PubMed Health⌕ Search

Biomedical subjects

H Frost

Publications and source records attributed to H Frost.

At least 19 recordsLinked to original sources
PubMed2002

A randomized controlled trial of exercise to improve mobility and function after elective knee arthroplasty. Feasibility, results and methodological difficulties.

OBJECTIVE: To assess the feasibility of comparing two types of exercise regime aiming to improve mobility and function following knee arthroplasty. DESIGN: A single-blind randomized controlled trial. SUBJECTS: Patients with primary, unilateral knee osteoarthritis undergoing elective knee joint replacement. INTERVENTION: Home-based traditional exercise group (TEG) or home-based functional exercise group (FEG) following discharge from hospital. OUTCOME MEASURES: These included goniometry; a knee-specific pain score, leg extensor power and a walking test. Patients were followed up at three, six and 12 months after surgery. RESULTS: Forty-seven patients met the study criteria, 24 were randomized to the TEG and 23 to the FEG. There were marked improvements in mobility, leg extensor power and pain in the year after surgery (MANOVA p < 0.001). There were no statistically significant differences between the two exercise groups. Knee flexion decreased during the follow-up period and had not recovered by 12 months. Retention of patients was a problem, with nearly 50% lost to follow-up at 12 months. These patients were assessed as having low motivation during inpatient rehabilitation (p < 0.05). CONCLUSIONS: There were trends in favour of the FEG that were of clinical relevance. A definitive study would need a sample size of at least 100 patients in each arm. It is essential to develop strategies to combat loss to follow-up.

Aged↗
PubMed2001

Reliability and responsiveness of the shuttle walking test in patients with chronic low back pain.

BACKGROUND AND PURPOSE: Walking is an important functional activity and the shuttle walking test has been shown to be a useful test for patients with chronic airways obstruction and heart failure. The test has been used in low back pain research over recent years and has increasingly been used as an outcome measure to investigate treatment efficacy in patients with low back pain. The aim of the present study was to determine the reliability and responsiveness of the shuttle walking test within a group of patients with low back pain (with or without sciatica). METHOD: Reliability of the shuttle walking test was determined on a group of patients with low back pain (n = 44) using the Bland and Altman (1986) limits of agreement and the intraclass correlation coefficient (ICC). Responsiveness was assessed using the standardized effect size. The mean distance walked within a patient population (n = 337) was compared with an age- and sex-matched group of healthy subjects (n = 122). RESULTS: The shuttle walking test obtained an ICC score of 0.99, whereas the limits of agreement test gave a mean difference of 2.5 m with upper and lower limits of agreement of 52 m and -47 m, respectively. Patients undertaking fitness training reached an effect size of 1.2 compared to a control group of 0.23 and 0.94 for a group undergoing various orthopaedic treatments. CONCLUSIONS: The present study has shown that the shuttle walking test is a reliable and responsive test within a group of patients with low back pain, with or without sciatica. It is simple to administer and provides a quick method of measuring one aspect of a patient's physical function.

Adult↗
PubMed1998

A fitness programme for patients with chronic low back pain: 2-year follow-up of a randomised controlled trial.

The aim of this study was to assess the long-term effect of a supervised fitness programme on patients with chronic low back pain. The design of the study was a single blind randomised controlled trial with follow-up, by postal questionnaire, 2 years after intervention. The Oswestry Low Back Pain Disability Index was used as the outcome measure to assess daily activity affected by back pain. Eighty-one patients with chronic low back pain, who were referred to the physiotherapy department of a National Health Service orthopaedic hospital, were randomised to either a supervised fitness programme or a control group. Patients in the intervention group and control group were taught specific exercises to be continued at home and referred to a backschool for back care education. In addition, the intervention group attended eight sessions of a supervised fitness programme. Sixty-two patients (76%) with a mean age of 37 years, returned the Oswestry Low Back Pain Disability Index questionnaire. Of these, 29 were in the intervention group and 31 in the control group. Patients in the intervention group demonstrated a mean reduction of 7.7% in the Oswestry Low Back Pain Disability Index score (95% confidence interval of mean paired difference 3.9, 11.6 P < 0.001), compared with only 2.4% in the control group (95% confidence interval of mean paired difference -2.0, 6.9 P > 0.05). Between group comparisons demonstrated a statistically significant difference in disability scores between the treatment and control group (mean difference 5.8, 95% confidence interval 0.3, 11.4 P < 0.04). This study supports the current trend towards a more active treatment approach to low back pain. We have demonstrated clinical effectiveness of a fitness programme 2 years after treatment but this needs to be replicated in a larger study which should include a cost effectiveness analysis, further analysis of objective functional status and a placebo intervention group.

Adolescent↗
PubMed1998

Leg extensor power and quadriceps strength: an assessment of repeatability in patients with osteoarthritic knees.

