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Biomedical subjects

D Holmes

Publications and source records attributed to D Holmes.

At least 55 records · Page 3Linked to original sources
PubMed1998

Laser wire for crossing chronic total occlusions: "learning phase" results from the U.S. TOTAL trial. Total Occlusion Trial With Angioplasty by Using a Laser Wire.

The Prima laser guidewire system (Spectranectics Corp., Colorado Springs, CO) consists of an 0.018" hypotube containing a bundle of 45-microm optical fibers coupled to a pulsed excimer laser operating at a tip fluence of 60 ml/mm2 and a repetition rate ranging from 25-40 Hz. This laser guidewire was specifically designed to cross total occlusions refractory to passage with conventional wires. The Prima wire was evaluated in a feasibility study at 15 U.S. centers. Following failure to cross a total occlusion with approved guidewires, the Prima wire was utilized in 179 patients. Average age of subjects was 61 yr. Lesion locations included left anterior descending (36%), right (45%), and circumflex (19%) coronary arteries. Mean angiographic age of total occlusions was 70 wk (range, 2-1,020 wk, median, 14 wk). The use of the Prima wire either solely or in combination with conventional guidewires resulted in successful crossing in 61% of these previously impenetrable occlusions. Failure of the device was commonly related to length of the occlusion and tortuosity along the occluded pathway. Major complications included myocardial infarction in 7 patients (3.9%), tamponade in 3 (1.7%), and death in 2 (1.1%). This "learning phase" pilot study confirmed the feasibility of a laser guidewire in chronic total occlusions that are resistant to passage of conventional guidewires. An extended registry at these investigative sites is planned.

Adult↗
PubMed1998

Prevalence estimates of cognitive impairment in medical model adult day health care programs.

Despite an increasing emphasis on adult day health care (ADHC) programs as alternatives to institutional care for persons with dementia, little research based on direct assessment of clients' cognitive status has been conducted in such settings. The goal of this analysis was to estimate the prevalence of cognitive impairment among ADHC clients using commonly used screening measures. Age-adjusted and non-age-adjusted prevalence estimates of cognitive impairment in New York State ADHC programs were developed using a probability sample of 336 clients. Estimates were made using traditional cutting scores on standard cognitive screening measures, such as the Mini-Mental State Examination (MMSE), as well as latent class analyses applied to the same item sets. Average prevalence estimates of cognitive impairment were 55% across age cohorts and 60% for persons aged 65 and over. The MMSE yielded a prevalence estimate of 58% across age cohorts and 63% for those aged 65 and over. Using a more conservative cut score, the estimate for the MMSE was 33%; latent class estimates of moderate to severe impairment indicate that approximately 30% of the ADHC clients had cognitive impairment suggestive of probable or definite dementia. Community alternatives to institutional care for the elderly are increasing in popularity. These findings suggest that 1. While institutions are serving the most severely cognitively impaired, age-adjusted prevalence ratios for the ADHC sample approach the bounds of the institutional estimates. 2. The institutional setting will continue to be an important mode of care for the more severely impaired individuals. 3. Daycare is serving a high proportion of the mildly and moderately cognitively impaired individuals. It follows, therefore, that such programs need to address the needs of these individuals by developing specialized care plans and tracks targeted for the cognitively impaired.

Adult↗
PubMed1998

HOX homeobox genes exhibit spatial and temporal changes in expression during human skin development.

The spatial and temporal deployment of HOX homeobox genes along the spinal axis and in limb buds during fetal development is a key program in embryonic pattern formation. Although we have previously reported that several of the HOX homeobox genes are expressed during murine skin development, there is no information about developmental expression of HOX genes in human skin. We have now used reverse transcriptase polymerase chain reaction, in conjunction with a set of degenerate oligonucleotide primers, to identify a subset of HOX genes that are expressed during human fetal skin development. In situ hybridization analyses demonstrated that there were temporal and spatial shifts in expression of these genes. Strong HOXA4 expression was detected in the basal cell layers of 10 wk fetal epidermis and throughout the epidermis and dermis of 17 wk skin, whereas weak signal was present in the granular layer of newborn and adult skin. The expression patterns of HOXA5 and HOXA7 were similar, but their expression was weaker. In situ hybridization analysis also revealed strong HOXC4 and weaker HOXB7 expression throughout fetal development, whereas HOXB4 was expressed at barely detectable levels. Differential HOX gene expression was also observed in developing hair follicles, and sebaceous and sweat glands. None of the HOX genes examined were detected in the adult dermis.

