Search PubMed⌕ Search

Biomedical subjects

K Smith

Publications and source records attributed to K Smith.

At least 397 records · Page 22Linked to original sources
PubMed1990

The epidermal growth factor receptor and the prognosis of bladder cancer.

Epidermal growth factor is found in high concentrations in urine, and its receptor (EGFr) has been identified in certain bladder tumors. This study was performed to determine whether receptor positivity in the tumor was associated with a poor clinical outcome. One hundred one patients with newly diagnosed bladder cancer were studied prospectively by immunohistochemical staining for the EGFr. There were 76 men and 25 women, with a mean follow-up of 30 months; 49 had tumors invading muscle: 18 were pTl (tumor invading lamina propia) and 34 were pTa (tumor confined to urothelium). Strong staining for the EGFr was found in 48% of tumors and was associated with high stage (P less than 0.001). Death of bladder cancer (40 of 101) was associated independently with high stage (P less than 0.0001) and EGFr positivity (P less than 0.001). In patients with pTa and pTl tumors, EGFr positivity was associated with multiplicity (P less than 0.01), time to recurrence (P less than 0.03), and recurrence rate (P less than 0.004). Tumor progression was associated with EGFr positivity (P less than 0.0001) and multiplicity (P less than 0.05). EGFr were found on a significant proportion of bladder tumors: such tumors were more likely to result in death, recurrence, and progression.

Aged↗
PubMed1990

Inability to stimulate skeletal muscle or whole body protein synthesis in type 1 (insulin-dependent) diabetic patients by insulin-plus-glucose during amino acid infusion: studies of incorporation and turnover of tracer L-[1-13C]leucine.

Despite its anabolic effects on protein balance, acute administration of insulin has been reported to have no effect on skeletal muscle or whole body protein synthesis in man. However, insulin also reduces plasma and intramuscular amino acid availability, which may limit protein synthesis. We have therefore measured the acute effects of insulin on skeletal muscle (anterior tibialis) protein synthesis and whole body leucine turnover in eight insulin-withdrawn Type 1 (insulin-dependent) diabetic patients. They were studied initially when insulin deficient, but during infusion of mixed amino acids at a rate sufficient to raise plasma amino acids by 30% i.e. to 4 mmol/l in total; measurements were continued when insulin was infused together with an increased rate of amino acids to maintain insulinopoenic plasma amino acid concentrations. Using 13C-alpha-ketoisocaproate in plasma as an index of the intracellular precursor labelling, incorporation of [1-13C]leucine into skeletal muscle protein was 0.068 +/- 0.007%/h during insulin withdrawal and was unaltered during insulin infusion. The value is higher than observed in muscle of healthy man, possibly because of a stimulatory effect of endogenous intramuscular amino acids. Also, calculated on the basis of alpha-ketoisocaproate labelling, non-oxidised whole body leucine disappearance (i.e. whole body protein synthesis) was 110 +/- 4 mumol.kg-1.h-1 during insulin withdrawal; this also was unchanged during insulin infusion. Despite stable or increased plasma concentrations of most amino acids, the intramuscular concentrations of a number of amino acids decreased during insulin infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Hydroxybutyric Acid↗
PubMed1990

Dose intensity of carboplatin in combination with cyclophosphamide or ifosfamide.

In two separate studies of patients with ovarian cancer, subjects were treated on a protocol comprising 400 mg/m2 carboplatin in combination with 1 g/m2 cyclophosphamide (group A) or 5 g/m2 ifosfamide with mesna (group B). The dose intensities achieved in group A were 87.2 mg/m2 carboplatin per week and 245.8 mg/m2 cyclophosphamide per week (34 patients). In group B, the dose intensities achieved were 124.1 mg/m2 carboplatin per week and 2,020 mg/m2 ifosfamide per week (25 patients). Two formulae for the prediction of the optimal dose of carboplatin based on renal function and degree of myelosuppression are compared with that based on surface area, and that recently proposed by Calvert is recommended. The importance of dose intensity and the total dose delivered in phase II and III studies is emphasized.

Antineoplastic Agents↗
PubMed1990

Prolactin response to thyrotropin-releasing hormone in normoprolactinemic patients with ovulatory dysfunction and its use for selection of candidates for bromocriptine therapy.

