Biomedical subjects
Publications and source records attributed to R Thomas.
A new biological active cyclic peptide (Nitro) Hymenamide A has been synthesized and the structure was established on the basis of analytical, IR, NMR and mass spectral data. The new compound was subjected to both antimicrobial and pharmacological studies.
Three free-ranging Florida panthers (Felis concolor coryi) were diagnosed with clinical dermatophytosis; two were infected with Trichophyton mentagrophytes, and one was infected with Microsporum gypseum. Two of these panthers were juvenile males that were diagnosed with focal to focally coalescing dermatophytosis; one caused by M. gypseum and the other by T. mentagrophytes. These animals were not treated, and clinical signs resolved spontaneously over 6 mo. The third panther, an adult male from southern Florida, presented with a diffuse dermatophytosis due to T. mentagrophytes infection. Initially, the panther had alopecia, excoriations, ulcerations, and multifocal pyoderma of the head, ears, neck, rear limbs, and abdominal region that progressed to lichenification of the skin and loss of nails from two digits. When topical therapy applied in the field at 45-day intervals was ineffective in clearing the infection, the animal was placed in captivity for intensive oral therapy to prevent further development of dermal mycosis, loss of additional nails, and spread of infection to other panthers. The panther was treated orally with itraconazole (9.5 mg/ kg) in the food s.i.d. for 6 wk. After treatment, nail regrowth occurred but the multifocal areas of alopecia remained. The panther was released back into the wild after two skin biopsy cultures were negative for fungal growth. Temporary removal of a free-ranging animal of an endangered species from its habitat for systemic treatment of dermatophytosis requires consideration of factors such as age, reproductive potential, holding facilities, treatment regimen, and the potential for successful reintroduction of the animal.
BACKGROUND AND AIM OF STUDY: This study was designed to determine: (i) Whether acute mitral valve regurgitation (MVR) due to chordal rupture can be reproducibly created under echocardiographic guidance; (ii) what degree of MVR can be created; (iii) what degree of acute regurgitation is survivable; and (iv) whether acute MVR due to chordal rupture progresses over time. METHODS: In a pilot group of six juvenile farm-bred sheep, selected chordae tendineae were ruptured using either a biopsy needle or endoscopic scissors under echocardiographic guidance, without need for cardiopulmonary bypass. Sheep were sacrificed acutely (n = 2), and at six weeks (n = 2) or eight weeks (n = 2). When the technique was optimized, five sheep entered a study group in which chords were ruptured using endoscopic scissors; the sheep were sacrificed 16 weeks after surgery. RESULTS: In the pilot study, acute MVR (grade 2-4+) was produced in all sheep, normal ventricular wall motion was maintained, with minimal progression of regurgitation over time. In one pilot sheep which did not survive, grade 4+ MVR was created acutely. Use of endoscopic scissors was preferable to the biopsy needle. In the study group, acute MVR (grade 2-4+) was produced in all five sheep, and was still present at 16 weeks, with progression in only one animal. CONCLUSIONS: This pilot study demonstrated that controlled degrees of survivable acute MVR due to chordal rupture can be created under echocardiographic guidance, with minimal progression of MVR over time. This animal model can be applied to investigate the pathogenesis of clinical MVR, and to suggest appropriate medical or surgical intervention.
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PURPOSE: To report the incidence, management and complications of nucleus dislocation into the vitreous during phacoemulsification. METHODS: Retrospective review of 1250 consecutive phacoemulsification performed by consultants and residents in a teaching hospital. RESULTS: The incidence of nucleus drops was 0.8% (10 out of 1250). Loss of nuclear fragments occurred during phacoemulsification in 9 patients. In one, the dislocation was caused by hydro-dissection. All except one patient (who refused further intervention) underwent pars plana vitrectomy with removal of nuclear fragments. Eight of them had intraocular lens (IOL) inserted at the time of cataract surgery or at vitrectomy; one patient was scheduled for a secondary IOL. Postoperative best corrected visual acuity ranged from 6/24-6/6; 8 patients achieved a vision of 6/12 or better. Complications included cystoid macular oedema (5 patients), retinal break (1 patient) and retinal detachment (1 patient). CONCLUSION: Appropriate management of posteriorly dislocated nucleus can restore good visual acuity. The use of phacoemulsification mandates availability of referral facilities for management of complications.