Adult↗
PubMed1998

Bone morphogenetic protein-2 induces scar formation and skin maturation in the second trimester fetus.

Fetal mammals heal skin wounds through the second trimester of development without evidence of scar. We have investigated the role of bone morphogenetic protein 2 (BMP-2), which is a member of the TGF-beta superfamily, in normal skin development and fetal wound healing. We first used RNA in situ hybridization to demonstrate that BMP-2 was expressed at low levels in the developing hair follicles and in the epidermis of normal human fetal skin. We then created an in vivo model to test how exogenous BMP-2 would affect fetal skin development and wound healing. Fifty micrograms of BMP-2 was implanted into the subcutis of five 70-day-old fetal lambs through a full-thickness linear incision. The BMP-2 was placed beneath the right half of the wound, whereas the left half served as an untreated control. In two of the five animals 1 microgram of TGF-beta was placed into the same position in addition to the 50 micrograms of BMP-2. Twenty days later (90 days gestation, term = 140 days) all the fetal wounds were examined for evidence of cellular hyperproliferation and scar formation. BMP-2 induced massive dermal and epidermal growth when compared with controls. This finding was characterized by marked epidermal thickening and keratinization, a dramatic increase in the number of hair follicles, and more than 50 percent thickening of the dermis. The dermal thickening was the result of both increased cellularity and deposition of large irregular collagen bundles. Wounds treated with both BMP-2 and TGF-beta healed also with an adult-like pattern of scar formation. Surprisingly, the wounds with BMP-2 alone healed with an equal pattern of scar, indicating that there was not an additive effect of combining BMP-2 and TGF-beta. We conclude that BMP-2 is a pleomorphic growth factor that induces cellular growth, maturation, and fibroplasia in both the dermis and epidermis. Further analysis of this growth factor in both fetal and adult wound healing may lead to important discoveries regarding the control of scar formation and fibrosis in many adult tissues.

Adult↗
PubMed1998

Co-trimoxazole desensitization in HIV-seropositive patients.

Co-trimoxazole (trimethoprim-sulphamethoxazole) is an effective prophylactic agent against Pneumocystis carinii pneumonia (PCP). However, it is associated with a high frequency of adverse reactions in immunocompromised patients which may preclude its use. Fourteen patients with a definite history of adverse reactions to co-trimoxazole on standard PCP prophylactic dosage were selected for desensitization using a regimen of gradual incremental exposure over an 11-day period. Eight (57.1%) were successfully desensitized and have continued on oral co-trimoxazole at maximum 21 months' follow-up. This report demonstrates that oral desensitization as an outpatient procedure is an effective and safe option for both primary and secondary PCP prophylaxis in HIV-seropositive patients with previous adverse drug reactions.

Adult↗
PubMed1997

Relation of operator volume and experience to procedural outcome of percutaneous coronary revascularization at hospitals with high interventional volumes.

BACKGROUND: Although an inverse relation between physician caseload and complications has been conclusively demonstrated for several surgical procedures, such data are lacking for percutaneous coronary intervention, and the ACC/AHA guidelines requiring > or = 75 cases per year for operator "competency" are considered by some physicians to be arbitrary. METHODS AND RESULTS: From quality-controlled databases at five high-volume centers, models predictive of death and the composite outcome of death, Q-wave infarction, or emergency bypass surgery were developed from 12,985 consecutively treated patients during 1993 through 1994. Models had moderate to high discriminative capacity (area under ROC curves, 0.65 to 0.85), were well calibrated, and were not overfitted by standard tests. These models were used for risk adjustment, and the relations between both yearly caseload and years of interventional experience and the two adverse outcome measures were explored for all 38 physicians with > or = 30 cases per year. The average physician performed a mean +/- SD of 163 +/- 24 cases per year and had been practicing angioplasty for 8 +/- 5 years. Risk-adjusted measures of both death and the composite adverse outcome were inversely related to the number of cases each operator performed annually but bore no relation to total years of experience. Both adverse outcomes were more closely related to the logarithm of caseload (for death, r = .37, P = .01; for death, Q-wave infarction, or bypass surgery, r = .58, P < .001) than to linear caseload. CONCLUSIONS: In this analysis, high-volume operators had a lower incidence of major complications than did lower-volume operators, but the difference was not consistent for all operators. If these data are validated, their implications for hospital, physician, and payer policy will require exploration.