It has been suggested in the past that some normoprolactinemic patients with amenorrhea or infertility respond to treatment with bromocriptine. However, the beneficial effect of this therapy in normoprolactinemic women remains controversial. Some authors have suggested that the responders suffer with "reactive" hyperprolactinemia and that this may be detected with thyrotropin releasing hormone (TRH) stimulation. In this study, we performed TRH stimulation tests in 538 patients with ovulatory dysfunction. Only those patients showing a peak prolactin response after TRH which exceeded 40 ng/ml were treated with bromocriptine. A direct correlation between peak prolactin level after TRH and a favorable response to treatment was observed. Serum testosterone and DHEA-sulfate levels did not correlate with prolactin response to TRH. A majority of patients with prolactin hyperresponse to TRH did not show a hyperresponse of TSH to TRH. This study suggests that incidence of beneficial response to bromocriptine therapy in normoprolactinemic women with ovulatory dysfunction is significantly higher in subjects exhibiting excessive prolactin response to TRH stimulation.

Adult↗
PubMed1990

Clonal variation in gene methylation: c-H-ras and alpha-hCG regions vary independently in human fibroblast lineages.

The stability of DNA methylation has been followed in clonal lineages of human diploid fibroblasts, for the gene regions encoding the c-H-ras proto-oncogene and the alpha subunit of human chorionic gonadotropin (alpha-hCG). Although methylation losses predominated, both de novo gains and losses of cytosine methylation were observed in subclones and sub-subclones, at frequencies which differed between individual clonal lineages, and between the 2 gene regions compared. Methylation of these loci varied independently among clones; e.g., a lineage which showed frequent methylation loss in the c-H-ras gene region remained highly methylated for alpha-hCG, and vice versa. Thus, the fidelity with which DNA methylation is inherited in specific endogenous gene regions must be governed by a clone-specific property affecting local chromatin structure, but apparently not by gene expression per se. Late in the replicative life-span of diploid fibroblasts, as cell replication slowed, restriction patterns for methylation-sensitive enzymes became simpler and more discrete, while those for other enzymes did not change. This is interpreted as a consequence of 'clonal succession', in which the fastest-replicating or longest-lived clones/subclones eventually predominate in a cell population; it could also reflect a decreased rate or a non-random selection of methylation changes in late-passage cells.

Cell Survival↗
PubMed1990

Complex maze performance in rats: effects of noradrenergic depletion and cholinergic blockade.

Noradrenergic (NA) involvement in acquisition (AQ) and retention (RET) of a shock-motivated 14-unit T-maze after intraperitoneal (ip) administration of DSP4, a neurotoxin that depletes forebrain NA, was evaluated in 2 experiments using 3-month-old male F-344 rats. Depletion of cortical NA level in DSP4-treated rats was verified by neurochemical assay and by latency to postdecapitation clonus reflex. In Experiment 1, DSP4 (50 mg/kg ip) rats did not differ from saline-treated (SAL) rats on any measure of maze performance (errors, alternation errors, run time, shock duration, or shock frequency) during AQ (DSP4 2 weeks prior to testing) nor during a RET test 2-3 weeks later (DSP4 immediately after the last AQ trial or 1 week after AQ). In Experiment 2, DSP4 and scopolamine (SCOP), a cholinergic (ACh) antagonist, were administered in combination to test for an NA-ACh interaction. DSP4 (50 mg/kg ip 2 weeks prior to AQ) again had no effect on AQ performance nor did DSP4 interact with either dose of SCOP (0.25 or 0.5 mg/kg ip 30 min prior to AQ) to further impair performance. Similar to previous studies SCOP impaired all measures of maze performance except shock duration. These experiments provide further evidence for involvement of ACh systems in the learning of this task and in the age-related impairments previously observed, but they suggest that central NA systems may not be involved directly or interactively with ACh systems required for efficient performance in this maze.

Acetylcholine↗
PubMed1990

Extended communication samples of augmented communicators. I: A comparison of individualized versus standard single-word vocabularies.

Vocabulary selection for linguistically intact augmented communicators is a growing clinical concern. The purpose of this study was to compare and contrast the relative benefits of word lists that were individualized for these augmented subjects to word lists selected from standard vocabulary sources. Communication samples were collected for 14 consecutive days from 10 subjects who used augmentative and alternative communication (AAC) devices. These samples were analyzed to determine the frequency of single word occurrence, and the results were compared with those obtained from analysis of standard vocabulary lists. The conclusions of the study were (a) that when vocabulary lists are individually created, based on the frequency of word occurrence in natural communication samples, relatively short lists can represent a large proportion of the total communication sample; (b) that individualized word lists are more efficient than standard vocabulary lists, if efficiency is defined as a large proportion of the total sample represented by a small list; and (c) that if used in their entirety, standard lists are not efficient because they contain a large number of words that are rarely used.

Adolescent↗
PubMed1990

Extended communication samples of augmented communicators. II: Analysis of multiword sequences.

