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PubMed1990

Training assistants in cleft palate speech therapy in the developing world: a report.

This paper describes the training, which took place in Sri Lanka, of five speech therapy assistants in cleft palate speech therapy. The context in which this training occurred is described. The original aims of the training and the criteria drawn up for the selection of the assistants are contrasted with the modifications required to these, once the British therapists started working in Sri Lanka. Information is given on the training objectives, syllabus, curriculum, and methods of evaluation of the assistants' progress. The achievements of the assistants are described. Factors relating to the difficulties and ease with which the assistants were trained are highlighted. The paper concludes with a discussion of the cultural, political, and clinical problems encountered in this type of training, and highlights the special difficulties encountered in the training of assistants in the field of speech therapy in developing countries.

Allied Health Personnel↗
PubMed1998

Improving patient outcomes through CQI: vascular access planning.

This article reports the use of the continuous quality improvement (CQI) process to improve patient outcomes. The FADE method (focus, analyze, develop, and execute) was used to focus on vascular access planning, analyze data concerning intravenous (i.v.) therapy, develop a vascular access planning algorithm, and execute implementation of the algorithm. An evaluation study revealed that patients whose vascular access planning was consistent with the algorithm reported fewer i.v.s, less difficulty starting i.v.s, and less stress; waited significantly less time until central venous line (CVL) placement (for those who received CVLs); and had significantly shorter lengths of stay.

Algorithms↗
PubMed1978

Carbenicillin nephrotoxicity.

A patient with biopsy-proven interstitial nephritis associated with nafcillin and dicloxacillin therapy developed fever, hematuria, pyuria, and renal insufficiency after the administration of carbenicilin five months later. Cephalosporin therapy was given to this patient without signs of renal toxicity. This is the first reported case of probable carbenicillin-induced interstitial nephritis and serves to emphasize the danger of giving any penicillin analogue to patients with a history of pencillin-induced interstitial nephritis.

Anemia, Aplastic↗
PubMed1990

Focal family therapy: theory and practice.

During the past 30 years, the prescription of neuroleptic medication has made a major impact on the treatment of symptoms in patients with schizophrenia. Nonetheless, for many patients, symptom remission and social functioning remain less than optimal. Consequently, clinicians have employed a combined approach of drugs, psychosocial therapies, and psychiatric rehabilitation to treat the range of deficits presented by individuals suffering with this illness. In this article, we describe Focal Family Therapy, a model of family therapy developed for working with families and patients who are struggling with schizophrenia. Using the example of a particular case, we illustrate the following: (a) the identification and formulation of the Focal Issue; (b) the targeting of behavior and attitudes that will constitute the Focal Change; and (c) the techniques of Focal Family Therapy.

Adult↗
PubMed1996

Amoxicillin for the treatment of Helicobacter pylori infection.

Amoxicillin is one of the most active antimicrobials against Helicobacter pylori in vitro, with a minimum inhibitory concentration (MIC) of < or = 0.01-0.1 mg/l. Thus far, neither primary nor secondary resistant strains have been found. Amoxicillin, which has a bactericidal effect on H. pylori, but is less inhibitory in the stationary growth phase and against cell-adherent or slowly growing H. pylori, probably has both topical and systemic activity. It is fairly acid stable and is less affected by gastric acidity than macrolides. Nevertheless, its activity in vivo is considerably enhanced when it is given concomitantly with proton pump inhibitors. Several amoxicillin-containing treatment regimes have yielded H. pylori eradication rates of > or = 90%. Of particular interest are 1-week treatment regimens containing amoxicillin + clarithromycin + omeprazole, or amoxicillin + metronidazole + omeprazole, as well as a 1-h topical therapy developed in Japan.

Amoxicillin↗
PubMed1992

Therapeutic immunosuppression of T cells.

