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Biomedical subjects

K Smith

Publications and source records attributed to K Smith.

At least 217 records · Page 12Linked to original sources
PubMed1998

Neuroaugmentation in the treatment of complex regional pain syndrome of the upper extremity.

The authors report their results on 36 patients with advanced stages of complex regional pain syndrome. They were treated with either spinal cord stimulation, or peripheral nerve stimulation, and in some cases with both modalities. Thirty six months after implantation the reported pain measured on visual analogue scales was an average of 53% better, this change was statistically significant. Analgesic consumption decreased by about 50% or was reportedly more effective. The authors conclude that in late stages of complex regional pain syndrome, neuroaugmentation is a reasonable option when alternative therapies have failed.

Adult↗
PubMed1998

Client satisfaction with the New Zealand National Poisons Information Service.

A telephone survey of a random sample of callers to the New Zealand National Poisons and Hazardous Chemicals Information Centre (NPC) was undertaken to assess public satisfaction with, and knowledge of, the NPC and to determine whether the NPC was meeting the needs of its users. The response from a sample of 433 individuals (354 members of the general public and 79 health professionals) was 79%. Maori and Pacific Island people were under--represented in the sample. Overall the level of satisfaction with the NPC was high with 91% of the respondents finding the information they received very useful. If the NPC had not been available, 81% of the public would have sought advice from a medical facility and 59% would have visited such a facility. It was estimated that the NPC could be saving the public health services in New Zealand (NZ) up to NZ $1.3 million annually. It was concluded that the NPC was meeting the needs of current users, although greater public awareness and improved access are needed particularly for Maori and Pacific Island people.

Awareness↗
PubMed1998

Neurocristic cutaneous hamartoma: a distinctive dermal melanocytosis with an unknown malignant potential.

Neurocristic hamartomas (NCHs) result from aberrant development of the neuromesenchyme. In addition to a dermal melanocytic component, these tumors can contain neurosustentacular and fibrogenic components and can undergo malignant transformation. Although NCHs have many features in common with other dermal melanocytic neoplasms, including cellular blue nevi and some congenital nevi, they have distinctive clinical and histologic features. We present a case report of a 27-year-old white woman with an NCH of the scalp. The clinical, histologic, and immunohistochemical features are compared with those of other dermal melanocytic neoplasms. The NCH contained epithelioid pigmented melanocytes positive for S-100 and HMB45, within which there were well-circumscribed nodules of S-100+/Leu 7+/HMB45- cells surrounded by a capsule composed of spindle cells positive for epithelial membrane antigen. The stromal cells throughout the tumor were diffusely CD34 positive, and hair follicles were decreased and dystrophic within the tumor. NCHs represent neoplastic dysplasia that involves not only melanocytic cells but also neurosustentacular and fibrocytic effector cells. The histologic and immunohistochemical features, along with the decreased and dystrophic hair follicles, suggest that the abnormalities in the mesenchyme are significant and result from the contribution of neural crest cells to the cellular and matrix components of the mesenchyme.

Adult↗
PubMed1998

A gentamicin order form improves its use.

To assess the effects of implementing a standardized order form on the prescribing and monitoring of gentamicin sulfate at a nonteaching Veterans Affairs Medical Center, we prospectively evaluated the prescribing and monitoring of gentamicin for 14 months after the use of such a form was implemented. The data collected included dosing, initial serum gentamicin concentrations, and serum creatinine measurements. These data were compared with similar data obtained during a period of 6 months before the order form was used. A total of 76 patient records were reviewed, 39 before the use of the order form and 47 after the order form was implemented. Gentamicin peak concentrations were statistically higher in the group treated after the order form was implemented. No differences were seen in gentamicin trough concentrations. The timely measurement of serum gentamicin concentrations and serum creatinine levels was improved in the group for whom the order form was used. The order form was completed satisfactorily in 44 patients (94%). We conclude that implementing a standardized order form improved the use of gentamicin.

Aged↗
PubMed1998

A clinical decision analysis of cryotherapy compared with expectant management for cervical dysplasia.

