Biomedical subjects
Publications and source records attributed to J T Brown.
A 17-year-old adolescent girl presented with tenosynovitis of the peroneal tendons following diagnosis and treatment of an endocervical gonococcal infection. The need for careful history in any sexually active adolescent is emphasized. Acute peroneal tenosynovitis, although not previously cited in the literature, can occur and should be suspected.
The widespread acceptance of photodynamic therapy (PDT), a potential adjuvant brain tumor therapy under clinical evaluation since 1980, has been partially restrained by its potential toxicity toward normal brain tissue. This study examined PDT-produced injury of normal rat brain as a function of photosensitizer dose. Brain injury was characterized by correlating measurements of the area of cerebral edema using T2-weighted magnetic resonance images, measurement of brain water content at the lesion site, microscopic examination of histological sections through the PDT lesion, and by evaluation of the area of blood brain barrier (BBB) disruption using computerized morphometric analysis of the region of Evans blue (EB) dye-labelled albumin extravasation. Monochromatic red light (630 nm) was delivered intracerebrally using a 5-mm-long cylindrical, diffusion-tip optical fiber at a constant energy dose of 15 joules. A Photofrin dose of 2 mg/kg of body weight produced a transient breakdown in the blood brain barrier around the site of the implanted optical fiber demonstrated by magnetic resonance imaging (MRI), extravasation of EB dye and pallor on hematoxylin and eosin-stained microscopic tissue sections. A much larger area of BBB disruption was seen at a dose of 4 mg/kg of Photofrin, and this drug dose resulted in significant permanent brain injury. In this model, a Photofrin dose of 4 mg/kg body weight is not tolerated by the normal brain.
Photofrin (a polyporphyrin mixture) distribution in a rat glioma model was studied in relation to changes in the blood brain barrier (BBB). At selected intervals after intraperitoneal injection of Photofrin, the concentration of polyporphyrins (PP) and Evans Blue Dye, an indicator of BBB permeability, were determined for tumor, brain adjacent to tumor (BAT), and normal brain tissue. Contrary to earlier reports of maximal accumulation at 4-24 hours, tumor levels of PP increased throughout the 96 hour measurement period. During the early stages of tumor development, PP uptake by tumor appeared to be less correlated to BBB disruption. We conclude that passive diffusion through an incompetent BBB does not completely explain PP accumulation in tumor tissue.
The effect on normal brain of continuous interstitial laser irradiation at 630 nm through an implanted cylindrical-shape, diffusion-tipped optical fiber was studied in the rat. Brain water content in the laser irradiation area (LIA) and Evans blue (EB) dye content in selected areas of the brain were measured for different laser power outputs from 0 to 250 mW after 5 minutes of photoradiation. The degree and nature of tissue damage was examined histologically and correlated with the laser power level. There is significant brain damage, blood brain barrier (BBB) disruption, and brain edema in LIA for laser power outputs in excess of 100 mW from the diffusion tip (p less than 0.001). Brain edema in the LIA is strongly correlated with BBB disruption indicated by the presence of EB. Histologically, the cortical surface was more susceptible than deeper white matter regions to interstitial laser irradiation. Possible indirect mechanisms of brain injury from interstitial laser irradiation are discussed.
The effectiveness of intratumoral photoradiation in photodynamic therapy (PDT) using a polyporphyrin photosensitizer was studied in the RT-2 rat glioma model. One week after intracerebral implantation of RT-2 cells, experimental rats received a single i.p. injection of 2 mg/kg of Photofrin. After administration of the photosensitizer (48 h), the tumors were partially resected and the exposed cavity was irradiated with 15 J of laser light at a wavelength of 630 nm. Further treatment with a large craniectomy significantly enhanced rat survival. Control rats which received no photosensitizer but were treated with surgery, alone or in combination with laser irradiation, succumbed from early tumor recurrence. Photodynamic therapy without decompressive surgery resulted in hemorrhagic infarction of residual tumor and adjacent brain with focal cerebral edema which resulted in cerebral herniation and early death. Our results indicate that photodynamic therapy is effective in treating residual brain tumor but at the expense of brain tissue surrounding the tumor. Unless relieved, intracranial pressure from photodynamic therapy-associated cerebral edema in this animal model resulted in shortened survival.
A case of traumatic spondylolisthesis of C6 and C7 is presented. The mechanism of injury and the therapeutic implications are discussed.
