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Biomedical subjects

L Kaiser

Publications and source records attributed to L Kaiser.

At least 91 records · Page 5Linked to original sources
PubMed1997

Postoperative radiation therapy in non-small cell lung cancer.

One hundred seventy-three patients with the diagnosis of non-small cell lung cancer (NSCLC) were treated with surgery and postoperative radiation therapy (RT) at the Radiation Oncology Center, Washington University, St. Louis. All patients had been retrospectively reviewed and restaged according to the new American Joint Committee (AJC) staging classification. Seventeen patients were stage I, 69 were stage II, 74 were stage IIIA, and 2 patients were stage IIIB. In 11 patients, accurate staging could not be determined. Indications for postoperative RT were positive surgical margins (32 patients), metastatic hilar nodes (78 patients), and metastatic mediastinal nodes (62 patients). Locoregional control for stages I, II, and IIIA was 85, 75, and 85%, respectively. Five-year actuarial survival was 35% for stage I and 20% for stages II and IIIA. Patients with N0 disease (positive margins) had 5-year survival of 25%, whereas patients with N1 and N2 disease had a 5-year survival of 20%.

Adenocarcinoma↗
PubMed1997

Dirofilaria immitis: heartworm infection alters pulmonary artery endothelial cell behavior.

The pathogenesis of filariasis has generally been attributed to either physical presence of the adult parasites or the host's immune response to the parasites. However, the spectrum of filariasis cannot be entirely explained by these causes, and other mechanisms must be operative. It is now evident that factors released by filarial parasites likely contribute to the pathogenesis of filarial diseases. Adult heartworms (Dirofilaria immitis) reside in the right heart and pulmonary artery, so the pulmonary artery should be exposed to the highest concentration of filarial factors. We tested the hypothesis that endothelium-dependent relaxation is altered in the in vitro pulmonary artery from heartworm-infected dogs. Relaxation responses to endothelium-dependent vasodilators (methacholine, bradykinin, substance P, and A-23187) and the nonendothelium-dependent vasodilator nitroglycerin and contractile responses were measured in rings of pulmonary artery from control and heartworm-infected dogs. Endothelium-dependent relaxation was assessed in the presence and absence of inhibitors of nitric oxide synthase, cyclooxygenase, and guanylate cyclase. Responses to methacholine, substance P, and A-23187, but not to bradykinin, nitroglycerin, norepinephrine, or KCl, were depressed in pulmonary artery from heartworm-infected dogs when compared with control, suggesting that changes in endothelial cell and not vascular smooth muscle behavior are involved in altered relaxation. The mechanism of endothelium-dependent relaxation in control pulmonary artery appears to involve nitric oxide in the case of methacholine and both nitric oxide and a cyclooxygenase product in the case of bradykinin and A-23187. The mechanism of endothelium-dependent relaxation in pulmonary artery from heartworm-infected dogs was not clearly elucidated. These data provide no evidence that heartworm infection globally influences either endothelial cell receptor function or the vascular smooth muscle guanylate cyclase guanosine 3',5'-cyclic monophosphate system, making it likely that changes in intracellular signaling are primarily responsible for the observed alteration of endothelium-mediated relaxation. Alteration of endothelial cell function by filarial parasites may be an important component in the pathology associated with filariasis.

Animals↗
PubMed1997

The Alzheimer's Disease Assessment Scale: patterns and predictors of baseline cognitive performance in multicenter Alzheimer's disease trials.

The cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-Cog) is used as an efficacy measure in clinical drug trials of Alzheimer's disease (AD). We used data from 1,648 AD participants in two identical 26-week multicenter drug trials to examine the distribution of baseline ADAS-Cog scores in relation to selected demographic and clinical variables, Mini-Mental State Exam (MMSE), Global Deterioration Scale (GDS), and Geriatric Evaluation by Relative's Rating Instrument (GERRI) scores. At baseline, the mean (+/-SD) MMSE score was 18 +/- 4, the ADAS-Cog score was 28 +/- 11, and most subjects were in GDS stage 4 or 5. The ADAS-Cog score was statistically significantly correlated with MMSE (R = -0.76, p < 0.0001) and GERRI (R = 0.40, p < 0.0001) total scores. Correlations among the ADAS-Cog items ranged from 0.19 to 0.59 and all were statistically significant (p < 0.0001). In a multiple regression model, younger age, male gender, older age at onset of dementia, use of concurrent estrogen, and use of concurrent anti-inflammatory agents were statistically significantly associated with superior cognitive performance. We also present data on the distribution of ADAS-Cog scores in relation to subjects' age, level of education, MMSE score, and GDS stage. Because age, MMSE score, and GDS stage (and not the ADAS-Cog) are commonly used to select subjects for AD clinical trials, our data should improve the ability of sponsors to predict ADAS-Cog scores of the subjects in their trials on the basis of the inclusion criteria used. Our data also suggest that age, gender, age at onset of dementia, level of education, and use of estrogen (in women) or anti-inflammatory drugs are related to cognitive abilities in AD. Further studies are needed to assess how and when cognitive differences related to these variables arise.

Aged↗
PubMed1997

Effect of arsenical drugs on in vitro vascular responses of pulmonary artery from heartworm-infected dogs.

OBJECTIVE: To test the effect of thiacetarsamide and melarsomine on vascular responses in isolated rings of pulmonary artery from heartworm-infected dogs. ANIMALS: 18 heartworm-infected dogs. PROCEDURE: Isolated rings of pulmonary artery from heartworm-infected dogs were randomly treated with thiacetarsamide (30 micrograms/ml) or melarsomine dihydrochloride (30 micrograms/ml) for 30 minutes; untreated rings from the same dog served as control. Cumulative dose-response relations to norepinephrine, nitroglycerin, and methacholine were determined. RESULTS: Norepinephrine-induced constriction was not altered by treatment with either thiacetarsamide or melarsomine. Treatment with thiacetarsamide depressed nitroglycerin-induced relaxation, compared with values for untreated control rings and rings treated with melarsomine. Treatment of rings with thiacetarsamide or melarsomine depressed methacholine-induced relaxation, compared with values for untreated rings. Histologic examination of rings indicated that treatment with thiacetarsamide or melarsomine resulted in loss of endothelial cells. CONCLUSION: Endothelial cell loss as a direct drug effect may be responsible for impaired endothelium-dependent relaxation in pulmonary artery from heartworm-infected dogs. Thiacetarsamide appears to have additional effects on vascular smooth muscle, which may explain why fewer complications are observed in dogs treated with melarsomine. CLINICAL RELEVANCE: Melarsomine may be a safer drug than thiacetarsamide and could be a better treatment for dogs with heartworm infection.

Animals↗
PubMed1997

Effect of heartworm infection on in vitro contractile responses of canine pulmonary artery and vein.

OBJECTIVE: To test the effect of heartworm infection on agonist-induced constriction of canine pulmonary artery and vein in vitro. PROCEDURE: Cumulative concentration-response relations to norepinephrine, serotonin, histamine, prostaglandin F2 alpha, and the thromboxane A2 analog U-44069 were determined, using isolated rings of pulmonary artery and vein from control and heartworm-infected dogs. To determine the role of endothelial cells in histamine constriction, some rings were denuded of endothelial cells in both artery and vein. ANIMALS: Noninfected control and heartworm-infected dogs. RESULTS: There was no difference in constriction response to norepinephrine, serotonin, prostaglandin F2 alpha, or U44069 of pulmonary artery or vein from control or heartworm-infected dogs. Histamine-induced constriction of pulmonary artery from heartworm-infected dogs was not different from control values, however, when endothelial cells were removed from control, but not heartworm-infected pulmonary artery, histamine-induced constriction was enhanced. Histamine-induced constriction of pulmonary vein from heartworm-infected dogs was significantly depressed, compared with that of control pulmonary vein. However, removal of endothelial cells in pulmonary vein from heartworm-infected, but not control dogs significantly increased constriction. CONCLUSION: Heartworm infection alters histamine-induced constriction responses of pulmonary artery and vein. These changes may reflect high circulating histamine concentrations in heartworm-infected dogs, compared with that in controls. Increased circulating histamine concentrations in vivo could bring about decreased sensitivity of histamine receptors o decreases in the number of receptors expressed. CLINICAL RELEVANCE: Mast cells and histamine may be important factors in altered endothelium-mediated responses associated with heartworm disease.