BACKGROUND: Screening for precursors of cervical cancer with colposcopic examination for women with abnormal Papanicolaou (Pap) smears identifies those with cervical dysplasia. Though the majority of mild dysplasias (CIN I) will regress, many are treated with cryotherapy. METHODS: We used decision analysis to compare immediate cryotherapy with expectant management (following with another Pap smear or colposcopy, with treatment reserved for progression or a duration of 2 years). The decision tree included the possibility of more invasive surgical procedures if the cryotherapy was ineffective or if the dysplasia progressed in extent of cervical involvement or in grade. Probabilities were derived from literature review and expert judgment. The analysis considered the disutility of the follow-up examinations, cryotherapy, and the more invasive procedures, using expert assessment. RESULTS: Using the baseline assumptions, expectant management led to a better outcome for most patients (57%), who recover with no procedure. However, more patients treated with expectant management required surgical procedures (loop electrosurgical excisional procedure, conization, or, rarely, hysterectomy) than did those treated with immediate cryotherapy. In the expected disutility analysis, expectant management was better than immediate cryotherapy. Sensitivity analysis showed that three factors had the potential to change the recommendation of the analysis: (1) the probability the dysplasia will regress, (2) the disutility of the process of expectant management, and (3) the disutility of invasive procedures compared with cryotherapy. CONCLUSIONS: The analysis indicated that expectant management is preferable to immediate cryotherapy for women with histologically proven mild cervical dysplasia. However, this conclusion depended on assumptions about three factors for which there is insufficient evidence in the literature. More research is needed.

Colposcopy↗
PubMed1998

Organ and tissue donation: are minorities willing to donate?

The Task Force on Organ Transplantation (DHHS,1986) addressed the issue of increasing organ donation. The Report of the Task Force recommended that "educational efforts aimed at increasing organ donation among minority populations be developed and implemented, so that the donor population will more closely reflect the ethnicity of potential transplant recipients, in order to gain the advantage of improved donor and recipient immunologic matching (DHHS,1986). Donor rates for minorities has increased as follows: 16% in 1988 to 23% in 1995 among cadaveric donors and 24% in 1988 to 28% in 1995 among living donors. The improvement in donor rates among minorities may positively affect the transplantation success rate experienced by organ recipients of the same race. Strategies must be implemented that will increase the effectiveness and frequency of communication between minority patients and the medical community. An increase in the effectiveness of communication between potential minority donor families and the health care community will contribute to the process of Consciousness Raising as discussed by Prochasksa. The result of increased awareness of the organ donation and transplantation process may have a favorable impact on organ donation. The media has, through public service announcements, paid advertising and entertainment programming, attempted to promote discussion of organ donation in the community and within families. Johnson et al. discussed Mexican-American and Anglo-American Attitudes Toward Organ Donation. The primary impediment contributing to the disparity of consent rates between Mexican-American and Anglo-American population occurs with regard to the donation of organs of relatives. Johnson stated that this impediment to organ donation can be effectively addressed by promoting family discussion. Communication within families will inform surviving next of kin of the desire of the deceased to be an organ donor and hence improve the likelihood of the donor family consenting to organ donation (Johnson et al., 1988). The promotion of communication within families must continue to be a goal of the transplant community regardless of race/ethnicity. Despite the efforts of the government, the transplant community, the media and the corporate sector to address the critical shortage of donors in the United States, the reality is that no community has the supply of donor organs suitable to meet the need.

Black or African American↗
PubMed1997

cDNA cloning of a human dishevelled DVL-3 gene, mapping to 3q27, and expression in human breast and colon carcinomas.

dishevelled (Dsh) is a member of the segment polarity gene family in Drosophila which plays an important role in the early developmental patterning processes. A human homologue of Dsh (DVL-1) has recently been described. Here, we report the cloning of a second human homologue of Dsh (called DVL-3) by cDNA library screening. The human DVL-3 gene encodes a predicted 716 amino acid protein which exhibits 98% amino acid identity with mouse Dvl-3 and 49% with Drosophila Dsh. DVL-3 was mapped to 3q27. The expression of DVL-3 mRNA was detected in 30 human cell lines and 2 primary cell cultures. DVL-3 mRNA was detected in normal human breast tissues (n = 4) and tumours (n = 25). Statistically, there was no difference in DVL-3 mRNA level between normal breast tissues and tumours. In human colorectal samples, DVL-3 was expressed equally in matched normal tissues, polyps and tumours. The data indicates that DVL-3 is widely expressed in human cells and supports the notion of a new developmental gene family for dishevelled which may have a widespread role in signal transduction.

