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At least 811 records · Page 45Linked to original sources
PubMed2005

[Intracavitary laser therapy and its effect on the kallikrein-kinin system of blood in children with pneumothorax].

The article presents the results of low-intensity laser application in complex treatment of 137 children with acute purulent destructive pneumonia complicated by pneumothorax with bronchial fistulas. A method of intracavitary laser therapy, developed in the clinic, allowed obliteration of bronchopleural fistulas without application of bronchial occlusion and other invasive techniques. Evaluation of the kallikrein-kinin system of blood revealed prominent reduction of kininogenesis in most (87%) patients upon admission (3 weeks after the onset of the disease), which is an important link of the pathogenesis of late stages of complicated acute purulent lung destruction in children. The study also demonstrated that low-intensity laser emission modulates pyoinflammatory process due to its effect on cell-mediated immunity, neutrophilic phagocytosis and the kallikrein-kinin system of blood. Intracavitary laser therapy is the treatment of choice in children with acute purulent destructive pneumonia complicated by pneumothorax with bronchial fistulas. Application of intracavitary laser therapy in complex therapy of complicated acute purulent lung destruction in children allowed discharge from the hospital 5 to 7 day earlier, and prevented lung inflammatory process chronization. None of the patients have died within last 10 years.

Acute Disease↗
PubMed2002

HIV-1 subtype C reverse transcriptase and protease genotypes in Zimbabwean patients failing antiretroviral therapy.

HIV-1 drug resistance mutations have been identified and characterized mostly in subtype B HIV-1 infection. The extent to which antiretroviral drugs select for drug resistance mutations in non-subtype B HIV-1 is not known. We obtained HIV-1 reverse transcriptase (RT) and protease sequences from 21 Zimbabwean patients failing antiretroviral drug therapy. We compared these sequences with 56 published RT and protease subtype C sequences from untreated patients, 990 RT and 1140 protease subtype B sequences from treated patients, and 340 RT and 907 protease subtype B sequences from untreated patients and identified four mutation categories of subtype C HIV-1. Seventeen of the 21 patients (81%) had known drug resistance mutations. Mutations at 15 RT and 11 protease positions were more common in subtype C isolates than in subtype B isolates. HIV-1 subtype C-infected individuals receiving antiretroviral therapy develop many of the known subtype B drug resistance mutations. Comparison of subtype C RT and protease sequences with a large database of subtype B sequences identified subtype C-specific polymorphisms and candidate drug resistance mutations.

Anti-HIV Agents↗
PubMedDate not supplied

Myopic excimer laser keratectomy: a preliminary report.

Six patients underwent excimer laser refractive keratectomy for the correction of myopia. All eyes, with the exception of patient 6, who underwent a previous failed epikeratophakia procedure and subsequent removal of the lenticule, had normal baseline ophthalmologic evaluations and best corrected visual acuities of 20/25 or better. Spherical equivalents ranged between -5.50 and -12.00 diopters. Under topical and peribulbar anesthesia, the central corneal epithelium was removed. The delivery system of the laser was programmed to ablate corrections onto the central 5.0 mm of the cornea that would result in approximate emetropia. Moderate fluctuation of refractive and topographic parameters was noted during the period of epithelial healing and remodeling. At the 12th postoperative week, five of the corneas were clear on biomicroscopic evaluation with best corrected acuities of 20/20. The final patient, who was noncompliant in the use of topical corticosteroid therapy, developed a central, 2-mm opacity and resulting best corrected acuity of 20/40. Overall, the group demonstrated that myopic excimer laser photorefractive keratectomy is consistent with good wound healing, insignificant corneal scarring, a stable refractive correction, and excellent visual acuity.

Adrenal Cortex Hormones↗
PubMed1999

Alopecia due to psychotropic medications.

