Search PubMed⌕ Search

Biomedical subjects

M Adams

Publications and source records attributed to M Adams.

At least 199 records · Page 11Linked to original sources
PubMed1995

High-dose folinic acid and 5-fluorouracil bolus and continuous infusion in advanced colorectal cancer: poor response rate in unselected patients.

We have conducted a retrospective study of high-dose folinic acid and 5-fluorouracil in 96 patients with advanced colorectal cancer. Patients received 200 mg m-2 (maximum 300-350 mg) folinic acid by infusion over 2 h followed by an i.v. bolus of 5-fluorouracil 400 mg m-2 then an infusion of 5-fluorouracil 600 mg m-2 over 22 h. This was repeated over the next 24 h. The schedule was given every 2 weeks for four cycles; thereafter patients with objective response continued to a maximum of eight cycles. The overall response rate was 10.6% in 85 evaluable patients. The median duration of response was 11 months. The median survival was 6 months. Toxicity was low, only one patient experiencing toxicity greater than WHO grade II (grade IV platelet toxicity). Diarrhoea, nausea, vomiting and mucositis also occurred but were mild and infrequent. Our low response rate may be related to factors such as patient characteristics or duration of treatment.

Adult↗
PubMed1995

Tropisetron alone or in combination with dexamethasone for the prevention and treatment of emesis induced by non-cisplatin chemotherapy: a randomized trial.

This study compared the efficacy and tolerability of tropisetron (Navoban, Novaban) alone or in combination with dexamethasone for the treatment of emesis induced by moderately emetogenic non-cisplatin chemotherapy. In total, 126 patients with cancer, who had never received chemotherapy and who required at least two courses of moderately emetogenic non-cisplatin chemotherapy each lasting for a minimum of 5 days, were recruited into the study. Patients were randomized to receive tropisetron, 5 mg o.d., plus either dexamethasone, 12 mg i.v. on day 1 followed by 4 mg orally b.i.d. on days 2-5, or placebo. Greater control of acute and delayed vomiting and nausea was achieved in patients given the tropisetron-dexamethasone combination than in those who received the tropisetron-placebo treatment. The majority of adverse events were mild and could be attributed to the chemotherapeutic regimen used or to the underlying disease. Patients and investigators both rated tropisetron alone or in combination with dexamethasone as a highly effective and well-tolerated antiemetic treatment. The results of this study show that tropisetron, 5 mg o.d., is an effective, well-tolerated and simple to use antiemetic treatment for patients receiving moderately emetogenic non-cisplatin chemotherapy. The addition of dexamethasone increases the efficacy of tropisetron without significantly decreasing its tolerability.

Antiemetics↗
PubMed1995

Oral and topical treatment of erectile dysfunction. Present and future.

A great deal of progress has been made in the pharmacological treatment of erectile dysfunction. At present, however, the most effective therapies require intracavernosal injections with a number of associated drawbacks. An increasing number of oral and transdermal agents have been introduced clinically or are at various phases in their development. It is evident that severe end-organ disease probably will not result in successful systemic therapy. Nevertheless, in men with intact or mildly dysfunctional erectile mechanisms, noninvasive treatments can offer some measure of success. Further study of individual and synergistic activity of available compounds is underway.

Administration, Oral↗
PubMed1995

[Intraoperative localization of metastases with a hand-held gamma probe].

A 50-y-old male patient with prostate cancer showed two suspicious lesions in bone scintigrams. They were assessed to be bone metastases by biopsy of the os ilium. After i.v. injection of 99mTc-HMDP a probe-guided localization permitted optimal surgical treatment. A bone metastasis in the os ilium was confirmed. The intraoperative detection with a hand-held gamma probe permitted accurate and complete excision of the tumour; the bone defect could thus be reduced to a minimum.

Bone Neoplasms↗
PubMed1995

Adverse effects of paternal opiate exposure on offspring development and sensitivity to morphine-induced analgesia.

