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Biomedical subjects

M Haas

Publications and source records attributed to M Haas.

At least 37 records · Page 2Linked to original sources

The news on health care funding: a study of reporting in the Australian print media for 1996.

OBJECTIVES: To review the coverage of health care funding and resourcing issues in the quality printed media in Australia. METHODS: Content analysis of all articles in six major print publications with detailed commentary on four major issues. RESULTS: One thousand one hundred and fifty articles were published over 12 months, most in the front three pages. Coverage of many issues was prompted by an event, such as an election, government budget or policy announcement. Although issues were rarely personalized, the use of an individual authoritative spokesperson was, with some individuals becoming well recognised as experts. In general, these experts represented vested interest or lobby groups. The media discussion rarely dealt with the system as a whole, and generally approached a topic or issue in isolation from its inter-relationships with other issues. CONCLUSION: Health care funding stories are newsworthy but more for their political interest than as reflection of a social debate about values. Media reports rarely deal with the complexity of health policy issues, or challenge the assumptions and positions put forward.

Australia↗

Assessing the value of hospital-in-the-home: lessons from Australia.

OBJECTIVES: To identify factors that influence the cost-effectiveness of hospital-in-the-home (HITH) and to discuss the impact of funding arrangements in creating incentives or disincentives for the establishment of HITH services. METHODS: A review of HITH services in Australia was undertaken. Based on the review, factors affecting the relative costs of HITH and conventional care were identified, in particular, the effect of funding and organisational arrangements on the incentives for managers and providers to choose between HITH and conventional care. RESULTS: The review of HITH services identified a wide range of models of HITH in Australia. Factors identified as important to the success of HITH included demographic and location issues, referral mechanisms, the choice of staffing and the management of the programme. However, it was clear that the structure of the programme often related to funding arrangements. Issues such as 'incentive funding', establishment costs and opportunity for cost-shifting were identified as being relevant to incentives for the efficient provision of HITH. CONCLUSIONS: Evaluations are essential to inform decisions about whether HITH is likely to be a viable and cost-effective alternative to inpatient care. However, the relative costs of HITH and conventional care will depend on local factors. From the point of view of the decision-maker, these will be affected by funding and organisational arrangements. Funders must be aware that complex financial incentives may mask the true costs of HITH services relative to hospital services. They need to ensure that the incentives created by funding arrangements are transparent.

Australia↗

Pain, disability, and satisfaction outcomes and predictors of outcomes: a practice-based study of chronic low back pain patients attending primary care and chiropractic physicians.

BACKGROUND: Few studies exist on the prognostic value of demographic, clinical, or psychosocial factors on long-term outcomes for patients with chronic low back pain. OBJECTIVE: This study reports on long-term pain and disability outcomes for patients with chronic low back pain, evaluates predictors of long-term outcomes, and assesses the influence of doctor type on clinical outcome. METHODS: Sixty chiropractic (DC) and 111 general practice (MD) physicians participated in data collection for a prospective, longitudinal, practice-based, observational study of ambulatory low back pain of mechanical origin. The primary outcomes, measured at 6 months and 12 months, were pain (by using the Visual Analog Scale), and functional disability (by using the Revised Oswestry Disability Questionnaire). Satisfaction was a secondary outcome. RESULTS: Overall, long-term pain and disability outcomes were generally equivalent for patients seeking care from medical or chiropractic physicians. Medical and chiropractic care were comparable for patients without leg pain and for patients with leg pain above the knee. However, an advantage was noted for chronic chiropractic patients with radiating pain below the knee after adjusting for baseline differences in patient and complaint characteristics between MD and DC cohorts (adjusted differences = 8.0 to 15.2; P <.002). A greater proportion of chiropractic patients were satisfied with all aspects of their care (P =.0000). The strongest predictors of primary outcomes included an interaction of radiating pain below the knee with provider type and baseline values of the outcomes. Income, smoking, comorbidity, and chronic depression were also identified as predictors of outcomes in this study. CONCLUSION: Chiropractic care compared favorably to medical care with respect to long-term pain and disability outcomes. Further study is required to explore the advantage seen for chiropractic care in patients with leg pain below the knee and in the area of patient satisfaction. Identification of patient and treatment characteristics associated with better or worse outcomes may foster changes in physicians' practice activities that better serve these patients' needs.