Despite evidence that annual mammographic screening in women 50 years and older reduces mortality, surveys of physicians and patients have repeatedly demonstrated that annual screening mammography is not performed. The fundamental question addressed in this chapter is: If the assumption is made that the scientific evidence supports the use of mammography, what, then, are physician-related barriers to mammographic screening of elderly women? Using a model that classifies barriers to implementing prevention protocols into three categories (predisposing, enabling, and reinforcing factors), literature is reviewed to help identify reasons for low mammographic screening rates, especially in elderly women. This article concludes with a discussion of strategies that may help overcome barriers to mammographic screening in elderly women.
OBJECTIVE: To determine whether an educational program featuring a drug cost manual can assist physicians in reducing their patients' out-of-pocket prescription drug expenses. DESIGN: Prospective controlled trial. SETTING: A general internal medicine-teaching clinic in a university hospital. PARTICIPANTS: Fifty-one medical interns. INTERVENTION: Thirty-one interns received a manual of comparative drug prices annotated with prescribing advice, two feedback reports, and weekly cost-oriented prescribing reminders. A control group concurrently participated in a manual-based educational program on cholesterol management. MEASUREMENTS: Copies of 3012 prescriptions written over 8 months were analyzed. MAIN RESULTS: Intervention group physicians prescribed less expensive drugs within classes of drugs. The change in drug price score per prescription was -0.15 (95% Cl, -0.27 to -0.04; P = 0.01). A score of 3 was assigned to the most expensive, 2 was assigned to intermediate-priced, and 1 was assigned to the least expensive drug or drugs in the class. An increase of 0.74 months' (Cl, 0.49 to 0.98; P less than 0.001) supply of medication was dispensed per prescription, reducing dispensing fees. The program was well accepted by the physicians. CONCLUSION: This relatively simple educational intervention can help physicians to reduce their patients' drug expenses and may serve as a model for incorporating cost information into the routine practice of medicine.
Despite numerous Federal and private funding programs aimed at increasing the numbers of underrepresented minorities in medicine, the participation of minority groups in the medical profession remains low and shows little sign of improvement. With the goal of improving minority representation in our primary care residency program, the Minority Medical Student Summer Fellowship started in July 1990. The program's purpose is to give minority medical students positive exposure to primary care and attract them back for residency training. In this four-week elective, students participate in seminars with our primary care residents, see patients in a variety of clinics, and complete a project. Key implementation issues include support of the medicine chairman and dean, funding, and malpractice coverage for the students. Program evaluation from the first two students rated the clinic experiences higher than the seminar sessions and the independent project. Both students stated our fellowship made them more likely to train at this medical center should they enter a primary care program. Implications for other programs are listed.
Annual mammography, in combination with clinical breast examinations, can reduce mortality from breast cancer. However, surveys of both patients and physicians suggest that mammography is underutilized. This study examined whether physicians' reported breast cancer screening practices and barriers to mammography varied with patients' age. Data from 576 primary care physicians (internal medicine, family/general practice, and obstetrics/gynecology) who participated in a mailed statewide survey were analyzed. Physicians reported screening elderly women significantly less often than younger women, regardless of family history of breast cancer. With the exception of medical specialty, physicians' demographic and practice characteristics were not associated with reported screening practices. However, physicians' knowledge and beliefs about breast cancer in older women were associated with reported screening practices. When analyzing barriers to ordering mammography, cost to the patient was viewed as a barrier for women of all ages, and pain was viewed as a greater barrier for younger women; otherwise, physicians consistently believed that their elderly patients faced considerably more barriers compared with younger women. Further investigation is required to examine why primary care physicians report age-related differences in both breast screening and barriers to mammography.
We have isolated and characterized three conditional hyporecombination mutants, rec1-1, rec3-1 and rec4-1, that define three REC genes of Saccharomyces cerevisiae required for spontaneous general mitotic interchromosomal recombination. Each MATa/MAT alpha rec/rec diploid is deficient in mitotic single site gene conversion, intragenic recombination, intergenic recombination and sporulation at the restrictive temperature (36 degrees C). The rec1-1 mutation also confers conditional enhanced sensitivity to the killing effects of X-rays. The rec1-1 and rec3-1 mutations have been mapped to chromosome VII. The rec1-1, rec3-1 and rec4-1 mutations exhibit complementation at 36 degrees C for both mitotic recombination and sporulation.
