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Biomedical subjects

R R Brown

Publications and source records attributed to R R Brown.

At least 19 recordsLinked to original sources
PubMed2006

Implementation impediments to institutionalising the practice of sustainable urban water management.

It is now well accepted that there are significant challenges to realising the widespread and self-sustaining implementation of sustainable urban water management. It is argued that these challenges are entrenched within the broader socio-political framework, yet often unsuccessfully addressed within the more narrow scope of improving technical knowledge and design capacity. This hypothesis is investigated through a comparative analysis of three independent research projects investigating different dimensions of the water cycle, including stormwater management in Australia and sanitary waste management and implementation of innovative technologies in the U.K. The analysis reveals significant and common socio-political impediments to improved practice. It was evident that the administrative regime, including implementing professionals and institutions, appears to be largely driven by an implicit expectation that there is a technical solution to solve water management issues. This is in contrast to addressing the issues through broader strategies such as political leadership, institutional reform and social change. It is recognised that this technocratic culture is inadvertently underpinned by the need to demonstrate implementation success within short-term political cycles that conflict with both urban renewal and ecological cycles. Addressing this dilemma demands dedicated socio-technical research programs to enable the much needed shift towards a more sustainable regime.

Cities↗
PubMed2004

A case-control study of erectile dysfunction among men diagnosed with panic disorder.

The association between panic disorder and erectile dysfunction (ED) among men was examined in the Integrated Healthcare Information Services National Managed Care Benchmark Database (IHCIS). The IHCIS is a fully de-identified, HIPAA compliant database and includes complete medical history for more than 17 million managed care lives; data from more than 30 US health plans, covering seven census regions; and patient demographics, including morbidity, age and gender. A total of 60,949 ED cases and 243,796 controls were included for analysis. Unconditional logistic regression analyses were first performed to assess the crude risk of ED, and adjusted risks of ED that accounted for comorbid conditions and comedications. A second set of analyses measured the crude and adjusted risks after restricting the patient population to men who were diagnosed with panic disorder at least 1 month prior to an ED diagnosis. In the first set of analyses, men with panic disorder were observed to have more than a two-fold increase in risk for ED (OR=2.29, 95% CI=2.03, 2.58). After adjusting for comorbid conditions, a 52% increase in risk of ED was observed (OR=1.52, 95% CI=1.34, 1.72). Following subsequent adjustment for comorbidities and comedications, a 33% increased risk of ED was detected (OR=1.33, 95% CI=1.17, 1.51). In the second set of analyses studying panic disorder that preceded ED, only a 13% higher risk was noted (OR=1.13, 95% CI=0.97, 1.31). However, after adjusting for comorbid conditions, a 25% reduction in risk was observed (OR=0.75, 95% CI=0.64, 0.88). A 35% risk reduction was seen after adjusting for comorbidities and comedications (OR=0.65, 95% CI=0.56, 0.77).

Adult↗
PubMed2003

Antihypertensive treatment and erectile dysfunction in a cohort of type II diabetes patients.

The association between different antihypertensive drugs and erectile dysfunction (ED) was examined in a cohort of type II diabetes patients identified in the UK General Practice Research Database (GPRD). The GPRD contains details of diagnoses, prescribing, investigations, risk factors, outcomes, and hospital referrals, together with basic demographic information for approximately six million patients from more than 450 representative general practices throughout the UK. A total of 634 cases and 2526 controls were included for analysis. Unconditional logistic regression analysis was performed to assess the risk of ED after adjusting for age at diabetes diagnosis date, cigarette smoking, depression, glycemic control, use of HMG-CoA reductase inhibitors, use of histamine receptor antagonists, use of digitalis medicines, and use of nitrates. Increased risk of ED was observed among patients taking the following antihypertensives: ACE inhibitors (OR=1.47, 95% CI=1.21, 1.80) and alpha blockers (OR=1.54, 95% CI=1.11, 2.12). However, we identified a nearly 30% reduction in risk among patients on diuretics (OR=0.73, 95% CI=0.54, 0.99). No statistically significant increase in risk was observed among users of beta blockers and calcium channel blockers (OR=1.05, 95% CI=0.85, 1.31) and (OR=1.14, 95% CI=0.91, 1.43), respectively. The results of this study confirm the strong and recognized effect of comorbidities in a diabetic population, but also require additional experimental and observational studies to further understand the potential benefit of diuretics and other ED treatments such as PDE5 inhibitors.

Adrenergic alpha-Antagonists↗
PubMed2001

The C sign: more specific for flatfoot deformity than subtalar coalition.