Animals↗
PubMed1997

Memory, language, and praxis in Alzheimer's disease: norms for outpatient clinical trial populations.

The cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-Cog) is designed specifically to assess memory, language, and praxis dysfunctions characteristic of Alzheimer's disease (AD). In this report, we use data from 1,648 AD participants in two identical 26-week multicenter drug trials to derive clinical trial population-based norms for ADAS-Cog subtest scores. All 11 ADAS-Cog item scores were sensitive to differences in dementia severity judged either by baseline Mini-Mental State Exam (MMSE) scores or by Global Deterioration Scale (GDS) stage of dementia. Using ADAS-Cog subtest scores alone, 85 percent of GDS 4 subjects and 69 percent of GDS 5 subjects could be classified correctly. In a stepwise discriminant analysis, orientation was the item with the greatest discriminatory power between subjects with GDS 4 and GDS 5 stages of dementia. ADAS-Cog subtest scores also varied by age, gender, educational level, and concurrent use of anti-inflammatory drugs or estrogen (in women). Such normative data may facilitate the selection of appropriate outcome measures to investigate differential treatment effects on specific cognitive domains or in specific AD subpopulations.

Aged↗
PubMed1996

Thiacetarsamide depresses relaxation of canine pulmonary artery in vitro.

Little information is available on the primary pharmacological effects of thiacetarsamide on mammalian systems, particularly on blood vessels. The effects of thiacetarsamide on arterial responses was studied in isolated rings from canine pulmonary artery. Vessels were exposed to thiacetarsamide and dose-response relationships were applied to methacholine and nitroglycerin. To rule out non-specific effects of antihelmintics, the effects of two other antifilarial drugs, diethylcarbamazine and ivermectin, were also tested. Thiacetarsamide significantly depressed relaxation of canine pulmonary artery to both methacholine and nitroglycerin, and significantly enhanced constriction to norepinephrine. Neither diethylcarbamazine nor ivermectin altered vascular response. These direct effects of thiacetarsamide on arterial responsiveness may be responsible, in part, for acute pulmonary complications observed in dogs infected with Dirofilaria immitis after adulticide treatment.

Animals↗
PubMed1996

Effects of antibiotic treatment in the subset of common-cold patients who have bacteria in nasopharyngeal secretions.

BACKGROUND: Upper-respiratory-tract infection is one of the main causes of overuse of antibiotics. We have found previously that bacteria such as Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae can be isolated from the nasopharyngeal secretions of a substantial proportion of adults with upper-respiratory-tract infections. We have assessed the efficacy of co-amoxiclav in patients with common colds but no clinical signs of sinusitis or other indications for antibiotics. METHODS: Between January, 1992 and March, 1994, 314 patients who presented to our outpatient clinic with common colds were enrolled in the double-blind, placebo-controlled study. They were randomly assigned 5 days' treatment with co-amoxiclav (375 mg three times daily) or identical placebo. Clinical examinations were done at enrolment and on day 5-7 to assess outcome (cured, persistent symptoms, worse symptoms). Seven patients were excluded after randomisation, seven did not have nasopharyngeal aspiration, and 12 did not return for followup assessment. FINDINGS: Of 300 patients with nasopharyngeal aspirates, 72 had negative bacterial cultures, 167 had cultures positive only for bacteria unrelated to respiratory infections, and 61 had cultures positive for H influenzae, M catarrhalis, or S pneumoniae. At 5-day follow-up of these culture-positive patients, the distribution of outcome was significantly better among co-amoxiclav-treated (n=30) than placebo-treated (n=28) patients (cured 27 vs 4%; persistent symptoms 70 vs 60%; worse symptoms 3 vs 36%; p=0.001). Patients on co-amoxiclav also scored their symptoms significantly lower than patients on placebo (p=0.008). Among culture-negative patients (n=230), the outcome distribution did not differ between the treatment groups (p=0.392). INTERPRETATION: The majority of patients with upper-respiratory-tract infection do not benefit from antibiotics and side-effects are frequent. However, for the subgroup whose nasopharyngeal secretions contain H influenzae, M catarrhalis, or S pneumoniae, antibiotics are clinically beneficial.