We have shown previously that chronic morphine administration to adolescent male rats produced a number of gender specific deficits in their offspring. The purpose of the present studies was to extend our earlier observations by examining the acute, direct effects of morphine exposure to male rats on their fertility and the development of viable offspring. Sexually mature male rats were injected with a single dose of morphine (25 mg/kg) and 24 hr later were bred with drug-naive females. Fertility rates (vaginal plugs and pregnancies) were monitored throughout the breeding period as was the development of the offspring. Our results showed that a large, acute dose of morphine given to drug-naive male rats 24 hr before the initiation of breeding had no effect on fertility rates, but produced several adverse effects on fetal outcome. Litter sizes in morphine-derived offspring were considerably smaller than in controls and mortality rates were more than 6 times higher. Moreover, morphine-derived male, but not female, offspring had a significantly enhanced sensitivity to the antinociceptive effects of morphine. Collectively, these data suggest that acute paternal morphine exposure just before breeding with drug-naive females had no effect on fertility, but exerted negative effects on the viability and development of their offspring. These results represent the most compelling evidence to date that paternal opiate exposure can adversely affect fetal outcome and are particularly striking in that they were produced by a single injection of morphine. We are aware of no animal studies, clinical cases or anecdotal reports in humans in which such a phenomenon has been described.

Analgesia↗
PubMed1995

Green fluorescent protein as a reporter of gene expression and protein localization.

The green fluorescent protein (GFP) from the jellyfish Aequorea victoria is rapidly becoming an important reporter molecule for monitoring gene expression and protein localization in vivo, in situ and in real time. GFP emits bright green light (lambda max = 509 nm) when excited with UV or blue light (lambda max = 395 nm, minor peak at 470 nm). The fluorescence excitation and emission spectra of GFP are similar to those of fluorescein, and the conditions used to visualize this fluorophore are also suitable for GFP. Unlike other bioluminescent reporters, the chromophore in GFP is intrinsic to the primary structure of the protein, and GFP fluorescence does not require a substrate or cofactor. GFP fluorescence is stable, species-independent and can be monitored non-invasively in living cells and, in the case of transparent organisms, whole animals. Here we demonstrate GFP fluorescence in bacterial and mammalian cells and introduce our Living Colors line of GFP reporter vectors, GFP protein and anti-GFP antiserum. The reporter vectors for GFP include a promoterless GFP vector for monitoring the expression of cloned promoters/enhancers in mammalian cells and a series of six vectors for creating fusion protein to either the N or C terminus of GFP.

3T3 Cells↗
PubMed1994

Functional analysis of a transactivation domain in the thyroid hormone beta receptor.

Hormone-dependent transcriptional activation (AF-2) by the thyroid hormone beta receptor (TR beta) localizes to its carboxyl-terminal domain. A putative transactivation sequence within this domain was analyzed by mutating individual residues to alanine. Mutant receptor carboxyl-terminal domains were tested coupled to the heterologous DNA binding domain of Gal4. A single mutant receptor (E460A) showed normal hormone binding and activation, whereas several others (P453A, F455A, L456A, F459A) exhibited impaired transactivation which correlated with their reduced ligand binding. Two mutations (L454A, E457A) were able to dissociate these properties, generating transcriptionally defective mutant proteins with preserved hormone binding. A further conservative substitution (E457D) was also nonfunctional, and these three mutations were equally deleterious when tested in the context of full-length TR beta with a natural thyroid hormone response element containing promoter. This loss of activity was not due to altered DNA binding or expression of mutant receptors in cultured cells. They also retained the ability to recruit VP16-tagged retinoid X receptor in vivo as well as bind the basal transcription factors TFIIB and TBP in vitro. Our observations indicate that conserved hydrophobic (Leu454) and charged (Glu457) residues mediate AF-2 activity of TR beta, possibly via a co-activator that has yet to be identified.

Amino Acid Sequence↗
PubMed1994

Randomised trial of intravenous immunoglobulin G, intravenous anti-D, and oral prednisone in childhood acute immune thrombocytopenic purpura.

