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Biomedical subjects

M Riddle

Publications and source records attributed to M Riddle.

At least 19 recordsLinked to original sources
PubMed2004

A picture of amputees and the prosthetic situation in Haiti.

PURPOSE: The purpose of this study is to present the situation of Haitian amputees and to outline some of the major barriers in Haiti that prevent people from receiving prosthetic treatment. METHOD: Interviews were conducted with amputees throughout Haiti using a 42-question questionnaire. Additionally, interviews were conducted with traditional healers, health care workers, and leaders of handicap associations. Each interview was manuscripted and the data were subsequently coded and analysed in the USA. RESULTS: There are three full-time prosthetic shops and two part-time prosthetic shops in Haiti, all of which are severely limited in the scope of services they are able to provide amputees due to insufficient supplies and inadequately trained personnel. Only 25% of the 164 amputees interviewed had ever had a prosthetic limb. Typically prosthetic treatment is inaccessible and unaffordable for amputees, which prevents many from seeking treatment. The most common cause of amputation in Haiti is infection, followed by motor vehicle accidents. CONCLUSION: There must be additional cooperation between Haitian patients, doctors, traditional healers, prosthetists, and government officials in order to provide more adequate prosthetic care. Prosthetic treatment in Haiti can be successful with cooperation of different entities, proper rehabilitation therapy, adequately trained personnel, and development of culturally appropriate limbs.

Adolescent↗
PubMed2001

Leader protein of encephalomyocarditis virus binds zinc, is phosphorylated during viral infection, and affects the efficiency of genome translation.

Encephalomyocarditis virus (EMCV) is the prototype member of the cardiovirus genus of picornaviruses. For cardioviruses and the related aphthoviruses, the first protein segment translated from the plus-strand RNA genome is the Leader protein. The aphthovirus Leader (173-201 amino acids) is an autocatalytic papain-like protease that cleaves translation factor eIF-4G to shut off cap-dependent host protein synthesis during infection. The less characterized cardioviral Leader is a shorter protein (67-76 amino acids) and does not contain recognizable proteolytic motifs. Instead, these Leaders have sequences consistent with N-terminal zinc-binding motifs, centrally located tyrosine kinase phosphorylation sites, and C-terminal, acid-rich domains. Deletion mutations, removing the zinc motif, the acid domain, or both domains, were engineered into EMCV cDNAs. In all cases, the mutations gave rise to viable viruses, but the plaque phenotypes in HeLa cells were significantly smaller than for wild-type virus. RNA transcripts containing the Leader deletions had reduced capacity to direct protein synthesis in cell-free extracts and the products with deletions in the acid-rich domains were less effective substrates at the L/P1 site, for viral proteinase 3Cpro. Recombinant EMCV Leader (rL) was expressed in bacteria and purified to homogeneity. This protein bound zinc stoichiometrically, whereas protein with a deletion in the zinc motif was inactive. Polyclonal mouse sera, raised against rL, immunoprecipitated Leader-containing precursors from infected HeLa cell extracts, but did not detect significant pools of the mature Leader. However, additional reactions with antiphosphotyrosine antibodies show that the mature Leader, but not its precursors, is phosphorylated during viral infection. The data suggest the natural Leader may play a role in regulation of viral genome translation, perhaps through a triggering phosphorylation event.

Amino Acid Motifs↗
PubMed2001

Combined effects of ultraviolet-B radiation and food shortage on the sensitivity of the Antarctic amphipod Paramoera walkeri to copper.