Adaptor Proteins, Signal Transducing↗
PubMed1997

Interstitial deletion of 2q associated with craniosynostosis, ocular coloboma, and limb abnormalities: cytogenetic and molecular investigation.

We report on the clinical and cytogenetic findings in a 9-year-old boy with a de novo deletion of 2q, shown by molecular analysis to have arisen from the paternal chromosome. Examination of microsatellite markers indicated deletion of bands 2q24.3 and 2q31. Clinical findings included craniosynostosis, bilateral ocular colobomata, and limb abnormalities, the latter being an emerging association with deletion of this region of 2q.

Abnormalities, Multiple↗
PubMed1997

Serotonin and aggressive motivation in crustaceans: altering the decision to retreat.

In crustaceans, as in most animal species, the amine serotonin has been suggested to serve important roles in aggression. Here we show that injection of serotonin into the hemolymph of subordinate, freely moving animals results in a renewed willingness of these animals to engage the dominants in further agonistic encounters. By multivariate statistical analysis, we demonstrate that this reversal results principally from a reduction in the likelihood of retreat and an increase in the duration of fighting. Serotonin infusion does not alter other aspects of fighting behavior, including which animal initiates an encounter, how quickly fighting escalates, or which animal eventually retreats. Preliminary studies suggest that serotonin uptake plays an important role in this behavioral reversal.

Aggression↗
PubMed1997

A reliable external control for ribonuclease protection assays.

A method is described for generating an external spiked human RNA control to enhance the reliability of assessment of gene expression in tumour extracts. Spiking with an external standard RNA controls for all subsequent steps of analysis on a lane by lane basis and allows for uniform comparison of the gene of interest as a fraction of total RNA, particularly when multiple samples are not available. The antisense probe that is being used to detect endogenous gene expression is also used as an external control. A sense riboprobe is made from the same vector. Because of the flanking RNA polymerase sites incorporated in both probes, hybridization with the sense riboprobe at a much lower concentration than the antisense probe generates a larger product that can be readily separated from the endogenous protected fragment. This method is generally applicable to any riboprobe that has a T3 and T7 RNA polymerase site and allows any externally added riboprobe use for assessing endogenous gene expression to be used as the external spike control.

DNA-Directed RNA Polymerases↗
PubMed1997

A novel human Wnt gene, WNT10B, maps to 12q13 and is expressed in human breast carcinomas.

Several members of the Wnt gene family have been shown to cause mammary tumors in mouse. Using degenerate primer polymerase chain reaction (PCR) on human genomic DNA, and specific PCR of cDNA libraries, we have isolated a WNT gene which has not previously been described in human. The gene is the human homologue of mouse Wnt10b, recently shown to be one of the oncogenes cooperating with FGF3 in the development of mouse mammary tumour virus (MMTV) induced mouse mammary carcinomas. The human WNT10B sequence was 88% and 95% identical to the murine gene at nucleotide and amino acid levels, respectively. YAC FISH mapping localises the gene to 12q13, a chromosomal region frequently rearranged in human tumours and also containing the WNT1 gene. In normal and benign proliferations of human breast tissue, WNT10B expression was not detected by ribonuclease protection assays but was found at low levels in RT-PCR experiments. In contrast, using both methods, WNT10B expression was found to be elevated in 3 of 50 primary breast carcinomas. Southern blot analysis of the carcinoma expressing the highest levels of WNT10B showed no amplification or rearrangement of the gene. The WNT10B gene was also expressed in some cancer and non cancerous breast cell lines. These findings suggest that the WNT10B gene may be involved in human breast cancer, and show that there is differential expression of the WNT10B gene in benign and malignant disease.

