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Biomedical subjects

D Armstrong

Publications and source records attributed to D Armstrong.

At least 487 records · Page 27Linked to original sources

Bacteremia and fungemia in patients with the acquired immunodeficiency syndrome.

Forty-nine episodes of bacteremia and fungemia occurred in 38 of 336 patients with the acquired immunodeficiency syndrome seen at our institution since 1980. There were five types of infections. Infections commonly associated with a T-cell immunodeficiency disorder comprised 16 episodes and included those with Salmonella species, Listeria monocytogenes, Cryptococcus neoformans, and Histoplasma capsulatum. Infections commonly associated with a B-cell immunodeficiency disorder included those with Streptococcus pneumoniae and Haemophilus influenzae. Infections occurring with neutropenia were caused by Pseudomonas aeruginosa, Staphylococcus epidermidis, and Streptococcus faecalis. Other infections occurring in the hospital were caused by Candida albicans, Staphylococcus epidermidis, enteric gram-negative rods, Staphylococcus aureus, and mixed S. aureus and group G streptococcus. Other infections occurring out of the hospital included those with S. aureus, Clostridium perfringens, Shigella sonnei, Pseudomonas aeruginosa, and group B streptococcus. Because two thirds of the septicemias were caused by organisms other than T-cell opportunists, these pathogens should be anticipated during diagnostic evaluation and when formulating empiric therapy.

Acquired Immunodeficiency Syndrome↗

Mycobacterium avium complex infections in patients with the acquired immunodeficiency syndrome.

Disseminated infection with Mycobacterium avium complex developed in 67 patients with the acquired immunodeficiency syndrome (AIDS) who were followed at Memorial Sloan-Kettering Cancer Center. Twenty-nine patients were treated with two or more antimycobacterial drugs for a mean of 6 weeks, and 7 patients received therapy for less than 1 month. Most patients received ansamycin, clofazimine, and ethionamide or ethambutol. Clinical improvement did not occur in treated patients, and microbiologic cure was never obtained. Mycobacterial bacteremia persisted in 24 of 26 treated patients. Colony counts of M. avium complex in sequential blood cultures decreased in 3 patients. Every autopsied patient with M. avium complex infection diagnosed before death, whether treated or not, had disseminated M. avium complex infection at autopsy.

Acquired Immunodeficiency Syndrome↗

Lumbo-peritoneal shunt malfunction. A new, simple and reliable CT sign.

Sixty CT scans in 31 patients who underwent lumboperitoneal shunting for communicating hydrocephalus showed that the size of the ventricles did not represent a good indicator of shunt malfunction. Instead, we discovered that the size of the basal cisterns around the brain stem enabled us to predict blockage earlier and more reliably. In a well functioning shunt, the basal cisterns are usually not visualized. In children with clinical shunt malfunction the cisterns dilate and become visible again. This occurs earlier and more frequently than ventricular enlargement. We therefore conclude that visible cisterns in association with persistent symptoms of malfunction are more reliable predictors of a true blockage that requires shunt revision than serial studies of ventricular size.

Brain↗

Discriminant analysis of the clinical indicants for bovine coliform mastitis.

We used discriminant analysis to assess the indicants most useful in predicting whether a cow had coliform bacterial mastitis. One hundred and twenty-nine mastitic cows were divided into two groups, namely those with milk cultures that yielded pure or mixed gram negative organisms, and cows with other organisms or negative culture. Of 21 indicants examined by discriminate analysis only a history of previous mastitis in the affected quarter, weakness, clear or white color of milk, swelling of the udder, water consistency of the milk, lack of previous mastitis in other quarters, lack of palpable udder abscesses, and elevated body temperature were significantly associated with coliform mastitis. Using these variables 78% of cases were correctly classified.

Animals↗

Disease-specific electrophysiological findings in adult ceroid-lipofuscinosis (Kufs disease).

Two adults with mild dementia and a history of memory loss and disequilibrium were seen in the eye clinic following complaints of acuity loss in the 20/30-20/70 (Snellen) range. Results from the fundus examination of one patient were entirely normal; the other showed minimal vascular attenuation and optic atrophy. Electrophysiology was remarkable: (1) Photopic ERG b-waves were reduced, delayed, and showed pronounced oscillations. (2) EOG 'light-rise' potentials were absent or very small. (3) Binocular pattern-VER signals showed addition of the monocular signal. Scotopic ERG signals were normal. Brain biopsy and microscopy showed intercellular, autofluorescent ceroid deposits which provided a clear diagnosis of Kufs disease. Histology of model animal retinal cells show ceroid deposits in cell classes implicated by the human retinal signals. The cluster of electrophysiological results point toward early changes in the pigment epithelium and inner plexiform layer cells as a means of noninvasive diagnosis.

