Counsellors in general practice.
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Delivery of Health Care↗
Biomedical subjects
K Green
Publications and source records attributed to K Green.
Evidence of a glycemic threshold for the development of cataracts in diabetic rats.
PURPOSE: This study was aimed to establish a possible correlation between the levels of plasma glucose and degree of lens opacification. Levels of glycation- and glycoxidation-products in different lens protein fractions were also estimated with an aim to determine the involvement of these products in lens opacification. METHODS: A wide range of hyperglycemia was induced by injecting different doses of streptozotocin to 1 month old rats and lenses were examined on the 75th, 90th and 150th day post-injection. Lens opacification was measured by Scheimpflug imaging and densitometry. Levels of plasma glucose and glycated hemoglobin were measured after overnight fasting. On 90th day, levels of Amadori products in lens water soluble (WS) fraction were measured by affinity chromatography. Similarly, advanced glycation end products (AGEs) in lens WS, urea soluble (US) and alkali soluble (AS) fractions were measured immunochemically using a monoclonal antibody against the major glycoxidation product, carboxymethyl lysine (CML). RESULTS: Different dosages of streptozotocin injection resulted in a broad range of plasma glucose levels in the rats which were grouped into three groups on the basis of their plasma glucose levels: mildly diabetic (< 170 mg/dl plasma glucose), moderately diabetic (190-350 mg/dl) and severely diabetic (> 400 mg/dl). On the 75th, 90th and 150th day post-injection, only the moderately and severely diabetic rats developed cataracts whereas lenses of the mildly diabetic rats remained clear. As seen on 90th day, levels of glycated hemoglobin and Amadori products in lens WS fraction increased significantly in the moderately and severely diabetic groups whereas in the mildly diabetic rats these levels remained more or less same as in the control group. Levels of CML in WS fractions remained unchanged between control rats and different diabetic groups, while US fractions showed a decrease in CML in both the moderately and severely diabetic groups compared to the controls and the mildly diabetic group. Interestingly, AS fractions contained the highest level of CML; the moderately and severely diabetic groups showed about 2-fold higher levels than the controls and the mildly diabetic group. CONCLUSIONS: This study strongly supports the existence of plasma glycemic threshold above which incidence of diabetic cataract formation increases exponentially. This threshold level seems to be at approximately 180 mg/dl or 10 mM plasma glucose. Significant increase in the levels of glycation and glycoxidation products mainly in cataract lenses suggests that glycation and glycation-mediated oxidation play an important role in the development of diabetic cataracts.
Animals↗
Intraocular pressure-lowering activity of phenolic antioxidants in normotensive rabbits.
PURPOSE: The purpose of this study was to determine the intraocular pressure (IOP)-lowering activity of phenolic antioxidants injected intravenously into normotensive rabbits. Antioxidants belonging to the following classes were tested: cinnamic acids; flavonols; flavanols; anthocyanidins; isoflavones; and tannic acid. METHODS: Test compounds were dissolved in either water or oil/saline as vehicle and injected intravenously into normotensive rabbits. IOP was monitored hourly after injection and expressed as a percent relative to preinjection values. Controls were conducted using vehicle alone. IOP from each eye was averaged to provide one value per rabbit. Dose-response data beginning at 0.01 mg-2 mg doses were collected for compounds shown to be active at 1 mg. RESULTS: Epigallocatechin, epigallocatechin gallate and myricetin lowered IOP below control levels at doses of 1 mg. Tannic acid was the most active, lowering IOP more than 30% at doses of 200 microg. CONCLUSION: Only phenolic antioxidants containing a pyrogallol B-ring system and nonaromatic C-ring (epigallocatechin, epigallocatechin gallate and myricetin) or possible galloyl glucosides as found in tannic acid were active in lowering IOP, with tannic acid being the most active. Other antioxidants were not active in this system suggesting a more specific structural requirement for interacting with appropriate ocular systems. The protein or proteoglycan-binding properties of these molecules may also be important in this activity.
Animals↗
An 18-year longitudinal study of untreated mucogingival defects.
