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Biomedical subjects

D Armstrong

Publications and source records attributed to D Armstrong.

At least 469 records · Page 26Linked to original sources

The role of cyclic AMP-dependent phosphorylation in the maintenance and modulation of voltage-activated calcium channels.

The predominant class of voltage-activated Ca channels in molluscan neurons (Helix) and a mammalian cell line (GH3) do not respond to membrane depolarization under conditions that prevent cAMP-dependent phosphorylation when the cytoplasm is replaced with standard physiological saline solutions. Under normal conditions, inactivation of these channels results from Ca ion entry and accumulation inside the cell. In dialyzed neurons, inactivation is enhanced in the presence of an exogenous Ca-dependent phosphatase, and inactivated channels appear to be susceptible to Ca-dependent proteolysis. Rephosphorylation of the channels by a cAMP-dependent kinase removes inactivation and protects the channels from proteolysis. Thus, phosphorylation/dephosphorylation reactions appear to be an important means of modulating Ca channel activity and may underlie both Ca-dependent inactivation and the metabolic maintenance of the channels.

Animals↗

Opportunistic infections in the acquired immune deficiency syndrome.

The acquired immune deficiency syndrome (AIDS) results in a T lymphocyte deficiency and, consequently, a susceptibility to opportunistic infections with organisms that previously were better known as causes of disease in patients with Hodgkin's disease or recipients of immunosuppressive therapy. Pneumocystis carinii, Candida albicans, and cytomegalovirus (CMV) are among the most frequently observed pathogens in AIDS patients, followed by atypical mycobacteria, Toxoplasma gondii, Mycobacterium tuberculosis, Salmonella sp, and herpes simplex virus. Cryptosporidia sp, rarely encountered in iatrogenically immunosuppressed patients, have also emerged as important pathogens in the setting of AIDS. Although some opportunistic infections in AIDS patients can be effectively treated, others are only temporarily suppressed or do not respond to the drugs currently available. The severity of the underlying immune deficit remains the most important prognostic factor, and opportunistic infection remains the cause of death in most AIDS patients.

Acquired Immunodeficiency Syndrome↗

Patterns of work in general practice in the Bromley health district.

The results of a survey of patterns of work in general practice over five days in one health district were linked to family practitioner committee data on individual general practitioners. Characteristics of doctors and practices were mostly unrelated to various aspects of workload. However, referral rates for pathological tests and to outpatient departments and claims for cervical cytology screening were significantly higher for younger principals than for older doctors, while younger doctors prescribed less frequently. Women general practitioners had significantly lower personal list sizes and claims for night visits and temporary residents than their male colleagues but saw only 10% fewer patients and made significantly more claims for cervical cytology screening. It was also found that UK graduates made more requests for pathological tests than doctors graduating in the Indian sub-continent. A correlation was found between list size and consultation rate, though the list size only explained a relatively small part of the variation in the rates.The results have been fed back to doctors in the area and it is hoped that this will increase awareness of the patterns of work in general practice.

Adult↗

Orbital rhabdomyosarcoma in childhood.

Rhabdomyosarcoma is a diagnostic and therapeutic problem in the management of pediatric tumors, representing the most common malignant orbital tumor of childhood. In this discussion of the diagnosis of rhabdomyosarcoma, the role of CT is detailed through the case reports and the radiographs presented. CT can accurately define the anatomic location of the orbital mass, the involvement of various intraorbital structures, and the extension of the pathologic process into the periorbital regions such as sinuses, nasal cavity, and intracranial compartment. Thin-needle aspiration biopsies can be done under CT guidance without complications as well as follow-up monitoring of tumor regression following therapy.

Adult↗

Management of infectious complications in acquired immunodeficiency syndrome.