The three primary purposes of this project are (a) to identify those word sequences that occur frequently across a group of 10 linguistically intact augmented communicators, (b) to determine the communality with which the various augmented communicators use specific word sequences, and (c) to evaluate the usefulness of word sequences in providing keystroke savings for users of augmentative and alternative communication (AAC) devices as compared to letter-by-letter spelling or single-word retrieval. Communication samples were collected for 14 consecutive days from 10 subjects who used AAC devices. These samples were analyzed with custom software to determine the frequency of occurrence of one-, two-, three-, four-, and five-word sequences. The results revealed that three-, four-, and five-word sequences occurred very infrequently within and across communication samples. Two-word sequences occurred much more frequently than the longer sequences. The authors concluded that clinicians should continue to encourage linguistically intact clients to select long messages (three words or more) for their AAC devices based on message content and the urgency with which messages need to be delivered rather than relying exclusively on statistical analysis. However, statistically based multiword analysis should not be abandoned. Frequently occurring one- and two-word sequences may be an important source of messages that will increase communication efficiency when stored and retrieved in an AAC device.

Adolescent↗
PubMed1990

The incidence of seizures during tricyclic antidepressant drug treatment in a brain-injured population.

Tricyclic antidepressants (TCAs) have been associated with the occurrence of seizures both with overdoses and with therapeutic doses. Seizures with therapeutic doses of TCA have been reported in patients both with and without previous histories of seizures. The incidence of seizures possibly precipitated by TCAs was examined retrospectively in a population of 68 severely brain-injured patients, all of whom were at high risk for the development of seizures. Seizure histories, anticonvulsant use, comedication use, and other pertinent data were recorded before, during, and after TCA use. We conclude that 14 patients (19%) developed seizures largely caused by TCAs. Other possible contributing factors, clinical outcomes, and some recommendations are discussed.

Adolescent↗
PubMed1990

Pharmacological 'rescue' of the corpus luteum results in increased inhibin production.

Inhibin production by the corpus luteum was investigated by undertaking pharmacological rescue of the corpus luteum with hCG in four healthy women. Blood samples were collected daily for two menstrual cycles. Starting 7 days after the LH surge in the second cycle, incremental doses of hCG (125-8000 IU) were administered daily for 7 days resulting in hCG levels comparable to those seen in normal pregnancy. Following hCG, the luteal phase was prolonged and there were significant increases in the plasma concentrations of inhibin (P less than 0.05), and oestradiol (P less than 0.05). The progesterone concentration was maintained at the mid-luteal phase peak and as a result was significantly higher than those on the equivalent days of the control cycle (P less than 0.05). It was concluded that rescue of the corpus luteum with physiological levels of hCG resulted in a significant output of inhibin, thus suggesting that the corpus luteum is a significant source of inhibin in early pregnancy.

Adult↗
PubMed1990

Daptomycin versus vancomycin treatment for Staphylococcus aureus bacteremia in a murine model.

Daptomycin (LY 146032), a new lipopeptide antimicrobial agent with activity against gram-positive bacteria, was compared to vancomycin in the treatment of staphylococcal bacteremia in a murine model. Two hundred and ninety-nine mice were inoculated with 1 x 10(8) bacteria by the tail vein, and treatment was begun 3 days later. Two dosage regimens of each drug were used: 10 mg/kg and 5 mg/kg administered every 12 h for 14 days. A control group received no therapy. Survival was determined 31 days after inoculation. There was no significant difference in survival in any of the four treatment groups. The survival in all treatment groups was significantly greater than in the control group. Serum levels of daptomycin remained longer in the therapeutic range than serum levels of vancomycin. In the murine model of staphylococcal disease, daptomycin treatment was as effective as treatment with vancomycin.

Animals↗
PubMed1990

Strength training effects in prepubescent boys.

Possible changes in muscle size and function due to resistance training were examined in prepubertal boys. Thirteen boys (9-11 yr) volunteered for each of the training and control groups. Progressive resistance training was performed three times weekly for 20 wk. Measurements consisted of the following: 1 repetition maximum (RM) bench press and leg press; maximal voluntary isometric and isokinetic elbow flexion and knee extension strength; evoked isometric contractile properties of the right elbow flexors and knee extensors; muscle cross-sectional area (CSA) by computerized tomography at the mid-right upper arm and thigh; and motor unit activation (MUA) by the interpolated twitch procedure. Training significantly increased 1 RM bench press (35%) and leg press (22%), isometric elbow flexion (37%) and knee extension strength (25% and 13% at 90 degrees and 120 degrees, respectively), isokinetic elbow flexion (26%) and knee extension (21%) strength, and evoked twitch torque of the elbow flexors (30%) and knee extensors (30%). There were no significant effects of training on the time-related contractile properties (time to peak torque, half-relaxation time), CSA, or %MUA of the elbow flexors or knee extensors. There was, however, a trend toward increased MUA for the elbow flexors and knee extensors in the trained group. Strength gains were independent of changes in muscle CSA, and the increases in twitch torque suggest possible adaptations in muscle excitation-contraction coupling. Improved motor skill coordination (especially during the early phase of training), a tendency toward increased MUA, and other undetermined neurological adaptations, including better coordination of the involved muscle groups, are likely the major determinants of the strength gains in this study.