Adult↗
PubMed1996

Acute right iliac fossa pain in acquired immunodeficiency: a comparison between patients with and without acquired immune deficiency syndrome.

A retrospective review was performed of the clinical features present in 17 patients who were human immunodeficiency virus (HIV) positive requiring a diagnostic or therapeutic procedure for suspected appendicitis. Patients who were acquired immune deficiency syndrome (AIDS) free (n = 11) and those with AIDS (n = 6) were compared. Ten of the 11 patients who were AIDS-free had appendicitis. The morbidity rate was 9 per cent, similar to that expected in seronegative patients, but the appendix perforation rate was 50 per cent. Only two of the six patients with AIDS had appendicitis. Three suffered from an HIV-related disease process. Computed tomography (CT) was performed in four of the six patients with AIDS, and was considered of diagnostic help in three. In patients with AIDS, the morbidity rate rose to 50 per cent. Surgical decision-making with regard to HIV-positive patients who were AIDS-free with suspected appendicitis should be similar to that for seronegative patients. For patients with AIDS, alternative diagnostic strategies, including preoperative CT, or possibly laparoscopy, should be considered.

Abdominal Pain↗
PubMed1996

Analysis of Epstein-Barr virus-associated posttransplantation lymphoproliferative disorder after lung transplantation.

BACKGROUND: Epstein-Barr virus (EBV)-associated posttransplantation lymphoproliferative disorder (PTLD) is a serious complication of lung transplantation. Besides immunosuppression the risk factors for PTLD development are largely unknown. METHODS: The incidence of PTLD was ascertained in a lung transplant population consisting of 45 patients. Nine patients (20%) experienced PTLD. The clinical, histologic, and human leukocyte antigen (HLA) data were collected on all patients. The incidence of EBV infection in lymphoid tissue taken at the time of engraftment was studied by using EBV in situ hybridization. RESULTS: All patients with PTLD had polymorphous lymphoproliferations, seven of which were polymorphous B-cell hyperplasias and two of which were polymorphous B-cell lymphomas. EBV was identified in all lesions. All patients with polymorphous B-cell hyperplasias had clinically unsuspected disease, five of which were identified at autopsy. The two polymorphous B-cell lymphoma lesions were monoclonal and regressed with immunosuppression reduction. EBV in situ hybridization on donor or recipient lymph nodes obtained at engraftment from the 45 transplant recipients showed no difference in the number of EBV positive cells in patients with and without PTLD. Cyclosporine and PTLD and azathioprine dosages and cyclosporine levels were similar between patients with and without PTLD. PTLD was seen in patients with high cumulative doses of antilymphocyte globulin. Analysis of HLA status showed a predominance of HLA A2 and DR7 in the donors of the patients with PTLD, whereas donor HLA B7 was more common in patients without PTLD> CONCLUSIONS: Detailed studies are necessary to further elucidate the risk factors for PTLD development in the lung transplant population.

Adult↗
PubMed1996

Phase II trial of all-trans retinoic acid in metastatic non-small cell lung cancer.

