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Biomedical subjects

D G Smith

Publications and source records attributed to D G Smith.

At least 91 records · Page 5Linked to original sources

Cash management in health care systems.

Cash is one of the most precious assets held by health systems. This article presents results of discussions on cash management and investment policies at a dozen major not-for-profit health systems. Health system data indicate that cash holdings have increased dramatically since 1993, mostly due to investment earnings. Discussions with chief financial officers of these health systems reveal that cash holdings are significant, that decisions about cash balances are strategic, and that most systems aim to increase cash balances to levels that permit access to capital markets on more favorable terms.

Accounts Payable and Receivable↗

The inhibition of human cytomegalovirus (hCMV) protease by hydroxylamine derivatives.

Aryl hydroxylamine derivatives have been synthesised that are some of the most potent inhibitors of hCMV protease prepared to date (IC50 14-60 nM). Mass spectrometry studies indicate that oxazinone derived hydroxylamines inhibit the enzyme by acylation of Ser132 whereas non-oxazinone derived hydroxylamines appear to inhibit via formation of a sulfinanilide at Cys138.

Amino Acid Sequence↗

Selective inhibition of low affinity IgE receptor (CD23) processing: P1' bicyclomethyl substituents.

Using a variety of alpha-hydroxy hydroxamic acid derivatives, the size and shape of the S1' pocket for the CD23 processing metalloprotease has been explored. It has been demonstrated that a P1' 2-naphthylmethyl group occupies most of the available space and gives excellent selectivity against fibroblast collagenase (matrix metalloproteinase-1, MMP-1) and other MMPs.

Bridged Bicyclo Compounds↗

Bioimpedance: novel use of a minimally invasive technique for cancer localization in the intact prostate.

BACKGROUND: Prostate cancer is presently diagnosed by transrectal ultrasound (TRUS)-guided sextant needle biopsy. While echo texture of the tissue can prompt localization of tumor, it is presently imprecise. From 50-75% of men biopsied, based on an abnormal digital rectal examination (DRE) or elevated prostate-specific antigen (PSA) level, have negative biopsy results. Improvements in tumor localization during TRUS-guided prostate biopsy are greatly needed. Bioimpedance is an electrical property of biologic tissue. Electric current is limited in living tissue by highly insulating cell membranes; however, different tissue architecture such as cancer may impede current differently and allow detection of differences between normal and abnormal or malignant prostate tissue. Our goal was to assess the utility of bioimpedance measurements in differentiating tumor from normal prostatic tissue in an ex vivo model. METHODS: Bioimpedance was measured in six ex vivo prostates, which were removed for clinically localized prostate cancer. Two bioimpedance needles, 1 mm apart, were inserted 3 mm into the posterior surface of the prostate an average of 16 times per gland. Frequencies ranging from 100 kHz-4 MHz were used to obtain 594 bioimpedance measurements from the six glands. These measurements were then correlated with histology to determine the presence or absence of prostate cancer. RESULTS: Prostate cancer was found to have a higher impedance, of 932+/-170 ohms, compared to areas of no cancer within the same prostate, 751+/-151 ohms, P < 0.0001, at 2 MHz. This phenomenon was observed across all frequencies tested. CONCLUSIONS: This study demonstrates for the first time application of bioimpedance to distinguish areas of prostate cancer from areas of normal prostate. This technology may improve identification and localization of cancer within the prostate. Moreover, bioimpedance can potentially guide needle placement during prostate biopsy and thus improve sampling of tumors. Currently, our ex vivo model is limited by variables such as temperature and lack of blood flow. Further studies in an in vivo model will be needed to assess their effect.

Diagnostic Techniques and Procedures↗

Distribution of mtDNA haplogroup X among Native North Americans.

Mitochondrial DNA (mtDNA) samples of 70 Native Americans, most of whom had been found not to belong to any of the four common Native American haplogroups (A, B, C, and D), were analyzed for the presence of Dde I site losses at np 1715 and np 10394. These two mutations are characteristic of haplogroup X which might be of European origin. The first hypervariable segment (HVSI) of the non-coding control region (CR) of mtDNA of a representative selection of samples exhibiting these mutations was sequenced to confirm their assignment to haplogroup X. Thirty-two of the samples exhibited the restriction site losses characteristic of haplogroup X and, when sequenced, a representative selection (n = 11) of these exhibited the CR mutations commonly associated with haplogroup X, C --> T transitions at np 16278 and 16223, in addition to as many as three other HVSI mutations. The wide distribution of this haplogroup throughout North America, and its prehistoric presence there, are consistent with its being a fifth founding haplogroup exhibited by about 3% of modern Native Americans. Its markedly nonrandom distribution with high frequency in certain regions, as for the other four major mtDNA haplogroups, should facilitate establishing ancestor/descendant relationships between modern and prehistoric groups of Native Americans. The low frequency of haplogroups other than A, B, C, D, and X among the samples studied suggests a paucity of both recent non-Native American maternal admixture in alleged fullblood Native Americans and mutations at the restriction sites that characterize the five haplogroups as well as the absence of additional (undiscovered) founding haplogroups.