Adult↗

Efficacy of spinal manipulation for chronic headache: a systematic review.

BACKGROUND: Chronic headache is a prevalent condition with substantial socioeconomic impact. Complementary or alternative therapies are increasingly being used by patients to treat headache pain, and spinal manipulative therapy (SMT) is among the most common of these. OBJECTIVE: To assess the efficacy/effectiveness of SMT for chronic headache through a systematic review of randomized clinical trials. STUDY SELECTION: Randomized clinical trials on chronic headache (tension, migraine and cervicogenic) were included in the review if they compared SMT with other interventions or placebo. The trials had to have at least 1 patient-rated outcome measure such as pain severity, frequency, duration, improvement, use of analgesics, disability, or quality of life. Studies were identified through a comprehensive search of MEDLINE (1966-1998) and EMBASE (1974-1998). Additionally, all available data from the Cumulative Index of Nursing and Allied Health Literature, the Chiropractic Research Archives Collection, and the Manual, Alternative, and Natural Therapies Information System were used, as well as material gathered through the citation tracking, and hand searching of non-indexed chiropractic, osteopathic, and manual medicine journals. DATA EXTRACTION: Information about outcome measures, interventions and effect sizes was used to evaluate treatment efficacy. Levels of evidence were determined by a classification system incorporating study validity and statistical significance of study results. Two authors independently extracted data and performed methodological scoring of selected trials. DATA SYNTHESIS: Nine trials involving 683 patients with chronic headache were included. The methodological quality (validity) scores ranged from 21 to 87 (100-point scale). The trials were too heterogeneous in terms of patient clinical characteristic, control groups, and outcome measures to warrant statistical pooling. Based on predefined criteria, there is moderate evidence that SMT has short-term efficacy similar to amitriptyline in the prophylactic treatment of chronic tension-type headache and migraine. SMT does not appear to improve outcomes when added to soft-tissue massage for episodic tension-type headache. There is moderate evidence that SMT is more efficacious than massage for cervicogenic headache. Sensitivity analyses showed that the results and the overall study conclusions remained the same even when substantial changes in the prespecified assumptions/rules regarding the evidence determination were applied. CONCLUSIONS: SMT appears to have a better effect than massage for cervicogenic headache. It also appears that SMT has an effect comparable to commonly used first-line prophylactic prescription medications for tension-type headache and migraine headache. This conclusion rests upon a few trials of adequate methodological quality. Before any firm conclusions can be drawn, further testing should be done in rigorously designed, executed, and analyzed trials with follow-up periods of sufficient length.

Chiropractic↗

Hypothyroidism as a cause of tacrolimus intoxication and acute renal failure: a case report.

The nephrotoxic side effects of cyclophilin-binding agents like cyclosporine A and tacrolimus are well characterized. In severe cases nephrotoxicity may profoundly deteriorate kidney function and even induce acute renal failure. In this report we describe the first case of excessive tacrolimus intoxication caused by hypothyroidism. The patient had undergone single-lung transplantation 6 months earlier, developed hypothyroidism, and was admitted with acute anuric renal failure. Thyroxin is a potent activator of the cytochrome P-450- CYP 3A enzyme system, which is crucial for tacrolimus metabolism. Hence, hypothyroidism reduces cytochrome P-450 activity and may result in drug accumulation. Rapid reversal of toxic drug levels could be achieved by reducing drug intake and increasing thyroxin levels by substitution therapy. In conclusion, it is important to consider thyroid function when prescribing medications with a narrow therapeutic range, which are metabolized by the cytochrome P-450 system such as tacrolimus, and the possible devastating effect of impaired drug metabolism during hypothyroidism.