Infectious complications are the most common cause of death in patients with acquired immunodeficiency syndrome (AIDS). Opportunistic infections associated with defects in both T and B lymphocyte function have been observed. Invasive infections, including those secondary to procedures both in and out of the hospital, must also be considered. Reliance on serologic antibody tests is ill-advised since antibody response is often not effective. Since simultaneous infections frequently develop in patients with AIDS, attempts to identify pathogens by culture and histopathology should be aggressive and thorough. With rapid diagnosis and therapy, many of the infections will respond. Prolonged treatment is indicated as recrudescence is common.

Acquired Immunodeficiency Syndrome↗

Quantitative analysis of retinal outer segments in ovine ceroid-lipofuscinosis.

Isolated outer segments from the photoreceptors of the eye were markedly reduced in young animals with ovine ceroid-lipofuscinosis. At 5 months of age, 68% of these structures were lost and by 18 months, no segments remained. Our results suggest that loss of these structures can be identified earlier by quantitative analysis, than by electroretinography.

Animals↗

Enhanced synthesis of prostaglandins and hydroxyeicosatetraenoic acids in retina from a canine model of Batten's disease.

The metabolism of [1-14C]arachidonic acid (20:4, n-6) was studied in intact retina and retinal pigment epithelial cells from normal English setters and English setters affected with hereditary canine ceroid lipofuscinosis. Acylation of arachidonic acid into membrane glycerolipids and oxygenation by lipoxygenase and cyclooxygenase to eicosanoids were measured by radiochromatographic techniques. In addition, the histopathology of accumulated ceroid particles in retinal ganglion cells and pigment epithelial cells was studied by electron microscopy. Synthesis of prostaglandins and hydroxyeicosatetraenoic acids was increased in canine ceroid lipofuscinosis retina, but not in retinal pigment epithelium. Prostaglandin D2, the putative neuronal eicosanoid, was increased nearly eightfold, whereas other eicosanoids increased two- to threefold. Ultrastructural studies revealed accumulation of ceroid and deterioration of neuronal and pigment epithelial cell architecture. These experiments demonstrate that, although lipopigment accumulates in both tissues, alterations of eicosanoid synthesis are specific for the retina, a neuronal tissue. The specific increase in prostaglandin D2 and the specificity of changes for the retina indicate that enhanced eicosanoid synthesis may be a result of an impairment of the control of oxygenation of arachidonic acid in neurons.

Animals↗

Intraventricular therapy of cryptococcal meningitis via a subcutaneous reservoir.

Intraventricular administration of amphotericin B for meningitis due to Cryptococcus neoformans is usually reserved for selected, seriously ill patients with recurrent disease. Between September 1973 and November 1983, 10 of 23 patients treated for cryptococcal meningitis at Memorial Sloan-Kettering Cancer Center received intraventricular amphotericin B through subcutaneous reservoirs, in addition to systemic therapy. The value of intraventricular amphotericin B was assessed in the 13 patients treated for first episodes of meningitis with systemic amphotericin B and flucytosine. Death during therapy occurred in one of six patients with intraventricular and systemic therapy compared with six of seven patients with systemic therapy alone (p = 0.025). The cerebrospinal fluid was sterilized in six of six patients given systemic and intraventricular therapy compared with three of seven given systemic therapy alone (p = 0.049), and the cerebrospinal fluid cryptococcal antigen titer declined in six of six patients given systemic and intraventricular therapy compared with two of seven given systemic therapy alone (p = 0.016). In the 10 patients who received intraventricular therapy, there were no complications related to reservoir insertion; however, complications related to reservoir use requiring replacement or revision occurred in two patients, and bacterial infection occurred in one but was treated successfully without removal of the reservoir. Although these data are retrospective, they suggest that early therapy with intraventricular amphotericin B in combination with systemic therapy may be beneficial and relatively safe in patients with cryptococcal meningitis and a poor prognosis.

Adult↗

Cryptosporidiosis. Case report in a health team worker.