Adult↗

The effectiveness of two sterilization methods when different precleaning techniques are employed.

The effectiveness was investigated of methods for the preparation of dental handpieces prior to sterilization procedures utilizing ethylene oxide (ETO) gas. The handpieces were cleaned using either a forced-air purging unit (group 1) or by flushing with air and water from the dental unit (group 2). They were inoculated with either Bacillus subtilis or Streptococcus mutans. After exposure to either steam or ETO gas, the handpieces were flushed with saline and the viability of recovered bacteria assessed. No viable bacteria were recovered from group 1 handpieces treated with either ETO gas or steam. However, viable S. mutans were recovered from group 2 handpieces following exposure to ETO gas. Thus, the use of a high-pressure forced-air purging unit may be required for the reliable sterilization of dental handpieces by ETO gas, as viable S. mutans could be recovered from untreated handpieces exposed to ETO gas.

Air Pressure↗

Prevalence of emergency events in British dental practice and emergency management skills of British dentists.

Medical emergencies in dental practice are generally perceived as being rare but when an emergency does occur it can be life-threatening. The ability of the dentist to initiate primary management is the key to minimising morbidity and mortality. Accurate data on the prevalence of emergency events, required so that dentists can adequately prepare to deal with emergency situations, is sparse and obsolete. This study aimed to determine the current prevalence of medical emergencies and the perceived emergency management skills of dentists. A questionnaire, distributed to 887 dentists working in general dental practice across five counties of Northern England, produced a response rate of 34%. The most frequently reported emergency was vasovagal syncope (1.9 cases, per dentist per year), followed by hypoglycaemia (0.17), angina (0.17), epileptic fit (0.13), choking (0.09), asthma (0.06), hypertensive crisis (0.023) and anaphylaxis (0.013). Myocardial infarction and cardiac arrest were extremely rare with an incidence of 0.003 and 0.002 cases per dentist per year, respectively. The total prevalence of all emergency events (excluding syncope) was 0.7 cases per dentist per year. Only 20.8% of dentists felt competent to diagnose the cause of a collapse in the dental surgery. However the majority believed that they would be able to undertake initial treatment of most common emergencies. Despite this more than 50% felt unable to manage a myocardial infarction or anaphylaxis, and 49.7% did not know how to insert an oral airway or undertake an intravenous injection. Future postgraduate training in emergency care for dentists needs to be more accurately targeted to the known prevalence of emergencies and deficiencies in dentists' emergency skills.

Adult↗

Phantom limb, residual limb, and back pain after lower extremity amputations.

This study describes the sensations and pain reported by persons with unilateral lower extremity amputations. Participants (n = 92) were recruited from two hospitals to complete the Prosthesis Evaluation Questionnaire which included questions about amputation related sensations and pain. Using a visual analog scale, participants reported the frequency, intensity, and bothersomeness of phantom limb, residual limb, and back pain and nonpainful phantom limb sensations. A survey of medication use for each category of sensations also was included. Statistical analyses revealed that nonpainful phantom limb sensations were common and more frequent than phantom limb pain. Residual limb pain and back pain were also common after amputation. Back pain surprisingly was rated as more bothersome than phantom limb pain or residual limb pain. Back pain was significantly more common in persons with above knee amputations. These results support the importance of looking at pain as a multidimensional rather than a unidimensional construct. They also suggest that back pain after lower extremity amputation may be an overlooked but very important pain problem warranting additional clinical attention and study.

Adult↗

Socket considerations for the patient with a transtibial amputation.

This paper reviews the theory of transtibial prosthetic socket designs from a historic perspective to the present. The patella tendon bearing socket originated in 1959, and is the standard from which the new alternative socket designs have evolved. Although the patella tendon bearing socket is still the most commonly prescribed socket for a transtibial prosthesis, the total surface bearing and hydrostatic sockets are becoming increasingly accepted. The total surface bearing socket still may incorporate the weightbearing characteristics of the patella tendon bearing socket, but often will be accompanied by a shock absorbing gel liner. The hydrostatic socket does not incorporate the standard patella tendon bearing design characteristics, but instead depends on a method of pressure casting that in theory produces a socket with equally distributed pressure over all of the residual limb soft tissue. These three designs are reviewed as current options for the socket portion of the transtibial prosthesis.