Acute Kidney Injury↗

Ouabain interaction with cardiac Na+/K+-ATPase initiates signal cascades independent of changes in intracellular Na+ and Ca2+ concentrations.

We have shown previously that partial inhibition of the cardiac myocyte Na(+)/K(+)-ATPase activates signal pathways that regulate myocyte growth and growth-related genes and that increases in intracellular Ca(2+) concentration ([Ca(2+)](i)) and reactive oxygen species (ROS) are two essential second messengers within these pathways. The aim of this work was to explore the relation between [Ca(2+)](i) and ROS. When myocytes were in a Ca(2+)-free medium, ouabain caused no change in [Ca(2+)](i), but it increased ROS as it did when the cells were in a Ca(2+)-containing medium. Ouabain-induced increase in ROS also occurred under conditions where there was little or no change in [Na(+)](i). Exposure of myocytes in Ca(2+)-free medium to monensin did not increase ROS. Increase in protein tyrosine phosphorylation, an early event induced by ouabain, was also independent of changes in [Ca(2+)](i) and [Na(+)](i). Ouabain-induced generation of ROS in myocytes was antagonized by genistein, a dominant negative Ras, and myxothiazol/diphenyleneiodonium, indicating a mitochondrial origin for the Ras-dependent ROS generation. These findings, along with our previous data, indicate that increases in [Ca(2+)](i) and ROS in cardiac myocytes are induced by two parallel pathways initiated at the plasma membrane: One being the ouabain-altered transient interactions of a fraction of the Na(+)/K(+)-ATPase with neighboring proteins (Src, growth factor receptors, adaptor proteins, and Ras) leading to ROS generation, and the other, inhibition of the transport function of another fraction of the Na(+)/K(+)-ATPase leading to rise in [Ca(2+)](i). Evidently, the gene regulatory effects of ouabain in cardiac myocytes require the downstream collaborations of ROS and [Ca(2+)](i).

Animals↗

Involvement of Src and epidermal growth factor receptor in the signal-transducing function of Na+/K+-ATPase.

Nontoxic concentrations of ouabain, causing partial inhibition of the cardiac myocyte Na(+)/K(+)-ATPase, induce hypertrophy and several growth-related genes through signal pathways that include the activation of Ras and p42/44 mitogen-activated protein kinase (MAPK). The aim of this work was to examine the ouabain-induced events upstream of the Ras/MAPK cascade. Treatment of myocytes with genistein antagonized ouabain-induced activation of the MAPK, suggesting that protein tyrosine phosphorylation has a role. Tyrosine phosphorylation of several myocyte proteins was increased rapidly upon cell exposure to ouabain. Lowering of extracellular K(+) had a similar ouabain-like effect. Ouabain also increased protein tyrosine phosphorylation in A7r5, HeLa, and L929 cells. In cardiac myocytes and A7r5 cells, herbimycin A antagonized the ouabain-induced increase in protein tyrosine phosphorylation and MAPK activation. In both cell types, ouabain stimulated Src kinase activity, Src translocation to the Triton-insoluble fraction, Src association with the epidermal growth factor receptor, and the tyrosine phosphorylation of this receptor on site(s) other than its major autophosphorylation site, Tyr(1173). The findings suggest that (a) the ouabain-induced activation of Src and the Src-induced phosphorylation of the growth factor receptor provide the scaffolding for the recruitment of adaptor proteins and Ras and the activation of Ras/MAPK cascade; and (b) the activation of such pathways may be a common feature of the signal-transducing function of Na(+)/K(+)-ATPase in most cells.

Amino Acid Sequence↗

Simultaneous enzyme overlay membrane (EOM)-based in situ zymography and immunofluorescence technique reveals cathepsin B-like activity in a subset of tumour vessels.