Investigations on the combined effects of ultraviolet (UV)-B radiation and anthropogenic toxicants have focused primarily on the chemical interactions between UV-B and organic compounds. Only a few studies have examined whether exposure to UV-B changes sensitivity to toxicants. This question is addressed in a laboratory study using the common shoreline Antarctic amphipod Paramoera walkeri and exposure to environmentally realistic levels of copper, UV-B radiation, and food shortage. Exposure to copper for 21 d in the absence of any additional stressors (food present, no UV-B) showed a lowest observable effective concentration (LOEC) of greater than 100 microg Cu/L. Exposure to copper and UV-B in combination, with no shortage of food, resulted in a LOEC of 45 microg Cu/L. When exposed to copper and UV-B, with shortage of food, a LOEC of 3 microg Cu/L was recorded. Hence, the combination of environmental stress from exposure to UV-B radiation and shortage of food increases the sensitivity of P. walkeri to copper more than 30-fold. Increased metabolic energy requirements for defense mechanisms in response to toxicants and UV-B are discussed as possible explanations. It is concluded that consideration of environmental stressors in combination with toxicants increases the accuracy of ecological risk assessments of toxicants and should be part of the process for developing guidelines for ecologically acceptable concentrations of contaminants in the environment.

Adaptation, Physiological↗
PubMed2000

Complex segregation analysis provides compelling evidence for a major gene underlying obsessive-compulsive disorder and for heterogeneity by sex.

Evidence from twin and family studies supports a genetic etiology for obsessive-compulsive disorder (OCD). The purpose of this study was to test whether a major gene is implicated in a proportion of families with OCD. Complex segregation analyses of 153 families (80 case and 73 control), ascertained in the Johns Hopkins OCD Family Study, provided strong evidence for a major gene. A Mendelian-dominant model, with significant sex effects and with residual familial effects, best explained the observed data. Stratification of the sample by the sex of probands provided further evidence of heterogeneity with respect to familial aggregation. Segregation analyses of 86 families with a female proband and of the 67 families with a male proband suggested that a Mendelian-dominant model with familial residual effects was the most parsimonious model explaining the inheritance of OCD in both subgroups.

Adolescent↗
PubMed2000

Effects of contaminants in the Antarctic environment - potential of the gammarid amphipod crustacean Paramorea walkeri as a biological indicator for Antarctic ecosystems based on toxicity and bioacccumulation of copper and cadmium.

This study provides information on LC(50) toxicity tests and bioaccumulation of heavy metals in the nearshore Antarctic gammarid, Paramorea walkeri. The 4 day LC(50) values were 970 µg/l for copper and 670 µg/l for cadmium. Net uptake rates and bioconcentration factors of these elements were determined under laboratory conditions. After 12 days of exposure to 30 µg/l, the net uptake rates were 5.2 and 0.78 µg/g per day and the bioconcentration factors were 2080 and 311 for copper and cadmium, respectively. The body concentrations of copper were significantly correlated with the concentrations of this element in the water. Accumulation of copper and cadmium continued for the entire exposure suggesting that heavy metals concentrations were not regulated to constant concentrations in the body. Using literature data about two compartments (water-animal) first-order kinetic models, a very good agreement was found between body concentrations observed after exposure and model predicted. Exposure of P. walkeri to mixtures of copper and cadmium showed that accumulation of these elements can be assessed by addition of results obtained from single exposure, with only a small degree of uncertainty. The study provides information on the sensitivity of one Antarctic species towards contaminants, and the results were compared with data of similar species from lower latitudes. An important finding is that sensitivity to toxic chemicals and toxicokinetic parameters in the species investigated are comparable with those of non-polar species. The characteristics of bioaccumulation demonstrate that P. walkeri is a circumpolar species with the potential to be a standard biological indicator for use in monitoring programmes of Antarctic nearshore ecosystems. The use of model prediction provide further support to utilise these organisms for biomonitoring.

Journal Article↗
PubMed2000

Combining sulfonylureas and other oral agents.