Adult↗

Change in content, incorporation and lipoxygenation of docosahexaenoic acid in retina and retinal pigment epithelium in canine ceroid lipofuscinosis.

We have examined the metabolism of docosahexaenoic acid (22:6, n-3) in retina and retinal pigment epithelium of normal dogs and those affected with canine ceroid lipofuscinosis (CCL), a hereditary degenerative neurological disorder. In the CCL retina, there was a decrease in 22:6 content in phospholipids, particularly phosphatidylethanolamine. This decrease in 22:6 was compensated by an increase in arachidonic acid (20:4, n-6). In contrast, CCL retinal pigment epithelium had higher levels of 22:6 and lower levels of 20:4 in phosphatidylethanolamine. The in vitro incorporation of radiolabeled 22:6 into glycerolipids of CCL retina and retinal pigment epithelium was increased as compared to control. The major lipoxygenase reaction product of 22:6, (11-hydroxy-4,7,9(trans)13,16,19)-22:6, increased 31% in CCL retina, but not in the retinal pigment epithelium. This is the first report describing alterations in content, incorporation and lipoxygenation of 22:6 in an animal model of a human disease (Batten's disease).

Animals↗

Arachidonic acid and other long-chain fatty acids in canine ceroid lipofuscinosis. Distribution in glycerolipids, metabolism, and pathophysiological correlations.

Dogs with canine ceroid lipofuscinosis (CCL)+ show an abnormal EEG as early as 5 mo of age and exhibited either severe disorganization or very low amplitudes by 24 mo. Ceroid particles accumulate with age and, within neurons, have a unique characteristic appearance consisting of lamellar patterns enclosed by a single unit membrane. Although the etiology of their formation has not been fully elucidated, isolated particles are enriched in phospholipids. Our present studies have examined microsomal enzymes involved in phospholipid synthesis and turnover and demonstrate that the acyl group composition of cerebral lipids from animals with CCL is similar to that from controls. However, the activation of palmitic, linoleic, arachidonic, and docosahexaenoic acids into their Coenzyme A thiol ester forms was significantly lower in cerebral and cerebellar microsomes of the diseased dogs than in those of the controls. In addition, the incorporation of arachidonic acid into phospholipids was significantly decreased in affected animals. These results suggest that the metabolism of arachidonic acid plays an important role in the pathogenesis of ceroid lipofuscinosis.

Animals↗

Continuous high-grade mycobacterium avium-intracellulare bacteremia in patients with the acquired immune deficiency syndrome.

Serial quantitative blood cultures were performed before and during treatment in four patients with the acquired immune deficiency syndrome (AIDS) and Mycobacterium avium-intracellulare bacteremia. Initial colony counts were 350 to 28,000 cfu/ml, the counts declined substantially with treatment in two patients, and they declined modestly with treatment but rose when it was stopped in the other two. In one patient who was studied in detail, most of the circulating organisms were within the leukocytes, colony counts in blood subjected to lytic agents were 1.9- to 5.2-fold higher than in unlysed blood, and there were 10(5) to 10(6) times more organisms per gram in several tissue specimens obtained at autopsy than per milliliter of blood. It is concluded that continuous high-grade bacteremia is common in patients with AIDS and severe M. avium-intracellulare infections and that serial quantitative blood cultures provide a potential means for studying treatment in these patients.

Acquired Immunodeficiency Syndrome↗

Infectious complications of neoplastic disease.

Progress has been made in the diagnosis and treatment of infection in patients with neoplastic disease. Among the advances is the appreciation that certain opportunistic infections occur in association with particular host immune defects and epidemiologic factors. Such immune defects are seen secondary to or as a consequence of treatment for the patient's basic disease. Improved methods such as serology, open lung biopsy, and fiberoptic bronchoscopy have allowed for earlier diagnosis and treatment of opportunistic infections. The development of empiric antibiotic regimens, particularly aminoglycosides and the antipseudomonal penicillins, have improved the outcome in the febrile neutropenic patient. The benefits of protective environments have been challenged; prophylactic antibiotics and various forms of immunotherapy are of interest but remain investigational.

Aspergillosis↗

Space and time in British general practice.

From the novel geography of the health centre to the meticulous concerns of appointment systems and patient records, British general practice, as this paper documents, has reordered its traditional activities over the last 30 years. These changes however suggest a more profound reorganisation of the spatial and temporal features of practice activity and a commensurate reassessment of the nature of illness.

Community Health Services↗

Humoral response to disseminated infection by Mycobacterium avium-Mycobacterium intracellulare in acquired immunodeficiency syndrome and hairy cell leukemia.