Current immunosuppressive therapy carries a range of unwanted side effects, and tends to penalize the whole immune system. It is desirable to develop therapies that are more selective for antigen-reactive cells. As T lymphocytes use a wide range of surface receptors to interact with antigen-bearing cells and with each other, much interest is devoted to trying to develop agents that selectively block the interaction of these receptors with their ligands, and others that could be used to reprogram the immune system so that it might become tolerant to the antigens rather than attack them.

Animals↗
PubMed1995

Urticarial vasculitis: an autoimmune disorder following therapy for Hodgkin's disease.

Immunological abnormalities have been described in patients with Hodgkin's disease, both associated with the malignancy itself and occurring secondary to therapy. These abnormalities often manifest as an immunodeficiency state, but can also present as immune dysregulation and autoimmune disease. We report two young patients with Hodgkin's disease who, following successful therapy, developed urticarial vasculitis (UV), a form of cutaneous autoimmune vasculitis. Both patients also had systemic symptoms including fever, an elevated erythrocyte sedimentation rate and serum copper, and abnormal in vitro studies of lymphocyte enumeration and proliferation. Distinguishing UV from recurrent Hodgkin's disease was especially difficult in one patient, and was possible only by lymph node biopsy. One patient has responded well to immunosuppressive therapy, while the other, who has more profound immune dysfunction, has developed a chronic autoimmune disorder. UV may thus occur in patients after therapy for Hodgkin's disease; we hypothesize that immune dysregulation, either associated with the malignancy or resulting from therapy, is important in the pathogenesis of this autoimmune process.

Adolescent↗
PubMed2003

Increased levels of immune transcript in patients with acute GVHD after allogeneic stem cell transplantation.

After allogeneic stem cell transplantation (SCT), donor T-cells are primarily responsible for the antihost activity, resulting in graft-versus-host disease (GVHD). Three effector pathways have been described for T-cell cytotoxicity: perforin/granzyme B; Fas/Fas ligand (FasL) and secreted molecules such as TNF-alpha. The goal of this pilot study was to utilize competitive reverse transcription (RT)-PCR to evaluate the pattern of granzyme B, perforin, FasL and TNF-alpha gene expression in peripheral blood in patients after SCT. Protein levels of granzyme B, soluble FasL (sFasL) and TNF-alpha in plasma were also analyzed. Eight patients who underwent allogeneic SCT were included; five were diagnosed with acute GVHD. In the patients diagnosed with acute GVHD, we found increased levels of granzyme B, perforin and FasL mRNA, although this did not correlate with the clinical severity. However, patients with increasing levels of gene expression during acute GVHD treatment may have an increased risk of developing severe acute GVHD, as two out of three patients with increasing immune transcript levels during GVHD therapy developed life-threatening acute GVHD. In conclusion, the quantitative RT-PCR of granzyme B, perforin and FasL may serve as a guide to the clinician in diagnosing acute GVHD and monitoring treatment.

Acute Disease↗
PubMed1999

[Effect of long-term hormone substitution therapy on serum TSH level in postmenopausal women].

OBJECTIVE: Dysfunction's of the thyroid gland are one of the most important endocrinological diseases. We report serum TSH levels in postmenopausal women before and during long-term hormone replacement therapy. MATERIAL AND METHODS: 107 postmenopausal patients participated in this study. Criteria for inclusion were: no known thyroid dysfunction and request for hormone replacement. Before starting therapy TSH serum levels were measured in each patient. If basal levels were within normal range TSH serum levels were reported over 4 years of hormone replacement therapy. RESULTS: More than 10% of the postmenopausal women showed pathological TSH-levels without clinical symptoms requiring further diagnostic. During subsequent treatment cycles (4 years) serum TSH in euthyroid patients did not show significant changes. Women using hormone replacement therapy developed no new manifestation of thyroid disease. CONCLUSION: In euthyroid women using long-term hormone replacement therapy are no changes in thyroid function caused by hormone replacement therapy to expect.

Climacteric↗
PubMed1992

[Megakaryoblastic leukemia which developed from therapy-related MDS with myelofibrosis].

