Biomedical subjects
Publications and source records attributed to D M Brown.
Professional caregivers often take on two patients for every one client: the patient requiring home care and that patient's informal caregiver. These caregivers need as much guidance and support as the home care professional can provide to ensure calm and effective patient care.
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The previously cited Indiana University School of Dentistry teaching monograph, "The Impact of Tobacco Use and Cessation on Nonmalignant and Precancerous Oral and Dental Diseases and Conditions," reviewed over 800 articles and concluded that tobacco use is strongly associated with many dental and oral mucosal diseases, and may contribute to others. Our study of a relatively small sample of 200 patients, of whom 33 percent were tobacco users, found statistically significant data correlating tobacco use with a higher Decayed, Missing and Filled Index (a measurement of caries and tooth loss experience of patients) and relating periodontal bone loss to smokeless tobacco use. And, while this investigation did not find a statistically significant correlation between smoking and periodontitis severity, there was a data trend in that direction. Conclusions about tooth loss in the Indiana monograph were limited to smokers; however, there was an association of ST use with gingival recession, which can become quite severe in the area in which the smokeless tobacco is placed. It might be theorized that the significantly larger number of missing teeth among ST users in our study is associated with the generally poor oral hygiene and less sophisticated outlook on health care that tobacco users often display. Indeed, of the 65 denture wearers in our study, 7.7 percent were ST users and 40.0 percent were tobacco users of some type. In view of the large amount of data in the scientific literature associating tobacco with dental diseases as summarized by the Indiana monograph, and the position of several groups such as the American Cancer Society that tobacco is one of the risk factors most associated with intraoral cancer, it would appear that dentists have a vested professional interest in promoting tobacco use cessation among their patients. Dentists should take every reasonable opportunity to persuade patients to discontinue the tobacco habit, thus preventing life-threatening malignancies as well as dental diseases.
4-, 5- and 6-Nitroindole have been investigated and compared with 3-nitropyrrole as universal bases in oligodeoxynucleotides. Of these the 5-nitroindole derivative was found to be superior giving higher duplex stability, and behaving indiscriminately towards each of the four natural bases in duplex melting experiments. 3-Nitropyrrole, whilst not discriminating between the natural bases, was found to lead to considerable destabilisation of the duplexes, particularly when multiple substitutions were made, in contrast to the 5-nitroindole nucleoside.
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Three new biflavonoids to which we have accorded the trivial names calycopterone (1), isocalycopterone (2), and 4-demethylcalycopterone (3) and the known flavone 4',5-dihydroxy-3,3',6,7-tetramethoxyflavone (4) were isolated as cytotoxic constituents from the flowers of Calycopteris floribunda Lamk. (Combretaceae). Compounds 1-3 showed a wide range of activity against a panel of solid tumor cell lines. Among the biflavonoids, calycopterone (1) is the major constituent.
The feasibility, safety, and efficacy of a new method of local, sustained-release chemotherapy by use of intralesional cisplatin implants were evaluated in the treatment of oral malignant melanoma. The implant is an injectable viscous gel composed of a protein carrier matrix, a vasoactive modifier, and a chemotherapeutic drug. Twenty dogs with biopsy-proven melanomas were treated at 1- to 2-week intervals by injection with cisplatin implant. Tumors were treated until they resolved or were judged to be unresponsive. In 3 dogs with tumors unresponsive to cisplatin implants, methotrexate implants were used, and in 2 of these dogs, carmustine implants followed the methotrexate. Tumor responses were evaluated by sequential measurements. Melanomas in 14 (70%) of 20 dogs had a > 50% decrease in volume, and in 11 (55%) of these dogs, had a complete response. Tumors with complete responses received a mean cisplatin dose of 11.7 +/- 1.8 mg, delivered in a mean of 2.6 treatments. Two of the dogs with complete response also were treated with methotrexate and carmustine. Implants were well tolerated. Local necrosis, limited to the treatment site, developed in most tumors (17/20) and was associated with tumor response. Systemic toxicosis was minimal; renal insufficiency after cisplatin implants was not evident. Median survival times of dogs with complete tumor response (51 weeks) was substantially greater than that of dogs without local tumor control (10.5 weeks). Recursive partitioning analysis of variables indicated that mandibular tumors of short duration were associated with a positive outcome.(ABSTRACT TRUNCATED AT 250 WORDS)
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A K+ channel was incorporated into voltage-clamped planar lipid bilayers from bovine chromaffin granules and resealed granule membranes ("ghosts"). It was not incorporated from plasma membrane-rich fractions from the adrenal medulla. The channel had a conductance of approximately 400 pS in symmetric 450 mM KCl, with the permeability sequence K+ > Rb+ > Cs+ > Na+ > Li+, and was insensitive to both Ca2+ and charybdotoxin. It exhibited complex gating kinetics, consistent with the presence of multiple open and closed states, and its gating was voltage-dependent. The channels appeared to incorporate into bilayers with the same orientation, and were blocked from one side (the side of vesicle addition) by 0.2-1 mM TEA+. The block was slightly voltage-dependent. Acidification of resealed granule membranes in response to external ATP (which activated the vacuolar-type ATPase) was significantly reduced in the presence of 1 mM intralumenal TEACl (with 9 mM KCl), and parallel measurements with the potential-sensitive dye Oxonol V showed that such vesicles tended to develop higher internal-positive membrane potentials than control vesicles containing only 10 mM KCl. 1 mM TEA+ had no effect on proton-pumping activity when applied externally, and did not directly affect either the proton-pumping or ATP hydrolytic activity of the partially-purified ATPase. These results suggest that chromaffin granule membranes contain a TEA(+)-sensitive K+ channel which may have a role in regulating the vesicle membrane potential.