OBJECTIVE: To review the literature and describe the incidence and nature of psychotropic drug-related alopecia to assist clinicians in their therapeutic decisions when this adverse event occurs. DATA SOURCES: A MEDLINE search (December 1966-March 1998), using each drug name and the keywords alopecia or hair loss, was conducted. A database from the Clarke Institute of Psychiatry in Toronto was also searched. Additional English-language articles were identified through the bibliography of the reviewed literature. Certain pharmaceutical companies were also consulted. STUDY SELECTION: All published case reports and review articles were considered for study evaluation. DATA EXTRACTION: When possible, details regarding psychotropic drug therapy, development of alopecia, and clinical outcomes were collected for each case. DATA SYNTHESIS: Hair loss from the scalp, eyebrows, and pubic area was identified as a possible, yet uncommon, adverse effect of most psychotropic medications. There are few effective management options for alopecia; however, resolution was achieved on discontinuation of the offending drug in almost all of the cases reported. Alopecia was perceived to be an undesirable effect by most patients, often resulting in poor compliance and hence therapeutic failures. CONCLUSIONS: Due to the self-limiting nature of mild to moderate hair loss with psychotropic medications, clinicians should consider continuing therapy if there is a good clinical response and the patient agrees with this decision. If severe alopecia occurs, it is recommended to discontinue the medication and pursue therapy with another agent. This is to ensure positive therapeutic outcomes and improved patient compliance.

Alopecia↗
PubMed2002

Novel trends in orphan market drug discovery: amyotrophic lateral sclerosis as a case study.

As new lead discovery technologies of high throughput screening and rational drug design have been incorporated into pharmaceutical and biotechnology drug discovery programs, researchers have focused on the applying these new technologies in diseases traditionally neglected by for-profit drug discovery efforts. This article reviews general trends in orphan disease lead discovery, identifies best practices of orphan market drug discovery and provides an overview of recent ALS lead discovery programs and drug development according to these metrics. Best practices in orphan market drug discovery embodied by programs like the NIH Anticonvulsant Screening Program include the (1) management of timelines and priorities, (2) engagement of for-profit partners, (3) creative application of technology, (4) collaboration, and (5) flexibility. Recent trends in ALS lead discovery have been shaped not only by the predominance of animal models of disease over in vitro models, but also by the successes and best practices of these earlier orphan market drug discovery programs. The ALS Treatment Initiative, the Johns Hopkins Center for ALS Research, the ALS Association, and the ALS Therapy Development Foundation have all initiated lead discovery programs in the past several years which seek to utilize existing experimental models of the disease and challenge assumptions about the linear nature of the lead discovery and development process. The compounds currently in clinical evaluation for ALS were identified as leads from a variety of sources, further reinforcing the transforming effect these new lead discovery programs have had on drug discovery and development in ALS. We conclude our review with an overview of the challenges and opportunities lead discovery in ALS currently faces, ultimately concluding that ALS lead discovery, and indeed orphan market drug discovery in general, would most benefit from more centralized lead discovery management, expanded national access to core facilities for lead discovery, and matrixed simultaneous screening of multiple compounds for multiple neglected diseases.

Amyotrophic Lateral Sclerosis↗
PubMed1991

[Study of the diffusion of therapeutic progress in a morbidity register. Exemplified by rectal cancer in Calvados].

Recent treatment trends have been studied among 614 rectal cancer cases collected in the Digestive Tract Cancer Registry in the "Département" of Calvados between 1978 and 1986. Of the 343 cases in which the tumour was resected, the sphincter was preserved in 32% of the cases (SP), and 30% had adjuvant radiotherapy (ART). The frequency of sphincter preservation (SP) and ART increased significantly during the study period. For both SP and ART, generalized use was less frequent and implemented later in unspecialized health care centres, even after adjustment for confounding. SP was more widely used in females and younger patients. Starting in 1984, the generalized use of ART - especially in pre-operative therapy - developed considerably, particularly for males and younger patients. Distance from the radiotherapy centre did not influence the radiotherapy rate. The use of morbidity registry data in assessing health care practices gives us a more precise view than hospital series, and provides information that can be extremely useful for formulating future guidelines for health care planning.

Aged↗
PubMed1970

Cryptococcal meningitis associated with steroid therapy.

