Neutering of feral cats as an alternative to eradication programs.
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Biomedical subjects
Publications and source records attributed to R E Smith.
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We studied two patients, a 43-year-old Hispanic man with a one-year history of acquired immunodeficiency syndrome (AIDS) and a 34-year-old Hispanic man with newly diagnosed AIDS. Both had necrotizing retinitis that progressed to panophthalmitis and orbital cellulitis. Toxoplasmosis was not diagnosed in the first patient early in the course of the disease. The second patient had a history of toxoplasmic retinochoroiditis. Despite anti-toxoplasmosis therapy, visual acuity deteriorated to no light perception in both patients. Diagnostic biopsy of the eye wall was performed on the first patient and enucleation of the globe on the second. Toxoplasmic panophthalmitis and orbital cellulitis were diagnosed in each patient by light microscopy and confirmed by electron microscopy. When patients with AIDS develop necrotizing retinitis, toxoplasmosis must be considered in the differential diagnosis, along with cytomegalovirus retinitis, progressive outer retinal necrosis, and syphilitic retinitis. Unlike cytomegalovirus retinitis, progressive outer retinal necrosis, and syphilitic retinitis, however, toxoplasmosis can cause a progressive intraocular infection, panophthalmitis, and orbital cellulitis in patients with AIDS.
The yellow color of atherosclerotic plaque is due to the presence of carotenoids, which absorb light between 430-530 nm and account for the preferential ablation of plaque by the pulsed dye laser operating at 480 nm. This study was designed to examine tissue uptake of beta-carotene and the effect of uptake on arterial plaque ablation. Forty-two atherosclerotic NZW rabbits were given intravenous beta-carotene at a dose of 40 mg/kg, twice weekly and killed between 1 hour and 28 days after the initial injection. beta-carotene was not detected in control specimens but was significantly greater in plaque than in normal wall at all time points following beta-carotene injection (P < 0.04 Mann Whitney U test). The ablation threshold was significantly lower in beta-carotene treated plaque than in untreated plaque or normal arterial wall (P < 0.01, Fisher's exact test). In this model beta-carotene is preferentially taken up into arterial plaque, resulting in increased absorption of laser radiation at 480 nm and enhanced tissue ablation.
We have established a non-human primate model of experimental ocular histoplasmosis. This model has been shown to result in chronic lesions that resemble typical 'histo spots' or choroidal scars but that contain infiltrates of lymphocytes for as long as 10 yr following intracarotid injection of live Histoplasma capsulatum. Using this model, we attempted to reactive these late choroidal lesions via intracarotid challenge with specific antigen (heat-killed H. capsulatum). No clinical changes suggestive of reactivation of these lesions were observed following this antigenic challenge. However, immunopathologic analysis of choroidal lesions at 1, 3 and 7 days after antigenic challenge revealed significant increases in both the numbers of inflammatory cells and the relative percentages of the helper/inducer lymphocyte and macrophage populations. Our results demonstrate that, following antigenic challenge, a cellular change, consistent with a type IV delayed hypersensitivity, can be observed in previously active, but clinically quiescent, histoplasmosis lesions. In light of the many parallels between our primate experimental model and human ocular histoplasmosis, our findings suggest that, in the human, significant immunopathologic activity may occur subclinically in the choroid of affected individuals. It is possible that repeated bouts of subclinical reactivation may induce or enhance chronic choroiditis and, over many years, ultimately produce slow progressive damage to the Bruch's membrane/retinal pigment epithelium complex, resulting in clinically 'active' macular disease and, in selected cases, subretinal neovascularization.
To identify the nucleotide sequences responsible for the tumorigenic specificity of myeloblastosis-associated virus (MAV) we have established the complete nucleotide sequences of three infectious clones inducing either both osteopetrosis and nephroblastoma [MAV2(O)/2 and MAV2(O)p9] or only nephroblastoma [MAV1(N)], and compared their biological properties in the same chicken host strain. The MAV2(O)p9 originally described as a type 2 strain was found to carry a hybrid env gene containing sequences of both the types 1 and 2, and it induced milder and less rapid osteopetrosis than the original MAV2(O) clone when injected into Brown Leghorn chickens. These results, together with sequence comparisons between the MAV strains examined, suggest that subtle changes in the primary structure of the TM env protein's extracellular domain are likely to affect the tumorigenic potential of MAV.
Although several recent papers have focused on the results of cataract surgery in patients with uveitis, little has been published on specific surgical techniques that are most appropriate to such cases. We have found that a combined anterior and posterior approach using extracapsular techniques (usually phacoemulsification) and pars plana vitrectomy, with or without intraocular lens placement, is best suited for selected uveitis patients who have cataract, vitreous opacities, and cystoid macula edema. This paper discusses the surgical techniques that we have found to be best for the management of these cases.