BACKGROUND: A study was conducted to observe the changes in areas with untreated mucogingival defects over an 18-year period. The results in this group after 4 and 10 years were previously published. METHODS: Upon entering dental school, a group of 39 freshman dental students were assessed for plaque index, gingival index, probing depth, and width of keratinized tissue. At that time, 112 sites of inadequate keratinized gingiva were found. Seventeen of the original 39 participants with a total of 61 sites were reassessed for the same parameters after 18 years. RESULTS: The results revealed that 19 sites showed a slight increase in keratinized tissue, 35 were unchanged (for a total of 54 stable sites), and 7 sites showed a slight decrease in keratinized tissue. The mean width of keratinized tissue at the beginning of the study was 1.74+/-0.545 mm and 2.02+/-0.885 mm after 18 years. This represented a small, but statistically significant increase in the width. The plaque index (PI) and gingival index (GI) of this group at baseline (PI = 0.77+/-0.439 and GI = 0.93+/-0.447) and at 18 years (PI = 0.36+/-0.344 and GI = 0.65+/-0.303) indicated a high level of oral hygiene and gingival health. CONCLUSIONS: It was concluded that in the absence of gingival inflammation, areas with small amounts of keratinized tissue may remain stable over long periods of time.
Dental Plaque Index↗
Second trimester levels of pregnancy associated plasma protein-A in cases of trisomy 18.
In a study of 70 cases of trisomy 18 and 450 matched controls in the second trimester we have measured the maternal serum levels of the analytes alpha feto protein (AFP), free beta-human chorionic gonadotrophin (hCG) and pregnancy associated plasma protein-A (PAPP-A). We have found the median multiple of the median (MoM) of maternal serum free beta-hCG to be significantly lower (0.327) than normal, as was the level of AFP (0.600). Levels of PAPP-A were reduced even further (0.108). Of the markers associated with trisomy 18 at this time PAPP-A was the most discriminatory, being lower than the 5 per cent centile of normal in 93 per cent of cases, compared with 57 per cent of cases for free beta-hCG and 32 per cent of cases for AFP. Combining free beta-hCG and PAPP-A or all three markers with maternal age would have the ability to detect 74 per cent of cases at a 0.5 per cent false positive rate (or 64 per cent at a 0.1 per cent false positive rate). Unlike in cases of trisomy 21, the low PAPP-A values observed in the first trimester are continued into the second trimester. Whether the good discriminatory power of PAPP-A can be realized in second trimester screening programmes will depend on developing two stage screening algorithms. This approach is unlikely to be better than the excellent detection rates achievable with free beta-hCG, PAPP-A and nuchal translucency in the first trimester.
Adult↗
Treatment strategies for adolescents with hemophilia: opportunities to enhance development.
For adolescents, negotiating developmental tasks while living with hemophilia can be difficult. Affected adolescents must somehow negotiate tasks inherent within normal adolescent development, along with the added complications of hemophilia. Complications may include changes in physical appearance due to a history of bleeding episodes and the need for adolescents to think about the consequences of neglected treatment before they are developmentally ready. However, current strategies employed in the treatment of hemophilia have provided adolescents, their families, and their caregivers with opportunities to minimize the impact of hemophilia on adolescent development. Self-infusion minimizes the social impact by allowing adolescents to quietly leave the classroom, treat themselves, and return to class without notice. Prophylactic care maintains a factor level that allows adolescents to participate in many more activities. A multidisciplinary treatment center model for care promotes focused care, education, and anticipatory guidance to minimize the impact and help families adjust to chronic illness. Strong state and national leadership provides research advocacy and funding support for adolescent programming.
Adolescent↗
Marijuana smoking vs cannabinoids for glaucoma therapy.
OBJECTIVE: To discuss the clinical effects, including toxicological data, of marijuana and its many constituent compounds on the eye and the remainder of the body. A perspective is given on the use of marijuana and the cannabinoids in the treatment of glaucoma. RESULTS: Although it is undisputed that smoking of marijuana plant material causes a fall in intraocular pressure (IOP) in 60% to 65% of users, continued use at a rate needed to control glaucomatous IOP would lead to substantial systemic toxic effects revealed as pathological changes. CONCLUSIONS: Development of drugs based on the cannabinoid molecule or its agonists for use as topical or oral antiglaucoma medications seems to be worthy of further pursuit. Among the latter chemicals, some have no known adverse psychoactive side effects. Smoking of marijuana plant material for the reduction of elevated IOP in glaucoma is ill-advised, given its toxicological profile.
Cannabinoids↗
Proteolysis of connexin43-containing gap junctions in normal and heat-stressed cardiac myocytes.