The paper by Rosser and Kasperski represents the positions of the Ontario College of Family Physicians. Their rostering proposal has been taken up by the Ministry of Health and the Ontario Medical Association. My comments will be largely on the ideas as seen in the light of their planned implementation.
Ophthalmologists are often confronted with difficult clinical management problems. In such cases, even published experience may be limited; consequently multiple, generally unproven management options are usually available. When placed in such situations, most of us decide on the most appropriate course of action based on intuition or (limited) previous experience. In this article, we use examples to introduce the concept of decision analysis, a method of generating objective decisions for complex clinical problems.
BACKGROUND: What is the molecular basis of the osteotrophic action of prostatic metastases? Demineralized bone matrix has the potential to induce new bone formation. The identification of bone morphogenetic proteins (BMPs) as the primary inducers of new bone formation in demineralized bone matrix has set the stage for studying prostate cancer-bone interrelationships. We have hypothesized that BMPs may be expressed in prostate and may be involved in the osteotrophic actions of metastatic prostate cancer cells. METHODS: Using polymerase chain reaction (PCR)-based quantitation, this study examined the presence of BMPs in mouse prostate and their potential regulation by orchidectomy and androgen replacement. RESULTS: BMP-7 and BMP-4 genes were expressed in mouse prostate. Quantitative PCR analysis showed that the BMP-7 mRNA level was significantly decreased following orchidectomy and increased by testosterone and dihydrotestosterone. Therefore, the BMP-7 mRNA level is androgen-dependent. On the other hand, BMP-4 was expressed constitutively in the prostate. CONCLUSIONS: The regulated expression of BMP-7 mRNA in the prostate suggests that BMP-7 may explain in part the stimulation of bone formation and osteosclerosis by metastatic prostate adenocarcinoma.
Thirty years ago, Waclaw and myself were working on the same organism and had the same type of interest. Since that happy time, our trajectories have diverged so much that I am afraid any paper I might offer for his jubilee would seem completely strange and irrelevant to him and as well to his colleagues. For this reason, I decided rather to offer Waclaw, as a modest present, a product of my recent work which I consider, perhaps presumptuously, as an 'oeuvre d'art' (of course, this qualification is not supposed to apply to this paper as a whole, just to the figure). Please note above the expressions 'divergent trajectories' and 'strange'; we will meet them again below in a different context.
Dendritic cells (DC) can be generated by culture of adherent peripheral blood (PB) cells in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4). There is controversy as to whether these DC arise from proliferating precursors or simply from differentiation of monocytes. DC were generated from myeloid-enriched PB non-T cells or sorted monocytes. DC generated from either population functioned as potent antigen-presenting cells. Uptake of [3H]-thymidine was observed in DC cultured from myeloid-enriched non-T cells. Addition of lipopolysaccharide or tumor necrosis factor-alpha led to maturation of the DC, but did not inhibit proliferation. Ki67(+) cells were observed in cytospins of these DC, and by double staining were CD3(-)CD19(-)CD11c-CD40(-) and myeloperoxidase+, suggesting that they were myeloid progenitor cells. Analysis of the starting population by flow cytometry demonstrated small numbers of CD34(+)CD33(-)CD14(-) progenitor cells, and numerous granulocyte-macrophage colony-forming units were generated in standard assays. Thus, production of DC in vitro from adherent PB cells also enriches for progenitor cells that are capable of proliferation after exposure to GM-CSF. Of clinical importance, the yield of DC derived in the presence of GM-CSF and IL-4 cannot be expanded beyond the number of starting monocytes.
