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Biomedical subjects

B Cunningham

Publications and source records attributed to B Cunningham.

At least 19 recordsLinked to original sources
PubMed2003

Oral vitamin B12 can change our practice.

Oral vitamin B12 can provide an effective alternative to intramuscular injections, so giving patients a choice and reducing costs in primary care. This study investigated the effectiveness, safety, and acceptability of oral vitamin B12 as replacement therapy in patients with vitamin B12 deficiency in a city general practice population. Forty patients previously maintained on vitamin B12 injections were given 1000 micro g of oral cyanocobalamin daily for up to 18 months. All the patients maintained satisfactory serum B12 levels and showed normal haematology and neurology. Compliance and acceptability was excellent. The time for a change in practice has indeed arrived.

Administration, Oral↗
PubMed2001

Aspergillus fumigatus infection in a mega prosthetic total knee arthroplasty: salvage by staged reimplantation with 5-year follow-up.

Fungal infection after total joint arthroplasty is an extremely serious complication and a challenge to the treating physician. When a fungal infection is compounded by a massive allograft or a metallic segmental replacement of the femur or other long bone, treatment options become increasingly limited and commonly have led to arthrodesis or amputation of the infected limb. We present the first case report of a low-grade osteosarcoma treated with a segmental distal femoral allograft prosthetic composite knee arthroplasty, which was complicated by infection with Aspergillus fumigatus. This complication was treated successfully with a staged reimplantation procedure, intravenous amphotericin, and oral fluconazole suppression. At 5 years after reimplantation, the patient has had no evidence of infection, no pain, and excellent range of motion without extensor lag. The Knee Society knee score improved from 50 to 100, and the function score improved from 40 to 100 (for both scores, 100 is the maximum).

Adult↗
PubMed2001

The health burden of breast hypertrophy.

Women seeking consultation for the surgical relief of symptoms associated with breast hypertrophy have been the focus of many studies. In contrast, little is known about those women with breast hypertrophy who do not seek symptomatic relief. The purpose of this study was to describe the health burden of breast hypertrophy by using a set of validated questionnaires and to compare women with breast hypertrophy who seek surgical treatment with those who do not. In addition, this latter group was compared with a group of control women without breast hypertrophy. Women seeking consultation for surgery were recruited from 14 plastic-surgery practices. Control subjects were recruited by advertisements in primary-care offices and newspapers. Women were asked to complete a self-report questionnaire that included the European Quality of Life (EuroQol) questionnaire, McGill Pain Questionnaire, Multidimensional Body Self Relations Questionnaire (MBSRQ), the Short Form-36 (SF-36) questionnaire, and questions regarding breast-related symptoms, comorbidities, and bra size. Descriptive statistics were compiled for three groups of women: (1) hypertrophy patients seeking surgical care, (2) hypertrophy control subjects (those whose reported bra-cup size was a D or larger), and (3) normal control subjects (those whose reported bra-cup size was an A, B, or C). The multiple linear regression method was used to compare the health burdens across groups while adjusting for other variables. Two hundred ninety-one women seeking surgical care and 195 control subjects were enrolled in the study. The 184 control subjects with bra-cup information available were further separated into 88 hypertrophy control subjects and 96 normal control subjects. In the control group, bra-cup size was correlated with health-burden measures, whereas in the surgical candidates, it was not. When scores were compared across the three groups, significant differences were found in all health-burden measures. The surgical candidates scored more poorly on the EuroQol utility, McGill pain rating index, MBSRQ appearance evaluation, physical component scale of the SF-36, and on breast symptoms than did the two control groups. In addition, the hypertrophy control subjects scored more poorly than the normal control subjects. With multiple linear regression analysis incorporating important potential confounders, the poorer scores in the surgical candidates remained statistically significant. It was concluded that breast hypertrophy in those seeking surgical care and those not seeking surgery has a significant impact on women's quality of life as measured by validated and widely used self-report instruments including the EuroQol, MBSRQ, McGill Pain Questionnaire, and the SF-36. Likewise, a new assessment instrument for breast-related symptoms also demonstrated greater symptomatology in women with breast hypertrophy.

Adult↗
PubMed2000

Receptor-selective variants of human vascular endothelial growth factor. Generation and characterization.

