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Biomedical subjects

D Armstrong

Publications and source records attributed to D Armstrong.

At least 19 recordsLinked to original sources

Application of DNA amplification to pneumocystosis: presence of serum Pneumocystis carinii DNA during human and experimentally induced Pneumocystis carinii pneumonia.

Pneumocystis carinii pneumonia is a leading cause of morbidity and mortality in patients with the acquired immunodeficiency syndrome (AIDS). Much remains unknown about the basic biology of P. carinii and studies of this infection have been hampered by the lack of cultivation methods. We developed a sensitive and specific assay for P. carinii by utilizing DNA amplification of the P. carinii dihydrofolate reductase (DHFR) gene. By this method, P. carinii DNA was detected in the lungs of rats with experimentally induced P. carinii pneumonia 2 wk before the onset of histopathological changes. DNA amplification analysis of serum demonstrated that by 10 wk of corticosteroid treatment, 12 of 12 (100%) infected rats had circulating DHFR DNA. P. carinii DHFR DNA also was detected in the serum of patients with AIDS and active P. carinii pneumonia (12 of 14 sera collected prospectively). Patients with advanced AIDS but without a history of P. carinii pneumonia were negative by this assay (0 of 6 sera examined). Serum polymerase chain reaction may facilitate investigations into the natural history and epidemiology of P. carinii infection, provide insight into the pathogenesis of parasite dissemination, and offer a useful, noninvasive diagnostic test for the detection of human pneumocystosis.

Acquired Immunodeficiency Syndrome

Chromatography and spectrofluorometry of brain fluorophores in neuronal ceroid lipofuscinosis (NCL).

The aim of the present work was to develop a chromatographic system for the separation of individual fluorophores extracted from neuronal ceroid lipofuscinosis (NCL) brain and isolated storage bodies. Extracts from gray matter were best resolved on silica-gel HPTLC plates using a mixture of chloroform/methanol/water (55:45:10 by vol.). Two other chromatographic systems were tested which gave poorer separation. Corrected fluorescence spectra were obtained on the original extract and fluorescence intensity, especially at longer wavelengths was increased in both samples. Yellow and blue fluorophores were detected on HPTLC plates using a primary violet and secondary yellow filter with cut-off levels of 400 and 520 nm, respectively. Plates were photographed at 20 min, 2 h and 1 week after chromatography. With this filter system, up to 12 yellow bands of differing intensity were observed at 20 min but with time, some of these changed to blue as a result of autoxidation. NCL tissues emit yellow fluorescence when viewed under light microscopy, however extracted material did not demonstrate a distinct peak in this region of the spectrum which should be around 575 nm. HPTLC confirmed this observation and time studies revealed that autoxidation changes occur and must be carefully controlled to reduce artifacts. The discrepancy between extracted and non-extracted observations may be the result of superposition of multiple fluorophores with differing maxima and/or a self-absorption phenomenon. The combination of chromatographic separation and spectral analysis as described in this study, may be a valuable technique to further clarify the characteristics of compound fluorescent lipopigments. It is suggested that NCL fluorophores of human brain differ in their properties from other models.

Brain Chemistry

Pneumocystis carinii pneumonia among patients without AIDS at a cancer hospital.

OBJECTIVES: To determine the predisposing factors, attack rate by underlying disease, and outcome of Pneumocystis carinii pneumonia among patients without the acquired immunodeficiency syndrome (AIDS) at a cancer center. DATA SOURCE: Twelve-year retrospective review from a tertiary-care cancer center. STUDY SELECTION: One hundred forty patients, constituting 142 cases, with morphologically proved P carinii pneumonia. DATA SYNTHESIS: Hematologic malignancy (47%) (including lymphoma [27%] and leukemia [18%]), solid tumor (31%), or bone marrow transplantation (18%) was the underlying condition in the majority of cases. Twenty-five cases (18%) were diagnosed at autopsy. All but seven patients had previously established predisposing factors for P carinii pneumonia, including corticosteroid use in 87%. The attack rate for hospitalized patients with primary or metastatic brain tumor increased during the 12-year interval. The attack rates for hospitalized patients with hematologic neoplasm or bone marrow transplantation were stable. The overall mortality rate did not change during the period reviewed. CONCLUSIONS: Despite the availability of effective prophylaxis, P carinii pneumonia continues to occur among patients with neoplastic disease. In addition to patients with certain hematologic neoplasms, those with primary or metastatic brain neoplasm who receive corticosteroids are at risk for the development of P carinii pneumonia and should receive P carinii pneumonia prophylaxis.