Anthropometry↗
PubMed1990

Regulation of brain Ca2+/calmodulin-dependent protein kinase II.

CaM-kinase II is a multifunctional protein kinase highly enriched in neural tissues where it modulates a variety of Ca2(+)-dependent processes. A complex regulatory domain in the kinase within residues 281-309 contains an autoinhibitory sequence, a CaM-binding region, and sites of regulatory autophosphorylation. Autophosphorylation on Thr286 converts the kinase to a Ca2(+)-independent form which could prolong physiological systems controlled by this kinase in response to transient Ca2+ elevations. Such properties appear to exist in dynamic equilibrium in the isolated postsynaptic density and in cultured brain cells. These unique biochemical regulatory properties, coupled with an unusual high concentration in the postsynaptic density of excitatory synapses, makes CaM-kinase II an attractive candidate for involvement in synaptic plasticity.

Amino Acid Sequence↗
PubMed1990

Isolated ventral pancreatitis in a patient with pancreas divisum.

A previously healthy 22-yr-old woman was found to have chronic pancreatitis restricted to the ventral pancreas in association with pancreas divisum. When conservative treatment failed, sphincteroplasty of both papillae was performed with good results. This well-documented case represents a clear exception to the commonly held concept that obstruction of the dorsal duct is the essential pathogenic factor in the development of pancreatitis associated with pancreas divisum. The importance of visualizing both the dorsal and ventral pancreatic ducts to direct therapy for patients with idiopathic pancreatitis is discussed. Theories of the pathogenesis of concomitant pancreatitis and pancreas divisum are reviewed.

Adult↗
PubMed1990

Repair of vaginal vault prolapse with abdominal sacropexy.

Ten women were treated for complete eversion of the vaginal vault with an abdominal sacropexy technique utilizing rectus fascia as graft material. The vault was suspended from the anterior sacral ligament by a strip of rectus fascia. Nine of ten patients had complete cure of the prolapse. All patients who remained sexually active have reported normal coital function. Abdominal sacropexy using rectus fascia is a safe, effective method for the long-term cure of vaginal vault prolapse.

Aged↗
PubMed1989

Characterization and quantitation of the epidermal growth factor receptor in invasive and superficial bladder tumors.

Epidermal growth factor receptors (EGFr) have been measured on primary human bladder tumor membranes by 125I-EGF ligand binding. High affinity receptors were detected on both superficial (Kd 0.2-1.45 nM; mean, 0.86 nM; median, 0.88 nM) and invasive tumors (Kd 0.19-2.38 nM; mean, 0.9 nM, median, 0.79 nM). There was one class of binding sites and EGFr concentration was quantified by competitive binding and Scatchard analysis. The EGFr was further characterized and shown to be cleaved at the major autophosphorylation site by a calcium-activated mechanism. Thus the EGFr from primary bladder tumors exhibits similar biochemical characteristics to those in established cell lines. Tumors classified as invasive on the basis of muscle invasion had higher EGFr levels [EGF binding, 99 +/- 252 (SD) fmol/mg protein; median, 21; n = 24] than superficial tumors (12 +/- 12 fmol/mg protein; median, 11; n = 23) or normal bladder mucosa (9 +/- 12 fmol/mg protein; median, 6; n = 6) (P = 0.05). When the two largest subgroups of superficial and invasive tumors were compared (15 pTa, 16 T3), the invasive tumors had significantly higher EGFr levels (P less than 0.05). EGFr may therefore be involved in mechanisms of tumor progression. EGFr may be a target for selective therapy with EGF-linked drugs in a subset of invasive bladder cancers.

Aged↗
PubMed1989

Induction of virus-producing tumours in athymic nude mice by bovine papillomavirus type 4.

Bovine papillomavirus type 4 (BPV-4), the causative agent of alimentary papillomatosis, has been used to infect, in vitro, fragments of palatine mucosa from late term bovine fetuses. These small explants were placed beneath the renal capsule of athymic nude mice where they grew to produce, at first, squamous epithelial cysts containing BPV-4 genomic DNA and, later, papillomas which were morphologically identical to those of cattle and which contained large amounts of replicating virus. The possible utility of this technique in assessing neutralising antibodies in vaccine development is discussed.

Animals↗