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PubMed2002

Glutamatergic mechanisms in different disease states: overview and therapeutical implications -- an introduction.

Glutamate is the most widely distributed excitatory transmitter in the central nervous system (CNS). It is acting via large - and still growing - families of receptors: NMDA-, AMPA-, kainate-, and metabotropic receptors. Glutamate has been implicated in a large number of CNS disorders, and it is hoped that novel glutamate receptor ligands offer new therapeutic possibilities in disease states such as chronic pain, stroke, epilepsy, depression, drug addiction and dependence or Parkinson's disease. While an extensive preclinical literature exists showing potential beneficial effects of NMDA-, AMPA-, kainate- and metabotropic receptor ligands, only NMDA receptor antagonists have been characterized clinically to any appreciable degree. In these trials it has been shown that while several compounds are therapeutically active, they also produce serious side effects at therapeutic doses. Current interest largely centers on the development of receptor subtype-selective compounds, namely compounds selective for receptors containing the NR2B subunit. Preclinical findings and the first clinical results are encouraging, and it may be that such subunit-selective compounds may have a sufficiently wide therapeutic window to be safe for human use.

Animals↗

PubMed2002

Correlations between light penetration into skin and the therapeutic outcome following laser therapy of port-wine stains.

For several years the flashlamp-pumped pulsed dye laser (FPDL) has been the favoured method for the treatment of port-wine stains (PWS). The therapeutic outcome of FPDL laser therapy depends on the anatomical location of the PWS and is mainly attributed to morphological parameters such as size and depth of the PWS blood vessels. The aim of this study was to show a correlation between the therapeutic outcome following FPDL therapy and the optical properties of the skin overlying the PWS vessels. For this purpose the therapeutic outcome following FPDL treatment (585 nm; 0.45 ms) of 884 PWS situated on different body sites was evaluated by judging the grade of fading of PWS colour. On the other hand the light penetration into 123 skin samples (thickness 0.10-1.35 mm) was determined between 450 nm and 1030 nm and compared with the PWS laser therapy outcome for equal locations by statistical analysis. PWS on the neck, trunk, arms or legs yielded a higher mean grade of fading as compared to PWS on the head. Within the face, a wide range of fading was evident. The light penetration into skin increased linearly with increasing wavelength and location-dependent differences were found. The attenuation coefficient was 22.8+/-5.3 mm(-1) at 585 nm. No significant or strong correlation was observed between the therapeutic outcome of PWS laser therapy and the light penetration into skin. However, a correlation was obvious by plotting the respective profile plots. Therefore, among other effects, in particular morphological parameters of PWS vessels, the optical properties of the skin contribute to a small extent to the clinical outcome of PWS laser therapy.

Adolescent↗

PubMed2005

Brain angiotensin II: new developments, unanswered questions and therapeutic opportunities.