Acquired Immunodeficiency Syndrome

The effect of continuous enteral nutrition on gastric acidity in humans.

The effect of continuous intraduodenal enteral nutrition on gastric pH was compared with the effects of fasting and of parenteral and standard nutrition control regimens containing equal amounts of carbohydrate, protein, and lipid. Eleven healthy volunteers underwent four 24-hour intragastric pH-metry studies; serum glucose, calcium, immunoreactive insulin and gastrin levels were determined during fasting and enteral and parenteral regimens. Median 24-hour gastric pH during enteral nutrition (group median pH 1.4) was lower than during parenteral nutrition (pH 1.9; P = 0.0039 vs. enteral) but was not different from fasting (pH 1.4) or standard nutrition (pH 1.6) values. Median 24-hour serum glucose levels during enteral nutrition (group median, 4.8 mmol/L) were higher than during fasting (4.0 mmol/L; P = 0.00098 vs. enteral) and lower than during parenteral nutrition (5.3 mmol/L; P = 0.0039 vs. enteral). Median 24-hour serum insulin levels during enteral nutrition (group median, 22.9 mU/L) were higher than during fasting (group median, 9.2 mU/L; P = 0.00098 vs. enteral) but similar to levels during parenteral nutrition (23.3 mU/L). Neither median 24-hour gastrin levels nor calcium levels were affected by any nutrition regimen. Thus, continuous enteral nutrition produces gastric pH values similar to those seen with fasting or standard nutrition, suggesting that, under most physiological conditions, gastric acidity is subject to close feedback control. Parenteral nutrition increases gastric pH, suggesting that systemic nutrients may influence this feedback mechanism.

Adult

Clinical surveillance of gynecologic cancer patients.

A survey of gynecologic oncologists was used to determine the optimum follow-up plan for asymptomatic, disease-free patients previously treated for a gynecologic malignancy. Ninety-four (91%) of 103 questionnaires were completed and returned. The majority of respondents recommended a clinic visit for these patients every 3 months for the first year after the completion of therapy, every 3 or 4 months for the second year, every 6 months for the following 3 years, and then annually after this initial 5-year period. Breast, abdominal, lymph node, and pelvic examinations, as well as a pap smear and stool guaiac, were done at each of these clinic visits. A yearly chest X ray was performed by the majority of the survey respondents for the first 3 years following initial treatment. Determinations of serum CA-125 and ovarian germ cell tumor markers were done at each follow-up appointment during the first 5 years after therapy if they were previously elevated. The patients' smoking habits were discussed with them by the majority of respondents. Mammograms were performed periodically before age 50 and then yearly after age 50 by most respondents. Serum cholesterol determinations were accomplished every 5 years or more frequently if indicated. Calcium supplementation was recommended for postmenopausal patients. The majority of respondents did not recommend routine vitamin supplementation or surveillance sigmoidoscopy.

Ambulatory Care

Pneumocystosis.

In much of the world, pneumocystosis remains the most common life-threatening opportunistic infection among patients with HIV disease. The infection is caused by Pneumocystis carinii--an organism whose identity as a fungus or parasite is still debated. What is no longer debated, after a decade of AIDS, is that pneumocystosis is almost entirely preventable and eminently treatable. Understanding has improved concerning when prophylaxis should be initiated. It is also recognized that, at least with the agents available today, antiretroviral therapy alone will not prevent pneumocystosis. Sputum induction and the use of monoclonal antibodies have modestly improved our ability to diagnose the infection; however, invasive procedures are still required for most patients, and unusual presentations of the disease, such as cavitary lesions, apical infiltrates, pneumothoraces, and extrapulmonary infection, are not infrequently seen. For treatment, trimethoprim-sulfamethoxazole and intravenous pentamidine remain the mainstays; oral therapy with dapsone and trimethoprim can be as effective as conventional therapy in mild disease, permitting treatment on an outpatient basis. Adjunctive steroids are useful for treatment of moderate to severe pneumocystosis, but clinicians should be alert to the possibility of activation of other latent infections during and after courses of steroids. Both aerosol pentamidine and trimethoprim-sulfamethoxazole are effective prophylaxis. The latter appears to be more effective and costs much less, but the results of comparative trials are not yet available. More data are also needed on the safety, efficacy, and relative advantages of dapsone for prophylaxis. The first decade of the AIDS epidemic has been a decade of progress against pneumocystosis. In the next decade, the emergence of new technologies for diagnosis and of new agents for prophylaxis and treatment will bring us closer to the goal of controlling this serious infection.