Although the CBFA1 gene encodes an osteoblast-specific transcription factor that regulates osteoblast differentiation, uncertainty exists about the organization of its 5' end and the relevance of a novel N-terminal sequence identified in the mouse Cbfa1/Osf2 isoform. We found the novel 5' Cbfa1/Osf2 sequence is encoded by a previously unrecognized upstream exon, designated exon -1, which is highly conserved in mouse, rat and human. In addition, two splice donor sites may be utilized to generate Cbfa1/Osf2 cDNAs containing different N-terminal sequences. The first ATG and splice donor site in exon -1 is predicted to transcribe a cDNA containing the unique Osf2 5' sequence, whereas a second donor splice site gives rise to cDNAs that contain sequences encoding an 11 amino acid insert. In the human CBFA1 gene, an additional 2-bp nucleotide insert shifts the reading frame and results in stop codons in the cDNA sequence derived from exon -1. The 5'-most exon of the human CBFA1 gene, therefore, contains the 5' non-coding region rather than a human OSF2 homolog. The absence of a homologous OSF2 coding sequence in the human CBFA1 cDNA suggests that the novel mouse N-terminal Osf2 sequence is not essential for functioning of the CBFA1 gene product. In addition, multiple transcripts derived from a single CBFA1/Cbfa1 gene were detected in osteoblasts by Northern analysis and RT-PCR, including additional Cbfa1/Osf2 isoforms containing deletions of exons 1 and 4. Thus, the alternative use of transcription start sites and splicing leads to the genesis of CBFA1/Cbfa1 isoforms with possible differences in transactivation potentials.
BACKGROUND: Empirical scores, computerized ST-segment measurements, and equations have been proposed as tools for improving the diagnostic performance of the exercise test. OBJECTIVE: To compare the diagnostic utility of these scores, measurements, and equations with that of visual ST-segment measurements in patients with reduced workup bias. DESIGN: Prospective analysis. SETTING: 12 university-affiliated Veterans Affairs Medical Centers. PATIENTS: 814 consecutive patients who presented with angina pectoris and agreed to undergo both exercise testing and coronary angiography. MEASUREMENTS: Digital electrocardiographic recorders and angiographic calipers were used for testing at each site, and test results were sent to core laboratories. RESULTS: Although 25% of patients had previously had testing, workup bias was reduced, as shown by comparison with a pilot study group. This reduction resulted in a sensitivity of 45% and a specificity of 85% for visual analysis. Computerized measurements and visual analysis had similar diagnostic power. Equations incorporating nonelectrocardiographic variables and either visual or computerized ST-segment measurement had similar discrimination and were superior to single ST-segment measurements. These equations correctly classified 5 more patients of every 100 tested (areas under the receiver-operating characteristic curve, 0.80 for equations and 0.68 for visual analysis; P < 0.001) in this population with a 50% prevalence of disease. CONCLUSIONS: Standard exercise tests had lower sensitivity but higher specificity in this population with reduced work-up bias than in previous studies. Computerized ST-segment measurements were similar to visual ST-segment measurements made by cardiologists. Considering more than ST-segment measurements can enhance the diagnostic power of the exercise test.
Infection with the human immunodeficiency virus (HIV) leads to a progressive immunodeficiency characterized by decreasing levels of CD4+ T lymphocytes. VaxSyn, a vaccine based on the recombinant envelope glycoprotein subunit (rgp160) of HIV-1IIIB, was used to immunize HIV-infected patients to determine whether its administration was beneficial with respect to slowing disease progression. A 3-year multicenter, randomized, placebo-controlled, double-blinded, efficacy and safety trial of repeated immunization with VaxSyn was used to evaluate the long-term impact on the progression of immunodeficiency. VaxSyn in alum, or alum alone, was given to 278 HIV-infected asymptomatic individuals with initial CD4 counts of > or =500 cells/mm3. Clinical findings, the CD4 count, and both virological and immunological parameters were followed. No significant differences were observed between the treatment and placebo control groups in rate of CD4 T cell decline, time to initiation of antiretroviral therapy, incidence of opportunistic infections, HIV RNA plasma viremia, HIV viral infectivity as measured by quantitative HIV coculture assay, and death. This study revealed no effect on either clinical or laboratory virological parameters from the administration of VaxSyn.