1. There are two Angiotensin II systems in the brain. The discovery of brain Angiotensin II receptors located in neurons inside the blood brain barrier confirmed the existence of an endogenous brain Angiotensin II system, responding to Angiotensin II generated in and/or transported into the brain. In addition, Angiotensin II receptors in circumventricular organs and in cerebrovascular endothelial cells respond to circulating Angiotensin II of peripheral origin. Thus, the brain responds to both circulating and tissue Angiotensin II, and the two systems are integrated. 2. The neuroanatomical location of Angiotensin II receptors and the regulation of the receptor number are most important to determine the level of activation of the brain Angiotensin II systems. 3. Classical, well-defined actions of Angiotensin II in the brain include the regulation of hormone formation and release, the control of the central and peripheral sympathoadrenal systems, and the regulation of water and sodium intake. As a consequence of changes in the hormone, sympathetic and electrolyte systems, feed back mechanisms in turn modulate the activity of the brain Angiotensin II systems. It is reasonable to hypothesize that brain Angiotensin II is involved in the regulation of multiple additional functions in the brain, including brain development, neuronal migration, process of sensory information, cognition, regulation of emotional responses, and cerebral blood flow. 4. Many of the classical and of the hypothetical functions of brain Angiotensin II are mediated by stimulation of Angiotensin II AT1 receptors. 5. Brain AT2 receptors are highly expressed during development. In the adult, AT2 receptors are restricted to areas predominantly involved in the process of sensory information. However, the role of AT2 receptors remains to be clarified. 6. Subcutaneous or oral administration of a selective and potent non-peptidic AT1 receptor antagonist with very low affinity for AT2 receptors and good bioavailability blocked AT1 receptors not only outside but also inside the blood brain barrier. The blockade of the complete brain Angiotensin II AT1 system allowed us to further clarify some of the central actions of the peptide and suggested some new potential therapeutic avenues for this class of compounds. 7. Pretreatment with peripherally administered AT1 antagonists completely prevented the hormonal and sympathoadrenal response to isolation stress. A similar pretreatment prevented the development of stress-induced gastric ulcers. These findings strongly suggest that blockade of brain AT1 receptors could be considered as a novel therapeutic approach in the treatment of stress-related disorders. 8. Peripheral administration of AT1 receptor antagonists strongly affected brain circulation and normalized some of the profound alterations in cerebrovascular structure and function characteristic of chronic genetic hypertension. AT1 receptor antagonists were capable of reversing the pathological cerebrovascular remodeling in hypertension and the shift to the right in the cerebral autoregulation, normalizing cerebrovascular compliance. In addition, AT1 receptor antagonists normalized the expression of cerebrovascular nitric oxide synthase isoenzymes and reversed the inflammatory reaction characteristic of cerebral vessels in hypertension. As a consequence of the normalization of cerebrovascular compliance and the prevention of inflammation, there was, in genetically hypertensive rats a decreased vulnerability to brain ischemia. After pretreatment with AT1 antagonists, there was a protection of cerebrovascular flow during experimental stroke, decreased neuronal death, and a substantial reduction in the size of infarct after occlusion of the middle cerebral artery. At least part of the protective effect of AT1 receptor antagonists was related to the inhibition of the Angiotensin II system, and not to the normalization of blood pressure. These results indicate that treatment with AT1 receptor antagonists appears to be a major therapeutic avenue for the prevention of ischemia and inflammatory diseases of the brain. 9. Thus, orally administered AT1 receptor antagonists may be considered as novel therapeutic compounds for the treatment of diseases of the central nervous system when stress, inflammation and ischemia play major roles. 10. Many questions remain. How is brain Angiotensin II formed, metabolized, and distributed? What is the role of brain AT2 receptors? What are the molecular mechanisms involved in the cerebrovascular remodeling and inflammation which are promoted by AT1 receptor stimulation? How does Angiotensin II regulate the stress response at higher brain centers? Does the degree of activity of the brain Angiotensin II system predict vulnerability to stress and brain ischemia? We look forward to further studies in this exiting and expanding field.

Angiotensin II↗

PubMed2026

Whole-genome analysis of Brevibacterium sanguinis AZMABM HM27: a bacterial isolate from the sea anemone Radianthus magnifica and exhibiting promising multi-therapeutic properties.

BACKGROUND: The marine anemone Radianthus magnifica harbors symbiotic microbes with promising biomedical potential, yet their diversity and therapeutic properties remain underexplored. This study aimed to characterize a symbiotic bacterium isolated from R. magnifica collected from Samalona Island, Indonesia, and to evaluate its multi-therapeutic potential. METHODS: Strain AZMABM HM27 was characterized using whole-genome sequencing, functional annotation, biosynthetic gene cluster prediction, molecular docking, and in vitro bioactivity assays. RESULTS: Phylogenetic and genome-based analyses confirmed AZMABM HM27 as Brevibacterium sanguinis, with an OrthoANI value of 97.37% and a dDDH value of 76.50% against the type strain. The genome comprises a 3,834,082 bp chromosome encoding 3,362 protein-coding genes, including 95 genes involved in secondary metabolite biosynthesis. Five biosynthetic gene clusters were predicted, including those associated with ectoine, terpene, and siderophore production. The crude extract demonstrated antioxidant activity (IC₅₀ = 0.87 mg/mL), anti-inflammatory activity (up to 60% inhibition), antidiabetic activity through α-glucosidase inhibition (up to 40% inhibition), and dose-dependent antiproliferative activity against MCF-7 breast cancer cells (74.10% viability at 1 mg/mL). Molecular docking identified a lead compound, 8,9,9,10,10,11-hexafluoro-4,4-dimethyl-3,5-dioxatetracyclo [5.4.1.0(2,6)0.0(8,11)] dodecane, with strong binding affinities to selected therapeutic targets. CONCLUSIONS: B. sanguinis AZMABM HM27 represents a marine symbiotic strain associated with R. magnifica and a promising source of bioactive compounds with antioxidant, anti-inflammatory, antidiabetic, and antiproliferative potential. Further purification, structural elucidation, and in vivo studies are warranted to validate its therapeutic potential.