Energy-coupled reactions of the Escherichia coli outer membrane transport proteins BtuB and Cir require the tonB product. Some point mutations in a region of btuB and cir that is highly conserved in TonB-dependent transport proteins led to loss of TonB-coupled uptake of vitamin B12 and colicin Ia, whereas binding was unaffected. Most other point mutations in this region had no detectable effect on transport activity. Mutations in tonB that suppressed the transport defect phenotype of these btuB mutations were isolated. All carried changes of glutamine 165 to leucine, lysine, or proline. The various tonB mutations differed markedly in their suppression activities on different btuB or cir mutations. This allele specificity of suppression indicates that TonB interacts directly with the outer membrane transport proteins in a manner that recognizes the local conformation but not specific side chains within this conserved region. An effect of the context of the remainder of the protein was seen, since the same substitution (valine 10----glycine) in btuB and cir responded differently to the suppressors. This finding supports the proposal that TonB interacts with more of the transport proteins than the first conserved domain alone.
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The functional outcomes of 185 patients with spinal cord injuries undergoing rehabilitation who were initially treated in a specialized short-term care unit (center patients) were compared with those of 153 patients initially treated in general hospitals (noncenter patients). After stabilization, all patients were admitted to the Rehabilitation Institute of Chicago (Ill) and received the same rehabilitation program. The groups were comparable in terms of demographic, injury, and medical characteristics at the time of rehabilitation center admission, but the duration from injury to rehabilitation was more than twice as long for noncenter patients. While center patients were discharged from the rehabilitation center at equivalent functional skill levels, their daily rate of functional gains during the rehabilitation center stay was significantly greater than that of noncenter patients although the length of stay at the rehabilitation center was comparable for the two groups. These results support the practice of specialized short-term spinal cord injury care as a means of enhancing rehabilitation outcome.
Chalcogenapyrylium (CP) dyes which are specifically activated by red and near infrared light (600-900 nm) were examined as potential photosensitizers for photochemotherapy of malignant gliomas. Eleven CP dyes of varying chemical structure and redox potential were evaluated for selective toxicity against glioma and normal skin fibroblast cell cultures both before and after light activation. Eight of eleven CP dyes exhibited differential toxicity to tumor over fibroblast cells at dye concentrations of 1.0 microM. Dose dependent toxicity was seen both in the dark and after laser light activation. The toxicity of two of the CP dyes was significantly enhanced by photoactivation with 800 nm light. The CP dyes that absorb light maximally between 775 and 850 nm, in the range of excellent light penetration through brain, appear to be promising candidates as photosensitizers for treating malignant brain tumors.
A chalcogenapyrylium dye 8b, which is under investigation for the photodynamic therapy of malignant gliomas (brain tumors), was evaluated for inhibition of mitochondrial function both before and after exposure to laser light of 800 nm. Neoplastic and normal cells forced to use mitochondrial substrates were killed by the light-activation of intracellular 8b as well as exposure to classic mitochondrial inhibitors, rotenone and sodium azide. Correspondingly, cells in glucose-rich media showed little decrease in viability due to the photolysis of intracellular 8b or the presence of mitochondrial toxins. The toxicity of 8b without light activation was found to be the same regardless of the cell's energy source. Measurement of cellular ATP generated during treatment also showed the photolysis of intracellular 8b to be more inhibitory towards mitochondrial function than the unactivated parent compound. We conclude that the chalcogenapyrylium dyes localize to the mitochondrion and that photoactivation results in mitochondrial injury.
The journal club is an established teaching modality in many house-staff training programs. To determine if a journal club improves house-staff reading habits, knowledge of epidemiology and biostatistics, and critical appraisal skills, we randomized 44 medical interns to receive either a journal club or a control seminar series. A test instrument developed by the Delphi method was administered before and after the interventions (mean, five journal club sessions). By self-report, 86% of the house staff in the journal club group improved their reading habits vs 0% in the control group. Knowledge scores increased more in the journal club group than in the control group, and a trend was found toward more knowledge gained as more sessions were attended. Ability to appraise critically a test article increased slightly in each group, but there was no significant difference between the groups. We conclude that a journal club is a powerful motivator of critical house-staff reading behavior and can help teach epidemiology and biostatistics to physicians-in-training.
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