Two patients on prolonged steroid therapy developed meningitis due to Cryptococcus neoformans. The first responded satisfactorily to treatment with amphotericin B, both initially and again following relapse. The second died shortly after treatment was begun. Pathogenicity studies suggest that the strain isolated from the fatal case was the more virulent. Cryptococcal meningitis probably occurs more often in Britain than is generally appreciated, and this possibility should be remembered when investigating patients with obscure forms of meningitis; if not, then the correct diagnosis may not be made. Attention is drawn to the increasing number of recently reported cases of this disease which have been associated with long-term steroid therapy.

Adult↗
PubMedDate not supplied

Clinical patterns of diarrhea in AIDS: etiology and prognosis.

OBJECTIVE: To define the etiology and prognosis of diarrhea (acute, intermittent or chronic) in AIDS patients. DESIGN: A retrospective analysis of patients with AIDS and diarrhea. Patterns of diarrhea were defined a priori. Endpoints of interest were etiology, rate of response to therapy, development of chronic diarrhea, and survival probability. Data were analyzed by means of univariate and multivariate tests (chi-square, ANOVA, Student's t test, Kaplan-Meier, logrank and logistic regression analysis). SETTING: A 170-bed tertiary-care university hospital which is one of the three most important referral centers for AIDS patients in Mexico City. PATIENTS: The records of the 279 AIDS patients admitted to the hospital between 1983 and 1989 were reviewed; 225 cases were suitable for analysis. MEASUREMENTS: The presence of a diarrheal episode, the diagnostic studies to which the patient was submitted, the etiology, the response to therapy and the survival time from the point at which the diarrhea started were all recorded. Diarrheal patterns were stratified by clinical patterns and outcomes compared. Possible clinical predictors of chronic diarrhea were analyzed. RESULTS: Seventy seven percent of the patients suffered at least one diarrheal episode. Diarrhea was in fact the most common AIDS-related complication in our series, and in 51% of the total cases (114/225), it was the first HIV-related symptom. The diarrheal pattern was intermittent in 47% of the cases, chronic in 36% and acute in the remaining 17%. An etiology was established in only 59% of the episodes, and Cryptosporidium was the etiologic agent most frequently isolated (30%). Other opportunistic pathogens prevailed in chronic and intermittent diarrheas. Chronic persistent diarrhea was related to a lower survival probability (60% at one year vs 90% for intermittent and 95% for acute diarrhea, p < 0.0001). When the performance of different diagnostic studies was analyzed, the combination of stool culture, serial parasitic examination and sigmoidoscopy with biopsies provided a high diagnostic accuracy (59%). Regardless of etiology, the rate of therapeutic success was directly related to the previous duration of diarrhea and the absolute lymphocyte count (p < 0.01). CONCLUSIONS: There are three distinct diarrheal patterns common to AIDS patients. Although the etiologic agents do not vary significantly, each pattern has unique characteristics regarding the timing of presentation, their survival and therapeutic success rate. Such differences should be taken into account when therapeutic trials are designed.

AIDS-Related Opportunistic Infections↗
PubMed2000

Relationship between pre-existing viral reservoirs and the re-emergence of plasma viremia after discontinuation of highly active anti-retroviral therapy.

We examined the pathogenic significance of the latent viral reservoir in the resting CD4+ T cell compartment of HIV-1-infected individuals as well as its involvement in the rebound of plasma viremia after discontinuation of highly active anti-retroviral therapy (HAART). Using heteroduplex mobility and tracking assays, we show that the detectable pool of latently infected, resting CD4+ T cells does not account entirely for the early rebounding plasma HIV in infected individuals in whom HAART has been discontinued. In the majority of patients examined, the rebounding plasma virus was genetically distinct from both the cell-associated HIV RNA and the replication-competent virus within the detectable pool of latently infected, resting CD4 + T cells. These results indicate the existence of other persistent HIV reservoirs that could prompt rapid emergence of plasma viremia after cessation of HAART and underscore the necessity to develop therapies directed toward such populations of infected cells.

Adult↗
PubMed1989

Breast microcalcifications after lumpectomy and radiation therapy.