In this phase III study, patients who had previously undergone surgery for colorectal cancer were studied using a technetium-99m (99mTc)-labeled anti CEA antibody (IMMU-4 [Immunomedics, Morris Plains, NJ] 1mg of protein) to evaluate recurrence. Total-body, planar, and single photon emission computed tomography (SPECT) images were performed within 6 hours of injection. Objectives were to evaluate the efficacy of the 99mTc-labeled anti-CEA antibody, to assess sensitivity and specificity of the agent in known lesions, and to detect occult disease. The impact of antibody study on subsequent surgery was also evaluated. The Fab' fragment has a molecular weight of 54,000 and is supplied as a lyophilized kit that can be instantaneously labeled with 20 to 30 mCi of [99mTc]pertechnetate. In 9 patients with known disease, planar spot imaging identified lesions in 7 (78% sensitivity), SPECT imaging detected lesions in 8 (88% sensitivity), and 1 patient did not have SPECT. In the group of 10 patients with occult (or equivocal) disease, planar imaging sensitivity was 50%, and SPECT sensitivity was 100%. Analysis by site showed 14 of 24 lesions detected by planar imaging (58% sensitivity), and SPECT detected 24 of 24 lesions (100% sensitivity). Tumors as small as .5 cm were visualized in the 19 patients studied. The surgeon judged the antibody study to be impact neutral in 73% of the cases and helpful in 27% of the cases when antibody study altered the presurgical plan.
The authors examined the impact of coaching behaviors on players' self-enhancement processes. Eight baseball coaches attended a preseason workshop designed to increase their supportiveness and instructional effectiveness. Behavioral guidelines were presented and modeled. A no-treatment control group had 10 coaches. Boys (N = 152) in both groups were interviewed pre- and postseason. Trained coaches differed from controls in player-perceived behaviors in accordance with the guidelines. They were evaluated more positively by their players, their players had more fun, and their teams exhibited a higher level of attraction among players, despite the fact that their teams did not differ from controls in won-lost records. Consistent with a self-esteem enhancement model, findings showed that boys with low self-esteem who played for the trained coaches exhibited significant increases in general self-esteem; low self-esteem youngsters in the control group did not.
Traditionally, the food industry has not been driven by technology. However, over the past decade, enormous changes have been introduced because of the changing demographics and evolving lifestyle of the consumer; the public health policies driving these lifestyle alterations; the growing fitness food market, which is a consequence of these changes; and the new aggressive posture taken by the food industry toward use of innovative technologies to satisfy consumer needs. This review is a brief description of the newer, nonbiotechnological food-science approaches that provide an unprecedented array of novel products to satisfy consumer preferences. These include engineered foods, aseptic processing, extrusion, hydroponics, intermediate-moisture foods, microencapsulation, supercritical-fluids extraction, and ingredient technology. Included under the last category is a brief description of fat substitutes that are likely to have a significant effect on the American diet.
The mechanisms of retention of anions on a new solvent-compatible, moderate capacity (170 microequivalent per column) anion-exchange column are described. Retention based on anion exchange is shown using both sodium hydroxide and 4-cyanophenolate eluants. Plots of the log k' vs. log C, (where k' is the capacity factor and C is the eluant concentration) are shown to be linear with slopes approximating the charge of the eluant as predicted by the standard anion-exchange equation. Sodium hydroxide is shown to be a relatively weak eluant, capable of separating monovalent anions that are difficult to separate on other columns. Sodium 4-cyanophenolate is shown to be a strong eluant, capable of eluting polyvalent anions. The retention of nonionic alkylphenones is also described. In plots of log k' vs. percentage acetonitrile in the eluant, these compounds were found not to follow the solvophobic mechanism typical of reverse-phase HPLC columns. Results are compared with other anion exchange columns. Applications include the determination of lysophosphatidyl inositol in brain microsomes and methacrylic acid in esterase-treated samples.