Antibody to Mycobacterium avium-Mycobacterium intracellulare antigen was measured by immunodiffusion, enzyme-linked immunosorbent assay (ELISA), and indirect immunofluorescence in sera from 30 patients with acquired immunodeficiency syndrome (AIDS), 10 patients with hairy cell leukemia, and 33 hospitalized and healthy controls. Ten patients with AIDS and three patients with hairy cell leukemia in the study population had disseminated M. avium-M. intracellulare infection. Patients with AIDS and disseminated infection had antimycobacterial antibody levels, demonstrated by ELISA, that did not differ significantly from those in uninfected patients with AIDS or controls. Infected patients with hairy cell leukemia had significantly higher levels of antimycobacterial antibody, demonstrated by ELISA, than did uninfected patients with hairy cell leukemia or controls (P less than .001). One patient with hairy cell leukemia, studied serially, showed a greater than 100-fold rise in antibody titer with the onset of infection. These results further demonstrate that AIDS involves a functional defect in humoral immunity, in addition to impairment of cellular immune function.

Acquired Immunodeficiency Syndrome↗

Stereoisomeric configuration of arabinitol in serum, urine, and tissues in invasive candidiasis.

Because routine analytical methods cannot differentiate D- from L-arabinitol, a combined microbiological and gas chromatographic method was developed to study the stereoisomeric configuration of the arabinitol in humans and rats with invasive candidiasis. D-Arabinitol was defined as the difference between arabinitol concentrations measured with and without incubation with 5.0 X 10(5) blastospores of Candida tropicalis strain CT 12 at 37 C for 24 hr. The yeast consumed at least 95% of the D-arabinitol and none of the L-arabinitol added to normal serum and urine. D-Arabinitol as a fraction of D,L-arabinitol was 0.43 +/- 0.15 (mean +/- SD) in the urine of 10 normal humans, 0.82 +/- 0.12 in the serum or urine of five patients with cancer and invasive candidiasis (P less than .001), and 1.0 in the kidneys of rats with candidiasis. Because most or all of the excess arabinitol in body fluids or tissues in candidiasis was the D isomer, which is produced by fungal metabolism, stereospecific quantitation of arabinitol should improve the sensitivity of this approach to diagnosis of candidiasis.

Animals↗

Use of a new bioassay to study pentamidine pharmacokinetics.

We developed a sensitive and specific agar-diffusion bioassay for pentamidine by using an amphotericin B-resistant isolate, Candida tropicalis ATCC 28707, as the test organism. We determined levels of pentamidine in serum of rats given intramuscular or intravenous injections and levels in serum, urine, and tissues of humans who had received the drug by slow intravenous infusion. Rats given intravenous pentamidine at a dose of 2 mg/kg had higher serum levels than those given intramuscular injection at a dose of 10 mg/kg; however, the drug was detectable in serum for 4 hr after intramuscular administration. The serum half-life in rats after intravenous injection was 2 min. Humans treated with 4 mg of pentamidine/kg by slow (1-2 hr) intravenous infusion had peak serum concentrations ranging from 0.5 to 3.4 micrograms/ml. The mean half-life of elimination from serum in humans was 17 +/- 4 min (n = 3). In two patients, studied after completion of therapy, urinary excretion rates declined with a half-life of five and nine days. In tissues obtained at autopsy from four patients who had received pentamidine, the drug was present in highest concentration in the spleen and liver, followed by kidneys, adrenals, and lungs.

Amidines↗

Distribution and activity of amphotericin B in humans.

Concentrations of amphotericin B (AmB) in tissues obtained at autopsy from eight patients were measured by high-performance liquid chromatography (HPLC). The patients had received doses of 101-2,688 mg of antibiotic. Highest concentrations of the drug were found in the liver; in one patient the amount of AmB in the liver was 41% of the total dose. No evidence of metabolism of the drug was observed, and bioassay of ethanol extracts of tissue showed that the drug retained activity. Three of the patients had histologic evidence of aspergillar or candidal infection in tissues with concentrations of AmB ranging from 2.5 to 166 micrograms/g. With two patients, the concentrations of the drug in the tissues exceeded by greater than or equal to 10-fold the minimum inhibitory concentrations of the drug in isolates that had been obtained from the same tissues. Unknown factors present in tissues appear to limit the in vivo activity of AmB.

Amphotericin B↗

Culture of retinal pigment epithelium from chorio-retinal biopsies.

The recently devised methods for surgical sampling of chorio-retinal tissue permits morphological evaluation of retina in various diseases. In the present report it is demonstrated, that the retinal pigment epithelium in such samples can be isolated as a viable cell population, and that the cell mass can be increased sufficiently in culture to permit biochemical as well as morphological studies. This procedure thereby expands the diagnostic potential of the sample tissue.

Animals↗