Animals↗

PubMed2005

Stabilizing peptide fusion for solving the stability and solubility problems of therapeutic proteins.

PURPOSE: Protein aggregation is a major stability problem of therapeutic proteins. We investigated whether a novel stabilizing peptide [acidic tail of synuclein (ATS) peptide] could be generally used to make a more stable and soluble form of therapeutic proteins, particularly those having solubility or aggregation problems. METHODS: We produced ATS fusion proteins by fusing the stabilizing peptide to three representative therapeutic proteins, and then compared the stress-induced aggregation profiles, thermostability, and solubility of them. We also compared the in vivo stability of these ATS fusion proteins by studying their pharmacokinetics in rats. RESULTS: The human growth hormone-ATS (hGH-ATS) and granulocyte colony-stimulating factor-ATS (G-CSF-ATS) fusion proteins were fully functional as determined by cell proliferation assay, and the ATS fusion proteins seemed to be very resistant to agitation, freeze/thaw, and heat stresses. The introduction of the ATS peptide significantly increased the storage and thermal stabilities of hGH and G-CSF. The human leptin-ATS fusion protein also seemed to be very resistant to aggregation induced by agitation, freeze/thaw, and heat stresses. Furthermore, the ATS peptide greatly increased the solubility of the fusion proteins. Finally, pharmacokinetic studies in rats revealed that the ATS fusion proteins are also more stable in vivo. CONCLUSION: Our data demonstrate that a more stable and soluble form of therapeutic proteins can be produced by fusing the ATS peptide.

Animals↗

PubMed1980

Therapeutic indices for transchest defibrillator shocks: effective, damaging, and lethal electrical doses.

Although prospective studies of defibrillator shock overdose cannot be performed in man, the therapeutic indices of various defibrillating current waveforms can be measured in animals. We determined the ratios TD50/ED50 and LD50/ED50 (where TD50 = median "toxic" or damage-inducing dose, ED50 = median effective or defibrillating dose, and LD50 = median lethal dose) as measures of the therapeutic index for damped sine wave defibrillator shocks in dogs. Death of an animal and/or any degree of cardiac damage found by gross or microscopic examination were defined as harmful effects of shock, analogous to drug toxicity. In terms of peak current, the ED50, TD50, and LD50 were 1.1, 5.8, and 24 amperes/kg.; the therapeutic indices were TD50/ED50 = 5 for morphologic damage and LD50/ED50 = 22 for death. In terms of delivered energy the ED50, TD50, and LD50 were 1.5, 30, and 470 joules/kg.; the therapeutic indices were TD50/ED50 = 20 for damage and LD50/ED50 = 320 for death. These data indicate a reasonable margin of safety for damped sine wave defibrillator shocks in dogs, and are consistent with reported incidences of suspected shock-induced damage in humans.

Animals↗

PubMed1982

Association between serum inhibitory and bactericidal concentrations and therapeutic outcome in bacterial endocarditis.

Several recent reviews on the therapy of bacterial endocarditis have recommended that a serum inhibitory and/or bactericidal concentration (SIC/SBC) of 1:8 or more be achieved to ensure successful therapeutic outcome. We conducted a methodologic and statistical analysis of the available literature on endocarditis to determine the association between SIC/SBC titers of 1:8 or more and therapeutic outcome. We reviewed 17 studies published between 1948 and 1980 in which both SIC/SBC and therapeutic outcome were available. Factors that affect outcome, such as age, duration of symptoms, organism, and valve status, varied widely among the 226 patients. The methods used to measure SIC/SBC differed with respect to the time of obtaining the blood specimen relative to the antibiotic dose, size of the bacterial inoculum, type of broth, and definition of the bactericidal end-point. None of the 17 studies showed a significant association between SIC/SBC titers of 1:8 or more and survival or bacteriologic cure. Fifteen of the 17 also failed to demonstrate a significant association between SIC/SBC titers of 1:8 or more and medical cure. However, each of the studies that failed to demonstrate an association between SIC/SBC titers of 1:8 or more and improved therapeutic outcome had an insufficient sample size to confidently exclude a false-negative result. Analysis of the published data reveals insufficient evidence to demonstrate that SIC and SBC titers are of prognostic value in the therapy of patients with bacterial endocarditis.