Angioplasty, Balloon, Coronary↗
PubMed1997

Reporting source bias in estimating prevalence of cognitive impairment.

Reporting source bias was examined using cognitive data from a probability sample of adult day health care (ADHC) clients. Data were obtained from four sources: client, family, staff, and chart. These data suggest that prevalence estimates are influenced by the reporting source and method of assessment, with chart diagnoses yielding the least convergent estimates. Examination of agreement summary statistics and bias indices show that both staff and family underreport prevalence of cognitive impairment, but that more bias is associated with staff than is with family sources. Such bias should be considered in studies of prevalence estimation of cognitive impairment.

Aged↗
PubMed1997

The human homeobox genes MSX-1, MSX-2, and MOX-1 are differentially expressed in the dermis and epidermis in fetal and adult skin.

In order to identify homeobox genes which may regulate skin development and possibly mediate scarless fetal wound healing we have screened amplified human fetal skin cDNAs by polymerase chain reaction (PCR) using degenerate oligonucleotide primers designed against highly conserved regions within the homeobox. We identified three non-HOX homeobox genes, MSX-1, MSX-2, and MOX-1, which were differentially expressed in fetal and adult human skin. MSX-1 and MSX-2 were detected in the epidermis, hair follicles, and fibroblasts of the developing fetal skin by in situ hybridization. In contrast, MSX-1 and MSX-2 expression in adult skin was confined to epithelially derived structures. Immunohistochemical analysis of these two genes suggested that their respective homeoproteins may be differentially regulated. While Msx-1 was detected in the cell nucleus of both fetal and adult skin; Msx-2 was detected as a diffuse cytoplasmic signal in fetal epidermis and portions of the hair follicle and dermis, but was localized to the nucleus in adult epidermis. MOX-1 was expressed in a pattern similar to MSX early in gestation but then was restricted exclusively to follicular cells in the innermost layer of the outer root sheath by 21 weeks of development. Furthermore, MOX-1 expression was completely absent in adult cutaneous tissue. These data imply that each of these homeobox genes plays a specific role in skin development.

DNA-Binding Proteins↗
PubMed1997

Intravitreal injection of octreotide acetate.

This study was conducted to determine the feasibility of injecting the somatostatin analogue, octreotide acetate (OA), into the vitreous cavity. Previous work suggests that octreotide effectively inhibits angiogenesis in vitro, thus its use in vivo may slow the progression of proliferative eye disease. Fifty micrograms of aqueous OA in 50 microliters aqueous solution was injected into the mid-vitreous of kitten eyes (n = 6), and OA levels were monitored over 4 days. A long-acting release form of octreotide (OA-LAR) was also injected into the mid-vitreous of rabbit eyes at doses of 0.36 (n = 16), 1.1 (n = 1), 2.1 (n = 1), 4.05 (n = 1), 8.2 (n = 1), and 36 mg (n = 3) in solution; and octreotide concentrations were measured at various time points over 42 days. OA concentrations were determined by a highly specific radioimmunoassay. Aqueous octreotide was eliminated rapidly (t1/2 = 16 hours) from the vitreous of the kitten eye, with only negligible amounts recoverable 4 days post-injection. In the long-acting form, OA in the rabbit eye reached peak levels at 28 days. By 42 days, OA levels had declined to the 14-day level. Doses of OA-LAR of 1.1 mg or less produced no gross evidence of clinical toxicity and elicited no grossly visible ocular side effects. Doses greater than 1.1 mg produced significant toxicity, including cataracts and rubeosis. The 28-day peak release for long-acting OA implies that monthly intravitreal injections could provide continual high levels of OA. Intravitreal injection of long-acting OA provides sustained, high concentrations of drug, and deserves further study as a potential treatment of proliferative eye diseases.