Type 2 diabetes mellitus is a progressive disorder, and although oral monotherapy is often initially successful, it is associated with a high secondary failure rate, which contributes to the development of long-term diabetes complications resulting from persistent hyperglycemia. For patients not taking insulin, accumulating evidence suggests that combination therapy using oral antidiabetic agents with different mechanisms of action may be highly effective in achieving and maintaining target blood glucose levels. Low-dose combination therapy may be associated with fewer side effects than higher-dose monotherapy and may achieve similar or better glycemic control. The best-studied combination is that of sulfonylurea compounds plus metformin, a therapeutic approach that addresses both underlying defects in the disorder: insulin deficiency and insulin resistance. Other multidrug regimens under investigation are sulfonylurea compounds plus either alpha-glucosidase inhibitors or thiazolidinediones, and combinations of various insulin-sensitizing agents. For many patients, combination oral therapy may be used appropriately as primary management early in the course of type 2 diabetes, along with diet modification and exercise. Later in the course of the disease, the use of combinations of oral agents may delay the need for insulin while maintaining glycemic control, thus making aggressive oral treatment more acceptable for many patients.

Acarbose↗
PubMed2000

A family study of obsessive-compulsive disorder.

BACKGROUND: The causes of obsessive-compulsive disorder (OCD) are as yet unknown. Evidence of familial aggregation is one approach for investigating the role of genetics in the etiology of this condition. The current study was conducted to determine ifOCD is familial and to investigate possible familial subtypes. METHODS: Eighty case probands were identified in 5 specialty OCD clinics and 73 community control probands were identified by random-digit dialing. These probands and their first-degree relatives (343 case and 300 control relatives) were blinded to group and evaluated by psychiatrists and doctoral-level clinical psychologists using semistructured instruments. Final diagnoses were assigned by a blinded-consensus procedure. The results were analyzed using logistic regression by the method of generalized estimating equations. RESULTS: The lifetime prevalence of OCD was significantly higher in case compared with control relatives (11.7% vs 2.7%) (P<.001). Case relatives had higher rates of both obsessions and compulsions; however, this finding is more robust for obsessions. Age at onset of obsessive-compulsive symptoms in the case proband was strongly related to familiality (odds ratio, 0.92; confidence interval, 0.85-0.99) (P = .05); no case of OCD symptoms was detected in the relatives of probands whose age at onset of symptoms was 18 years or older. Probands with tics or obsessive-compulsive personality disorder were not more likely to have relatives with OCD than those without these features. CONCLUSIONS: Obsessive-compulsive disorder is a familial disorder. Obsessions are more specific to the phenotype than are compulsions. Age at onset of OCD is valuable in characterizing a familial subtype.

Adolescent↗
PubMed1999

Rapid gas chromatographic analysis of drugs of forensic interest.

High-speed gas chromatographic (GC) screening for drugs of forensic relevance is performed using a commercial Flash GC instrument in which the chromatographic column is resistively heated at rates of up to 30 degrees C/s. Temperature programming conditions are varied in an experiment designed to evaluate trade-offs between resolution and analysis time for a mixture of 19 drugs of abuse. All 19 components can be separated with excellent resolution in 90 s. Specific analytes can be analyzed even faster; for example, amphetamine analysis is completed in less than 20 s. Case studies of confiscated street drugs containing amphetamine, cocaine, and heroin are analyzed to evaluate the retention time repeatability. Ten replicate injections over a 2-day period for 3 different drug samples achieved retention time relative standard deviations in the range of 0.48 to 0.81%.

Amphetamine↗
PubMed1998

Assessment issues in treatment research of pediatric anxiety disorders: what is working, what is not working, what is missing, and what needs improvement.