A 56-year-old man had a leiomyosarcoma of the small intestine in 1987. After surgery, he received cyclophosphamide for 2 years. In December, 1990, he exhibited severe pancytopenia. His hematological data were as follows: Hb 7.4g/dl, ret. 0.8%, WBC 1,700/microliters with leukoerythroblastosis and 2.8 x 10(4)/microliters platelets. A bone marrow aspiration was a dry tap. A bone marrow biopsy specimen showed a hypercellular marrow with myelofibrosis, leukemic infiltration (10.2%) and slight dyserythropoiesis. Both PPO and GPIIb/IIIa reaction were positive for blast cells and atypical megakaryoblasts. A diagnosis of MDS with an abnormality in megakaryocytic lineage was made. The patient was treated with 1,25-dihydroxy-vitamin D3, however this therapy was temporary and he developed into acute megakaryoblastic leukemia (M7). This report suggested that some cases of therapy-related leukemia (TRL) mainly involve megakaryocytic lineage and are diagnosed as MDS with myelofibrosis which transform to M7. The fact that PAS stain of erythroblasts in the patient reported here was positive may suggest involvement of development of more precise immunological markers of differentiation and EM study will permit better diagnosis of TRL and may therefore facilitate new therapeutic approaches.

Chemotherapy, Adjuvant↗
PubMed1999

Antibody-targeted therapy for myeloid leukemia.

The availability of antibodies reactive with antigens expressed only by hematopoietic cells has provided clinical investigators with new tools for use in developing therapies for acute myeloid leukemia (AML). Studies performed to date have investigated the use of such antibodies in an unmodified state, combined with potent chemicals to form immunotoxins or combined with various radionuclides. Encouraging results have been obtained in all three settings. The CD33 antigen is expressed by most early myeloid cells and by more than 90% of cases of AML but is not present on the hematopoietic stem cell. Initial in vivo studies with an unmodified murine anti-CD33 antibody in patients with AML demonstrated that the antibody quickly bound to leukemia cells and that the antigen-antibody complex rapidly internalized following cell binding. However, when administered to patients with overt leukemia, unmodified antibody resulted in only brief decreases in peripheral blast counts, not in sustained response. A number of CD33-based immunotoxins have also been studied, including a calicheamicin conjugate, CMA-676. In a phase I dose-escalation study of patients with refractory AML, CMA-676 was well tolerated with the only consistent toxicities being the development of fevers and chills several hours after administration and the subsequent development of temporary pancytopenia. A phase III study has been performed involving patients with AML in first relapse. An interim analysis of the first 23 patients found that in 10, treatment with CMA-676 resulted in elimination of blasts from peripheral blood and marrow. This was achieved with far less toxicity than seen with standard chemotherapy. Radiolabeled antibodies have been explored as a stand-alone treatment or in the context of bone marrow transplantation. In an effort to avoid toxicities to normal stem cells residing alongside leukemic cells in the marrow, studies have been performed to explore the use of 231Bi conjugated to an anti-CD33 monoclonal antibody. The short path length of this alpha-emitter could theoretically allow killing of the targeted leukemic cell without damage to normal neighbors. Of 12 patients with recurrent AML who received this drug, eight had reductions in marrow and peripheral blast counts. Complete remissions (CRs) have not been observed to date. Another set of studies focused on the use of radiolabeled antibodies to deliver radiation specifically to sites of leukemia as part of a transplant preparative regimen. In a phase I clinical trial, 131I-labeled anti-CD45 antibody delivered at least threefold more radiotherapy to spleen and marrow than any other organ. In a phase II trial, among 25 AML patients in first remission, 22 are alive and in remission for periods up to 6 years.

Antibodies, Monoclonal↗
PubMed2000

[Tuberculous infection and prevention].