Acquired Immunodeficiency Syndrome

Three-drug synergistic inhibition of HIV-1 replication in vitro by 3'-fluoro-3'-deoxythymidine, recombinant soluble CD4, and recombinant interferon-alpha.

3'-Fluoro-3'deoxythymidine (FLT), recombinant soluble CD4 (CD4), and recombinant interferon-alpha (IFN alpha) were evaluated in two- and three-drug regimens against HIV-1 replication in vitro. Peripheral blood mononuclear cells were studied using p24 antigen production as the virologic endpoints. FLT showed 2.5-fold higher efficacy and a similar selectivity index to zidovudine. Drug interactions were evaluated by the median effect principle and the isobologram technique. FLT, CD4, and interferon alpha at noncytotoxic concentrations inhibited HIV-1 synergistically in two- and three-drug combinations with a combination index smaller than one and dose reduction index greater than one. The three-drug regimen provided greater virus suppression than the two-drug regimen. These results suggest that FLT is an alternative agent to AZT for the treatment of HIV infection either as a single agent or in combination with CD4 and/or interferon-alpha.

Antiviral Agents

Disseminated Nocardia brasiliensis infection with septic arthritis.

An unusual case of disseminated Nocardia brasiliensis infection is presented. The patient, who had been receiving chronic dexamethasone therapy for 4 years, had pneumonia and septic arthritis of the left knee due to N. brasiliensis. To our knowledge, this is the first report from the United States of a synovial joint infection with this organism. Disseminated disease due to N. brasiliensis is infrequently reported; it is most often seen in the immunocompromised patient and is often unresponsive to therapy.

Adult

Evaluation of new anti-infective drugs for the treatment of febrile episodes in neutropenic patients. Infectious Diseases Society of America and the Food and Drug Administration.

The use of empirical antimicrobial therapy has significantly reduced the morbidity and mortality associated with untreated infections in febrile neutropenic patients. This guideline describes clinical trials of the safety and efficacy of new antimicrobial drugs in this population of patients. Fever and neutropenia should be precisely defined in each protocol. Patients should be randomized to treatment with a new or active-control drug regimen, stratified on the basis of type of cancer and age, and treated until resolution--as defined in the protocol--is attained. Outcome should be assessed both for cases with a defined microbial etiology and for those without. Final microbiological outcome is important for cases with identified pathogens, but clinical outcome is paramount.

Anti-Infective Agents

Aspergillus species colonization and invasive disease in patients with AIDS.

Invasive aspergillosis is an uncommon infectious complication in patients with AIDS. Of the 972 patients with AIDS who were observed at our institution over a 10-year period, Aspergillus species were isolated from the respiratory sites of 45 patients before death. Invasive aspergillosis was documented at autopsy in four of these patients and was strongly suspected in an additional patient on whom an autopsy was not performed. A fifth case was documented at autopsy (no antemortem respiratory sample was obtained from this patient). Traditional risk factors for the development of invasive disease (neutropenia, hematologic malignancy, and/or corticosteroid use) were present in all of our patients with invasive aspergillosis. A review of the literature revealed reports of an additional 13 cases of invasive aspergillosis in patients with AIDS. Therapy with amphotericin B should be considered for neutropenic patients with AIDS who have pneumonia of uncertain etiology and from whom Aspergillus species have been isolated from a respiratory specimen.