The analysis of the invasion front of oral squamous cell carcinoma (OSCC) has revealed a fundamental invasion-associated remodelling of the extracellular matrix as the result of a complex regulated interplay of matrix synthesis and matrix degradation. Cysteine proteinases, in particular cathepsin B, are implicated in tumour invasion in vivo and in vitro and are thought to be important mediators of metastasis. An in situ zymographic assay based on enzyme overlay membranes (EOMs) was established to define the tissue localisation of cathepsin B activity in OSCC. Using confocal laser scanning microscopy we present a double-labelling method for the rapid and reproducible simultaneous detection of cathepsin B-like activity and cellular or extracellular antigens based on an EOM and immunofluorescence technique on frozen sections. Applying this method, cathepsin B-like activity was mainly found in vascular structures within the invasive front of OSCC. Therefore, the results suggest a particular pathogenic role of cathepsin B in tumour angioneogenesis. The method can simply be transferred to other enzymes and can be recommended for more extensive studies of proteolytic activity in human malignancies.

Carcinoma, Squamous Cell↗

[Laminin-5 in diseases of the oral cavity].

The basement membrane molecule laminin forms a family of proteins. Laminin-5 was identified as key protein in the anchoring filaments of the basement membrane. The anchoring filaments connect the basement membrane to the epithelial cells and together form the epithelial adhesion complex. Disturbances in the epithelial adhesion complex result in subepithelial blistering dermatosis. Autoantibodies against laminin-5 are found in cicatricial pemphigoid. Mutations in genes of laminin-5 with loss of the protein cause epidermolysis bullosa Herlitz. It can be determined during prenatal genetic diagnostic testing. Laminin-5 supports migration of keratinocytes and forms the basis for migrating keratinocytes in oral wound healing. Positive re-epithelialization via laminin-5 has been the subject of experimental studies. Oral squamous cell carcinomas are found to have a focal loss of laminin-5 in conjunction with a loss of the cellular receptor, and increased synthesis of laminin-5 by budding tumor cells has been observed along with deposition of the protein in the stroma. As a result of these observations laminin-5 has been suggested as a route of invasion. Quantitative assessment of this phenomenon and the modulation of laminin-5-tumor cell interaction offer new and hopeful means of describing and affecting the invasive behaviour of oral squamous carcinoma.

Adult↗

Etiologies and outcome of acute renal insufficiency in older adults: a renal biopsy study of 259 cases.

Acute renal insufficiency is a common problem, yet one that is frequently reversible with proper diagnosis and treatment. Although it has been argued that a renal biopsy is not needed for diagnosis in most cases of acute renal failure in the elderly, other studies have shown frequent disagreements between clinical and renal biopsy diagnoses in such cases. To investigate the causes of acute renal insufficiency in patients aged at least 60 years who underwent a renal biopsy and possible correlations between biopsy findings and renal survival, we first identified all native renal biopsy specimens from patients aged 60 years or older processed at The University of Chicago Medical Center (Chicago, IL) from 1991 through 1998 and reviewed the clinical records to determine the indication for the biopsy. We then reviewed again the records of those patients who underwent biopsy because of acute renal insufficiency, recorded the primary renal biopsy diagnosis in each of these cases, and obtained follow-up information for patients who underwent biopsy before July 1996. During the study period, 1,065 of 4,264 biopsy specimens (25.0%) received were obtained from patients aged 60 years or older, and acute renal insufficiency was the indication for biopsy in 259 of these patients (24.3%). The most frequent primary diagnoses on these latter biopsy specimens were pauci-immune crescentic glomerulonephritis (GN) with or without arteritis, 31.2% of biopsy specimens; acute interstitial nephritis, 18.6%; acute tubular necrosis (ATN) with nephrotic syndrome, 7.5%; atheroemboli, 7.1%; ATN alone, 6.7%; light chain cast nephropathy (LCCN), 5.9%; postinfectious GN, 5.5%; anti-glomerular basement membrane antibody nephritis, 4.0%; and immunoglobulin A (IgA) nephropathy and/or Henoch-Schönlein nephritis, 3.6%. Eight biopsy specimens (3.2%) showed only benign nephrosclerosis without an apparent cause of acute renal insufficiency, and another six specimens were inadequate. The renal biopsy diagnosis was in agreement with the prebiopsy clinical diagnosis (or differential diagnosis) in 107 of the 161 cases (67%) in which such information was provided. The distribution of diagnoses was similar in patients in the age groups of 60 to 69, 70 to 79, and 80 years or older, although younger age correlated significantly with improved renal and patient survival. The relative risk for progression to end-stage renal disease (ESRD) also increased according to diagnostic categories: LCCN (greatest risk) > GN other than pauci-immune > atheroemboli congruent with pauci-immune crescentic GN > tubulointerstitial diseases other than LCCN (the latter category including ATN with nephrotic syndrome). Development of ESRD correlated significantly with decreased patient survival. In summary, renal biopsy in patients aged 60 years or older with acute renal insufficiency uncovered the cause in greater than 90% of the cases and provided clinically useful information with respect to expectation for renal survival and potential treatment options.