In Japan, the number of tuberculosis infected patients has been increasing again, especially in the elderly. The incidence of newly registered tuberculosis patients who are over 70 years is 34%. The outbreak of tuberculosis also has been increasing, and has become a serious social problem. The elderly have a high risk of developing tuberculosis because of their immunosuppressed condition due to underlying disease and aging. Elderly active tuberculous people also confer a risk of tuberculosis infection to the non-tuberculosis infected young generation. In this symposium, we discussed about 1) the tuberculosis outbreak related to the strategy for tuberculous prevention, 2) the health examination to detect tuberculous people in the middle-aged and elderly, 3) the nosocomial transmission of tuberculosis in the hospital, 4) the nutritional damage and immunosuppressive state in elderly people related to developing active tuberculosis in latent tuberculous infection, and 5) the organ transplantation and tuberculosis focusing on living related liver transplantation. Seven cases of tuberculosis outbreak were reported in Osaka from 1989 to 1998, 2 cases in the hospital and 5 in others. Tuberculous infection index (maximum sputum Gaffky score multiplied by the number of months of persisted cough) was 8 and 15 in the hospital, 3, 0, 84, 14, and 27 in others. Three cases (43%) were observed in persons with less than 10 of this index. It is essential to evaluate carefully for tuberculosis outbreak in extraordinary examination, if the tuberculous infectious index is low. There are various immunosuppressive patients with malignancy and other underlying disease in the hospital, so we have to pay careful attention for tuberculous outbreak when there is an active tuberculous patient. In these seven cases of extraordinary examination for tuberculous epidemic, only one (0.4%) of 241 cases who received isoniazide prophylactic therapy developed active tuberculosis. Isoniazide prophylactic therapy was an important strategy for the prevention of tuberculous outbreak. (Isamu TAKAMATSU, Osaka Prefectural Habikino Hospital, Osaka). It is essential to prevent tuberculosis in the elderly to achieve tuberculosis control in public health. The health examination was an important strategy for the detection of tuberculosis in the middle-aged and elderly. The incidence of tuberculosis detection is only 9.3% by the health examination at this age. However, the health examination has well detected active tuberculosis patients in elderly (34.5%), and also 16.8% in smear positive cases with pulmonary cavitary formation. The early detection of persons with active tuberculosis is essential, and further discussion regarding cost-performance and accuracy of the health examination for tuberculosis should also be essential. Prophylactic therapy of isoniazide also might be considered for the high risk middle-aged and elderly people with underlying diseases. (Masako OMORI et al., Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association, Tokyo). The cases of nosocomial transmission of tuberculosis in the hospital have been increasing. In younger persons, the incidence of tuberculosis infected nurses and doctors is relatively higher than healthy control. The transmission of tuberculosis from elder active tuberculosis patients to healthy non-tuberculosis infected medical workers has been well recognized. It is very essential to follow guidelines for the prevention of tuberculous transmission in the hospital from the Japan Tuberculosis Society including routine tuberculin skin test for fresh medical workers. Primary education for tuberculosis in medical and nursing school is also an important strategy. Further discussion might be essential that BCG could prevent tuberculosis transmission in tuberculin skin test negative adults. (ABSTRACT TRUNCATED)

Adult↗
PubMed2005

Prospective identification of tumorigenic prostate cancer stem cells.

Existing therapies for prostate cancer eradicates the bulk of cells within a tumor. However, most patients go on to develop androgen-independent disease that remains incurable by current treatment strategies. There is now increasing evidence in some malignancies that the tumor cells are organized as a hierarchy originating from rare stem cells that are responsible for maintaining the tumor. We report here the identification and characterization of a cancer stem cell population from human prostate tumors, which possess a significant capacity for self-renewal. These cells are also able to regenerate the phenotypically mixed populations of nonclonogenic cells, which express differentiated cell products, such as androgen receptor and prostatic acid phosphatase. The cancer stem cells have a CD44+/alpha2beta1hi/CD133+ phenotype, and we have exploited these markers to isolate cells from a series of prostate tumors with differing Gleason grade and metastatic states. Approximately 0.1% of cells in any tumor expressed this phenotype, and there was no correlation between the number of CD44+/alpha2beta1hi/CD133+ cells and tumor grade. The identification of a prostate cancer stem cell provides a powerful tool to investigate the tumorigenic process and to develop therapies targeted to the stem cell.