OBJECTIVE: The present studies were performed to examine the degradation of connexin43-containing gap junctions by the lysosome or the proteasome in normal and heat-stressed cultures of neonatal rat ventricular myocytes. METHODS: Primary cultures were prepared from neonatal rat ventricular myocytes. Connexin43 was detected by immunoblotting, immunofluorescence, or immunoprecipitation. Gap junction profiles were detected by transmission electron microscopy. RESULTS: Immunoblots of whole cell lysates demonstrated increased levels of connexin43 in cultures treated with lysosomal inhibitors (chloroquine, leupeptin, E-64, or ammonium chloride) or proteasomal inhibitors (lactacystin or ALLN). Pulse-chase experiments showed that the half-life of connexin43 was 1.4 h in control cultures, but was prolonged to 2.0 or 2.8 h in cultures treated with chloroquine or lactacystin, respectively. Immunofluorescence and electron microscopy showed a significant increase in the number of gap junction profiles in myocytes treated with either chloroquine or lactacystin. Heat treatment of cultures (43.5 degrees C for 30 min) produced a rapid loss of connexin43 as detected by immunoblotting or immunofluorescence. Heat-induced connexin43 degradation was prevented by simultaneous treatment with lactacystin, ALLN, or chloroquine. Connexin43 levels and distribution returned to normal by 3 h following a heat shock and were resistant to a subsequent repeat heat stress. The heat shock also led to production of HSP70 as detected by immunoblotting. CONCLUSIONS: These data suggest that Cx43 gap junctions in myocytes are degraded by the proteasome and the lysosome, that this proteolysis can be augmented by heat stress, and that inducible factors such as HSP70 may protect against Cx43 degradation.
Acetylcysteine↗
A minimal avian retroviral packaging sequence has a complex structure.
We have defined a 160-nucleotide region, Mpsi, from the 5' leader region of the Rous sarcoma virus genome that is sufficient to direct the packaging of a heterologous RNA. Mpsi contains the putative O3 stem structure that has previously been shown, and that has been confirmed in this study, to be important for the efficient packaging of avian leukosis-sarcoma virus RNA. Analyses of several O3 stem mutants revealed that other regions within Mpsi can interfere with the proper folding of altered sequences which are predicted to form a wild-type O3 stem.
Avian Sarcoma Viruses↗
Adiposity and serum leptin increase in fatty (fa/fa) BNZ neonates without decreased VMH serotonergic activity.
Decreased ventromedial hypothalamic (VMH) serotonergic activity occurs in genetic and diet-induced animal models of obesity. We previously found that this activity was lower in adult and in 12-day-old Zucker fa/fa vs. Fa/Fa pups, the fa/fa animals being identified by their greater adiposity. In the present study, we evaluated fa/fa rats (Brown Norway-Zucker hybrids) at ages 2, 4, 7, and 12 days to test the hypothesis that lower VMH serotonergic activity occurs before increased adiposity and/or attenuated energy expenditure. Our results negate this hypothesis. VMH serotonergic activity showed no consistent genotype differences even at 12 days of age. In contrast, by day 7, fa/fa vs. Fa/Fa pups had higher serum leptin concentrations, greater percent body fat, lower resting and cold-induced energy expenditure, and lower activity of brown fat thyroxine 5'-deiodinase, an enzyme that converts thyroxine to triiodothyronine. We conclude that the onset of increased adiposity induced by the fa gene does not require decreased VMH serotonergic activity and that the lower serotonergic activity seen in older fa/fa pups may be secondary to metabolic consequences of the disruption of the leptin regulatory pathway.
Adipose Tissue↗
Kinetics of fluid delivery from methylcellulose sponges.
PURPOSE: The authors quantitatively evaluate the kinetics of fluid transfer from microsurgical sponges in a laboratory model to understand the kinetics of mitomycin C (MMC) delivery. METHODS: The amount of fluid transferred from soaked methylcellulose (Weck-cel, Weck Inc., Durham, NC, U.S.A.) sponges to small pieces of hydrated or dry filter paper used to simulate episcleral tissue and Tenon fascia was measured as a function of time, sponge size, hydration status of the filter paper, and technique of sponge application. RESULTS: The time course of fluid delivery from methylcellulose sponges to filter paper was nonlinear and characterized by a rapid delivery phase over the first 15 to 30 seconds, followed by a slow phase extending to at least 5 minutes. Sponge size and baseline hydration of the paper significantly influenced the rate and amount of fluid delivered, as did replacing the sponge every minute with a new sponge. CONCLUSION: The transfer of fluid from a microsurgical sponge displays nonlinear kinetics, with the majority of delivery occurring in the first 15 to 30 seconds. Sponge size, hydration of the recipient tissue, and technique of sponge application are significant variables influencing the amount of fluid, and therefore mitomycin C, delivered.