Vascular endothelial growth factor (VEGF) is a pleiotropic factor that exerts a multitude of biological effects through its interaction with two receptor tyrosine kinases, fms-like tyrosine kinase (Flt-1) or VEGF receptor 1 and kinase insert domain-containing receptor (KDR) or VEGF receptor 2. Whereas it is commonly accepted that KDR is responsible for the proliferative activities of VEGF, considerable controversy and uncertainty exist about the role of the individual receptors in eliciting many of the other effects. Based on a comprehensive mutational analysis of the receptor-binding site of VEGF, an Flt-1-selective variant was created containing four substitutions from the wild-type protein. This variant bound with wild-type affinity to Flt-1, was at least 470-fold reduced in binding to KDR, and had no activity in cell-based assays measuring autophosphorylation of KDR or proliferation of primary human vascular endothelial cells. Using a competitive phage display strategy, two KDR-selective variants were discovered with three and four changes from wild-type, respectively. Both variants had approximately wild-type affinity for KDR, were about 2000-fold reduced in binding to Flt-1, and showed activity comparable with the wild-type protein in KDR autophosphorylation and endothelial cell proliferation assays. These variants will serve as useful reagents in elucidating the roles of Flt-1 and KDR.

Endothelial Growth Factors↗
PubMed2000

The effect of kyphosis on the mechanical strength of a long-segment posterior construct using a synthetic model.

STUDY DESIGN: This experimental study used synthetic spine models to compare the effect of the angle of kyphosis, rod diameter, and hook number on the biomechanical stiffness of a long-segment posterior spinal construct. OBJECTIVE: To examine the biomechanical effects of incremental kyphosis on variously instrumented long-segment posterior spinal constructs. SUMMARY OF BACKGROUND DATA: Euler's formula for loading of curved long columns would suggest that kyphosis has a profound impact on the biomechanical behavior of long-segment posterior spinal constructs. The effects of sagittal contour on the mechanical properties of long-segment posterior spinal constructs have not been well documented. METHODS: Kyphotic and straight synthetic spine models were used to test long-segment posterior instrumentation constructs biomechanically while varying rod diameter and the number of hook sites. The synthetic spines, composed of polypropylene vertebral blocks and isoprene elastomer intervertebral spacers, were fabricated with either 0 degrees, 27 degrees, or 53 degrees of sagittal contour. The models were instrumented with 5.5- or 6.35-mm titanium rods, and with either 8 or 12 hooks. The models were loaded from 0 to 300 N in a cyclical ramp fashion using an MTS 858 Bionix testing device testing device. Construct stiffness (force and displacement) during axial compression was determined. RESULTS: Straight model: Changing the hook number from 8 to 12 caused a 32% increase in construct stiffness with the 5.5-mm rod. Changing the rod diameter from 5.5 to 6.35 mm caused a 36% increase in construct stiffness with the 8-hook pattern. Changing both the rods and hooks caused the stiffness to increase 44%. 27 degrees MODEL: Changing the hook number from 8 to 12 caused a 20% increase in construct stiffness with the 6.5-mm rod. Changing the rod diameter from 5.5 to 6.35 mm caused a 29% increase in construct stiffness with the 12-hook pattern. Changing both the rods and hooks caused the construct stiffness to increase 26%. 53 degrees MODEL: Changing the hook number from 8 to 12 caused a 14% increase in construct stiffness with the 6.35-mm rod. Changing the rod diameter from 5.5 to 6.35 mm caused a 17% (P<0.0005) increase in construct stiffness with the 12-hookpattern. Changing both rods and hooks caused the stiffness to increase 21%. Summary data on angular kyphosis: Using the same rod diameter and the same number of hooks, and progressing from a straight alignment to 27 degrees of sagittal contour decreased construct stiffness 32%. Going from straight alignment to 53 degrees decreased the stiffness 59.6%. All reported values were statistically significant (P < 0.0005). CONCLUSIONS: The biomechanical stiffness of the straight spine was sensitive to both an increase in hook fixation sites and an increase in rod diameter. The kyphotic spines, however, were more sensitive to variations in rod diameter. Although with increasing kyphosis, the optimum instrumentation strategy will maximize both rod diameter and the number of hook sites, instrumented kyphotic spines remain biomechanically "disadvantaged" as compared with nonkyphotic instrumented spines.

Bone Nails↗
PubMed2000

Silicon micromachining to tissue engineer branched vascular channels for liver fabrication.