Reviewing the strengths and weaknesses of the rating scales for anxiety disorders makes it possible to select appropriate measures for use in a multisite treatment study of children and adolescents with DSM-IV-diagnosed anxiety disorders. Categorical diagnosis for study inclusion is provided by the K-SADS-PL, which has strong published psychometrics for anxiety disorders. Broadband symptom ratings of diverse pediatric psychiatric disorder can be obtained at baseline by the parent-scored Child Behavior Checklist. Anxiety symptom monitoring may be provided by the use of two psychometrically strong self-report measures, the MASC and the SCARED. Weekly global ratings are provided by the CGI whose scale points have been enhanced by detailed anchors; in addition, the raters all trained on practice vignettes to calibrate their scoring. Clinician-based ratings of the patient's anxiety symptoms can be carried out in adolescent patients using the HAM-A. The newly developed Children's Anxiety Rating Scale promises to cover the full pediatric age range as a clinician-based anxiety rating instrument, but must first be subjected to formal psychometric and treatment sensitivity evaluation.

Anxiety Disorders↗
PubMed1998

Obsessive-compulsive disorder in children and adolescents.

BACKGROUND: Obsessive-compulsive disorder (OCD) is a common psychiatric condition that usually emerges during childhood or adolescence. Over 80% of individuals with OCD have their onset before age 18 years. Epidemiologic studies suggest a prevalence of 1-2% for adolescents. METHOD: This article reviews current knowledge of paediatric OCD in the following areas: age of onset, nosology and classification, subtypes, prevalence, aetiology, pathophysiology, assessment, prognosis and treatment. RESULTS: Essential components of treatment include long-term commitment, care management and illness education. Specific components of treatment include cognitive-behavioural therapy, parent behaviour management training and medication. CONCLUSIONS: The most effective treatments are selective serotonin reuptake inhibitors (e.g. fluvoxamine, sertraline) and exposure/response prevention.

Adolescent↗
PubMed1996

Elevated cerebrospinal fluid corticotropin-releasing factor in Tourette's syndrome: comparison to obsessive compulsive disorder and normal controls.

Stress- and anxiety-related fluctuations in tic severity are cardinal features of Tourette's syndrome (TS), and there is evidence for involvement of noradrenergic mechanisms in the pathophysiology and treatment of the disorder. To examine further the pathobiology of this enhanced vulnerability to stress and anxiety, we measured central activity of corticotropin-releasing factor (CRF) in patients with TS and the related condition, obsessive compulsive disorder (OCD). Lumbar cerebrospinal fluid (CSF) was obtained in a standardized fashion for measurement of CRF from 21 medication-free outpatients with TS, 20 with OCD, and 29 healthy controls. The TS patients had significantly higher levels of CSF CRF than both the normal controls and the OCD patients. However, there was no difference in CSF CRF between the OCD patients and the normal controls. Group differences in CSF CRF were unrelated to current clinical ratings of depression, anxiety, tics, and obsessive compulsive behaviors. Although the functional significance of this finding remains to be elucidated, these results are consistent with the hypothesis that stress-related neurobiological mechanisms may play a role in the pathobiology of TS.

Adolescent↗
PubMed1994

Enhanced stress responsivity of Tourette syndrome patients undergoing lumbar puncture.

Tourette's syndrome (TS) is a complex inherited neuropsychiatric disorder that is characterized by multiple motor and phonic tics. Stress-related fluctuations in symptom severity and medication responsiveness are common, and patients often report that tics are worsened by fatigue, emotional trauma, and anxiety. We examined the effects of lumbar puncture (LP) stress on plasma adrenocorticotropin (ACTH) and cortisol, urinary catecholamines, and self- and clinician ratings of anxiety in 13 medication-free TS patients and 10 normal controls, ages 17 to 41 years. The TS patients secreted significantly more ACTH than the normal controls in response to the stress of the lumbar puncture. Compared to the controls the TS patients had significantly greater postLP mean and postLP peak ACTH levels. The TS patients also excreted significantly more norepinephrine in the 20 hr preceding the lumbar puncture and reported higher levels of anxiety before and during the procedure than the controls. In addition, urinary norepinephrine excretion of the TS patients was significantly correlated with clinician ratings of tic severity. The results were not related to current levels of depression and anxiety. Taken together, these findings suggest that a subset of TS patients may be characterized by heightened reactivity of the hypothalamic-pituitary-adrenal axis and related noradrenergic sympathetic systems.