Anti-Bacterial Agents↗

PubMed1983

Hepatotoxicity following the therapeutic use of antipyretic analgesics.

The potential for hepatic injury associated with the therapeutic use of salicylates and acetaminophen has recently attracted considerable attention. About 300 cases have been reported in which elevated transaminase levels or other evidence of hepatic injury developed following treatment with salicylates. Review of the spectrum of abnormalities reveals a group of patients (4 percent) with symptomatic liver damage in whom progressive or chronic liver disease is a possibility with continued use of the drug. In a few patients in this group, jaundice developed; several had abnormal prothrombin times; 11 (70 percent) had transaminase values in excess of 500 units; and five patients (30 percent) had encephalopathy and/or Reye's syndrome. In several reports liver damage has also been associated with the use of acetaminophen in therapeutic or near-therapeutic dosages. Of 18 patients, nine appeared to have ingested acetaminophen in amounts approaching overdose. Of the remaining nine patients, six were alcoholics. In the entire group, only five patients did not have a history of alcohol abuse; in three, glutathione depletion was suggested as a possible explanation for hepatotoxicity. The association with alcoholism or glutathione depletion suggests that host susceptibility may play a critical role. In two patients, long-term use of acetaminophen resulted in liver injury suggestive of chronic active hepatitis, possibly on the basis of an idiosyncratic reaction. In a study of chronic liver disease, acetaminophen half-life was prolonged (168 percent) without accumulation at 4 g a day over five days. In a double-blind, two-week, cross-over study, no clinical or laboratory evidence of adverse effects was found. There is, therefore, no evidence that chronic liver disease increases the risk of hepatotoxicity following the administration of acetaminophen in therapeutic doses. Thus, acetaminophen is the preferred antipyretic analgesic in patients with liver disease. Salicylates should be avoided since many of the adverse effects associated with these drugs are similar to the complications of chronic liver disease.

Acetaminophen↗

PubMed1975

Comparative pharmacologic effects of pilocarpine administered to normal subjects by eyedrops or by ocular therapeutic systems.

Normal volunteers used 1, 2, and 4% pilocarpine eyedrops, three times daily, or ocular therapeutic systems placed in the conjunctival cul-de-sac to control intraocular pressure. The systems continuously release 20 and 40 mug/hour of pilocarpine for one week. Although the amount of drug delivered to the eye from the ocular therapeutic system was one fifth that obtained from the eyedrops, the decrease of intraocular pressure was comparable. The ocular therapeutic systems produced small, constant effects on visual acuity, refractive error, and miosis that did not cause visual handicaps or require correction. The effects of eyedrops on these visual factors were large and varied and produced marked visual handicaps that were not correctable with spectacles. Despite its comparable hypotensive effect in normal subjects, continuous delivery of pilocarpine by means of an ocular therapeutic system elicits less severe side effects than pilocarpine eyedrops.

Adult↗

PubMed1983

Squamous cell carcinoma of the mobile tongue. Clinical behavior and results of current therapeutic modalities.

A retrospective review of 122 patients who received therapy at the Massachusetts General Hospital for squamous cell carcinoma of the mobile tongue from January 1962 through December 1976 was analyzed for clinical patterns of behavior and results of current therapeutic modalities. The results were compared with a previously reported series from our surgical service. Our series showed a dramatic increase in the proportion of women with carcinoma of the tongue from the 10 to 30 percent distribution reported 20 to 30 years ago to the 45 percent female to male ratio we observed. Only 38 percent of patients who had a regional recurrence of disease after initial therapy responded to secondary therapeutic measures. We therefore encourage that initial treatment offer the patient the optimal chance for cure. No significant increase in survival with the current therapeutic modalities of surgery, radiation, or combined therapy was noted; we observed 55 percent 2 year and a 34 percent 5 year overall survival rates. It is our belief that randomized, prospective, therapeutic protocols are essential for further progression of treatment success for patients with this devastating disease.

Adult↗

PubMed1982

Therapeutic response of leukemic mice treated with fluorinated pyrimidines and inhibitors of deoxyuridylate synthesis.