AC133 Antigen↗
PubMed1997

Prolactin serum levels in postmenopausal women receiving long-term hormone replacement therapy.

In the literature there are different opinions about serum prolactin levels after the menopause and in women using hormone replacement therapy. We report serum prolactin levels of 165 women after surgical or natural menopause who received different kinds of hormone replacement therapies over 2 years and 6 months. Surgically or naturally menopausal women showed no significant differences in serum prolactin levels. After starting hormone replacement therapy, the serum prolactin levels decreased. During subsequent treatment cycles, serum prolactin showed varying levels within the reference limits. Women using hormone replacement therapy developed no new manifestation of hyperprolactinemia.

Estrogen Replacement Therapy↗
PubMed1987

The Sydney multicentre study of Parkinson's disease. The first 18 months.

Low-dose bromocriptine therapy and low-dose levodopa-carbidopa therapy are being compared in a double-blind study over a five-year period as treatment for newly-diagnosed patients with Parkinson's disease. Ninety-four patients had entered the study by January 1986 and of these, 50 had been followed for six months or more. Preliminary results confirm that many patients with Parkinson's disease can be managed satisfactorily in the early stages of the disease with low-dose therapy. Three patients, all of whom were receiving levodopa-carbidopa therapy, developed dyskinesia. Twelve patients who had received bromocriptine had an inadequate response or developed confusion or postural hypotension. Of these patients, six had a poor response to subsequent levodopa-carbidopa therapy. While the initial improvement that results from low-dose bromocriptine therapy and low-dose levodopa-carbidopa therapy is less than one would expect with conventional doses of these agents, it is hoped that this approach will reduce the incidence of long-term side-effects such as dyskinesia and fluctuations.

Australia↗
PubMed1992

Pseudomembranous and membranous conjunctivitis. Immunohistochemical features.

A 63-year-old man, who had for one month been on sulfasalazine therapy, developed general malaise, high fever, severe stomatitis, and bilateral necrotizing pseudomembranous conjunctivitis with corneal erosion, identical to that seen in the Stevens-Johnson syndrome. Topical therapy with antibiotics and aprotinin rapidly healed the corneal surfaces, while densely adherent true membranes developed on the conjunctiva, and were removed surgically several times during the next week. After the acute stage, subtle subepithelial conjunctival scarring, superficial punctate keratitis, dry eye syndrome and fluctuating irregular corneal astigmatism became evident, but good visual acuity, lid function and ocular motility were retained. Histopathologic study of conjunctival membranes from two cases of membranous conjunctivitis revealed polymorphonuclear leukocytes within a matrix composed of fibrin, tenascin and fibronectin. In older membranes, histiocytes were additionally found. Surgical debridement of such membranes removes a substratum of inflammatory debris that is likely to promote secondary infection, fibrosis and symblepharon formation, and may decrease rather than increase subsequent scarring of the necrotized conjunctiva.

Adult↗
PubMed2001

[Development of gene therapy for pancreatic cancer].

In order to develop the new therapeutic intervention for pancreatic cancer, we have examined the effect of gene therapy for this miserable pancreatic disease. The transfection of UPRT, a 5-FU converting enzyme, gene resulted in the significant change in sensitivity of pancreatic cancer cells against 5-FU. Anti-angiogenesis gene therapy has been also demonstrated to be a promising strategy for pancreatic cancer. It has been revealed that replication-competent adenoviruses are not only the strong weapon themselves but also useful carriers of genes possessing anti-tumor activities as virus vectors specific to tumors without normal p53 function nor intact Rb pathway. Whether these experimental results are universally true require the clinical trials in future.

Adenoviridae↗