The most serious complication of childhood acute immune thrombocytopenic purpura (ITP), intracranial haemorrhage, occurs in about 1% of children with platelet counts below 20 x 10(9)/L. We conducted a randomised study to explore three treatment options in this high-risk group. 146 children (> 6 months and < 18 years old) with typical acute ITP and platelet counts of 20 x 10(9)/L or lower were randomised to receive high-dose intravenous immunoglobulin G (IVIgG) 1 g/kg on 2 consecutive days (n = 34), 0.8 g/kg once (n = 35), intravenous anti-D 25 micrograms/kg on 2 consecutive days (n = 38), or oral prednisone 4 mg/kg per day with tapering and discontinuation of prednisone by day 21 (n = 39). The rate of response as reflected by the number of days with platelet counts at 20 x 10(9)/L or lower and the time taken to achieve a platelet count 50 x 10(9)/L or more was significantly faster for both IVIgG groups than for the anti-D group (p < 0.05); the difference between prednisone and IVIgG was significant (p < 0.05) only for the IVIgG 0.8 g/kg group, and responses to the two IgG groups were similar. These differences in response rates were reflected in the percentages of children with platelet counts of 20 x 10(9)/L or lower at 72 hours following the start of treatment: 3% (IVIgG 0.8 g/kg x 1), 6% (IVIgG 1 g/kg x 2), 18% (anti-D), and 21% (oral prednisone 4 mg/kg/day). Treatment-associated toxicities included a fall in haemoglobin with anti-D (to less than 100 g/L in 24% of cases); weight gain with oral prednisone; and fever, nausea, vomiting, and headache with IVIgG. On the basis of these results, intravenous anti-D cannot be recommended as initial therapy for children with acute ITP and platelet counts of 20 x 10(9)/L or lower. A single dose of 0.8 g/kg IVIgG offers the fastest recovery for the least treatment; additional IgG or oral prednisone can be reserved for the one-third of children who continue to have platelet counts of 20 x 10(9)/L or less at 48-72 hours after the start of treatment.

Adolescent↗
PubMed1994

ADP-ribosylation factor (ARF)-like 3, a new member of the ARF family of GTP-binding proteins cloned from human and rat tissues.

The human and rat homologues of a new member of the ADP-ribosylation factor (ARF) family of 21-kDa GTP-binding proteins, termed Arl3, were identified as an expressed sequence tag (human) and as a product of polymerase chain reaction amplification using degenerate probes derived from conserved sequences in members of the ARF family (rat). Alignments of the full-length open reading frames of the human and rat homologues revealed the encoded proteins to be over 97% identical to each other and 43% identical to human ARF1. Northern blots of mRNA from seven human tissues and four rat tissues revealed the presence of a ubiquitous band of about 1 kilobase in length that hybridized with the corresponding Arl3 probes. A number of human tumor cell lines expressed Arl3, as determined by immunoblotting with an Arl-specific antibody, raised against a peptide derived from the human Arl3 sequence. The level of Arl3 expressed in these cell lines was on the order of 0.01% of total cell protein. Purified recombinant human Arl3 was shown to bind guanine nucleotides but lacks ARF activity and intrinsic or ARF GTPase-activating protein-stimulated GTPase activity. In contrast to ARF proteins, the Arl3 protein has reduced dependence on phospholipids and magnesium for guanine nucleotide exchange. Thus, Arl3 is a ubiquitously expressed GTP-binding protein in the ARF family with distinctive biochemical properties consistent with its having unique, but unknown, role(s) in cell physiology.

ADP-Ribosylation Factor 1↗
PubMed1994

Cellular latency in human immunodeficiency virus-infected individuals with high CD4 levels can be detected by the presence of promoter-proximal transcripts.

We have investigated the molecular basis of human immunodeficiency virus type 1 (HIV-1) latency in a tissue culture model and in HIV-infected people. We show that increased levels of Tat, but not Rev, can release the proviruses from latency in U1 cells. The absence of Tat in these cells is manifested by the accumulation of promoter-proximal viral transcripts, whereas the presence of Tat correlates with increased expression of viral proteins and an increase in promoter-distal transcripts. The presence of promoter-proximal transcripts also serves as a marker for latency in humans. We observed the exclusive presence of promoter-proximal viral transcripts in peripheral mononuclear cells from the majority (10/11) of asymptomatic HIV-infected individuals examined. Activation of these cells in vitro, and viremia in vivo, correlated with a switch from promoter-proximal transcription to promoter-distal transcription. These results suggest that the control between latency and replication of HIV in vivo is at the level of transcription elongation.

Base Sequence↗
PubMed1994

Venous thromboembolic complications (VTE) in children: first analyses of the Canadian Registry of VTE.