Animals↗
PubMed1997

Prevalence of behavior disorder and disturbance to family and staff in a sample of adult day health care clients.

Latent class-derived prevalence estimates of behavior disorder are provided for adult day health care (ADHC) clients; informal and formal caregivers reported 11% and 14%, respectively, of these clients as engaging in severe disturbed behavior (95% confidence intervals across sources are from 7% to 18%). The prevalences, estimated for informal and formal caregivers respectively, were 12% and 16% for affective disorder, 15% and 18% for cognitive disorders, 16% and 13% for verbal-vocal agitation, and 6% and 8% for socially inappropriate behavior. These rates can be contrasted with those of the institutional population which, while higher, overlap with the distribution of behavior disorder for ADHC community residents. The degree of reported disturbance to family and staff was similar across items.

Adult↗
PubMed1997

The Histopathology of Angiographic Chronic Total Coronary Artery Occlusions Ñ Changes in Neovascular Pattern and Intimal Plaque Composition Associated with Progressive Occlusion Duration.

The current study describes the histopathology of angiographic chronic total occlusions including residual lumen patency, intimal plaque composition, patterns of neovascular channel formation, intimal plaque calcification, and cellular inflammation, analyzed according to occlusion duration and intimal plaque type (fibrocalcific vs. lipid laden vs. mixed). Histologic findings are related to previously described clinical and angiographic predictors of successful chronic total occlusion revascularization.

Journal Article↗
PubMed1997

Sexual expression and dementia. Views of caregivers: A pilot study.

OBJECTIVE: To measure the attitudes of health professionals in nursing homes towards sexuality and sexual expression in cognitively impaired and cognitively intact residents. DESIGN: Postal survey. PARTICIPANTS: The staff (administrators, clinicians, social workers and others) of 300 randomly selected nursing homes located in three states. Of these, 114 representatives responded. MAIN OUTCOME MEASURE: A measure of attitudes towards resident sexuality developed during a prior study. RESULTS: Results suggest that respondents held a generally positive orientation towards residents' sexual expression which was expressed with respect to cognitively impaired residents as well as to those who were cognitively intact. Possibly because of the small sample size and resulting low statistical power, statistical analyses failed to demonstrate any significant differences among the groups of residents: administrators, clinicians, social workers, and undifferentiated 'others'. However, while non-significant, there was a consistent tendency for administrators to be relatively more conservative than were the other groups. Almost all respondents agreed that additional staff training should focus specifically on dealing with resident sexual expression. CONCLUSIONS: Overall, the sample reported generally positive attitudes towards resident sexuality and sexual expression.

Aged↗
PubMed1997

Measurement choices in multi-site studies of outcomes in dementia.

This paper summarizes the measurement choices made by selected current or recently completed multi-site projects with a common emphasis on measuring outcomes in dementia. Information on number of items and scoring, reason(s) for selecting the measure, and reliability and validity of the measure (either citations providing this information or a report of pertinent unpublished findings) is presented for eight domains: cognition, behavioral symptoms, physical health status, physical functioning and self-care abilities, quality of life, family/staff caregiver outcomes, service use, and cost. We found considerable reliance on the published literature as a guide to measurement choice, motivated largely by measures' superior psychometric properties, their ubiquity in the literature, and/or their brevity or ease of use. There is still evidence of "starting from scratch" in some domains, however. To the extent that these projects reflect the state of the art in dementia-relevant outcomes research, we conclude that comparison of outcomes across studies will continue to be problematic. However, as long as dissemination of methodological as well as substantive findings continues to characterize outcome studies in dementia, there is hope that a more congruent view of how to assess key outcomes in dementia will emerge.

Caregivers↗
PubMed1997

Methodological issues in cognitive assessment and their impact on outcome measurement.

Assessment of cognitive impairment in chronic care populations is complicated by several factors that may interfere with the assessment process: physical frailty and disability; comorbid conditions such as depression; and decrements in vision, hearing, speech, and general communication. Moreover, cognitive impairment itself affects assessment of outcome domains such as depression, behavior, and function, thus contributing to several sources of measurement bias. Sources of bias are discussed in the context of findings from the literature relating individual and cognitive factors to outcome measurement. Recommendations for further methodological research are provided.

Alzheimer Disease↗