Adrenocorticotropic Hormone↗
PubMed1994

Effects of vitamin D on insulin and glucagon secretion in non-insulin-dependent diabetes mellitus.

Vitamin D has been shown to increase insulin release from pancreatic islet cells in vitro, and to improve insulin secretion in vitamin D-deficient animals. Few attempts have been made to evaluate this issue directly in humans. We studied 35 otherwise healthy diabetic subjects in the early spring at the seasonal nadir of 25-hydroxyvitamin D [25(OH)D] concentrations (mean 35 +/- 7 nmol/L). Fasting glucose, insulin, C-peptide, and glucagon concentrations, and their responses to Sustacal stimulation were not related to indexes of mineral metabolism. In 20 subjects, a double-blinded, placebo-controlled, crossover trials of 1,25-dihydroxyvitamin D[1,25](OH)2D] treatment (1 micrograms/d for 4 d) had no effect on fasting or stimulated glucose, insulin, C-peptide, or glucagon concentrations. However, insulin and C-peptide responses to Sustacal after 1,25(OH)2D treatment were related to duration of diabetes (r2 = 0.28, P = 0.052 and r2 = 0.25, P = 0.002, respectively) in that short duration correlated with improvement after 1,25(OH)2D treatment. Hence, vitamin D nutrition, or 1,25(OH)2D therapy, had no major effect on glucose homeostasis in non-insulin-dependent diabetes mellitus.

Adult↗
PubMed1993

The hypotriglyceridemic effect of fish oil in adult-onset diabetes without adverse glucose control.

Diabetic control as judged by five criteria did not deteriorate after 6 months of fish oil compared to 6 months of olive oil supplementation in 16 patients with NIDDM who were eating a low fat, high complex carbohydrate diet. Plasma total and VLDL triglyceride and cholesterol decreased significantly after fish oil supplementation; plasma total and HDL cholesterol concentrations did not change. The LDL cholesterol level was significantly increased with fish oil supplementation, suggesting that patients with NIDDM who are given a fish oil supplement to decrease the plasma total and VLDL triglyceride levels may also need further dietary and/or pharmaceutical therapy to maintain an LDL cholesterol level compatible with a low risk of coronary disease. The study emphasizes the safe use of fish oil over a 6-month period in diabetic patients.

Aged↗
PubMed1992

Combined therapy for obese type 2 diabetes: suppertime mixed insulin with daytime sulfonylurea.

Combined insulin and sulfonylurea therapy for type 2 diabetes may improve the effectiveness of a single injection of insulin, thereby postponing the need for multiple injections. This concept was tested in 21 obese subjects imperfectly controlled by 20 mg of glyburide daily in a double masked, placebo-controlled, parallel design, 16-week protocol. Premixed 70% NPH/30% Regular insulin was taken before supper, and the dosage was adjusted weekly by an algorithm seeking nearly normal fasting glycemia. Eleven subjects using insulin plus 10 mg glyburide before breakfast had lower mean fasting glucose at 10-16 weeks than 10 subjects using insulin with placebo (mean +/- SEM; 5.9 +/- 0.3 versus 7.5 +/- 0.7 mmol/L; p less than 0.05), and had a greater decrement of glycosylated hemoglobin from baseline values (1.3 +/- 0.1 versus 0.8 +/- 0.2% A1, p less than 0.05). After 16 weeks the combined therapy group used half as much insulin as the insulin-only group (50 +/- 5 versus 101 +/- 13 units/d; p less than 0.01). Fasting serum free insulin values increased 58% from baseline after insulin therapy in the insulin-only group (p less than 0.05) but did not increase with combined therapy. Weight gain was similar in the two groups. These data support this form of combined therapy as one option for treating obese persons with type 2 diabetes no longer responsive to oral therapy alone.

Adult↗