The therapeutic efficacy of combinations of fluorinated pyrimidines and inhibitors of either ribonucleotide reductase or deoxycytidylate deaminase was evaluated for the treatment of the L1210 mouse leukemia in DBA/2 mice. Therapeutic synergisms were observed with optimal combinations of 5-fluor-2'-deoxyuridine and either hydroxyurea or guanazole. In addition, mice treated with guanazole combined with 5-fluorouracil survived longer than was observed with any dose of guanazole or with 5-fluorouracil alone. Tetrahydrodeoxyuridine, a potential prodrug of a transition-state analog of deoxycytidylate deaminase, did not have antitumor activity by itself nor did it improve the therapeutic response of leukemic mice to 5-fluoro-2'-deoxyuridine. These results are consistent with the hypothesis that deoxyuridylate accumulation was limited by inhibition of ribonucleotide reductase but not by administration of tetrahydrodeoxyuridine. It is suggested that combination chemotherapy with fluorinated pyrimidines and inhibitors of deoxyuridylate synthesis may improve the therapeutic response to these drugs.

Animals↗

PubMed1988

Enhancing effect of bromovinyldeoxyuridine on antitumor activity of 5-fluorouracil against adenocarcinoma 755 in mice. Increased therapeutic index and correlation with increased plasma 5-fluorouracil levels.

A marked inhibition of the growth of solid tumor adenocarcinoma 755 was achieved by the combination of 5-fluorouracil (5-FU) with bromovinyldeoxyuridine (BVDU). The therapeutic index (LD50/ED50) for the combination of BVDU plus 5-FU was 8.1 and 3.9 upon intraperitoneal (i.p.) or oral (p.o.) administration, respectively. The therapeutic index of i.p. 5-FU given alone was 2.3, whereas for p.o. 5-FU given alone no therapeutic index could be established because of insufficient activity of the compound. Thus, the therapeutic index of 5-FU increased significantly when combined with BVDU. Pharmacokinetic studies revealed that upon i.p. or p.o. 5-FU administration plasma 5-FU levels rapidly declined, but that, in the combination with BVDU, the plasma clearance of 5-FU, especially following p.o. administration, was slowed down considerably. Antitumor activity of 5-FU correlated with AUC (area under the concentration x time curve), within the plasma 5-FU concentration range from 0.02 to 0.4 microgram/ml.

Adenocarcinoma↗

PubMed1984

Management of regional lymph nodes in penile carcinoma. Five-year results following therapeutic groin dissections.

Twenty-two patients with squamous carcinoma of the penis underwent groin dissections for histologically proved inguinal lymph node metastases, either around the time that the primary tumor was treated (early therapeutic dissection, 14 patients) or later, after they had been clinically judged free of regional nodal metastases at diagnosis (late therapeutic dissections, 8 patients). Three- and five-year survival rates for the patients who underwent early therapeutic dissections were 71 per cent and 57 per cent, respectively, as opposed to 50 per cent and 13 per cent, respectively, for patients who underwent late therapeutic dissections. These findings suggest that a "wait and watch" policy in patients with clinically negative nodes at diagnosis is no longer justified.

Adult↗

PubMed1989

Therapeutic effect and titers of the specific IgE and IgG antibodies in patients with sea squirt allergy (Hoya asthma) under a long-term hyposensitization with three sea squirt antigens.

Hyposensitization therapy with each of three sea squirt antigens, Gi-rep (molecular weight [MW] 106,000), Ei-M (MW 22,800), and DIIIa (MW 9980), have succeeded in 72%, 90%, and 36% of patients with sea squirt allergy, respectively, within the first year, and the effect has been maintained during subsequent 4-year maintenance therapy. All available sera from some of the hyposensitized patients were also examined for IgE and IgG titers against the most effective therapeutic antigen, Ei-M, and it was revealed that the Ei-M-specific IgG titer increased rapidly in the successfully hyposensitized patients, regardless of the therapeutic antigen used, except for a few patients. Furthermore, the high specific IgG titer, as well as the therapeutic effect, was maintained during the subsequent maintenance therapy. No such increase in the specific IgG titer was detected in all unsuccessfully hyposensitized patients. In contrast, the Ei-M-specific IgE titer was practically unchanged in all allergic patients, independent of the therapy. Therefore, the effect of the hyposensitization therapy was closely dependent on the induction of the specific IgG capable of competing with the specific IgE for a certain asthma-inducing antigen, like DIIIa. The apparently low therapeutic efficiency of DIIIa was attributed to its relatively low immunogenicity to induce the specific IgG.

Allergens↗

PubMed1988

Radioprotectors in tumor radiotherapy: factors and settings determining therapeutic ratio.

