short breaks (3-4 h) by an outside agency, and overnight respite outside of home. They highly valued overnight respite outside the home. There was some overlap but also notable differences between parents' and providers' categorizations of respite care and the value attached to different forms of respite provision. Parents and nurses valued overnight respite outside the home unlike social workers who preferred to provide respite without separating children from their families. DISCUSSION: Appropriate provision of respite care and communication with parents requires understanding of the meaning of respite to parents. The meanings attached to respite care by parents and providers should be considered in attempts to understand and address problems of inappropriate provision and/or dissatisfaction with respite services.

Adolescent↗
PubMed1998

CPAN, a human nuclease regulated by the caspase-sensitive inhibitor DFF45.

Induction of apoptosis by death receptors such as Fas or tumour necrosis factor (TNF) R1 leads to distinct changes in cell morphology, activation of the caspase protease cascade, and the degradation of nuclear chromatin by activated nucleases. Here, we describe the purification and cDNA cloning of a novel 40 kDa endonuclease from Jurkat cells that is activated by caspases. This protein, designated caspase-activated nuclease (CPAN), is sufficient to degrade naked DNA and to induce apoptotic morphology and DNA fragmentation in naive nuclei. CPAN is highly homologous to a recently described mouse nuclease, CAD [1], and may represent the human homologue. Our data on the human cDNA as well as additional data on the mouse homologue suggest that a 30 amino-acid portion of the recently published mouse sequence [1] is incorrect. We show that the activity of human CPAN is regulated by DFF45 [2], an inhibitor necessary for CPAN expression and stabilization in an inactive state in living cells. Proteolytic cleavage of DFF45 by caspases in vitro leads to dissociation of DFF45 fragments from CPAN and activation of CPAN as an endonuclease. CPAN is a tightly regulated endonuclease with unique characteristics that might represent a distinctive family of endonucleases.

Amino Acid Sequence↗
PubMed1997

Activation of hPAK65 by caspase cleavage induces some of the morphological and biochemical changes of apoptosis.

Apoptosis is a highly regulated form of cell death, characterized by distinctive features such as cellular shrinkage and nuclear condensation. We demonstrate here that proteolytic activation of hPAK65, a p21-activated kinase, induces morphological changes and elicits apoptosis. hPAK65 is cleaved both in vitro and in vivo by caspases at a single site between the N-terminal regulatory p21-binding domain and the C-terminal kinase domain. The C-terminal cleavage product becomes activated, with a kinetic profile that parallels caspase activation during apoptosis. This C-terminal hPAK65 fragment also activates the c-Jun N-terminal kinase pathway in vivo. Microinjection or transfection of this truncated hPAK65 causes striking alterations in cellular and nuclear morphology, which subsequently promotes apoptosis in both CHO and Hela cells. Conversely, apoptosis is delayed in cells expressing a dominant-negative form of hPAK65. These findings provide a direct evidence that the activated form of hPAK65 generated by caspase cleavage is a proapoptotic effector that mediates morphological and biochemical changes seen in apoptosis.

Animals↗
PubMed1995

Candida: the hidden deterrent to breastfeeding.

The '80s and '90s have been characterized by an increase in the number of breastfeeding mothers. The added health benefits of breastfeeding for both mother and child, the father's influence, maternal age, family practices and education all may contribute to a mother's decision to breastfeed. Although the incidence of mothers choosing to breastfeed their infants has increased, both research and practice indicate that a significant number of mothers stop breastfeeding long before their target date. Among the many reasons given for the early cessation of breastfeeding is the complaint of persistently sore and red nipples. Such a complaint should raise a red flag to the hospital or community nurse. The pain and redness could be due to Candida albicans.

Adult↗
PubMed1994

Pain after laparoscopy: an observational study and a randomized trial of local anesthetic.

Our objective was to determine if local anesthesia reduces pain after a laparoscopy. Eighty women were assigned randomly 10 ml of 0.5% bupivacaine or 0.9% saline flushed over the peritoneal folds and into the abdominal wall after laparoscopy under general anesthesia. Pain scores from the deep abdomen, skin, shoulder, and back were collected 30 min, 2 h, 4 h, and the day following laparoscopy. Pain scores also were correlated with patients' height, weight, operative findings, surgical technique and procedure, and volume of gas insufflated into the abdomen. Bupivacaine has a small effect on abdominal and skin pain 2 h after surgery (p = 0.01) but has no effect on shoulder or back discomfort. Women who have been sterilized, have not had previous abdominal surgery, or have evidence of old pelvic inflammation report more postoperative backache and deep abdominal pain but no greater skin or shoulder discomfort. Weight, height, whether the abdominal wall was picked up, and the volume of gas used to insufflate the abdomen are independent of all postoperative pain scores. Local anaesthetic instilled down the laparoscopy trocar reduces skin discomfort 2 h after surgery, but this beneficial effect is small compared with other factors influencing pain after laparoscopy.