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PURPOSE: Vitreoretinopathies are disorders characterized by an abnormal vitreous gel structure and associated retinal changes. The authors report a pedigree with vitreous changes characteristic of the vitreoretinopathies, but with retinal pigment epithelial changes, electroretinographic abnormalities, and a clinical course distinct from previously described entities. METHODS: Twenty-six family members were examined. Complete ophthalmologic examinations, electroretinography, and perimetry were performed on patients who were at genetic risk for the disease. Particular attention was given to vitreous morphology and examination of the retinal and retinal pigment epithelium (RPE). RESULTS: Fifteen individuals affected with an autosomal dominant vitreoretinal degeneration were identified. The disease is characterized by nyctalopia, progressive visual field loss, marked vitreous syneresis, progressive RPE atrophy, and combined traction-rhegmatogenous retinal detachments (11 patients). Thinning or "erosion" of the RPE in younger patients permits increased visualization of the choroidal vessels. In advanced conditions, equatorial areas are seen that appear clinically devoid of RPE, with extensive posterior atrophy in older patients. Diffuse rod-cone dysfunction is demonstrated by electroretinography. High myopia, epiphyseal dysplasia, orofacial anomalies, and systemic manifestations characteristic of other vitreoretinopathies are not present. CONCLUSION: The authors describe an entity clinically distinct from other vitreoretinopathies. The disease is characterized by pronounced vitreous abnormalities, complicated retinal detachments, and a progressive pigmentary retinopathy. The most unusual and constant feature is the progressive change in RPE with concurrent visual field constriction and electroretinographic abnormalities. Because the RPE initially seems normal and progressively thins or "erodes" in the equatorial periphery, the descriptive name "erosive" vitreoretinopathy is proposed.
Visual outcome was analysed in 16 consecutive eyes with symptomatic retinal arteriolar macroaneurysms treated by direct laser photocoagulation and 26 consecutive symptomatic eyes followed with no treatment. No difference existed between groups in presenting visual acuity, macular involvement, presence of macular subretinal fluid, or presence or location of associated haemorrhage. The mean follow up was 41 months. In the 26 untreated eyes, visual acuity was improved by 2 or more lines in 13 (50%), was unchanged in nine (35%), and decreased in four cases (15%). In the 16 treated cases, three improved (19%), seven were unchanged (43%), and six had decreased visual acuity (38%). The average minimum angle of resolution improved 0.53 log units in untreated cases and decreased 0.14 log units in treated cases (p = 0.02). Multivariable logistic regression modelling analysis revealed that laser treatment remained a significant risk factor for final visual acuity of less than 20/80 even when controlling for the effects of subretinal haemorrhage and foveal subretinal fluid (odds ratio 8.4, p = 0.01). Laser photocoagulation directly to the macroaneurysm did not improve the visual outcome in this series.