Cryptosporidium is a coccidial protozoan of the intestinal tract; cryptosporidiosis in veterinarians has been reported as a cause of diarrhea. It has also been reported as a cause of diarrhea in marrow transplant recipients. Cryptosporidiosis has gained attention recently because of its occurrence in patients with the acquired immune deficiency syndrome (AIDS). A healthy intensive care unit nurse who acquired cryptosporidiosis from a bone marrow transplant recipient with diarrhea caused by cryptosporidiosis is described. Results of laboratory examination, including T lymphocyte subsets, were normal. She was treated with bed rest and a liquid diet and her symptoms completely resolved after 15 days. Health care workers should be aware that cryptosporidiosis can be transmitted to them from patients and should follow precautions to avoid acquiring the disease.

Adult↗

Changes in lymphoma development in female SJL/J mice as a function of the ratio in low polyunsaturated/high polyunsaturated fat diet.

A diet of low polyunsaturated-to-saturated fatty acid (P/S) ratio known to alter fatty acid composition of lymphocyte membranes and retard the progressive changes which result in loss of suppressor capacity in SJL/J female mice, was fed to these mice from conception to study its effect on the development of lymphoma. Between 12 and 14 months, at a time when 100% of mice on a diet of high polyunsaturated-to-saturated fatty acid ratio showed lymphoma, only 70% of the mice fed the low P/S diet had developed lymphoma. Dietary fatty acid levels would appear to have a significant effect on the rate of progression of lymphoma in SJL/J female mice.

Animals↗

Flavobacterium meningosepticum bacteremia in an adult with acute leukemia. Use of rifampin to clear persistent infection.

A case of Flavobacterium meningosepticum bacteremia complicating the course of a patient with leukemia is described. The patient was treated successfully when rifampin was added to the antibiotic therapy. Unusual organisms should be considered as agents of infection in immunocompromised hosts and susceptibility testing with drugs not commonly employed for gram-negative rods should be performed in complicated cases.

Acute Disease↗

Electrocardiographic and histologic abnormalities in canine ceroid-lipofuscinosis (CCL).

Electrocardiograms were recorded in a longitudinal study on six adult dogs with canine ceroid-lipofuscinosis (CCL) and compared with those of four unaffected animals. Two dogs exhibited minor conduction abnormalities, QRS-notching and LVH at 12 months of age. By 24 to 25 months of age, the underlying cardiac rhythm was that of a pronounced sinus arrhythmia. Some dogs developed premature atrial beats, A-V dissociation or tachycardia. No gross cardiac abnormalities were noted at necropsy, but histologically, autonomic ganglion cells in the atrium, near the conducting system and in ventricular myocardial cells were filled with autofluorescent lipopigments. Quantification by micro-spectrophotometry showed peak emission at 538 nm. At the ultrastructural level, these fluorescent particles consisted of collections of curvilinear and lamellar profiles, similar to those present in other viscera. Ceroid-lipofuscinosis has been utilized for many years as a model for human ceroid-lipofuscinosis and the results described here are similar to those previously reported in hearts of patients with this disease. Because related lipopigments accumulate in normal aging of the heart and contraction/conduction abnormalities develop with time, the canine model may also be useful in aging studies as well. The studies described here are the first to demonstrate possible structural-functional relationships in the heart of dogs with CCL.

Animals↗

cAMP induction of prespore and prestalk gene expression in Dictyostelium is mediated by the cell-surface cAMP receptor.

Extracellular adenosine 3',5'-cyclic monophosphate (cAMP) is required for cell-type-specific gene expression in developing Dictyostelium discoideum. We have developed a microassay for the expression of these genes, using antibodies directed against their protein products. To characterize the transduction mechanism, we have used in this assay cAMP analogues that preferentially activate either the cell-surface cAMP receptor or the internal cAMP-dependent protein kinase. N6-(aminohexyl) cAMP activates the Dictyostelium cAMP-dependent protein kinase but does not bind to the cell-surface cAMP receptor and does not cause cell-type-specific gene expression. 2'-Deoxy-cAMP does not activate the cAMP-dependent protein kinase but binds to the receptor and causes cell-type-specific gene expression. Cyclic AMP-induced accumulation of prestalk mRNA in shaking cultures still occurs in the presence of caffeine, which blocks the receptor-coupled activation of adenyl cyclase. This suggests that the extracellular cAMP induction of cell-type-specific gene expression in developing Dictyostelium cells is mediated by the cell-surface cAMP receptor and that activating adenyl cyclase by this receptor is not essential. Using the N6-(aminohexyl) cAMP to competitively inhibit phosphodiesterase, we show that 30 nM cAMP is sufficient to induce prestalk or prespore gene expression.