Acquired Immunodeficiency Syndrome

Extraneural cysticercosis presenting as a tumor in a seronegative patient.

A case of cysticercosis involving only the sternocleidomastoid muscle of an otherwise-healthy pregnant woman is presented. An enzyme-linked immunoelectrotransfer blot assay for cysticercosis was nonreactive. The clinical features of extraneural cysticercosis are reviewed with special attention to musculocutaneous involvement. The results of serological tests for such patients may not be positive and histopathology remains the only reliable method for confirming the diagnosis of cysticercosis.

Adult

Meningitis due to beta-hemolytic non-A, non-D streptococci among adults at a cancer hospital: report of four cases and review.

Four cases of meningitis due to beta-hemolytic non-A, non-D streptococci among adult patients with neoplastic disease are reported. All four patients had head or neck tumors for greater than or equal to 4 years, and all had undergone surgery for these tumors. Three of four patients had received local radiation therapy. None of the patients were neutropenic. One patient died. A review of the literature revealed that most patients with non-A, non-D streptococcal meningitis had disruption of the normal barrier protecting the CNS due to trauma, surgery, or the presence of a tumor, or had extensive exposure to animals or an underlying medical disease. Infection with non-A, non-D streptococci should be considered in any patient with meningitis who has a tumor of the head or neck and who has undergone surgery and/or radiation therapy.

Female

Sepsis due to Rhodotorula related to use of indwelling central venous catheters.

With increased use of surgically implanted silastic central venous catheters, there has been an increase in the recovery from blood cultures at Memorial Sloan-Kettering Cancer Center (New York) of environmental and skin organisms including the red yeast Rhodotorula. From 1985 through 1989, 23 patients had catheter-related Rhodotorula sepsis. All 23 patients had indwelling central venous catheters that had been in place from 1 to 22 months (average, 9.3 months) prior to the detection of fungemia. All patients had blood drawn both through the catheter and from a peripheral source, and only one patient had a peripheral blood culture positive for Rhodotorula. Colony counts of yeast from the catheter cultures often exceeded 100 (15 patients) and even 1,000 (seven patients) cfu/mL of blood. Thirteen of the patients were treated with antifungal therapy and had the catheter removed, and five patients received antifungal therapy without catheter removal (suggesting that compulsory removal of the catheter may not always be required). Five patients had the catheter removed without antifungal therapy. All patients survived the fungemic episode and experienced no recurrence of the infection.

Adolescent

Perceptions of psychological problems in general practice: a comparison of general practitioners and psychiatrists.

All general practitioners and psychiatrists working in a single health district were sent a questionnaire on their perceptions of the prevalence of psychological problems among patients consulting in general practice. One hundred and twenty-one GPs (75%) and 10 (83%) psychiatrists responded. GPs and psychiatrists agreed that up to 20% of consulting patients were likely to be clinically depressed; they also agreed on the most appropriate management, although GPs tended to be more conservative than psychiatrists would advise on making use of hospital services. GPs, however, believed non-specific psychological problems to be significantly less common than did psychiatrists. This expectation may help explain the reported failure of GPs to diagnose all psychological problems identified by formal psychiatric instruments.

Adult

Cryptococcal meningitis: outcome in patients with AIDS and patients with neoplastic disease.

A retrospective analysis of 41 patients with cryptococcal meningitis and AIDS or neoplastic disease was done. Patients with AIDS were younger and predominantly male; they had a shorter duration of prior illness, higher initial serum cryptococcal antigen titers, and lower initial cerebrospinal fluid white blood cell counts than those with neoplastic disease. The median overall survival for patients with AIDS was 9 months compared with 2 months for those with neoplastic disease (P = .004). Seventy-eight percent of patients with AIDS and 43% of those with neoplastic disease were cured or improved 6 months after diagnosis (P = .039). Toxicity from amphotericin B and flucytosine was similar for both groups. One patient with AIDS relapsed. Multivariate predictors of survival included headache (P = .007) and an AIDS diagnosis (P = .009). Examination of outcomes for other opportunistic infections associated with AIDS and other immunosuppressive illness may distinguish prognostic features for different patient populations.

Acquired Immunodeficiency Syndrome