Deep vein thrombosis (DVT) and pulmonary embolism (PE) occur in pediatric patients; however, the incidence, associated morbidity, and mortality are unknown. A Canadian registry of DVT and PE in children (ages 1 month to 18 years) was established July 1, 1990 in 15 tertiary-care pediatric centers. One-hundred thirty-seven patients were identified prospectively and are the subject of this report. The incidence of DVT/PE was 5.3/10,000 hospital admissions or 0.07/10,000 children in Canada. Infants under 1 year old and teenagers predominated with equal numbers of both sexes. DVT were located in the upper (n = 50) and lower (n = 79) venous system, or as PE alone (n = 8). Central venous lines (CVLs) were present in approximately 33% of children with DVT (n = 45). Associated conditions were present in 96% of children and 90% of children had two or more associated conditions for DVT. DVT was diagnosed by venography (n = 83), duplex ultrasound (n = 37), and other combinations (n = 17). Twenty-two of the 31 ventilation/perfusion scans performed were interpreted as high-probability scans for PE. Therapy consisted of heparin (n = 115), thrombolysis (n = 15), surgical removal of a CVL or thrombus (n = 22), and oral anticoagulant therapy (n = 103). Significant bleeding complications did not occur. However, three (2.2%) children died as a direct consequence of their thromboembolic disease; DVT reoccurred in 23 children and postphlebitic syndrome (PPS) occurred in 26. In conclusion, DVTs occur in a significant number of hospitalized children with a mortality of 2.2%. Complications are not hemorrhagic, but thrombotic, and characterized by PE, recurrent disease, and PPS. In contrast to adults, the upper venous system is frequently affected because of the use of CVLs. The frequency of DVT/PE justifies controlled trials of primary prophylaxis in high-risk groups, and therapeutic trials to determine optimal treatment.

Administration, Oral↗
PubMed1994

Evaluation of an automated DNA profiling system employing multiplex amplification of four tetrameric STR loci.

We have examined the performance and reproducibility of an automated DNA profiling system which is based on the multiplex amplification of 4 tetrameric STR loci-HUMVWFA31/A. HUMTH01, HUMF13A1 and HUMFES/FPS. The system was able to type 100 pg of purified, undegraded, genomic DNA. At lower concentrations of DNA (below 100 pg), allelec drop-out occurred due to stochastic differences in allele copy number. Minor variation of individual PCR reagent concentrations or cycling temperatures did not result in a significant effect on the efficiency of amplification of any of the 4 loci in the quadruplex system. More substantial variation of reagent concentrations or cycling temperatures outside the optimum range of the system resulted in a reduction or complete loss of signal for one or more loci. This was also observed at high ionic strength or extreme pH. However, under all reagent concentrations and conditions studied, no artefact bands that could potentially result in the mistyping of a sample were apparent within the read region (130-240 bases) of the gel. Evaluation of both native and denaturing polyacrylamide gels revealed that, although native gels displayed faster run times, the sizing precision of such gels for certain STR loci was lower than that of denaturing gels. Also, artefact bands may be present within the read region of native gels. In conclusion the quadruplex amplification system described, coupled with automated fluorescence-based detection on denaturing polyacrylamide gels, appeared to be a robust and reliable system for individual identification.

Alleles↗
PubMed1994

Auditory M100 component 1: relationship to Heschl's gyri.

This study was designed to localize the neuroanatomic generator of the 100 ms latency magnetic auditory evoked field (EF) component (M100) activated by an unattended tone pip. Magnetic EFs in response to 25 ms duration, 90 dB, 1 kHz tone pips were recorded from both hemispheres of nine normal adults, five males and four females, using a seven-channel second-order gradiometer. The source of the M100 was estimated, with confidence intervals, by a least squares based inverse solution algorithm. Magnetic resonance (MR) images of the brain were acquired with a 1.5 T system using a standard head coil. The superior temporal gyri (STG) were manually segmented from 1.7 mm thick coronal images, and the superior surfaces were then rendered from the 3-D volume data. Translation and rotation matrices were identified to locate the magnetoencephalography (MEG) determined sources within the reconstructed STGs. This population of 18 STGs in 9 individuals demonstrated two transverse gyri in 4 of 9 left hemispheres, and 5 of 9 right hemispheres. All 9 left hemisphere M100 sources were in or included Heschl's gyrus(i) in the confidence intervals. Seven of the 9 included Heschl's gyrus(i) on the right: the remaining two, both males, had sources slightly anterior to Heschl's gyrus(i). We conclude that all M100 source location estimates were compatible with an auditory koniocortex source in or adjacent to Heschl's gyri.

Adult↗