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Biomedical subjects

M Armstrong

Publications and source records attributed to M Armstrong.

At least 91 records · Page 5Linked to original sources

Comparative ability of various prescription and over-the-counter topical antifungal drug products to inhibit the growth of C. albicans.

On September 23, 1993, the Food and Drug Administration (FDA) published the final monograph and rule for topical antifungal drug products. This monograph specifies the ingredients, concentration, and labeling under which over-the-counter (OTC) topical antifungal drug products may be marketed without further FDA approval. Currently, the nine products tested are labeled as antifungal because of their ability to inhibit the growth of yeast (C. albicans) in vitro. Over-the-counter products containing 2% miconazole nitrate--an ingredient and concentration identified as safe and effective--were found to inhibit the growth of C. albicans as effectively as mycostatin cream. Two percent miconazole nitrate was also inhibitory to C. albicans at greater dilutions than five other antifungal products containing chloroxylenol and clotri mazole. Chloroxylenol and clotrimazole are nonmonographed ingredients.

Administration, Topical↗

The laboratory investigation of infective keratitis.

Microbial keratitis is an infectious inflammation of the cornea which, if not rapidly diagnosed, may lead to loss of vision. The investigative procedures are demanding for the ophthalmologist and confirmative diagnosis a formidable challenge to the microbiologist. Most, if not all, bacteria can cause keratitis. To establish a diagnosis culture is essential, since it is not possible clinically to distinguish between one type of infective keratitis and another. A relatively new and worrying problem is acanthamoebic keratitis, which is significantly associated with contact lens wear. It is increasing in incidence as lens wear becomes more popular. Although Acanthamoebae are easily isolated, many laboratories are not familiar with laboratory methods for diagnosis.

Acanthamoeba Keratitis↗

Promoting informed decision-making about tattooing for adolescents.

In the February issue, the authors identified tattooing as an adolescent at-risk behavior, summarizing adverse purchase and possession factors as well as potential health threats of blood-borne disease. This information stems from a study of adolescents in five suburban high schools and one large urban school district in Texas. Promoting self-identity seems to be the key motivation for the tattooing. Investigating specific risk-taking behaviors of adolescents is important in order to create applicable health-promotion strategies. This article summarizes the development of a health education brochure, which was created on the basis of a review of the literature, an analysis of data, and field testing of the product. The purpose of the health information is to emphasize potential risks, pose definite questions and actions to minimize the risks, and encourage reconsideration or postponement of tattoo decisions.

Adolescent↗

Phenotype/genotype relationships for the cytochrome P450 enzyme CYP2D6 in rheumatoid arthritis: influence of drug therapy and disease activity.

OBJECTIVE: To determine whether particular genotypes for the cytochrome P450 enzyme CYP2D6, a polymorphic enzyme, are associated with susceptibility to rheumatoid arthritis (RA) and whether CYP2D6 enzyme activity is altered as a result of the disease or its treatment. METHODS: CYP2D6 genotypes and metabolic phenotypes were determined for 53 patients with RA and 73 healthy controls. Genotyping was carried out by restriction fragment length polymorphism analysis with the restriction enzyme XbaI and by 2 separate polymerase chain reaction assays; phenotyping was by analysis of in vivo metabolism of the probe drug debrisoquin. RESULTS: No significant difference in the distribution of overall genotypes between the 2 groups was observed. When the frequency of individual alleles was investigated, a significant difference in allele frequency for the CYP2D6D allele (p < 0.005) was observed with fewer patients with RA showing this mutation. Metabolic phenotypes were broadly similar between the patients and controls. However, a number of the patients with RA showed higher than expected metabolic ratios for their particular genotype due to interference by the analgesic dextropropoxyphene in the phenotyping procedure. CONCLUSION: Our findings demonstrate that CYP2D6 activity is not impaired in RA.

Adult↗

Genotyping of the CYP2D6 gene in Norwegian lung cancer patients and controls.

Genotyping of five CYP2D6 alleles (wt, A,B,D,E) has been performed in 218 lung cancer patients and 289 healthy controls. PCR-methods were used to determine the CYP2D6A and CYP2D6B alleles. Both patients and controls were of Caucasian Norwegian origin. In the lung cancer group all major histological types were represented. The frequency of the CYP2D6B allele which is associated with poor metabolizers (PM), was 0.235 in the lung cancer population and 0.200 in the control population. The frequencies of the CYP2D6A allele, another mutant allele associated with the PM-phenotype, were 0.007 and 0.013 in the lung cancer and control population respectively. RFLP analysis using the restriction enzyme Xba I to determine the D and E alleles, was also performed on 178 of the patients and on 118 of the controls. The frequency of the deletion variant CYP2D6D (13 kb) was 0.025 in the lung cancer group and 0.012 in the control group. None of these frequencies in the lung cancer patients were statistically significantly different from the frequencies of the control population. When combining the PCR-typing results (CYP2D6A, CYP2D6B) 20 individuals were found to carry two PM-associated alleles in the lung cancer group (n = 204) compared with only six among the controls (n = 117). This corresponds to a PM frequency of 9.8% in the lung cancer population compared with 5.1% in the control population which is, however, not significantly different from each other. These results are not in concordance with previous results which suggest that the EM-phenotype is a susceptibility marker for lung cancer.