The toxicity and marginal effectiveness of cytotoxic chemotherapy in metastatic non-small cell lung cancer (NSCLC) necessitates the search for new agents. Preliminary data in lung cancer and other malignant and premalignant disorders have identified retinoid compounds as potentially useful antitumor agents. Twenty-eight patients with metastatic NSCLC were treated with oral all-trans retinoic acid in a phase II trial. The study population consisted of patients with excellent performance status and minimal weight loss. Toxicities were generally mild and included cutaneous effects, headache, and myalgia. A significant number of patients developed elevations of hepatic transaminases or hyperlipidemia and 3 patients had treatment-related leukocytosis. Two patients (8%) achieved a partial response, and 1 had a mixed response. The duration of remission in the 2 responders was 7 and 13 months and the median survival of all patients 7 months. Therefore, all-trans retinoic acid has minimal activity as a single agent in NSCLC but warrants further study in combination with biological agents and chemotherapy.

Adult↗
PubMed1996

Brugia pahangi-induced contractility of bovine mesenteric lymphatics studied in vitro: a role for filarial factors in the development of lymphedema?

Products generated by filarial nematodes depress vascular reactivity by mechanisms involving endothelial cells. We hypothesized that comparable filarial-induced alterations might occur in lymph vessels. Experiments were designed to test the hypothesis that spontaneous contractions of bovine mesenteric lymphatics studied in vitro are altered by the filarial parasite Brugia pahangi. Rings of bovine mesenteric lymphatics were suspended in tissue baths and spontaneous contractions were evaluated for rate, rhythm, and amplitude. Rings that met inclusion criteria (rate > 1.8/min, regular rhythm, and an amplitude > 500 mg) were randomly exposed to B. pahangi or used as controls. Parasites were added to the bath at time zero. Changes in rate, rhythm, and magnitude of spontaneous contractions were evaluated every 10 min. Comparisons were made within control or Brugia-infected groups over time and between groups (B. pahangi versus controls). The presence of B. pahangi significantly depressed the frequency of spontaneous contractions when compared with controls. Control rings were stable over time, without changes in rate, rhythm, or amplitude. However, B. pahangi alter both the rate and rhythm of spontaneous contractions. Since spontaneous contractile activity is likely to be important in the propulsion of lymph, alterations of contractile activity could result in lymphedema. Thus, filarial factors may be responsible, in part, for altered lymphatic function seen in lymphedema. Pharmacologic intervention aimed toward influencing host-parasite metabolic interactions may, in this complicated scenario, prove useful.

Animals↗
PubMed1996

The physician glut: a different view. Interview by Donna Vavala.

An interview with nationally known futurist Leland Kaiser, PhD, on the changes physician executives are likely to face as a result of the coming dislocation in the health professions. Or will there be a shrinking career pie at all? The real question is: What new mental models are we going to use and as a result of the new models, what new jobs are going to be created that will ameliorate some of the surplus we've created in the old model? Dr. Kaiser predicts a model will soon emerge that will open a myriad of new career opportunities for physicians. The new model he foresees is community-based medicine.

Career Mobility↗
PubMed1996

Effect of heartworm infection on fade of norepinephrine-induced constriction in canine pulmonary vein.