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OBJECTIVE: To evaluate cerebrospinal fluid (CSF) levels of amyloid beta protein ending at amino acid 42 (Abeta42) and tau as markers for Alzheimer disease (AD) and to determine whether clinical variables influence these levels. DESIGN: Cohort study. SETTING: Six academic research centers with expertise in dementia. SUBJECTS: Eighty-two patients with probable AD, including 24 with very mild dementia (Mini-Mental State Examination score >23/30) (AD group); 60 cognitively normal elderly control subjects (NC group); and 74 subjects with neurological disorders, including dementia (ND group). MAIN OUTCOME MEASURES: Levels of Abeta42 and tau were compared among AD, NC, and ND groups. Relationships of age, sex, Mini-Mental State Examination score, and apolipoprotein E (Apo E) genotype with these levels were examined using multiple linear regression. Classification tree models were developed to optimize distinguishing AD from NC groups. RESULTS: Levels of Abeta42 were significantly lower, and levels of tau were significantly higher, in the AD group than in the NC or ND group. In the AD group, Abeta42 level was inversely associated with Apo E epsilon4 allele dose and weakly related to Mini-Mental State Examination score; tau level was associated with male sex and 1 Apo E epsilon4 allele. Classification tree analysis, comparing the AD and NC subjects, was 90% sensitive and 80% specific. With specificity set at greater than 90%, the tree was 77% sensitive for AD. This tree classified 26 of 74 members of the ND group as having AD. They had diagnoses difficult to distinguish from AD clinically and a high Apo E epsilon4 allele frequency. Markers in CSF were used to correctly classify 12 of 13 patients who later underwent autopsy, including 1 with AD not diagnosed clinically. CONCLUSIONS: Levels of CSF Abeta42 decrease and levels of CSF tau increase in AD. Apolipoprotein E epsilon4 had a dose-dependent relationship with CSF levels of Abeta42, but not tau. Other covariates influenced CSF markers minimally. Combined analysis of CSF Abeta42 and tau levels discriminated patients with AD, including patients with mild dementia, from the NC group, supporting use of these proteins to identify AD and to distinguish early AD from aging. In subjects in the ND group with an AD CSF profile, autopsy follow-up will be required to decide whether CSF results are false positive, or whether AD is a primary or concomitant cause of dementia.
A quiet magnetic resonance (MR) imaging technique for detecting changes in cerebral activity functions is presented. This single-shot method, functional Burst imaging (FBI), combines elements of Burst imaging with an offset technique known as asymmetric spin echo (ASE). The FBI sequence has the unique feature of being nearly silent, because of the low number of gradient switching steps involved. Furthermore, this approach has the key advantage that it can be implemented on conventional MR systems. Established auditory and visual paradigms were used to evaluate whether FBI can detect changes in cerebral activity using a 1.5 Tesla MR system. In a second set of experiments, the FBI technique was used to evaluate cerebral activity changes during different sleep stages in humans. The results obtained demonstrate that the FBI sequence provides an alternative approach for functional imaging of brain activity in primary and secondary sensory areas of the human brain. Furthermore, in using this quiet MR technique, it was possible to scan continuously during different stages of human sleep without acoustic noise perturbation.
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Pulmonary alvelolar proteinosis (PAP) is a rare cause of chronic respiratory failure due to progressive alveolar accumulation of a periodic acid-schiff (PAS) positive proteinaceous material. In some cases, the rapid accumulation of intra-alveolar material leads to acute respiratory failure (ARF). We report the causative role of secondary PAP in the case of a 26-year-old man with acute myeloid leukemia who developed fever, increased serum lactate dehydrogenase level and ARF, and required mechanical ventilation. The diagnosis of PAP was established by the examination of material obtained by bronchoalveolar lavage (BAL). Respiratory improvement occurred several days after the patient had recovered from neutropenia. This report underlines the importance of the early diagnosis of PAP as a potential cause of ARF in leukemic patients. Adequate stain on BAL fluid provides the diagnosis and avoids repeated invasive procedures and inappropriate treatments.