Adult↗

Fibroblast behavior in the embryonic chick heart.

Intracardiac fibroblasts (mesenchymal cells) of Hamburger and Hamilton stage 36 chick heart reside in the epicardium and atrioventricular valves. The characteristics of the epicardial fibroblasts include segregation from the myocytes of the heart wall myocardium, voluminous extracellular matrix production, and some cell proliferation activity. The atrioventricular fibroblasts intermingle with myocytes at the mutual border between these tissues, produce smaller amounts of extracellular matrix, and show very active cell proliferation. Is the behavior of each population of fibroblasts predetermined or is each responding in a reversible fashion to local environment? A cell aggregate culture system, which permits 3-dimensional cell-cell and cell-matrix interactions, is used to study the behavior of each isolated population of fibroblasts in vitro. In the presence of serum-free medium, each population produces very little extracellular matrix, has relatively low mitotic activity, and does not segregate from myocytes when the aggregate is composed of randomly intermixed myocytes and fibroblasts. In the presence of chicken serum, each population increases matrix production, increases cell proliferation, and sorts from myocytes. Thus, we suggest that the two populations of fibroblasts in the developing heart are responding to local environments and the differences observed in vivo are not the consequence of irreversible states of cellular differentiation.

Animals↗

Clinical worsening in multiple sclerosis is associated with increased frequency and area of gadopentetate dimeglumine-enhancing magnetic resonance imaging lesions.

It is now well established that clinically stable patients with relapsing-remitting multiple sclerosis have ongoing disease activity when evaluated by serial gadolinium-enhanced (Gd-DTPA) magnetic resonance imaging (MRI) scans. Despite this, the relationship between clinical disease and MRI lesions, though suspected, has not been extensively documented. The relationship between Gd-DTPA MRI lesions and clinical disease was examined in this study of 9 patients with mild relapsing-remitting multiple sclerosis (Expanded Disability Status Scale [EDSS] < 3.5) who had 24 to 37 monthly Gd-DTPA MRI scans, neurological examinations, and EDSS score assignments. The area and frequency of Gd-DTPA lesions were examined during months with and without clinical worsening as measured by EDSS. Forty-one episodes of clinical worsening were noted during the study. A significant association was observed between these periods of clinical worsening and MRI parameters, including increases in total number, number of new lesions, and the total area of enhancement. Logistic regression analysis showed a significant effect of the number and area of Gd-DTPA MRI lesions on both the onset and continuation of clinical worsening, confirming an important relationship between clinical disease and an increase in cerebral Gd-DTPA MRI activity. A relationship with long-term disability was suggested, but cannot be confirmed without longer follow-up of these patients.

Adult↗

Canalicular infection caused by Actinomyces.

We present 7 cases of canalicular involvement with Actinomyces collected over a 5-year period. All patients had involvement of one canaliculus, upper or lower, with lacrimal drainage patent to syringing. Curettings obtained by incising the involved canaliculi yielded Actinomyces species (5 cases) and Arachnia propionica (2 cases), typically in association with a mixed bacterial growth. Our results show that these patients often remain undiagnosed for months or even years, and are treated inappropriately for their recurrent symptoms. Despite sensitivity of Actinomyces to a broad spectrum of antibiotics, medical therapy alone does not eradicate the disease, and surgical evacuation of all concretions is essential to achieve a cure.

Actinomycosis↗

ANP inhibits NaCl absorption and elicits Cl secretion in porcine colon: evidence for cGMP and Ca mediation.

The effects of atrial natriuretic peptide (ANP) on ion transport were examined in the isolated, short-circuited proximal colon epithelium of the pig. Addition of ANP to the serosal solution decreased the rate of neutral Na and Cl absorption and elicited electrogenic Cl secretion. Amiloride, at a concentration that inhibits Na-H exchange, produced an identical inhibition of Na transport and abolished the ANP-induced decrease in Na absorption. In contrast, serosal addition of bumetanide, an inhibitor of Na-K-2Cl cotransport, partially inhibited the short-circuit current (Isc) response to ANP. Whereas 8-bromoguanosine 3',5'-cyclic monophosphate (8-BrcGMP) produced qualitatively similar effects as ANP, relatively high concentrations of N6,2'-O-dibutyryladenosine 3',5'-cyclic monophosphate (DBcAMP) or prostaglandin E2 were required to alter NaCl transport. Furthermore, incubation of colonic mucosa with ANP induced a threefold increase in cGMP content, whereas cAMP was unaffected. The ANP-induced Cl secretion and Isc were diminished with tetrodotoxin and verapamil, whereas these agents were without effect on the ANP-induced inhibition of Na and Cl absorption. Results indicate that ANP inhibits net colonic absorption of ions by antiabsorptive and secretory mechanisms that are dependent on both cGMP and Ca.