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Structural aspects requisite for allosteric function in the regulatory chain of aspartate transcarbamoylase were explored by site-specific amino acid insertion or substitution within the zinc domain in the region of contact between the catalytic and regulatory chains. Amino acid substitution at two positions yielded enzymes which retained a maximum velocity similar to that of the wild-type enzyme but responded differently from the native enzyme in the presence of regulatory nucleoside triphosphates. A change of zinc coordinate amino acid C109 to histidine and a change of E119 to aspartic acid resulted in enzymes which demonstrated synergistic inhibition by CTP and UTP but not inhibition by CTP in either phosphate buffer or a morpholino-based tri-partate (TP) buffer at pH 7. At pH 8.3, where there is a higher proportion of T-state conformers in the native enzyme, the mutants diverged from their similar kinetic behavior. C109H remained an enzyme which was not inhibited by CTP but was still inhibited by CTP+UTP. E119D was inhibited by both CTP and CTP+UTP. Activation of the mutants by ATP was found to vary either with pH or with phosphate as a buffer component. C109H was activated by ATP in phosphate, while in TP at either pH 7 or 8.3 its activation by ATP was diminished or absent. E119D was activated by ATP in phosphate at pH 7 or in TP at pH 8.3, but not in TP at pH 7. In TP at pH 7, where neither mutant was activated by ATP, the S values and Hill coefficients of the unliganded mutant enzymes resembled those of the ATP-liganded wild-type enzyme. While neither mutation would be predicted to alter the net charge of the holoenzyme, differences in the isoelectric point of the mutants were observed if phosphate was present. This result suggests that the isoelectric point of aspartate transcarbamoylase is conformationally dependent and that the mutants exist in an altered conformation. In addition, the stabilities of both mutant holoenzymes were reduced substantially from those of the wild-type enzyme in 4 M urea. C109H was more stable at pH 8.25 in a Tris buffer; E119D was more stable at pH 7 in the phosphate buffer. Potential effects of these mutations on the active site chemistry and geometry are discussed.
Methoxyamine, N4-methoxycytidine and its 2'-deoxyribo analogue are transition mutagens. The mechanism by which the latter acts after incorporation into or generation within DNA has been ascribed to the ability of the base analogue to pair effectively with both adenine and guanine. To obtain a detailed understanding of these interactions, the solution structures of the self-complementary octanucleotide d(CGGATCCG) and its analogues d(CGGATTCG), d(CGGATMCG) and d(CGGATPCG) (designated 8mer-GC, -GT, -GM and -GP, respectively) were investigated by 1H nuclear magnetic resonance spectroscopy; M is N4-methoxycytosine (mo4C) and P is an analogue, the bicyclic dihydropyrimido[4,5-c][1,2] oxazin-7-one. A variable temperature study showed the order of stability as 8mer GC > GP > GT > GM. Nuclear Overhauser spectroscopy permitted the assignment of the base, anomeric and H2'/H2" protons in these 8mers. All had spectra consistent with regular B-DNA duplex structures. Imino proton spectra showed that the 8mers GC, GP and GM involved Watson-Crick base-pairing but that the G.P and to a greater extent G.M base-pairs were in slow exchange on the nuclear magnetic resonance time-scale with the wobble configuration. Indeed, the G.M pair showed an additional exchange process interpreted in terms of the presence of syn and anti conformers of the methoxy group in the wobble pair. This accounts for the destabilization of M compared with the P-containing duplex. The observations are compared with those made earlier on the corresponding AT, AP and AM octamers. It is evident that M and P can form stable base-pairs with both A and G with essentially Watson-Crick geometry. This confirms the earlier, although unsubstantiated explanation for the transition mutational propenstty of methoxyamine which, in turn, was based on the fact that methoxycytosine bases have tautomeric constants (KT) much nearer to unity than the normal bases. The same general explanation for hydroxylamine and hydrazine-induced mutations is correspondingly rendered more certain.
Macromastia is a common cause of physical and emotional suffering. Reduction mammoplasty can provide relief from shoulder grooving, back and neck pain, intertrigo, and symptoms of ulnar nerve compression. Similarly, emotional well being is enhanced by improved self-image, increased capacity to participate in sports and work, and the ability to wear normal, attractive clothes. In the last three years, we have performed reduction mammoplasty using the inferior pedicle technique or free nipple graft in 75 patients. Preoperative symptoms typically included back pain, shoulder grooving, and a stooped posture. Fat necrosis was the most common complication and was associated with large resections. Patient satisfaction was high for both procedures.
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The hand is a commonly injured part of the body that frequently becomes infected. Improperly treated hand infections can lead to severe disability including stiffness, contracture, and amputation. This article describes the current concepts of diagnosis and treatment of common hand infections.