Antibiotics, Antineoplastic↗
Marketing health care products on the Internet: a proposal for updated federal regulations.
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Consumer Product Safety↗
Population-based surveillance for group A streptococcal necrotizing fasciitis: Clinical features, prognostic indicators, and microbiologic analysis of seventy-seven cases. Ontario Group A Streptococcal Study.
PURPOSE: To determine the incidence of group A streptococcal necrotizing fasciitis in Ontario, Canada, and to describe the clinical features, outcome, and microbiologic characteristics of this infection. PATIENTS AND METHODS: Prospective, population-based surveillance for invasive group A streptococcal infections was conducted in Ontario from November 1991 to May 1995. All 77 patients meeting clinical and/or histopathologic criteria for streptococcal necrotizing fasciitis were included. Demographic and clinical information was obtained by patient interviews and chart review. Group A streptococci were characterized by M-protein and T-agglutination typing, and polymerase chain reaction (PCR) detection of streptococcal pyrogenic exotoxin genes A and C (speA; speC). RESULTS: The incidence of group A streptococcal necrotizing fasciitis increased during the study from 0.085 per 100,000 population in the first year to 0.40 per 100,000 population in the last year (P < 0.001). The median age of cases was 57.5 years and the rate of disease increased with increasing age. Seventy-nine percent of cases were community-acquired, 11% were nosocomial, and 10% were acquired in a nursing home. Forty-seven percent of cases were associated with the presence of streptococcal toxic shock syndrome (Strep TSS) and 46% were bacteremic. Thirty-four percent of cases died and mortality was correlated with increasing age (P = 0.006), presence of hypotension (P = 0.01), and bacteremia (P = 0.03). The most common streptococcal serotypes were M1 (35%) and M3 (25%). Forty-one percent of strains possessed the speA gene and 30% the speC gene. Outcome was not correlated with M-type or the presence of spe genes. CONCLUSIONS: The incidence of necrotizing fasciitis caused by group A streptococcus increased in Ontario between 1992 and 1995. Elderly individuals were more likely to acquire the disease and to die from it. Mortality because of streptococcal necrotizing fasciitis was also associated with the presence of hypotension, Strep TSS, or bacteremia, but not with M-type or the presence of pyrogenic exotoxin genes.
Aged↗
Perceptual adjustment to highly compressed speech: effects of talker and rate changes.
This study investigated the perceptual adjustments that occur when listeners recognize highly compressed speech. In Experiment 1, adjustment was examined as a function of the amount of exposure to compressed speech by use of 2 different speakers and compression rates. The results demonstrated that adjustment takes place over a number of sentences, depending on the compression rate. Lower compression rates required less experience before full adjustment occurred. In Experiment 2, the impact of an abrupt change in talker characteristics was investigated; in Experiment 3, the impact of an abrupt change in compression rate was studied. The results of these 2 experiments indicated that sudden changes in talker characteristics or compression rate had little impact on the adjustment process. The findings are discussed with respect to the level of speech processing at which such adjustment might occur.
Female↗
Evidence against cannabinoid receptor involvement in intraocular pressure effects of cannabinoids in rabbits.
Cannabinoid receptor involvement in the intraocular-pressure (IOP)-lowering effect of the cannabinoids has not been determined. These receptors bind four structural classes of agonists: the classical and the nonclassical cannabinoids, the aminoalkylindoles and the arachidonylethanolamides (the endogenous ligands). We examined the IOP effect in normotensive rabbits after systemic administration of an aminoalkylindole, WIN-55,212-2, and of (R)-(+)-methanandamine, a hydrolysis-resistant endogenous ligand derivative. The decrease in IOP for 6 animals treated with WIN-55,212-2 was marginal and for 6 animals treated with (R)-(+)-methanandamide was negligible compared to animals treated with vehicle alone. These studies suggest that the IOP-lowering effects of cannabinoids are not mediated by a cannabinoid receptor in rabbits.
Animals↗
Invasive group A streptococcal infections in Ontario, Canada. Ontario Group A Streptococcal Study Group.