Anesthesia, General↗
PubMed1994

Sequence of the murine Huntington disease gene: evidence for conservation, alternate splicing and polymorphism in a triplet (CCG) repeat [corrected].

Huntington disease (HD) is associated with significant expansion of a CAG trinucleotide repeat within a novel gene. However, no clues to the function of this gene were apparent by sequence alignment to other proteins. We have therefore sought to identify the mouse gene (hd) as a first step in the development of an animal model for HD to provide insights into the molecular pathogenesis of this disease. Here, we report the sequencing of cDNA clones spanning 9,992 nucleotides encoding the murine HD homologue (hd), which exhibits 90% peptide sequence identity, including conservation of the CAG and adjacent CCG repeats. In addition, we show that the CCG is polymorphic in the mouse. Sequence analysis provides strong evidence that the first in frame methionine 5' to the CAG repeat, is the translational start site, for both the mouse and human transcript. As in human, the gene appears expressed in the mouse as 2 large transcripts. We observe evidence for alternate splicing of the hd gene in mouse tissues which would predict two protein products differing by 480 amino acid residues with a molecular mass difference of approximately 54 kilodaltons.

Alternative Splicing↗
PubMed1993

Differential 3' polyadenylation of the Huntington disease gene results in two mRNA species with variable tissue expression.

Recently a novel gene containing a CAG trinucleotide repeat that is expanded on HD chromosomes has been identified(1). This gene was shown to detect a single transcript of 10-11 kb by RNA hybridization. We have however, previously identified three cDNAs which are part of the same gene that have been shown to detect two distinct transcripts of 10 kb and one that is significantly larger(2,3). These different mRNA species could be due to use of alternate transcription start sites, alternate splicing or selection of different polyadenylation sites. We have identified cDNA clones spanning the HD gene including two (HD12 and HD14) that share identical protein coding sequences but differ in size and sequence of their 3' untranslated region. HD14 has 3,360 base pairs of additional sequence distal to the previously published 3' end (1). RNA hybridization has revealed that the larger 13.7 kb fragment is the predominant transcript in human brain. cDNA fragments unique to HD14 detected only the larger transcript. Sequence analysis identified two different putative polyadenylation sequences at position 10,326 and 13,645 of the HD14 cDNA. These findings indicate that the two observed mRNA species originate from a single gene and that differential polyadenylation leads to transcripts of different size. The relative increased abundance of the larger transcript in human brain may provide some insights into the mechanism by which a widely expressed gene may exert tissue specific effects.

Base Sequence↗
PubMed1992

Results of the National Cancer Institute early breast cancer trial.

In 1979, a prospective, randomized trial was begun at the National Cancer Institute comparing lumpectomy, axillary dissection, and radiation therapy (XRT) to modified radical mastectomy for the treatment of invasive breast cancer, clinical stage T1-2, N0-1, M0. Treatment in the radiation arm consisted of full axillary dissection and gross removal of the tumor, followed by 4500 to 5000 cGy to the whole breast and a boost to the tumor bed of 1500 to 2000 cGy. Patients with positive axillary dissections received radiation to the supraclavicular nodes, in addition to cyclophosphamide and doxorubicin. Two hundred thirty-seven patients entered in the trial between 1979 and 1987 are available for analysis, 116 in the mastectomy arm and 121 in the radiation arm. With a median follow-up of 67.7 months, there are no significant differences in 5-year overall survival (85% vs 89%, mastectomy vs radiation) or 5-year disease-free survival (82% vs 72%, mastectomy vs radiation). Patients in the radiation arm had an actuarial in-breast recurrence rate of 12% at 5 years and 20% at 8 years. There were no major differences between complication rates in the treatment arms. The results of the study indicate that patients with invasive breast cancer, stage I and II, can be treated with lumpectomy, axillary dissection, and radiation therapy with results comparable to those with modified radical mastectomy.