WR-2721 and DDC have been used most frequently in our studies on radioprotective agents. WR-2721 was a much more potent radioprotector of murine normal tissues, both against early and late injuries of several organs and tissues, than was DDC. Protection factors for WR-2721 usually ranged between 1.5 and 2.5. Both agents protected solid murine tumors only minimally. While WR-2721 increased therapeutic ratios commonly, DDC did so only rarely. Micrometastatic foci were amenable to radioprotection more than established solitary tumors. Additional factors that influenced the degree of therapeutic benefit included dose of WR-2721, dose of irradiation (single versus fractionated), and time of WR-2721 administration in relation to radiation delivery. The ability of WR-2721 to prevent radiation-induced immunosuppression, metastatic spread, and carcinogenesis are additional benefits in the therapeutic use of this agent. Our current research on the improvement of radioprotectors for therapeutic use is focused on (a) a search for new radioprotective agents that are equal to or better than WR-2721 but less toxic and/or more specific for normal tissue, (b) understanding the basic mechanisms of action of these radioprotective agents at the molecular level, both in cells and tissues, and thus understanding the mechanisms leading to selective or preferential radioprotection of normal tissues, and (c) in vitro testing of primary human tumor cultures for their (non)susceptibility to radioprotection.

Amifostine↗

PubMed1993

Beneficial effects of SK&F 105685 in rat adjuvant arthritis: prophylactic and therapeutic effects on disease parameter progression.

Prophylactic administration of SK&F 105685 (N, N-dimethyl-8,8,-dipropyl-2-azaspiro[4.5]decane-2-propanamine dihydrochloride) at 30 mg/kg/day inhibited hindpaw lesions in adjuvant arthritic (AA) rats following 16 (84% inhibition) and 24 (70% inhibition) days of treatment. In a therapeutic protocol, where dosing was initiated on day 10 after disease induction, SK&F 105685 (20 mg/kg/day) effectively halted disease progression, and the inflammatory lesion was suppressed by 70% following treatment for 20 days. Histological evaluation of the joint periarticular soft tissue, bone and articulation (joint space and joint surface) from therapeutically treated rats showed a clear beneficial effect. Most rats presented moderate lesions rather than the severe lesions seen in the AA animals. AA control rats and AA rats treated prophylactically or therapeutically with SK&F 105685 had significant and similar increases in their total white blood cell (WBC), neutrophil, monocyte and platelet counts. Although increases were seen in the absolute number of neutrophils and platelets, there were no differences in the levels of leukotriene B4 (LTB4) and hydroxyheptadecatrienoic acid (HHT), per cell when these cells were stimulated with the calcium ionophore A23187. These results, describing the beneficial effects of SK&F 105685 administered therapeutically to the AA rat, indicate that this compound possesses properties desirable of an anti-arthritic agent and may potentially modify the disease outcome.

Adjuvants, Immunologic↗

PubMed1984

Multiple therapeutic use in urban Nepal.

Studies of resort to healers in medically pluralistic settings in different geographic and cultural areas reveal two basic patterns of resort--illness specific and multiple use. This paper suggests that the particular pattern inferred from a study may depend largely upon whether the data consist of general attitudes and preferences or actual therapeutic choices. Moreover, it proposes that interview responses concerning general attitudes toward and preferences for available therapies tend to show illness-specific patterns, while observations of actual therapeutic choices during illness episodes more often portray multiple use. Consistent with this proposition are findings presented here from a recent study of attitudes and help seeking behavior in Kathmandu, Nepal as well as the overall results of twenty-four other ethnographic studies reviewed of therapeutic resort in medically pluralistic settings. An important implication of these findings for the validity of ethnographic description is that attitudes and preferences of individual patients do not necessarily predict or describe actual strategies of resort. Finally, this paper present a partial explanation for the pervasiveness of multiple therapeutic use and the disparity between attitudes and behavior in Kathmandu.

Attitude to Health↗

PubMed1983

Treatment outcome and compliance with therapeutic regimens: long-term follow-up of a multidisciplinary pain program.

Fifty-seven patients (74%) who had completed a multidisciplinary pain program returned mailed questionnaires assessing both outcome and compliance measures. Significant treatment gains were observed at follow-up. Compliance with prescribed therapeutic regimens was low, averaging around 42% for individual regimens. Compliance with any one therapeutic regimen was generally unrelated to rate of compliance with other therapeutic regimens. Discriminant relationships were observed between the various therapeutic regimens and outcome measures.

Adult↗