OBJECTIVE: To test the possible role of endothelial cells in mediating fade of norepinephrine-induced constriction and the effect of heartworm infection on these responses. DESIGN: Rings of pulmonary vein from control and heartworm-infected dogs were constricted with norepinephrine (10(-5.5)M) and followed over 65 minutes. Time profiles were established by measuring active tension every 2 minutes for the first 10 minutes, then every 5 minutes for 15 minutes, then every 10 minutes for 40 minutes. Time profiles were done in pulmonary vein rings with and without endothelial cells, and in the presence and absence of N-nitro-L-arginine methyl ester (L-NAME; nitric oxide synthase inhibitor), mefenamic acid (cyclooxygenase inhibitor), or methylene blue (guanylate cyclase inhibitor). ANIMALS: 12 noninfected control and 11 heartworm-infected dogs. RESULTS: Pulmonary vein constricted with norepinephrine spontaneously loses tension (fades) over time. Fade was not different between control and heartworm-infected dogs. In pulmonary vein from control dogs, methylene blue decreased fade while L-NAME and mefenamic acid did not. In pulmonary vein from heartworm-infected dogs, L-NAME and methylene blue significantly decreased fade, but mefenamic acid did not. CONCLUSION: Nitric oxide, but not cyclooxygenase products, mediates fade of norepinephrine-induced constriction in pulmonary vein from heartworm-infected dogs. In control dogs, neither nitric oxide nor cyclooxygenase products appear to be involved in fade. We conclude that in canine pulmonary vein, fade of norepinephrine-induced constriction is mediated, in part, by endothelial cells. CLINICAL RELEVANCE: Altered production of endothelium-derived relaxing factors may be important in the pathogenesis of heartworm disease.

Animals↗
PubMed1996

[Aspergillus lung pathology in transplant patients].

Invasive pulmonary aspergillosis, with or without dissemination to other organs, is a severe complication in patients who have undergone transplantation. The incidence of this disease is conditioned by the type of transplantation, the intensity of immunosuppressive regimens, and local epidemiology. The latter factor underscores the importance of air conditioning systems, and special caution is needed in case of hospital renovation. The clinical picture is frequently characterized by persisting fever, despite antibiotic treatments, but is otherwise non specific. Computerized tomography and magnetic resonance imaging show typical lesions more often than do conventional chest x-ray films. The sensitivity of broncho-alveolar lavage is poor, and DNA amplification techniques for Aspergillus might increase the diagnostic yield in the future. Also, detection of Aspergillus antigens in serum and urine might prove useful, but further studies are needed before a standardized test can be recommended for diagnostic purpose. Intravenous amphotericin B is the treatment of choice. Liposomal and other lipid formulations of this drug represent interesting alternatives, although very expensive. Itraconazole is emerging as a promising drug, because of fewer side effects than amphotericin. However, improvement of its formulation is still necessary.

Air Conditioning↗
PubMed1995

Early and prolonged decrease of viremia in HIV-1-infected patients treated with didanosine.

Fourteen patients previously treated with zidovudine were monitored for laboratory parameters and clinical events during 1 year after introduction of didanosine (ddI) monotherapy. Proviral human immunodeficiency virus type 1 (HIV-1) copy numbers (cell-associated DNA) and concentration of free virions (viremia) were determined using a semiquantitative polymerase chain reaction (PCR). High levels of circulating virus were detected in all patients (range, 17 to 5,934 x 10(3)/ml of serum). Within 4 weeks of therapy, a decrease of viremia (60 to 98%) was observed in nine patients. After 1 year of treatment, eight of these nine patients still had decreased viremia when proviral HIV DNA was decreased or stable, and CD4+ lymphocytes were stable or higher in seven of these eight patients. Antiviral effect was more pronounced in the six patients with CD4+ > 100/mm3 at entry, five of them belonging to the subgroup of the seven responding patients as compared to two of eight patients with CD4+ < 100/mm3. Clinical events in this small group were not statistically correlated with virologic parameters; however, responding patients had a tendency to stabilize or gain weight. This study suggests that measurement of viremia deserves further study as a marker of antiviral efficacy and might predict, even at 4 weeks, the beneficial potential of ddI.

AIDS-Related Opportunistic Infections↗
PubMed1995

[Uveitis associated with rifabutin treatment. Apropos of 3 patients].

Disseminated Mycobacterium-avium complex (MAC) infection develops in most patients with AIDS. We report three cases of anterior uveitis with vitritis in AIDS patients treated by the combination of rifabutin, clarithromycin and ethambutol for MAC bacteremia. Uveitis secondary to the introduction of rifabutin treatment is suggested.

AIDS-Related Opportunistic Infections↗