OBJECTIVE: The aim was to examine the effect of coronary artery disease on human left ventricular energetics by a comparison of left ventricular oxygen consumption and heat production. The usefulness of measurement of left ventricular heat production for the detection of the expected change in left ventricular energetics produced by atrial pacing to a faster heart rate was also assessed. METHODS: Forty six patients (mean age 57 years; 31 men) undergoing cardiac catheterisation and coronary arteriography for the investigation of chest pain were studied. Normal left ventricular function and normal coronary arteries were present in eight and 38 had atheromatous coronary artery disease. Left ventricular heat production was calculated from coronary blood flow, the coronary arteriovenous (aorta-coronary sinus) temperature difference, and the areas under thermodilution curves recorded in the aorta and coronary sinus after injection of cold saline into the pulmonary artery. Mean external left ventricular power was calculated from mean arterial blood pressure and cardiac output. Left ventricular mechanical efficiency was derived from heat production and the energy value of myocardial oxygen use, assuming aerobic metabolism. In 27 patients studies were repeated during atrial pacing from the coronary sinus. RESULTS: At rest under basal conditions left ventricular heat production was 2.4(SD 1.0) W in patients with normal hearts and 3.1(1.4) W in patients with coronary disease (NS). Mechanical efficiency was 44.2(9.7)% in the normal patients and 30.7(10.9)% in those with coronary disease (p = 0.003). During atrial pacing to a faster heart rate left ventricular energy supply increased from 4.6(2.7) W to 5.9(3.3) W (p < 0.0005), and heat production increased from 3.0(1.6) W to 4.6(2.4) W (p < 0.0005), but mean external power was not altered. As the extra energy used during pacing was "wasted" as heat, there was a significant fall in left ventricular mechanical efficiency with pacing from 33.9(13.5)% to 18.9(15.2)% (p < 0.0005). CONCLUSIONS: These results show the effect of coronary artery disease on the energetics of left ventricular function. They also show that the method and equipment can detect the expected alteration in left ventricular energetics produced by atrial pacing. The measurement of left ventricular heat production and oxygen consumption allows assessment of the total left ventricular energy flux, and may be useful for the evaluation of drug treatment with such as inotropes and vasodilators, and for the investigation of the functional consequences of left ventricular disease.
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Intraerythrocytic malaria parasites degrade hemoglobin as a principal source of amino acids for parasite protein synthesis. We have previously identified a Plasmodium falciparum trophozoite cysteine proteinase as a putative hemoglobinase and shown that specific inhibitors of this proteinase block the hydrolysis of globin and the development of cultured parasites. We now show that the murine malaria parasite Plasmodium vinckei has an analogous cysteine proteinase with similar biochemical properties to the P. falciparum proteinase, including an acid pH optimum, a preference for the peptide proteolytic substrate benzyloxycarbonyl (Z)-Phe-Arg-7-amino-4-methylcoumarin, and nonomolar inhibition by seven peptide fluoromethyl ketone proteinase inhibitors. Thus, P. vinckei offers a model system for the in vivo testing of the antimalarial properties of cysteine proteinase inhibitors. One of the proteinase inhibitors studied, morpholine urea (Mu)-Phe-Homophenylalanine (HPhe)-CH2F strongly inhibited the P. vinckei cysteine proteinase in vitro and rapidly blocked parasite cysteine proteinase activity in vivo. When administered four times a day for 4 d to P. vinckei-infected mice, Mu-Phe-HPhe-CH2F elicited long-term cures in 80% of the treated animals. These results show that peptide proteinase inhibitors can be effective antimalarial compounds in vivo and suggest that the P. falciparum cysteine proteinase is a promising target for chemotherapy.
Indigenous ocular flora has been presumed to be a source of infectious organisms in postoperative bacterial endophthalmitis. While bacteria have been recovered from the anterior chamber at the time of cataract wound closure in a significant percentage of cases, and bacteria from the vitreous of endophthalmitis cases have appeared genetically to be very similar to bacteria recovered from the adnexa and/or nares at the time of vitrectomy for endophthalmitis, no study has examined the relationship between organisms isolated from the eyelid and conjunctiva, and organisms recovered from the aqueous humor at the time of wound closure. This study examined 59 eyes undergoing cataract and other intraocular surgeries. Cultures of the eyelids and conjunctiva were taken before and after routine preparation with povidone-iodine solution. Cultures also were taken of the aqueous humor at the time of incision into the anterior chamber and at the time of wound closure. No organisms grew from aqueous humor samples taken at the time of incision. However, 13 eyes (22%) grew gram-positive organisms from samples taken at the time of wound closure. Eight of the 13 eyes (62%) had organisms with identical typing and antibiotic sensitivities to organisms isolated from the eyelids and conjunctiva before or after disinfection. This study suggests that a significant number of cases had inoperative bacterial contamination of the aqueous humor by the time of wound closure and that organisms from the eyelids and conjunctiva are an important source of contamination in these cases.