BACKGROUND: Several reports suggest that the incidence of invasive group A streptococcal infections, including streptococcal toxic shock syndrome and necrotizing fasciitis, is increasing. METHODS: During 1992 and 1993 we conducted prospective, population-based surveillance of invasive group A streptococcal disease in Ontario, Canada. We reviewed clinical and laboratory records, searched for secondary cases of invasive disease, and cultured specimens from household contacts. RESULTS: We identified 323 patients with invasive group A streptococcal infections, for an annual incidence of 1.5 cases per 100,000 population. The rates were highest in young children and the elderly. Fifty-six percent of the patients had underlying chronic illness. Risk factors for disease included infection with the human immunodeficiency virus, cancer, diabetes, alcohol abuse, and chickenpox. The most common clinical presentations were soft-tissue infection (48 percent), bacteremia with no septic focus (14 percent), and pneumonia (11 percent). Necrotizing fasciitis occurred in 6 percent of patients, and toxic shock in 13 percent. The mortality rate was 15 percent overall, but it was 29 percent among those over 64 years of age (P<0.001) and 81 percent among those with toxic shock (P<0.001). Fourteen percent of the cases were nosocomial, and 4 percent occurred in nursing home residents, often in association with disease outbreaks. Invasive disease occurred in 2 household contacts of patients with infection, for an estimated risk of 3.2 per 1000 household contacts (95 percent confidence interval, 0.39 to 12 per 1000). CONCLUSIONS: The elderly and those with underlying medical conditions are at greatest risk for invasive group A streptococcal disease, toxic shock, and necrotizing fasciitis. Invasive steptococcal infection is associated with a substantial risk of transmission in households and health care institutions.
Adolescent↗
Inhibition of cataracts in moderately diabetic rats by aminoguanidine.
The effect of aminoguanidine (AG), an inhibitor of advanced glycation, on the development of cataracts was studied in diabetic rats. Rats were made diabetic with streptozotocin, and based on the level of plasma glucose they were grouped as moderately (< 350 mg dl-1 plasma glucose) and severely (> 350 mg dl-1 plasma glucose) diabetic. One half of the animals in each group received AG (25 mg kg-1 body weight each day), intraperitoneally, starting from the day of streptozotocin injection. Progression of lens opacification was recorded using Fundus and Scheimpflug photography at regular time intervals. On the ninetieth day all the rats were killed and the levels of advanced glycation end products (AGE) was determined by measuring the non-tryptophan fluorescence of the lens soluble and insoluble fractions. Densitometric analysis of Scheimpflug images showed that in diabetic rats lens opacification progressed in a biphasic manner, an initial slow progression for the first 60 days, followed by a steep increase during next 30 days. Moderately and severely diabetic rats developed lens opacities more or less at the same time. AGE fluorescence in the lens soluble fractions increased three-fold and seven-fold in the moderately and severely diabetic rats, respectively; whereas in insoluble fractions there was a 30% and three-fold increase in the moderately and severely diabetic rats, respectively. Although AG treatment inhibited the AGE fluorescence of lens soluble and insoluble fractions by about 56% and 75% in moderately diabetic and by 19% and 52% severely diabetic rats, respectively, the development of cataracts was delayed only in the moderately diabetic rats. These results thus suggest that the effect of AG is indeed inhibition of the formation of AGEs. However, in the severely diabetic rats the beneficial effect of AG is overwhelmed by the excessive accumulation of AGEs.
Animals↗
Longitudinal tear study after cyclosporine in kidney transplant recipients.
PURPOSE: To determine Schirmer wetting (tear flow) in patients before and after kidney transplantation where systemic cyclosporine was used as an immunosuppressive. METHODS: Patients with end-stage renal disease who received living donor or cadaveric kidney transplants and simultaneous systemic cyclosporine were recruited. A 4-minute Schirmer test with topical anesthetic was performed in both eyes of each person before cyclosporine was initiated and three times after transplantation. The tear flow values from both eyes were averaged before analysis. RESULTS: Tear flow increased significantly from precyclosporine levels of 19.4 +/- 1.5 mm/4 minutes (mean +/- standard error of the mean, n = 7; readings at 1 to 3 days before cyclosporine was begun) to 28.4 +/- 2.4 mm/4 minutes at 1 to 2 months after cyclosporine (P < 0.01), 26.4 +/- 2.0 mm/4 minutes at 3 to 5 months (P < 0.05), and 24.4 +/- 2.1 mm/4 minutes at 9 to 18 months (P < 0.05) after initiation of cyclosporine therapy. No relation existed between tear flow and systemic cyclosporine concentration. CONCLUSION: Tear flow was significantly enhanced by systemic cyclosporine when given to renal allograft recipients as an immunosuppressive. The increased flow rate was sustained over the maximum follow-up of 18 months and indicates an unexpected, beneficial side effect of cyclosporine, even in the absence of a deficit in baseline tear production.
Adult↗