Ten of 152 (7%) consecutive breast cancer patients who underwent excisional biopsy and radiation therapy developed suspect microcalcifications at the biopsy site. All ten patients underwent reexcision. Seventeen other patients developed scattered, coarse, benign macrocalcifications that have remained stable as determined with mammographic follow-up. Of the ten patients who underwent reexcision, six had clusters of calcifications that were benign, and four had malignant calcifications. The morphologic appearance of the microcalcifications was similar in both malignant and benign disease, although the malignant calcifications tended to appear earlier than the benign ones. Three of the four patients with recurrent carcinoma had had calcifications in the original cancer. The mammographic features of the microcalcifications were not specific enough to distinguish recurrent malignancy from benign disease. Unless calcifications that occur in the breast after lumpectomy and radiation therapy have an unequivocally benign appearance (ie, scattered, round, homogeneous-appearing macrocalcifications), they should be viewed with suspicion and subjected to excisional biopsy.

Adult↗
PubMed1988

[Transcatheter arterial chemoembolization in liver metastases of colorectal cancer (lipiodol cisplatin sandwich therapy].

The transcatheter arterial chemoembolization (LPD-CDDP Sandwich Therapy) developed by us was applied to 15 patients with unresectable liver metastases (H2-H3) of colorectal cancer. Computed tomography or ultra-sonography revealed an overall response rate of 27%. Serum CEA values decreased to lower than the pre-TACE value in 11 (78%) of 14 patients excluding one showing the normal range before TACE. The post-TACE CEA values were completely normalized in 2 of the 11 patients. One-year cumulative survival rate was 72% and median survival was 18 months, showing a prolongation compared with intraarterial or systemic chemo-immunotherapy. The histological antitumor effect of LPD-CDDP Sandwich Therapy was examined in the hepatic specimens from 6 patients who underwent hepatectomy after this therapy for liver metastases (H1-H2) of colo-rectal cancer. The necrotic area in the main tumor was 95-100% in 3 patients, 75-94% in 2 patients and 50-74% in one patient. LPD-CDDP sandwich therapy was considered an effective treatment without any serious side effects for liver metastases of colo-rectal cancer.

Cisplatin↗
PubMed2000

Traumatic Acremonium atrogriseum keratitis following laser-assisted in situ keratomileusis.

A 52-year-old man underwent bilateral laser-assisted in situ keratomileusis. Eight months later, he sustained a penetrating corneal injury to the left eye. A dense white infiltrate, unresponsive to antimicrobial therapy, developed in the corneal stroma. Corneal biopsy and eventual penetrating keratoplasty were performed, and both specimens demonstrated fungal elements with branching, septate hyphae. Culture identified the organism as Acremonium atrogriseum. Histopathologic features of this organism and its differentiation from other, more common fungal organisms are discussed herein.

Acremonium↗
PubMed2007

A systematic review of intervention studies about anxiety in caregivers of people with dementia.

BACKGROUND: There is considerable literature on managing depression, burden and psychological morbidity in caregivers of people with dementia (CG). Anxiety has been a relatively neglected outcome measure but may require specific interventions. OBJECTIVE: To synthesise evidence regarding interventions that reduce anxiety in CGs. METHODS: Twenty-four studies met our inclusion criteria. We rated the methodology of studies, and awarded grades of recommendation (GR) for each type of intervention according to Centre for Evidence Based Medicine guidelines, from A (highest level of evidence) to D. RESULTS: Anxiety level was the primary outcome measure in only one study and no studies were predicated on a power calculation for anxiety level. There was little evidence of efficacy for any intervention. The only RCT to report significantly reduced anxiety involved a CBT and relaxation-based intervention specifically devised to treat anxiety, and there was preliminary evidence (no randomised controlled trials) that caregiver groups involving yoga and relaxation without CBT were effective. There was grade B evidence that behavioural management, exercise therapies and respite were ineffective. LIMITATIONS: Many interventions were heterogeneous, so there is some overlap between groups. Lack of evidence of efficacy is not evidence of lack of efficacy. CONCLUSIONS: CBT and other therapies developed primarily to target depression did not effectively treat anxiety. Good RCTs are needed to specifically target anxiety which might include relaxation techniques. Some of the interventions focussed on reducing contact with the care recipients but caregivers may want to cope with caring and preliminary evidence suggests strategies to help CGs manage caring demands may be more effective.