Acute Kidney Injury↗

Review article: the stages of gastrointestinal carcinogenesis--application of rodent models to human disease.

The development of gastrointestinal cancer in humans and animals occurs through a consecutive series of stages termed initiation, promotion and progression. The characterization of each of these stages has been elucidated in several model systems as well as in human neoplasms. Both single, putatively initiated cells and preneoplastic foci have been identified by marker protein differences as well as by mutational changes. The promotion stage involves the clonal expansion of single initiated cells. Such expansion can be rapidly reversed by a variety of means, of which acute fasting (as exemplified in rat hepatocarcinogenesis) is among the most rapid and efficient. This reversal involves a selective apoptosis of preneoplastic cells and preneoplastic lesions, associated with a marked increase in expression of the proto-oncogene c-myc. Transition of cells from the stage of promotion to that of progression initially involves specific karyotypic alterations, as noted in both the rat liver model and human colon carcinogenesis. In the former, the transition appears to be associated with enhanced expression of the H119 imprinted putative tumour suppressor gene. Thus, the use of model systems may be applied directly to the human circumstance, increasing the potential both for rational prevention of gastrointestinal neoplasia and for new approaches to the therapy of neoplastic disease in the progression stage.

Animals↗

ANCA-associated crescentic glomerulonephritis with mesangial IgA deposits.

Antineutrophil cytoplasmic autoantibodies (ANCA) are commonly associated with a necrotizing and crescentic glomerulonephritis (GN) that is pauci-immune, with few or no glomerular immune complex deposits detectable by immunofluorescence (IF) or electron microscopy (EM). Immunoglobulin A (IgA) nephropathy may also be manifest as a crescentic GN, but it is characterized by mesangial immune complex deposits containing IgA and is rarely associated with myeloperoxidase (MPO)- or proteinase 3 (PR3)-specific ANCA when an enzyme immunoassay is used to detect these antibodies. This report describes six patients with severe crescentic GN with mesangial IgA deposits by IF and mesangial electron-dense deposits by EM in patients with positive ANCA serological test results (four patients, anti-PR3; one patient, anti-MPO; one patient, anti-PR3 and anti-MPO). Patients presented with acute or progressive renal insufficiency, hematuria, proteinuria (nephrotic range in two patients), and hypertension. Three patients had evidence of systemic vasculitis: two patients at initial presentation and one patient later in the clinical course. Renal biopsy specimens showed crescents in greater than 50% of glomeruli in all cases, but only mild, focal and segmental mesangial and endocapillary hypercellularity, more typical of ANCA-associated crescentic GN than of crescentic IgA nephropathy without associated ANCA. Semiquantitative analysis of mesangial and endocapillary cellularity performed on renal biopsy slides from these six patients and from eight ANCA-negative patients with IgA nephropathy and crescents in greater than 50% of glomeruli showed significantly greater hypercellularity in the ANCA-negative cases. Three of five ANCA-positive patients for whom follow-up clinical data were available showed improved renal function after treatment with cyclophosphamide and corticosteroids and have not developed end-stage renal disease 17, 20, and 25 months postbiopsy. The remaining two patients were dialysis dependent at the time of biopsy and have remained so despite treatment with cyclophosphamide and corticosteroids. The findings suggest an overlap syndrome of ANCA-associated crescentic GN and IgA nephropathy that resembles the former both histologically and in its potential to respond to aggressive therapy if detected relatively early in its course.