OBJECTIVE: To assess the sensitivity and specificity of the C sign, a C-shaped line created by the outline of the talar dome and the inferior margin of the sustentaculum tali on lateral ankle radiographs, for patients with both flatfoot deformity and specifically talocalcaneal (TC) coalition. DESIGN AND PATIENTS: All patients in this retrospective study were under 35 years of age and had a lateral ankle radiograph and follow-up CT scan for a non-traumatic indication. Forty-eight cases over the past 5 years fulfilled these criteria. Two masked musculoskeletal radiologists determined the presence or absence of the C sign for each lateral radiograph by consensus. Each CT study was then assessed by a third musculoskeletal radiologist for the presence of tarsal coalition. Observations were correlated with clinical history regarding presence or absence of flatfoot deformity. RESULTS: Ten cases of TC coalition were diagnosed, four of which demonstrated a C sign (40%). Eight cases with a C sign were encountered, four of which had TC coalition (50%) and four did not. All patients with a positive C sign had a flatfoot clinically (100%), while only eight of 24 flatfooted patients had a C sign (33%). CONCLUSION: The C sign is specific, but not sensitive, for flatfoot deformity, and is neither sensitive nor specific for subtalar coalition.

Adolescent↗
PubMed2001

Single-dose gabapentin pharmacokinetics and safety in healthy infants and children.

Gabapentin (Neurontin) is a gamma-aminobutyric acid analogue indicated in adults for adjunctive treatment of partial seizures with or without secondary generalization. Two studies were conducted to determine the single-dose pharmacokinetics of gabapentin in healthy subjects age 1 month to 12 years and to guide dose selection in safety and efficacy trials in pediatric patients. Forty-eight subjects were given single oral doses of gabapentin (10 mg/kg) while fasting. Enrollment was homogeneously distributed throughout the age range. Plasma samples were drawn predose and then serially for 24 hours postdose. Single doses of gabapentin were well tolerated by healthy pediatric subjects. Plots of pharmacokinetic parameters versus age suggested significant differences between younger (1 month to < 5 years) and older (> or =5 to 12 years) subjects. Mean area under the plasma concentration-time curve from zero to infinity (AUC(0-infinity)) was 25.6 microg x h/mL in younger subjects and 36.0 microg x h/mL in older subjects (p < 0.001). Corresponding mean peak plasma concentrations (Cmax) were 3.74 and 4.52 microg/ml (p < 0.05). Oral clearance (normalized for body weight) was 7.40 and 4.41 mL/min/kg in younger subjects and older subjects, respectively (p < 0.001). It was concluded that children between 1 month and < 5 years of age require approximately 30% higher daily doses of gabapentin than those > or =5 to 12 years of age.

Acetates↗
PubMed2001

MR imaging of exercise-induced lower leg pain.

MR imaging of the lower leg is frequently performed to evaluate the active patient who presents with an exercise-induced injury. This article discusses both common and obscure osseous and soft tissue conditions that are seen in the athletic population with leg pain.

Athletic Injuries↗
PubMed2000

Flt3-ligand induces transient tumor regression in an ectopic treatment model of major histocompatibility complex-negative prostate cancer.

We assessed the in vivo efficacy of Flt3-ligand (Flt3-L) treatment in C57BL/6 mice bearing a well-established MHC class I-negative prostate carcinoma TRAMP-C1. Flt3-L immunotherapy was initiated approximately 30 days after tumor inoculation, a time when > or =80% of the mice had palpable TRAMP-C1 tumors. Treatment with Flt3-L at 10 microg/day for 21 consecutive days suppressed TRAMP-C1 tumor growth and induced tumor stabilization (P = 0.0337). Enhanced tumor regression was demonstrated at a higher dose of 30 microg/day (P < 0.0001). Tumors excised from mice treated with Flt3-L were smaller than carrier-treated controls and contained a more pronounced mixed inflammatory cell infiltrate primarily composed of mphi. In regressor nice, tumors reappeared at the site of injection when Flt3-L therapy was terminated. When the experiment was repeated with MHC class I-positive TRAMP-C1 cells, tumor stabilization and/or regression was again observed after treatment (P < 0.0001); however, once again, tumors reappeared after the termination of therapy despite an extended treatment schedule (35 days). MHC class I-negative variants were present in tumors isolated from carrier- and Flt3-L-treated mice, and this phenotype could be reversed by IFN-gamma treatment in vitro. Thus, Flt3-L treatment of mice with preexisting transplantable prostate tumors results in tumor regression that is dose-dependent and accompanied by a pronounced mixed-cell inflammatory tumor infiltrate. However, disease relapse was invariably observed after the termination of therapy, which suggests that Flt3-L treatment of advanced MHC- prostate cancers will require adjuvant modalities to achieve a durable response.