Actuarial Analysis↗
PubMed1990

Influence of microscopic residual disease on survival for stage IB and IIA carcinoma of the cervix following intracavitary irradiation.

From 1977 to 1982, 102 patients with Stage IB and IIA carcinoma of the cervix underwent preoperative intracavitary caesium irradiation followed by radical hysterectomy and pelvic lymphadenectomy at the Wessex Radiotherapy Centre. The actuarial 5-year survival rate for Stage IB is 80% and for Stage IIA is 62%. Patients who had microscopic residual disease in the hysterectomy specimen and negative nodes showed an actuarial 10-year survival rate of 62% as opposed to 82% in patients with no residual disease and negative nodes (P less than 0.05).

Adenocarcinoma↗
PubMed1988

O6-methylguanine-DNA methyltransferase-defective human cell mutant: O6-methylguanine, DNA strand breaks and cytotoxicity.

We have isolated an isogenic O6-methylguanine (O6-MeG)-DNA methyltransferase-defective mutant from a HeLa cell line. This mutant exhibits excess DNA strand breaks and considerable cytotoxicity after N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) treatment. The increased frequency of strand breaks after MNNG treatment was not abolished by DNA synthesis inhibitors. We propose that the presence of unrepaired O6-MeG lesions leads to excess strand breaks and these, in turn, are mainly responsible for the cytotoxicity.

Cell Survival↗
PubMed1986

Influence of definitive radiation therapy for primary breast cancer on ability to deliver adjuvant chemotherapy.

Primary radiotherapy as a means of managing stage I and II breast cancer is receiving increasing attention. In a prospectively randomized trial comparing modified radical mastectomy to lumpectomy followed by definitive radiotherapy, we evaluated whether radiotherapy has a deleterious effect on the ability to administer adjuvant doxorubicin and cyclophosphamide to patients with histologically positive axillary lymph nodes. All patients were treated with an identical regimen, and doses were escalated to the same degree until myelosuppression occurred. There were no significant differences in the amount of chemotherapy administered to either treatment group. Patients in both groups received approximately 100% of the predicted dose of doxorubicin and approximately 117% of the predicted dose of cyclophosphamide. At present, we have no evidence that there are differences in recurrence rates as a function of the quantity of drug received, although longer follow-up is required.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1985

Isolation, characterization and complementation analysis of nirB mutants of Escherichia coli deficient only in NADH-dependent nitrite reductase activity.

Mutants have been isolated which lack NADH-dependent nitrite reductase activity but retain NADPH-dependent sulphite reductase and formate hydrogenlyase activities. These NirB- strains synthesize cytochrome c552 and grow normally on anaerobic glycerol-fumarate plates. The defects map in a gene, nirB, which is extremely close to cysG, the gene order being crp, nirB, cysG, aroB. Complementation studies established that nirB+ and cysG+ can be expressed independently. The data strongly suggest that nirB is the structural gene for the 88 kDal NADH-dependent nitrite oxidoreductase apoprotein (EC 1.6.6.4). The nirB gene is apparently defective in the previously described nirD mutant, LCB82. The nirH mutant, LCB197, was unable to use formate as electron donor for nitrite reduction, but NADH-dependent nitrite reductase was extremely active in this strain and a normal content of cytochrome c552 was detected. Strains carrying a nirE, nirF or nirG mutation gave normal rates of nitrite reduction by glucose, formate or NADH.

Chromosome Mapping↗
PubMed1985

Cisplatin combination chemotherapy versus chlorambucil in advanced ovarian carcinoma: mature results of a randomized trial.

A randomized study to compare the efficacy of combination chemotherapy (cisplatin, doxorubicin, cyclophosphamide: PACe) with chlorambucil (CB) in International Federation of Gynecology and Obstetrics (FIGO) stage III and IV ovarian carcinoma was conducted between May 1979 and October 1983. Patients failing initial CB were subsequently eligible for treatment with PACe. Eighty-nine patients were randomized and 85 were eligible for analysis; as of date, 72 of these patients have died. The majority of patients in this study had bulky residual disease after their initial laparotomy (76%). Complete response (CR) was documented by a second laparotomy after five cycles of combination therapy or 6 to 12 months alkylating agent therapy. The overall response rate (CR plus partial response [PR]) for the combination (PACe, 68%) was significantly higher (P = .0004) than that for the chlorambucil (CB, 26%). However, the median survival was not improved (PACe, 13 months; CB, 11 months) and the survival curves were not significantly different (log rank test P = .25). The results of this study are comparable to preliminary data reported from other similar randomized studies. PACe, as administered in this study, is not indicated as routine therapy in patients with bulky residual ovarian carcinoma.