To date, many approaches to engineering new tissue have emerged and they have all relied on vascularization from the host to provide permanent engraftment and mass transfer of oxygen and nutrients. Although this approach has been useful in many tissues, it has not been as successful in thick, complex tissues, particularly those comprising the large vital organs such as the liver, kidney, and heart. In this study, we report preliminary results using micromachining technologies on silicon and Pyrex surfaces to generate complete vascular systems that may be integrated with engineered tissue before implantation. Using standard photolithography techniques, trench patterns reminiscent of branched architecture of vascular and capillary networks were etched onto silicon and Pyrex surfaces to serve as templates. Hepatocytes and endothelial cells were cultured and subsequently lifted as single-cell monolayers from these two-dimensional molds. Both cell types were viable and proliferative on these surfaces. In addition, hepatocytes maintained albumin production. The lifted monolayers were then folded into compact three-dimensional tissues. Thus, with the use microfabrication technology in tissue engineering, it now seems feasible to consider lifting endothelial cells as branched vascular networks from two-dimensional templates that may ultimately be combined with layers of parenchymal tissue, such as hepatocytes, to form three-dimensional conformations of living vascularized tissue for implantation.

Animals↗
PubMed1999

Lack of long-term effects of in utero exposure to zidovudine among uninfected children born to HIV-infected women. Pediatric AIDS Clinical Trials Group Protocol 219/076 Teams.

CONTEXT: With the success of zidovudine chemoprophylaxis for prevention of perinatal transmission of the human immunodeficiency virus (HIV), an increasing number of HIV-exposed but uninfected children will have in utero exposure to zidovudine and other antiretroviral drugs. OBJECTIVE: To evaluate the long-term effects of in utero exposure to zidovudine vs placebo among a randomized cohort of uninfected children. DESIGN: Prospective cohort study based on data collected during Pediatric AIDS Clinical Trials Group Protocol 076, a perinatal zidovudine HIV prevention trial, and Protocol 219, a long-term observational protocol. SETTING: Pediatric research clinics in the United States. PATIENTS: Two hundred thirty-four uninfected children born to 230 HIV-infected women enrolled in Protocol 076 and followed up through February 28, 1997, in Protocol 219 (122 in the zidovudine group and 112 in the placebo group). MAIN OUTCOME MEASURES: Physical growth measurements, immunologic parameters, cognitive/developmental function, occurrence of neoplasms, and mortality data assessed every 6 months for children younger than 24 months and yearly thereafter or as clinically indicated. Baseline echocardiogram and funduscopic evaluations were collected before 36 months of age. RESULTS: Median age of children at time of last follow-up visit was 4.2 years (range, 3.2-5.6 years). There were no significant differences between children exposed to zidovudine and those who received placebo in terms of sequential data on lymphocyte subsets; weight, height, and head circumference z scores; and cognitive/developmental function. No deaths or malignancies occurred. Two children (both exposed to zidovudine) are being followed up for abnormal, unexplained ophthalmic findings. One child exposed to zidovudine had a mild cardiomyopathy on echocardiogram at the age of 48 months; the child is clinically asymptomatic. CONCLUSIONS: No adverse effects were observed in HIV-uninfected children with in utero and neonatal exposure to zidovudine followed up for as long as 5.6 years. Continued prospective evaluations of children born to HIV-infected women who are exposed to antiretroviral or immunotherapeutic agents are critical to assess the long-term safety of interventions that prevent perinatal HIV transmission.

Anti-HIV Agents↗
PubMed1999

8-methyl-pyridoxatin: A novel N-hydroxy pyridone from fungus OS-F61800 that induces erythropoietin in human cells.

In the course of screening for small-molecule modulators of erythropoietin gene expression, a novel N-hydroxy pyridone was isolated from a culture of OS-F61800. Its structure was elucidated by extensive 1H and 13C NMR spectroscopic and chemical studies. This compound induced erythropoietin gene expression fivefold at a concentration of 0.3 microM, which is about threefold greater potency than our previously identified erythropoietin inducers.

Cell Line↗
PubMed1999

The concentrations of clinafloxacin in alveolar macrophages, epithelial lining fluid, bronchial mucosa and serum after administration of single 200 mg oral doses to patients undergoing fibre-optic bronchoscopy.

The concentrations of clinafloxacin were measured in serum, bronchial mucosa, alveolar macrophages and epithelial lining fluid after single 200 mg oral doses of clinafloxacin had been administered to 15 subjects who were undergoing bronchoscopy. Concentrations were measured using a microbiological assay method. Mean concentrations in serum, bronchial mucosa, alveolar macrophages and epithelial lining fluid at a mean of 1.27 h post-dose were 1.54, 2.65, 15.60 and 2.71 mg/L respectively. These site concentrations exceeded the MIC90 for common respiratory pathogens and indicate that clinafloxacin is likely to be effective in the treatment of a wide range of respiratory tract infections.

Administration, Oral↗
PubMed1998

Epolones: novel sesquiterpene-tropolones from fungus OS-F69284 that induce erythropoietin in human cells.