Amino Acid Sequence↗
PubMed1997

Expression of the angiogenic factors vascular endothelial cell growth factor, acidic and basic fibroblast growth factor, tumor growth factor beta-1, platelet-derived endothelial cell growth factor, placenta growth factor, and pleiotrophin in human primary breast cancer and its relation to angiogenesis.

Angiogenesis is a significant prognostic factor in breast cancer, but the factors that control angiogenesis in vivo are not well defined. Multiple angiogenic polypeptides are known, and we have determined the expression of seven of these in primary human breast cancers; the relationship of expression to estrogen receptor and vascular density was also examined. Vascular endothelial growth factor (VEGF) and its four isoforms (121, 165, 189, and 206 amino acids), transforming growth factor (TGF)-beta1, pleiotrophin, acidic and basic fibroblast growth factor (FGF), placental growth factor, and thymidine phosphorylase (platelet-derived endothelial cell growth factor) were quantitated by RNase protection analysis. beta-FGF was also measured by ELISA. The estrogen receptor (ER), epidermal growth factor receptor, and vascular density were analyzed in 64 primary breast cancers. All tumors expressed at least six different vascular growth factors. VEGF was most abundant, and the transcript for the 121-amino acid form predominated. Other angiogenic factors expressed at high levels were thymidine phosphorylase and TGF-beta1. Expression of most of the angiogenic factors did not correlate with that of ER or vascular density. However, thymidine phosphorylase did, with a correlation coefficient of 0.3 (P = 0.03). There were significant associations of pleiotrophin with acidic FGF expression (P = 0.001) and TGF-beta with platelet-derived endothelial cell growth factor expression (P = 0.001). Thus, angiogenesis may involve a coordinate regulation of some vascular growth factors. High VEGF expression correlated with poor prognosis in univariate analysis (P = 0.03), as did ER and epidermal growth factor receptor expression. Basic FGF was also assessed by ELISA and was more highly expressed in tumors than normal breast tissues (median, 346 microg/ml cytosol; range, 54-1323 versus median, 149; range, 32-509; P = 0.01). Implications for therapy are that broad spectrum agents that block features common to these factors may be useful (e.g., antagonism of heparin-binding activity agents), because so many angiogenic factors are expressed. Inhibiting endothelial migration or agents directly toxic to endothelium would be of value in a combined approach to therapy.

Breast Neoplasms↗
PubMed1997

Nurses' and GPs' views of the nurse prescribers' formulary.

This article presents the findings from the evaluation of nurse prescribing, undertaken in eight demonstration sites since October 1994. The authors examine in particular the nurses' prescribing behaviour and the type of items nurses and GPs would like to see added to the formulary. The opportunities for prescribing and the limitations of the formulary for health visitors and practice nurses are highlighted.

Attitude of Health Personnel↗
PubMed1997

Physical growth of low birthweight infants in the first year of life: impact of maternal behaviors.

Physical growth of preterm infants relates to many medical factors, such as birthweight, severity of medical illnesses, and nutritional status. We previously reported that maternal behaviors influence developmental outcomes in low birthweight infants (birthweight < 1600 g); we now hypothesize that maternal behaviors also influence physical somatic growth in low birthweight (LBW) infants. We serially followed 218 mother-infant pairs from birth through 12 months of age. One-hundred thirteen LBW infants were categorized based on severity of early medical complications. Low Risk infants (LR, n = 71) had acute respiratory distress and/or grade 1-2 intraventricular hemorrhage (IVH), or grade 3 IVH without hydrocephalus. High Risk infants (HR, n = 42) had chronic lung disease, grade 3 IVH with hydrocephalus or grade 4 IVH, and/or periventricular leukomalacia. We also studied 105 socioeconomic (SES) matched Full Term (FT) controls. Maternal behaviors were assessed during home visits with global ratings of Warm Sensitivity and Punitiveness. Infant weight was measured at birth and at 38 weeks, 6 months and 12 months corrected gestational age. We examined alternative expressions of weight growth across the three groups by developing the Weight Quotient (WQ), which is the ratio of actual measured weight to the median weight for age. For each infant the regression of the WQ ratio against correct gestational age was analyzed. We used a General Linear Model to compare the relation of the maternal variables to the weight quotients for the three groups. We determined the catch up growth as the slope of each regression. Results indicated that higher levels of maternal Punitiveness were related to slower rates of growth for High Risk (R2 = 0.36), but not Low Risk or Full Term. For maternal Warm Sensitivity (R2 = 0.36), there were significant (P < 0.05) inverse relations with weight gain growth for the Full Term infants. These data suggest that some maternal behaviors are related to the growth of term and premature infants, although the mechanisms through which this occurs is unclear.