Amputation, Surgical↗

Transtibial amputations.

The transtibial amputation is one of the most frequently performed major limb amputations in the United States. The long posterior flap technique has become the most frequently recommended technique; however, the surgeon performing amputations needs to be comfortable with the alternative techniques as well. Situations occasionally do arise where the sagittal or skew techniques may be more applicable. With careful surgery and soft tissue handling, wound healing can be expected in the majority of patients. Aggressive rehabilitation is possible in many patients, and with good prosthetic intervention, return to ambulation at or near the preoperative level of function can be expected in most patients.

Activities of Daily Living↗

Levels of high energy phosphate in the dorsal skin of the foot in normal and diabetic adults: the role of 31P magnetic resonance spectroscopy and direct quantification with high pressure liquid chromatography.

Determining viability of tissues and wound-healing potential in diabetic patients remains a significant challenge. Current methods for preoperative assessment of wound-healing potential (pressures in the ankle, temperature of tissues, transcutaneous measurements of oxygen, and systemic nutritional status) are indirect, in that they characterize the delivery of oxygen or other nutrients to the cells. A noninvasive means to measure adenosine triphosphate (ATP) and phosphocreatine (PCr), the fundamental high energy phosphate substrates of oxidative energy-metabolism in the skin, has been devised by using magnetic resonance spectroscopy (MRS). The signal-to-noise ratio of bioenergetic metabolites in the skin was 86% lower in five patients with diabetes who had ischemia of the lower extremity compared with five control subjects (P < 0.0001), suggesting that the concentration of high energy metabolites in diabetic patients was reduced. The ratio of ATP/phosphocreatine (PCr) in patients with diabetes was also significantly lower than in controls (P < 0.01). Chewing a single piece of nicotine gum reduced the measured concentrations of ATP and PCr in control subjects by an average of 18% and by an average of 75% in subjects with diabetes. To verify these results in a second experiment, skin was harvested from the surgical wound sites in eight patients with diabetes undergoing elective amputation, eight patients with diabetes undergoing elective foot surgery, and ten age-matched control (nondiabetic) patients undergoing elective foot surgery. Analysis of ATP and PCr using high pressure liquid chromatography corroborated MRS findings, showing a significant reduction in ATP and PCr in diabetic skin. Depression of metabolites was more severe in the patients with diabetes undergoing amputation than in the ones undergoing elective surgery. Results demonstrate depression of metabolites in the skin of patients with diabetes and suggest that MRS with 31p may be useful in characterizing metabolites in the skin.

Adenosine Triphosphate↗

Causal pathways for incident lower-extremity ulcers in patients with diabetes from two settings.

OBJECTIVE: To determine the frequency and constellations of anatomic, pathophysiologic, and environmental factors involved in the development of incident diabetic foot ulcers in patients with diabetes and no history of foot ulcers from Manchester, U.K., and Seattle, Washington, research settings. RESEARCH DESIGN AND METHODS: The Rothman model of causation was applied to the diabetic foot ulcer condition. The presence of structural deformities, peripheral neuropathy, ischemia, infection, edema, and callus formation was determined for diabetic individuals with incident foot ulcers in Manchester and Seattle. Demographic, health, diabetes, and ulcer data were ascertained for each patient. A multidisciplinary group of foot specialists blinded to patient identity independently reviewed detailed abstracts to determine component and sufficient causes present and contributing to the development of each patient's foot ulcer. A modified Delphi process assisted the group in reaching consensus on component causes for each patient. Estimates of the proportion of ulcers that could be ascribed to each component cause were computed. RESULTS: From among 92 study patients from Manchester and 56 from Seattle, 32 unique causal pathways were identified. A critical triad (neuropathy, minor foot trauma, foot deformity) was present in > 63% of patient's causal pathways to foot ulcers. The components edema and ischemia contributed to the development of 37 and 35% of foot ulcers, respectively. Callus formation was associated with ulcer development in 30% of the pathways. Two unitary causes of ulcer were identified, with trauma and edema accounting for 6 and < 1% of ulcers, respectively. The majority of the lesions were on the plantar toes, forefoot, and midfoot. CONCLUSIONS: The most frequent component causes for lower-extremity ulcers were trauma, neuropathy, and deformity, which were present in a majority of patients. Clinicians are encouraged to use proven strategies to prevent and decrease the impact of modifiable conditions leading to foot ulcers in patients with diabetes.