In the course of our screening for small molecule modulators of erythropoietin gene expression, two novel sesquiterpene tropolones and pycnidone were isolated from a culture of OS-F69284 (ATCC 74390). Their structures were elucidated by extensive 1H and 13C NMR spectroscopic studies and chemical reactions. These compounds induced erythropoietin gene expression 5-fold at a concentration of 1-1.6 microM.

Carbohydrate Sequence↗
PubMed1998

Requirements for binding and signaling of the kinase domain receptor for vascular endothelial growth factor.

Vascular endothelial growth factor (VEGF) is a dimeric hormone that controls much of vascular development through binding and activation of its kinase domain receptor (KDR). We produced analogs of VEGF that show it has two receptor-binding sites which are located near the poles of the dimer and straddle the interface between subunits. Deletion experiments in KDR indicate that of the seven IgG-like domains in the extracellular domain, only domains 2-3 are needed for tight binding of VEGF. Monomeric forms of the extracellular domain of KDR bind approximately 100 times weaker than dimeric forms showing a strong avidity component for binding of VEGF to predimerized forms of the receptor. Based upon these structure-function studies and a mechanism in which receptor dimerization is critical for signaling, we constructed a receptor antagonist in the form of a heterodimer of VEGF that contained one functional and one non-functional site. These studies establish a functional foundation for the design of VEGF analogs, mimics, and antagonists.

Dimerization↗
PubMed1997

A biomechanical study of the flexor digitorum superficialis: effects of digital pulley excision and loss of the flexor digitorum profundus.

Many reports have been devoted to characterizing the significance of the pulleys for the flexor digitorum profundus (FDP). However, no comparable work has been published on the flexor digitorum superficialis (FDS). This study characterized the FDS in a human cadaver model. Eleven fresh-frozen cadaver hands were used. By using a tensiometer, data were gathered for tendon excursion, tendon load, and work of flexion. Changes in efficiency were caused by excision of annular pulleys A1, A2, A3, and the palmar aponeurotic pulley. We also measured the effect of FDP excision on FDS efficiency. Sectioning of the A2 and A3 pulleys together caused statistically significant losses of efficiency in all three parameters (work, load, and excursion). When the FDP was removed from a finger with an intact pulley system, losses in both work and excursion efficiencies were significant. Removing the FDP while cutting different pulleys caused significant decrease in FDS excursion efficiency. We conclude that A2 and A3 are the most important pulleys for maintaining normal FDS function, and that the presence of the FDP in the digital sheath is essential for optimal FDS excursion efficiency.

Biomechanical Phenomena↗
PubMed1997

Concentrations of trovafloxacin in bronchial mucosa, epithelial lining fluid, alveolar macrophages and serum after administration of single or multiple oral doses to patients undergoing fibre-optic bronchoscopy.

Concentrations of trovafloxacin were measured in serum, alveolar macrophages, epithelial lining fluid and bronchial mucosa following single and multiple oral doses. Concentrations were determined using a microbiological assay method. There were 18 subjects in the single dose and nine subjects in the multiple dose groups. After single dosing, mean concentrations in serum, alveolar macrophages, epithelial lining fluid and bronchial mucosa at 6, 12 and 24 h were as follows: 6 h, 1.41 mg/L, 19.06 mg/L, 3.01 mg/L and 1.52 mg/kg; 12 h, 0.85 mg/L, 16.22 mg/L, 4.8 mg/L and 1.01 mg/kg; 24 h, 0.37 mg/L, 10.23 mg/L, 0.93 mg/L, and no measurable concentration, respectively. After multiple dosing (approximately 6 h post-dose) the corresponding concentrations were 1.47 mg/L, 34.3 mg/L, 10.21 mg/L and 1.67 mg/kg, respectively. These concentrations exceed the MIC90s for the common respiratory pathogens, Haemophilus influenzae 0.06 mg/L, Moraxella catarrhalis 0.008 mg/L and Streptococcus pneumoniae 0.12 mg/L and suggest that trovafloxacin should be efficacious in the treatment of community- and hospital-acquired respiratory infections.

Administration, Oral↗
PubMed1997

Concentrations of levofloxacin (HR 355) in the respiratory tract following a single oral dose in patients undergoing fibre-optic bronchoscopy.