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PURPOSE: We have previously reported that corneal endothelial modulation takes place when rabbit corneal endothelial (CE) cells are exposed to corneal endothelium modulation factor (CEMF) released by polymorphonuclear leukocytes (PMN) (Kay, E. P., L. Rivela, and Y. G. He, 1990. Invest Ophthalmol Vis Sci. 31:313-322). The modulation was involved in phenotypic switches from polygonal cell shape to fibroblastic morphology and from basement membrane collagen (type IV-rich) synthesis to fibrillar collagen (type I-rich) synthesis. In the current study, we tested the effect of several growth-modulating factors on corneal endothelial modulation. METHODS: The effect of basic fibroblast growth factor (bFGF) on cell proliferation was measured by [3H]thymidine incorporation into DNA and cell numbers. Collagen expression was determined by SDS-polyacrylamide gel electrophoresis and by Northern blot analysis. Transcription rate was determined by nuclear run-off assay. Basic fibroblast growth factor synthesis was analyzed by immunoblot assay and quantitated by ELISA assay. Immunofluorescent staining was used for in vivo localization of bFGF and its receptors. RESULTS: Basic fibroblast growth factor (bFGF) supplemented with heparin is able to modulate the same phenotypes as observed in CEMF-induced modulation. Basic fibroblast growth factor has a marked stimulatory effect on cell proliferation, as shown by increased cell numbers and [3H]thymidine incorporation into DNA. It also has a strong effect on modulation of cell morphology and collagen phenotypes; the polygonal endothelial cells are induced to assume an elongated shape, and fibrillar collagen synthesis (types I and V) is turned on by bFGF, whereas type IV synthesis is markedly reduced. Such modulating effects of bFGF are augmented by CEMF. Furthermore, CEMF significantly increases production of bFGF in CE cells; the CEMF-treated CE cells synthesized bFGF seven times more than did the control cells. The induced bFGF has a major peptide band of 18.4 kD. Immunohistochemical analysis demonstrates that rabbit corneal endothelium in vivo stains for bFGF, while Descemet's membrane requires prior digestion with proteinase K. In situ localization of bFGF receptors demonstrates that high affinity receptors for bFGF are present in corneal endothelium. However, neither transforming growth factor (TGF-beta), epidermal growth factor (EGF), nor retinoic acid (RA) alters qualitative collagen phenotypes; rabbit CE cells continue to synthesize type IV collagen as a predominant species under the influence of these factors. Unlike rabbit CE cells, bovine CE cells in culture produce predominantly fibrillar collagens (I, III, and V). Transforming growth factor enhances type III collagen synthesis and induces type I collagen, but none of these factors affects type IV collagen synthesis by bovine cells. Neither steady-state levels of collagen RNA nor relative transcription rates of the collagen genes are changed significantly by TGF-beta, EGF, or RA in either rabbit or bovine CE cells. CONCLUSIONS: These findings suggest that bFGF is able to simultaneously modulate three phenotypic aspects of rabbit CE cells (cell proliferation, cell shape, and collagen expression). Furthermore, CEMF induces de novo synthesis of biologically active bFGF, indicating that bFGF, through the action of CEMF, is the key molecule during corneal endothelial modulation, which ultimately leads to corneal fibrosis (retrocorneal fibrous membrane).
OBJECTIVES: (1) To introduce a partial shift system to reduce the hours of work of preregistration house surgeons to an average of 64 a week to comply with the New Deal for junior doctors; (2) to test linking the partial shift concept to an existing structure of "on call" firms. DESIGN: Formal assessment after three months of a pilot partial shift system for eight house surgeons on three firms instituted on 1 November 1991, followed by questionnaire and interview evaluation at three and six months of a revised system implemented on 1 February 1992. SETTING: Department of general surgery at St Bartholomew's Hospital, London. SUBJECTS: 24 house surgeons attached to three surgical firms. RESULTS: In eight weeks each house surgeon worked one week (five shifts) of night duty, one week of "cover" (afternoon and evening) duty, and six weeks of normal daytime hours. Each weekday a house surgeon from the firm on call worked an extended daytime on call shift until 10 pm. Weekend duties were split between two house surgeons from the firm on call. A computer generated graphical display of the rota was used to facilitate leave planning. Average working hours were reduced to below 64 per week, including prospective cover, without detriment to patient care and educational standards. Within the shift system individual house surgeons could be on call with their own firm by day and at weekends. Opinions were equally divided among junior staff as to their preference for either on call or partial shift systems. CONCLUSIONS: The principles of this partial shift system are generally applicable and the model can readily be adopted by district general hospitals.
A flashlamp-pumped pulsed dye laser operating at either 480 or 504 nm, coupled to an integral ball-tipped optical fibre, was used to recanalize occluded lower limb arteries. All channels created by the laser were augmented with balloon dilatation. We have treated 78 limbs in 71 patients; 46 limbs (59 per cent) had rest pain and 22 (48 per cent) of these had tissue loss. The median occlusion length was 18 (range 0.5-58) cm. Technical success was achieved in 58 limbs (74 per cent) with clinical success in 46 (59 per cent). Success rates fell with increasing length of occlusion. Two patients died in the perioperative period. A subgroup of 22 patients with marked discrete arterial calcification had a lower technical success rate than the subgroup without calcification (50 per cent versus 84 per cent, P less than 0.01). Both subgroups displayed a similar pattern of reclosure during follow-up. The cumulative patency rate after technical success was 67 per cent at 6 months and 45 per cent at 12 months. Forty-six (59 per cent) limbs avoided bypass surgery or amputation. Laser-assisted angioplasty may offer an alternative to femoropopliteal bypass, although the former procedure is not as durable.