Adult↗

Lower-extremity amputation in diabetes. The independent effects of peripheral vascular disease, sensory neuropathy, and foot ulcers.

OBJECTIVE: To identify risk factors for lower-extremity amputation (LEA) in individuals with diabetes and to estimate the incidence of LEA. RESEARCH DESIGN AND METHODS: This is a prospective study of 776 U.S. veterans in a general medicine clinic in Seattle, Washington. The outcome was first LEA during follow-up. Potential risk factors evaluated in proportional hazards models included, among others, peripheral vascular disease (PVD), sensory neuropathy, former LEA, foot deformities and ulcers, diabetes duration and treatment, and hyperglycemia. RESULTS: Associated with an increased risk for LEA were PVD defined as transcutaneous oxygen < or = 50 mmHg (relative risk [RR] = 3.0, 95% CI 1.3-7.1), insensitivity to monofilament testing (RR = 2.9, odds ratio = 1.1-7.8), lower-extremity ulcers (RR = 2.5, CI 1.1-5.4), former LEA, and treatment with insulin when controlling for duration of diabetes and other factors in the model. PVD defined as absent or diminished lower-extremity pulses or an ankle arm index < or = 0.8 was also associated with a significantly higher risk of LEA in separate models. Foot ulcers were associated with an increased ipsilateral risk of amputation. The age-adjusted incidence among men only for LEA standardized to the 1991 U.S. male diabetic population was 11.3/1,000 patient-years. CONCLUSIONS: This prospective study shows that peripheral sensory neuropathy, PVD, foot ulcers (particularly if they appear on the same side as the eventual LEA), former amputation, and treatment with insulin are independent risk factors for LEA in patients with diabetes.

Adult↗

A prospective study of risk factors for diabetic foot ulcer. The Seattle Diabetic Foot Study.

OBJECTIVE: Little prospective research exists on risk factors for diabetic foot ulcer that considers the independent effects of multiple potential etiologic agents. We prospectively studied the effects of diabetes characteristics, foot deformity, behavioral factors, and neurovascular function on foot ulcer risk among 749 diabetic veterans with 1,483 lower limbs. RESEARCH DESIGN AND METHODS: Eligible subjects included all diabetic enrollees of a general internal medicine clinic without foot ulcer, of whom 83% agreed to participate. Baseline assessment included history and lower-limb physical examination, tests for sensory and autonomic neuropathy, and measurements of macro- and microvascular perfusion in the foot. Subjects were followed for the occurrence of a full thickness skin defect on the foot that took > 14 days to heal, with a mean follow-up of 3.7 years. RESULTS: Using stepwise Cox regression analysis, the following factors were independently related to foot ulcer risk: foot insensitivity to the 5.07 monofilament (relative risk [95% CI]) 2.2 (1.5-3.1), past history of amputation 2.8 (1.8-4.3) or foot ulcer 1.6 (1.2-2.3), insulin use 1.6 (1.1-2.2), Charcot deformity 3.5 (1.2-9.9), 15 mmHg higher dorsal foot transcutaneous PO2 0.8 (0.7-0.9), 20 kg higher body weight 1.2 (1.1-1.4), 0.3 higher ankle-arm index 0.8 (0.7-1.0), poor vision 1.9 (1.4-2.6), and 13 mmHg orthostatic blood pressure fall 1.2 (1.1-1.5). Higher ulcer risk was associated with hammer/claw toe deformity and history of laser photocoagulation in certain subgroups. Unrelated to foot ulcer risk in multivariate models were diabetes duration and type, race, smoking status, diabetes education, joint mobility, hallux blood pressure, and other foot deformities. CONCLUSIONS: Certain foot deformities, reduced skin oxygenation and foot perfusion, poor vision, greater body mass, and both sensory and autonomic neuropathy independently influence foot ulcer risk, thereby providing support for a multifactorial etiology for diabetic foot ulceration.

Amputation, Surgical↗

Principles of partial foot amputations in the diabetic.

Unfortunately, amputation surgery is still a very important part of the treatment for diabetic foot problems. The decision-making process must be done thoughtfully, remembering that blood flow is not the only issue. Many factors enter into the decision to perform a partial foot amputation or to perform a more proximal level amputation. Adherence to good surgical principle, proven techniques, and gentle soft-tissue handling can make the difference between a successful and durable amputation or continued complications and frustrations.

Amputation, Surgical↗