Animals↗
PubMed2000

Melorheostosis: case report with radiologic-pathologic correlation.

Melorheostosis is an unusual mesenchymal dysplasia, which commonly presents on radiographs as longitudinal bars of hyperostosis in osseous structures. We present a case of melorheostosis in the lower extremity of a 20-year-old woman for which detailed radiologic- pathologic correlation was achieved due to amputation of the involved limb.

Acetabulum↗
PubMed2000

A new classification for cervical vertebral injuries: influence of CT.

OBJECTIVE: Computed tomography (CT) has been demonstrated to be superior to radiography in identifying cervical vertebral injuries. However, many of these injuries may not be clinically significant, and require only minimal symptomatic and supportive treatment. It is therefore imperative that radiologists and spine surgeons have criteria for distinguishing between those injuries requiring surgical stabilization and those that do not. The authors propose a new classification of cervical vertebral injuries into two categories: major and minor. DESIGN AND PATIENTS: A data base, acquired on 1052 separate cervical injuries in 879 patients seen between 1983 and 1998, was reviewed. Four categories of injury based on mechanism [hyperflexion (four variants), hyperextension (two variants), rotary (two variants), and axial compression (five variants)] were identified. "Major" injuries are defined as having either radiographic or CT evidence of instability with or without associated localized or central neurologic findings, or have the potential to produce the latter. "Minor" injuries have no radiographic and/or CT evidence of instability, are not associated with neurologic findings, and have no potential to cause the latter. RESULTS AND CONCLUSIONS: Cervical injury should be classified as "major" if the following radiographic and/or CT criteria are present: displacement of more than 2 mm in any plane, wide vertebral body in any plane, wide interspinous/interlaminar space, wide facet joints, disrupted posterior vertebral body line, wide disc space, vertebral burst, locked or perched facets (unilateral or bilateral), "hanged man" fracture of C2, dens fracture, and type III occipital condyle fracture. All other types of fractures may be considered "minor".

Cervical Vertebrae↗
PubMed2000

Allometric pharmacokinetic scaling: towards the prediction of human oral pharmacokinetics.

PURPOSE: To evaluate (1) allometric scaling of systemic clearance (CL) using unbound drug concentration, (2) the potential usage of brain weight (BRW) correction in allometric scaling of both CL and oral clearance (CL/F). METHODS: Human clearance was predicted allometrically (CLu = a x W(biv)) using unbound plasma concentration for eight Parke-Davis compounds and 29 drugs from literature sources. When the exponent b(iv) was higher than 0.85, BRW was incorporated into the allometric relationship (CLu*BRW = a x W(biv)). This approach was also applied to the prediction of CLu/F for 10 Parke-Davis compounds. Human oral t1/2, Cmax, AUC, and bioavailability were estimated based on allometrically predicted pharmacokinetic (PK) parameters. RESULTS: Human CL and CL/F were more accurately estimated using unbound drug concentration and the prediction was further improved when BRW was incorporated into the allometric relationship. For Parke-Davis compounds, the predicted human CL and CL/F were within 50-200% and 50-220% of the actual values, respectively. The estimated human oral t1/2, Cmax, and AUC were within 82-220%, 56-240%, and 73-190% of the actual values for all 7 compounds, suggesting that human oral PK parameters of those drugs could be reasonably predicted from animal data. CONCLUSIONS: Results from the retrospective analysis indicate that allometric scaling of free concentration could be applied to orally administered drugs to gain knowledge of drug disposition in man, and to help decision-making at early stages of drug development.

Area Under Curve↗
PubMed2000

Traumatic musculotendinous injuries of the knee: diagnosis with MR imaging.

Magnetic resonance (MR) imaging is the imaging modality of choice for evaluation of acute traumatic musculotendinous injuries of the knee. Three discrete categories of acute injuries to the musculotendinous unit can be defined: muscle contusion, myotendinous strain, and tendon avulsion. Among the quadriceps muscles, the rectus femoris is the most susceptible to injury at the myotendinous junction due to its superficial location, predominance of type II fibers, eccentric muscle action, and extension across two joints. Among the muscles of the pes anserinus, the sartorius is the most susceptible to strain injury due to its superficial location and biarticular course. The classic fusiform configuration of the semimembranosus along with a propensity for eccentric actions also make it prone to strain injury. MR imaging findings associated with rupture of the iliotibial tract include discontinuity and edema, which are best noted on coronal images. The same mechanism of injury that tears the arcuate ligament from its fibular insertion can also result in avulsion injury of the biceps femoris. The gastrocnemius muscle is prone to strain injury due to its action across two joints and its superficial location. Injuries of the muscle belly and myotendinous junction of the popliteus are far more common than tendinous injuries.