Caffeine↗

Reasons for referral to hospital: extent of agreement between the perceptions of patients, general practitioners and consultants.

A sample of referrals to hospital out-patient clinics by general practitioners was examined from the points of view of the patient, general practitioner and consultant with regard to the perceived reason for the referral. A considerable degree of disagreement was found between the opinions of the three parties involved. Possible explanations for, and the consequences of this lack of agreement are considered and certain remedies suggested.

Consultants↗

Comparison of mannitol regimens in patients with severe head injury undergoing intracranial monitoring.

Eighty patients sustaining head injuries and presenting with Glasgow Coma Scale scores of 8 or less were entered into a prospective randomized study to assess the benefit of intracranial pressure (ICP) monitoring with two regimens of mannitol administration. Group I was treated with mannitol for ICP elevations greater than 25 mm Hg, while Group II received empirical mannitol therapy irrespective of ICP readings. No statistically significant differences in mortality rate or neurological outcome were demonstrated between the two groups. These results are comparable to those of several published series of head-injured patients receiving similar treatment from 1977 to 1982. However, those series must be reassessed in light of recently published studies with treatment initiated at lower levels of ICP.

Adolescent↗

Bacterial pneumonia in patients with the acquired immunodeficiency syndrome.

Eighteen episodes of community-acquired bacterial pneumonia were diagnosed in 13 patients among 336 with the acquired immunodeficiency syndrome (AIDS) cared for at Memorial Sloan-Kettering Cancer Center since 1979. Bacterial pathogens isolated in 16 of 18 episodes were Haemophilus influenzae in 8, Streptococcus pneumoniae in 6, group B streptococcus in 1, and Branhamella catarrhalis in 1. Eight episodes were presumed Pneumocystis carinii pneumonia until cultures obtained at bronchoscopy confirmed a bacterial cause. Specific antibacterial therapy was curative in 16 of 18 episodes; 2 patients died. Given an estimated yearly incidence of pneumococcal pneumonia in the general population of 2.6/1000, 1.09 cases were expected in our patients with AIDS; we saw 6 (p = 0.001), for an attack rate of 17.9/1000. Bacteria associated with B-cell defects should be anticipated when formulating empiric antibiotic therapy, pending a definitive diagnosis, for pulmonary infiltrates in patients with AIDS.

Acquired Immunodeficiency Syndrome↗

Rapid immunodiagnosis of cytomegalovirus pneumonia by bronchoalveolar lavage using human and murine monoclonal antibodies.

Bronchoalveolar lavage material from 54 immunocompromised patients with interstitial pneumonia was examined by immunofluorescence with cytomegalovirus-specific monoclonal antibodies. Twelve patients (22%) had cytomegalovirus detected in their lavaged cells, and 9 of these patients (17%) had proven cytomegalovirus pneumonitis. This assay detected all samples with cytomegalovirus when the virus was detected by established methods either at the time of lavage or after any other procedure in the subsequent 2 months; that is, it had a sensitivity of 100%. Cytomegalovirus could be detected within 3 hours of the lavage, and a clear correlation was seen between the number of fluorescent cells and the presence of cytomegalovirus pneumonia. All 9 patients with pneumonitis had more than 0.5% fluorescent cells, whereas the 3 patients in whom cytomegalovirus was detected without pneumonia had significantly fewer fluorescent cells. This method provides a sensitive, rapid, and quantifiable system for detection of cytomegalovirus, facilitating the early diagnosis and treatment of cytomegalovirus pneumonia.

Acquired Immunodeficiency Syndrome↗