Anxiety↗
PubMed1986

Granulopoiesis in long-term culture by marrow from mice with busulfan-induced chronic latent aplasia.

Mice given high-dose busulfan therapy develop a chronic latent marrow aplasia characterized by normal peripheral blood neutrophil numbers, hematocrits and marrow cellularity but reduced numbers of pluripotent hemopoietic stem cells (CFU-s) and granulocyte-monocyte progenitor cells (CFU-gm). To study the pathogenesis of this lesion, bone marrow was propagated in long-term marrow cultures (LTMC). Small amounts of normal marrow readily established and sustained long-term granulopoiesis in vitro. In contrast, inocula of marrow from busulfan-treated animals containing three to five times as many stem and progenitor cells failed to establish long-term granulopoiesis in vitro. These results suggest that high-dose busulfan therapy produces a qualitative defect in either the hemopoietic stem cells, the stromal-forming elements, or both, rendering them incapable of establishing long-term granulopoiesis in vitro. Furthermore, mixing experiments employing normal and busulfan-damaged marrow demonstrate that this qualitative defect is not due to the emergence of a suppressor cell population. LTMC can show types of marrow damage not detectable by other techniques currently available and represent a powerful tool for studying latent bone marrow failure.

Anemia↗
PubMed1991

The therapeutic use of tape-recorded repetitions of flooding stimuli.

This clinical report describes an enhancement of imaginal flooding therapy developed in clinical practice with outpatient phobics. During the session, anxiety-producing fantasies are solicited, and the verbalizations immediately preceding peaks in emotional arousal are captured on a three-minute repeating "endless loop" cassette tape. Patients' repeated exposure to the recording, in the office and as homework, enhances the efficiency and economy of imaginal flooding.

Adult↗
PubMed2005

The metabolic basis of atherogenic dyslipidemia.

Atherogenic dyslipidemia is one of the major components of the metabolic syndrome, a complex cluster of several risk factors within a single patient that according to the National Cholesterol Education Program (NCEP) Adult Treatment Panel III includes at least 3 of the following: large waist circumference, elevated triglyceride levels, low levels of high-density lipoprotein cholesterol (HDL-C), hypertension, and elevated fasting glucose levels, which are directly related to the incidence of coronary heart disease. Atherogenic dyslipidemia clinically presents as elevated serum triglyceride levels, increased levels of small dense low-density lipoprotein (sdLDL) particles, and decreased levels of HDL-C. An important component of atherogenic dyslipidemia is central obesity, which is defined as increased waist circumference and has recently been identified as a chief predictor of the metabolic syndrome in certain patients. Another recent study found that both body mass index and waist circumference were highly predictive of eventual development of the metabolic syndrome. Because atherogenic dyslipidemia usually precedes the clinical manifestation of the metabolic syndrome, strategies to treat it are the focus of pharmacologic intervention. For example, the 3-hydroxy-3-methylglutaryl coenzyme-A reductase inhibitors, commonly known as statins, benefit hypercholesterolemic patients who have atherogenic dyslipidemia that is associated with the metabolic syndrome. Pioglitazone, an antidiabetic agent that acts primarily by decreasing insulin resistance, improves sensitivity to insulin in muscle and adipose tissue and inhibits hepatic gluconeogenesis. Pioglitazone improves glycemic control while reducing circulating insulin levels. The investigational agent, rimonabant--a centrally and peripherally acting, selective cannabinoid type-1 receptor blocker--is the first therapy developed for managing several cardiovascular risk factors at one time. Rimonabant has shown promise in attacking atherogenic dyslipidemia from several vantage points by affecting glucose, HDL-C, triglycerides, and waist circumference in patients who are prone to atherogenic dyslipidemia.