Behavior↗
PubMed1997

Characterization of the peptide substrate specificity of glutathionylspermidine synthetase from Crithidia fasciculata.

Trypanothione, a metabolite specific to trypanosomatid parasites, is enzymatically synthesized from spermidine and glutathione by the consecutive action of the ATP-dependent carbon-nitrogen ligases, glutathionylspermidine synthetase and trypanothione synthetase. As part of our programme aimed at developing inhibitors of these enzymes, we have synthesized a series of analogues of glutathione (gamma-L-Glu-L-Cys-Gly) and tested them as substrates or inhibitors of glutathionylspermidine synthetase. Recognition at the gamma-glutamyl moiety appears to be essential, as any modification of this part of glutathione results in a total loss of activity as a substrate. Alkylation of the thiol side chain of cysteine with methyl, ethyl or propyl groups yields analogues with catalytic efficiencies (kcat/Km) as substrates equivalent to or better than glutathione. In contrast, the bulkier S-butyl analogue was a much poorer substrate. Substitution of L-Cys by amino acids with an alkyl side-chain is also well tolerated giving relative catalytic efficiencies of 1.1 and 1.5 for peptide analogues containing L-Val and L-Ile respectively. Other analogues, where the bulk of the alkyl chain is increased further (as in L-Leu or L-Phe) or where the glycine moiety is replaced with L-Ala, are inhibitors rather than substrates.

Amide Synthases↗
PubMed1997

Effect of enzyme replacement therapy on bone formation in a feline model of mucopolysaccharidosis type VI.

A range of skeletal abnormalities are evident in mucopolysaccharidosis type VI (MPS VI, Maroteaux-Lamy syndrome) including short stature and dysostosis multiplex, resulting from a deficiency in the lysosomal hydrolase N-acetylgalactosamine-4-sulphatase (4S). In this article, bone pathology was assessed in a feline model of MPS VI to evaluate the efficacy of enzyme replacement therapy (ERT) as a treatment modality for this genetic disorder. Osteopenia is clearly evident in MPS VI animals, with bone mineral volume (BV/TV) falling well below that of normal animals (4.39% vs. 20.11%, respectively). Trabecular bone architecture was also affected in MPS VI with fewer, thinner, and more widely spaced trabeculae apparent. Bone formation rate (BFR/BS) was also lower in MPS VI animals than controls (0.0011 mm3/mm2 per day vs. 0.008 mm3/mm2 per day, respectively). Vertebral and tibial bone length in MPS VI animals progressively fell behind normal values with increasing age, as did cortical bone thickness. Vertebral body shape was also altered. ERT with recombinant human 4S (rh4S) resulted in a vertebral BV/TV of 8.23% in animals treated with an intravenous enzyme dose of 1 mg/kg and a BV/TV of 14.33% in animals treated with a dose of 5 mg/kg. BFR/BS also increased to 0.0034 mm3/mm2 per day in animals treated with enzyme doses of either 1.0 or 5.0 mg/kg rh4S. All other affected histomorphometric parameters also improved with ERT to a level intermediate between MPS VI untreated animals and normals. However, individual animals treated with 0.2 mg/kg rh4S intravenously or 1.0 mg/kg rh4S administered subcutaneously did not exhibit an improvement over untreated MPS VI animals. Vertebral and tibial bone lengths, tibial cortical bone thickness, and vertebral body shape also responded to ERT, with a trend away from the untreated group. Thus, ERT had a positive effect on bone development in MPS VI animals that was dependent upon the dose of enzyme administered and the route of administration.

Animals↗