Actuarial Analysis↗
PubMed1984

Abnormal laboratory test values during ceftriaxone therapy.

Laboratory tests were conducted to determine the safety of ceftriaxone during clinical use. Laboratory test values were evaluated in 153 individual clinical studies. A total of 2,640 patients received ceftriaxone at various doses, ranging from a single dose to six weeks of administration. The most frequently encountered laboratory test abnormalities in the overall population were hematologic (14.4 percent), hepatic (5 percent), and renal (1.4 percent). When analyzed separately, the incidences of hematologic, hepatic, and renal laboratory test abnormalities in the pediatric population were 30.8, 7.7, and 0.7 percent, respectively. The incidence of abnormal laboratory test results for once- and twice-daily drug administration was comparable. There were no significant differences except for the frequency of thrombocytosis for which the incidence for once-daily administration was 1.8 percent and for twice-daily administration 5.3 percent. The incidence of abnormal laboratory test values during ceftriaxone therapy (19.0 percent) was comparable to that observed with the cephalosporins (18.3 percent) and other comparative drugs used in these studies. Ceftriaxone is at least as safe and as well tolerated as other currently available antimicrobial agents used in the therapy of serious bacterial infections.

Adolescent↗
PubMed1981

The interaction of yeast RNA polymerase I and Cibacron blue F3GA.

The interaction between yeast RNA polymerase I and Cibacron blue F3GA has been studied by difference spectrophotometry and column chromatography. The enzyme is reversibly inhibited by the dye. 50% inhibition is obtained with 7.5 x 10(-6) M Cibacron blue. 1 mol Cibacron blue binds per mol enzyme. This interaction, which is inhibited by salt, occurs at a site different from the active site. When RNA polymerase I is chromatographed in Blue dextran-Sepharose columns, two polypeptides, of 48 000 and 36 000 daltons, are dissociated from the enzyme. The resulting enzyme is completely inactive, ATP (5 mM) present in the elution buffer prevents both the dissociation of the polypeptides and the inactivation of the enzyme.

Adenosine Triphosphate↗
PubMed1980

Effect of the 5-hydroperoxide of eicosatetraenoic acid and inhibitors of the lipoxygenase pathway on the formation of slow reacting substance by rat basophilic leukemia cells; direct evidence that slow reacting substance is a product of the lipoxygenase pathway.

Previous studies in a line of rat basophilic leukemia (RBL 1) cells have indicated that the slow reacting substance (SRS) made during stimulation with the divalent cation ionophore, A23187, is derived from arachidonic acid (AA). In the present report, various inhibitors of AA metabolism were compared with regard to their effects on SRS formation and incorporation of radioactivity from [1-14C]-AA into known metabolites of the lipoxygenase and cyclooxygenase pathways. An apparently close parallel between lipoxygenase product formation and SRS synthesis is demonstrated. In addition, exogenous 5-hydroperoxy-eicosatetraenoic acid (5-HPETE) has been shown to markedly enhance SRS synthesis, even when A23187 is absent. The data provide very strong evidence that SRS is produced through the lipoxygenase pathway.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1980

Pulmonary yellow hyaline membranes in neonates.

The recent increase in the occurrence of pulmonary yellow hyaline membranes correlates with improved therapy for premature infants with the respiratory distress syndrome and with their prolonged survival. We compared the clinicopathologic features in 54 cases with pulmonary yellow hyaline membranes with those in 56 cases with conventional hyaline membranes seen during the same interval at Magee-Womens Hospital. Kernicterus, intraventricular hemorrhage, intrahepatic bile stasis, pulmonary hemorrhages, and disseminated intravascular coagulation were significantly frequent in the yellow hyaline membrane group. Clinical problems of hypoglycemia, hypocalcemia, jaundice, and endotracheal hemorrhages and also treatment with endotracheal intubation, ventilatory assistance, and phototherapy were much more common in the yellow hyaline membrane cases. The yellow pigment was identified as unconjugated bilirubin by histochemical and biochemical techniques. A plausible hypothesis for the pathogenesis is presented wherein intrapulmonary hemorrhages lay an important role. The frequent association of yellow membranes and kernicterus in premature infants at relatively low serum levels of bilirubin is significant.

Birth Weight↗