Contusions↗
PubMed2000

Is a mixture of gadolinium and iodinated contrast material safe during MR arthrography?

OBJECTIVE: This study was designed to determine whether a mixture of iodinated contrast material and gadopentetate dimeglumine used during MR arthrography yields free gadolinium ion, a systemically toxic metal. MATERIALS AND METHODS: Mixtures of commercially available nonionic and ionic iodinated contrast agent, gadopentetate dimeglumine, lidocaine, and epinephrine were analyzed using a spectrophotometric titration with a gadolinium ion titrant and methyl thymol blue indicator. RESULTS: We found no significant dissociation of gadolinium ion when gadopentetate dimeglumine was mixed with iodinated contrast agents, lidocaine, or epinephrine in any of the dilutions tested. CONCLUSION: Gadopentetate dimeglumine and iodinated contrast material can be mixed before MR imaging without any release of free gadolinium and are therefore safe for confirming the intraarticular placement of contrast material before MR arthrography.

Arthrography↗
PubMed1999

Vitamin effects on tryptophan-niacin metabolism in primary hepatoma patients.

Metabolism of 14C-labeled tryptophan and 3-hydroxyanthranilic acid were administered to early hepatoma patients to evaluate the conversion of these precursors to niacin metabolites and to assess the effect of dietary supplementation with vitamin B-6, riboflavin, thiamin and vitamin C on the extent of conversion. Expired labeled carbon dioxide and urinary excretion of picolinic acid (PA), quinolinic acid (QA), nicotinic acid (NA), N1-methylnicotinamide (N1MeNAm) and N1-methyl-2-pyridone-5-carboxamide (MPCA) were measured by carrier isolations. There were no consistent statistical differences in these conversions before and after vitamin supplementation, suggesting that the patients' nutrition was adequate and that none of the vitamins were rate-limiting under these conditions.

3-Hydroxyanthranilic Acid↗
PubMed1999

Evaluation of the postoperative meniscus of the knee: a study comparing conventional arthrography, conventional MR imaging, MR arthrography with iodinated contrast material, and MR arthrography with gadolinium-based contrast material.

OBJECTIVE: To compare four imaging methods in the evaluation of the postoperative meniscus: conventional arthrography, conventional MR imaging, MR arthrography with iodinated contrast material, and MR arthrography with gadolinium-based contrast material. DESIGN AND PATIENTS: Thirty-three patients referred for knee MR examinations with a history of meniscal surgery were studied prospectively. At the first patient visit, conventional MR examination was followed by an MR arthrogram with gadolinium-based contrast material. At the second visit, a conventional arthrogram with iodinated contrast material was followed immediately by an MR examination. Imaging examinations were interpreted by a masked reader, and then compared with the results of repeat arthroscopic surgery in 12 patients. RESULTS: The correct evaluation of the status of postoperative menisci was allowed in 12 of 13 patients (92%) by MR arthrography using gadolinium-based contrast agent, 10 of 13 patients (77%) by conventional MR examination, 9 of 12 patients (75%) by MR arthrography, and 7 of 12 patients (58%) by conventional arthrography. CONCLUSION: Intra-articular fluid is advantageous in the evaluation of patients with a suspected meniscal retear. MR arthrography with gadolinium-based contrast material is the most accurate imaging method for the diagnosis of meniscal retears.

Adult↗
PubMed1998

Purified streptococcal cell wall (PG-APS) causes experimental otitis media.

Purified peptidoglycan-polysaccharide from Group A Streptococcus pyogenes cell wall (PG-APS) was prepared under sterile, pyrogen-free conditions and injected percutaneously into the middle ear cavities (MEC) of groups of gerbils. Each group was observed otoscopically at 1, 2, 5, 7, 9, 12 and 14 days. Histologic specimens were obtained from each group at 2, 5, 7, 9 and 14 days. Histologically, PG-APS produced mild, acute inflammation during the first 3 days and mild to moderate inflammation with features of both acute and chronic pathology from days 5 through 9. An early response by plasma cells and macrophages was seen. Most animals had recovered with minor sequelae by day 14. Challenge intraperitoneally with 20 micrograms of PG-APS at 14 days following MEC injection of PG-APS did not exacerbate the middle ear inflammation. Five chinchillas, tested for comparison, responded similarly to PG-APS.

Administration, Cutaneous↗