Arteriosclerosis↗
PubMed2000

WAP-TAg transgenic mice and the study of dysregulated cell survival, proliferation, and mutation during breast carcinogenesis.

Understanding the process of carcinogenesis is key to developing therapies which might interrupt or reverse tumor onset and progression. Cell growth and death signals are dependent not only upon molecular mechanisms within a cell but also upon external stimuli such as hormones, cell - cell signaling, and extracellular matrix. Mouse models can be used to dissect these complex processes, to identify key signaling pathways operating at different stages of tumorigenesis, and to test the strength of specific interventions. In the WAP-TAg mouse model, carcinogenesis is initiated by expression of the Simian Virus 40 T antigen (TAg). TAg expression is triggered by hormonal stimulation, either during estrus or pregnancy. Breast adenocarcinomas (ranging from well to poorly differentiated) develop in 100% of the female mice by approximately 8 - 9 months of age. Three distinct stages of tumorigenesis are easily identified: an initial proliferation, hyperplasia, and adenocarcinoma. The mean time to first palpable tumor in mice which undergo at least one pregnancy is 6 months. The tumorigenic process is marked by a competition between proliferation and apoptosis and is characterized by cellular acquisition of genetic mutations and increased stromal fibrosis. Protein levels of cell cycle control genes cyclin D1, cdk2, and E2F-1 are increased in these adenocarcinomas. c-Fos protein levels are slightly increased in these cancers, while c-Jun levels do not change. Hormonal exposure alters progression. Estrogen plays a role during the early stages of oncogenesis although the growth of the resulting adenocarcinomas is estrogen-independent. Transient hormonal stimulation by glucocorticoids that temporarily increases the rate of cell proliferation results in tetraploidy, premature appearance of irreversible hyperplasia, and early tumor development. Tumor appearance also can be accelerated through over expression of the cell survival protein, Bcl-2. Bcl-2 over expression not only reduces apoptosis during the initial proliferative process but also decreases the total rate of cell proliferation. This block in cell proliferation is lost selectively as the cells transition to adenocarcinoma. The WAP-TAg model can be utilized to investigate how the basic processes of cell proliferation, apoptosis, DNA mutation, and DNA repair are modified by external and internal signals during mammary oncogenesis.

Animals↗
PubMed2000

Current status of prevention, diagnosis, and management of coronary artery disease in patients with kidney failure.

BACKGROUND: Patients with kidney failure have a heavy burden of coronary artery disease. The results of preventive, diagnostic, and therapeutic measures developed in nonuremic populations cannot automatically be extrapolated to this unique group of patients. METHODS AND RESULTS: Articles were reviewed if they contained English language text or an abstract identified by MEDLINE search from 1980 to 1999, supplemented by manual review of bibliographies of published articles and abstract issues of national cardiology meetings, studies on diagnostic techniques, risk modification measures, pharmacologic agents, and coronary revascularization procedures in patients with uremia. Descriptive and quantitative data as appropriate were extracted. Lipid-lowering agents may be safely administered to uremic patients. Direct evidence of lipid lowering in this population is not available and is not likely to be forthcoming. Erythropoietin therapy is effective in reversing the cardiovascular perturbations of uremic anemia, but an approach of normalizing the hematocrit cannot be recommended. Glycoprotein IIb/IIIa inhibitors used in acute coronary syndromes require downward dose adjustment or are contraindicated. Thrombolytic agents are underutilized in the management of myocardial infarction. Noninvasive testing is less accurate than in nonuremic populations. Coronary revascularization offers relative clinical advantages over medical therapy similar to non-kidney failure populations, even though the results in uremic patients is significantly less favorable than for nonuremic patients. Stenting is the preferred revascularization approach, and conventional balloon percutaneous transluminal coronary angioplasty the least favorable. CONCLUSIONS: Many but not all of the benefits of therapies developed in nonuremic patients extend to patients with kidney failure. Physicians should be familiar with the advantages and limitations of each of these modalities in this population.

Coronary Angiography↗