Concentrations of levofloxacin were measured in bronchial biopsies, alveolar macrophages (AM), epithelial lining fluid (ELF) and serum following a single oral dose. Concentrations were measured by a microbiological assay method. A total of 35 patients undergoing fibre-optic bronchoscopy were studied. Mean serum, AM, ELF and biopsy concentrations were as follows. 0.5 h: 4.73 mg/L, 19.1 mg/L, 4.74 mg/L and 4.3 mg/kg; 1 h: 6.6 mg/L, 32.5 mg/L, 10.8 mg/L and 8.3 mg/kg; 2 h: 4.9 mg/L, 41.9 mg/L, 9.0 mg/L and 6.5 mg/kg; 4 h: 4.1 mg/L, 27.7 mg/L, 10.9 mg/L and 6.0 mg/kg; and 6-8 h: 4.0 mg/L, 38.4 mg/L, 9.6 mg/L and 4.0 mg/kg respectively. Mean serum and AM concentrations at 12-24 h were 1.2 and 13.9 mg/L respectively (concentrations in biopsy and ELF were only measurable in three of the six patients). These concentrations exceed the MIC90s of the common respiratory pathogens, Haemophilus influenzae (0.015 mg/L), Moraxella catarrhalis (0.06 mg/L) and Streptococcus pneumoniae (1 mg/L) and suggest that levofloxacin should be efficacious in the treatment of community- and hospital-acquired respiratory infection.

Administration, Oral↗
PubMed1997

The Bentham Unit: a pilot remand and assessment service for male mentally disordered remand prisoners. II: Report of an independent evaluation.

BACKGROUND: Findings are presented from an evaluation of a pilot remand and assessment service--the Bentham Unit. The aims of the Bentham Unit are to provide rapid assessment, identify mentally disordered remand prisoners, and speed their transfer from prison to NHS care, where a need is indicated. METHOD: The number, rate and speed of referral, assessment and transfer to NHS care of offenders remanded to Wormwood Scrubs prison during periods before and after the Bentham Unit opened were compared. RESULTS: The service attracted a large volume of referrals. Between the two periods, significant increases in the numbers of referrals and hospital disposals, and major reductions in the interval between reception on remand into the prison, NHS assessment and transfer to NHS care, were observed. CONCLUSIONS: The aims of the unit were met. Implications for service configurations are discussed.

England↗
PubMed1997

Ruptured or intact: what can linear echoes within silicone breast implants tell us?

OBJECTIVE: During sonographic evaluation of silicone breast implants for possible rupture, we have frequently encountered several patterns of linear echoes within the implants. To our knowledge, the significance of this finding has not been established in the literature. The purpose of this study was to determine whether internal echoes are significant in predicting implant rupture. SUBJECTS AND METHODS: Thirty-three patients with 64 silicone implants were prospectively entered into a study that included gray-scale sonography of the implants and subsequent surgical removal. Echo patterns within the implants were retrospectively evaluated on hard-copy films and compared with the integrity of the implant at surgery. RESULTS: Three categories of internal echo patterns were identified: "thick linear echoes." "thin linear echoes," and "commas." One or more of these echo patterns were seen in 57 (89%) of the 64 implants. Thick linear echoes were seen in 23 (36%) of the 64 implants, thin linear echoes were seen in 33 (52%) of the 64 implants, and commas were seen in 47 (73%) of the 64 implants. All echo patterns were seen in intact and ruptured implants with nearly equal frequency. We found no statistical significance for any echo pattern in predicting whether an implant was ruptured or intact. Of the 64 implants, four were entirely free of internal echoes. All four implants were intact. CONCLUSION: A variety of linear echoes can be seen in most silicone breast implants on gray-scale sonography. The presence or absence of linear echoes is not useful in predicting implant rupture. Complete absence of internal echoes, while highly predictive of an intact implant, is infrequently seen.

Adult↗
PubMed1997

Oxygen protocols for the prevention of hypoxemia. A review for case managers.

Case managers are challenged by the need to ensure quality care for patients in the face of increasing demands on the health care system to provide more economic care. These economic pressures often cause hospitalized patients to be transferred from critical care areas earlier than in years past. As a result, hypoxemia-inadequate oxygenation of the blood-is emerging as a serious patient safety problem in noncritical care areas of the hospital. The medical literature recently has begun to document hypoxemia in some patient groups on the general care floor, where continuous monitoring of patients' respiratory status usually is no longer employed. The serious health consequences of hypoxemia, the fact that it can affect nearly any hospitalized patient, and the potentially high cost of treating hypoxemia-related morbidity are drawing the attention of the medical community. Case managers are in a position to address this emerging problem by working with hospitals and health care institutions to identify at-risk patients and develop strategies to improve both clinical and financial outcomes. Patient care protocols are one effective strategy to standardize monitoring of patients deemed to be at risk. Early detection and treatment of hypoxemia have the potential to improve patient care while significantly reducing medical costs.

Case Management↗