Absorption↗

Radiographic imaging of sinusitis in HIV infection.

Magnetic resonance images (MRI) of the brain from 75 homosexual men were reviewed to evaluate the frequency and severity of incidental sinus disease associated with human immunodeficiency virus (HIV). All scans had been performed for reasons other than a history of sinus disease. The opacification of each sinus cavity was scored such that 0 = normal, 1 = < 25%, 2 = 25% to 75%, and 3 = > 75% opacification. Subjects were then stratified by clinical status into four groups: HIV-, HIV+ without HIV-related symptoms, AIDS-related complex (ARC), or AIDS. Grade 1 mucosal thickening was present in 52% to 55% of HIV- and HIV+ subjects alike. Moderate disease (grade 2 or 3) was seen in seven of 52 HIV+ subjects, but none of the 23 HIV- controls. The incidence of maxillary sinus thickening was 69% in men with AIDS, compared to 30% in HIV- men (chi 2 = 4.1, p < 0.05). Mean maxillary sinus scores were 1.25 +/- 0.29 in those with AIDS compared to 0.43 +/- 0.15 in HIV- men (f = 5.11, p < 0.05). Our results suggest that maxillary sinus disease is more common and more severe in patients who have AIDS.

AIDS-Related Opportunistic Infections↗

Effect of pentoxifylline [corrected] on myocutaneous flap viability in pigs.

Partial necrosis of a skin flap can complicate reconstructive surgery. We performed a double-blinded crossover study to determine if pentoxifylline improves perfusion and survival of a myocutaneous flap. Ten 20-kg pigs were fed pentoxifylline (400 mg three times a day) or placebo for 1 week before and after raising a 5 x 30 cm panniculus carnosus flap on one flank. After 1 week of washout, each pig began the opposite drug treatment and the surgery was repeated on the opposite flank. Immediately after surgery, perfusion dermofluorometry and laser Doppler velocimetry demonstrated a significant increase in the perfusion of pentoxifylline-treated flaps compared to control flaps. On postoperative day 7, the mean area of clinical necrosis was 39.7 +/- 4.7 cm2 on the placebo sides and 30.1 +/- 4.6 cm2 on the pentoxifylline sides (t = 2.21, p < 0.05). We conclude that pentoxifylline improves perfusion and survival of myocutaneous flaps in pigs. Clinical trials appear to be indicated on the basis of the findings of this experiment.

Administration, Oral↗

Mutant debrisoquine hydroxylation genes in Parkinson's disease.

The frequency of fifteen genotypes of CYP2D6 (debrisoquine 4-hydroxylase) in 53 patients with Parkinson's disease was determined by the polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analyses and compared with the findings in 72 healthy controls. The commonest mutant allele, CYP2D6B, was twice as frequent among patients as in controls, with an approximate relative risk ratio of 2.70 (95% confidence interval 1.14-6.41; p = 0.0063) for subjects homozygous or heterozygous for this allele.

Aged↗

Sinusitis in HIV-infected patients: a clinical and radiographic review.

PURPOSE: To describe the clinical, radiographic, and laboratory features of sinus disease in human immunodeficiency virus (HIV)-infected individuals. PATIENTS: Seventy-two patients with a history of sinusitis identified from 1,461 consecutive admissions (667 patients) to the HIV ward at The Johns Hopkins Hospital. METHODS: Retrospective chart review. SETTING: The Johns Hopkins Hospital. RESULTS: Sinusitis was identified in 72 HIV-infected patients, predominantly individuals with a CD4 cell count of less than 200/mm3. A history of respiratory infections such as bacterial pneumonia, bronchitis, and otitis media was common. Although nasal congestion and postnasal drainage were found in the majority of patients, symptoms of sinusitis were often nonspecific and the diagnosis was incidental in 28 patients (33%). Magnetic resonance imaging or computed tomography was significantly more sensitive than plain radiography (p less than 0.001) in defining the extent of the disease, particularly with posterior sinus involvement, which occurred in the majority of the patients. The number of radiologically abnormal sinuses correlated inversely with the CD4 count. Although the majority of patients responded at least partially to antibiotic therapy, only 15% had complete resolution of clinical symptoms. Fifty-eight percent of patients had clinical and/or radiographic evidence of recurrent/persistent sinus infection, and chronicity correlated with a CD4 count less than 200/mm3 (p less than 0.001). CONCLUSIONS: Sinusitis in HIV-infected patients is common, severe, and difficult to treat. Patients with CD4 counts less than 200/mm3 are prone to disease involving multiple sinuses that responds incompletely to antibiotic therapy, often resulting in chronic sinusitis. Unlike the immunocompetent host, the majority of the HIV-infected patients with advanced immunodeficiency develop posterior sinus disease.

Adult↗