Adrenal Cortex Hormones↗

Granulomatous tubulointerstitial nephritis in the renal allograft.

Granulomatous tubulointerstitial nephritis has rarely been described in renal allografts. Of 1,574 renal allograft tissue specimens obtained from 514 patients in the period 1993 to 1998, we report three cases (0.6%) with interstitial nephritis containing multiple noncaseating granulomas. Biopsy specimen 1 was obtained from a 44-year-old woman with a 6-day history of systemic Candida albicans infection and showed multiple granulomas containing budding yeasts. Biopsy specimen 2 was from a 33-year-old man who presented with miliary spread of Mycobacterium tuberculosis 12 days before the allograft biopsy. Biopsy specimen 3 was from a 23-year-old woman who presented with Escherichia coli urinary infection and bacteremia that was treated with antibiotics for 10 days before the biopsy. Granulomatous inflammation in reponse to infectious agents or drugs in immunosuppressed kidney transplant recipients can rarely give rise to allograft interstitial nephritis that is distinct from acute rejection. To our knowledge, there are no prior reports of granulomatous tubulointerstitial nephritis associated with C albicans and E coli infection or antibiotic therapy in human renal allografts.

Adult↗

A practical approach to planning health services: using PBMA.

Planning health services is a difficult and often complex task. There are many approaches to planning, including the use of tools such as needs assessment, goals and targets, as well as economics-based tools such as cost of illness or economic evaluation. It is not always clear which planning tool is the most appropriate. In this paper we compare an economics approach to planning using program budgeting and marginal analysis (PBMA) with other approaches. We provide an overview of the methods of PBMA, report on experience with its use, and draw conclusions about its likely usefulness to health services planners.

Australia↗

The Na-K-Cl cotransporter of secretory epithelia.

The Na-K-Cl cotransporters are a class of ion transport proteins that transport Na, K, and Cl ions into and out of cells in an electrically neutral manner, in most cases with a stoichiometry of 1Na:1K:2Cl. To date, two Na-K-Cl cotransporter isoforms have been identified: NKCC1, which is present in a wide variety of secretory epithelia and non-epithelial cells; and NKCC2, which is present exclusively in the kidney, in the epithelial cells of the thick ascending limb of Henle's loop and of the macula densa. Both NKCC isoforms represent part of a diverse family of cation-chloride cotransport proteins that share a common predicted membrane topology; this family also includes Na-Cl cotransporters and multiple K-Cl cotransporter isoforms. In secretory epithelia, the regulation of NKCC1, which is typically present on the basolateral membrane, is tightly coordinated with that of other transporters, including apical Cl channels, to maintain cell volume and integrity during active salt and fluid secretion. Changes in intracellular [Cl] ([Cl]i) appear to be involved in this regulation of NKCC1, which is directly phosphorylated by an unknown protein kinase in response to various secretagogues as well as reductions in [Cl]i and cell volume. This review focuses on structure-function relationships within NKCC1 and on recent developments pertaining to NKCC1 regulation at cellular and molecular levels.

Animals↗