OBJECTIVE: To assess the repeatability of two muscle function measures -- leg extensor power (LEP) and isometric quadriceps force (IQF) -- in a population of patients with osteoarthritis of the knee. DESIGN: Repeat measures of LEP and IQF at 25 degrees and 50 degrees knee flexion were taken within seven days. Both legs were measured and a numerical rating scale was used to assess pain on the two occasions. SUBJECTS: Patients who were on a waiting list for a primary unilateral knee replacement for osteoarthritis were invited to take part in the study. SETTING: The physiotherapy department of a National Health Service Orthopaedic Hospital in Oxford, UK. INTERVENTION: Subjects were measured using a Kin-Com dynamometer to assess maximum isometric force and a leg extensor power rig to assess maximum single leg explosive power. RESULTS: Twenty-six patients (mean age: 72 years; SD: 8 years; range: 50-87 years) were included in the study following informed consent. A weak relationship was found between LEP, IQF and pain scores which reached the 5% significance level for the LEP measures only. The level of repeatability for both measures was found to be acceptable. CONCLUSION: Both LEP and IQF are recommended as repeatable measures for assessment of muscle function in patients with osteoarthitis of the knee. However, the LEP rig has the added advantage of being quicker, cheaper and simpler to use in the clinical setting.

Aged↗
PubMed1996

A placebo controlled double blind trial to evaluate the effectiveness of pulsed short wave therapy for osteoarthritic hip and knee pain.

The aim of this study was to investigate the effectiveness of pulsed short wave (PSW) in the relief of pain in osteoarthritis of the hip and knee. Ninety-two patients, mean age 63 years, (34 men and 58 women) were randomly allocated to one of three groups: (1) Active PSW, using the dosage found in a pilot study to be non-significantly most effective, (2) Placebo PSW, (3) No treatment control group. Nine sessions of treatment were provided over a 3-week period, each application lasting for 15 min. The machine was modified by the manufacturers so that the therapist was able to administer the treatment and carry out assessments without being aware of the treatment allocation. Outcome measures included sensory and affective pain diary reports averaged over days and weeks, self-reported benefit and the General Health Questionnaire. Analysis of variance with repeated measures over time was used to find out if the active treatment had a specific effect, incremental to the placebo effect. There were no significant differences between the active and placebo groups over time. According to the pain diary reports, both active and placebo groups tended to improve slightly during treatment, but worsened after its withdrawal. Patients who were given the placebo application tended to report more benefit than those who had the active treatment, although this did not quite reach statistical significance (P < 0.06). Patients who were not on a waiting list for surgery did significantly better over time than those who were (P < 0.03). There were no significant differences between the groups over time for the other outcome variables. Any treatment effect on this patient population appears to have been largely placebo-mediated. No evidence was found therefore for the specific effectiveness of PSW for treatment of osteoarthritic hip or knee pain.

Affect↗
PubMed1995

Randomised controlled trial for evaluation of fitness programme for patients with chronic low back pain.

OBJECTIVE: To evaluate a progressive fitness programme for patients with chronic low back pain. DESIGN: Single blind randomised controlled trial. Assessments were carried out before and after treatment by an observer blinded to the study and included a battery of validated measures. All patients were followed up by postal questionnaire six months after treatment. SETTING: Physiotherapy department of orthopaedic hospital. SUBJECTS: 81 patients with chronic low back pain referred from orthopaedic consultants for physiotherapy. The patients were randomly allocated to a fitness programme or control group. INTERVENTION: Both groups were taught specific exercises to carry out at home and referred to a back-school for education in back care. Patients allocated to the fitness class attended eight exercise classes over four weeks in addition to the home programme and backschool. RESULTS: Significant differences between the groups were shown in the changes before and after treatment in scores on the Oswestry low back pain disability index (P < 0.005), pain reports (sensory P < 0.05 and affective P < 0.005), self efficacy reports (P < 0.05), and walking distance (P < 0.005). No significant differences between the groups were found by the general health questionnaire or questionnaire on pain locus of control. A benefit of about 6 percentage points on the disability index was maintained by patients in the fitness group at six months. CONCLUSION: There is a role for supervised fitness programmes in the management of moderately disabled patients with chronic low back pain. Further clinical trials, however, need to be established in other centres to confirm these findings.

Adult↗
PubMed1993

Pharmacokinetics and immunomodulatory effects on monocytes during prolonged therapy with liposomal muramyltripeptide.

The macrophage activator muramyl tripeptide-phosphatidyl ethanolamine (MTP-PE) was infused in liposomal form in 14 metastatic cancer patients (4 mg i.v. during 30 min twice weekly for 12 weeks). Clinical, pharmacokinetic and immunological parameters were studied before and 0.5, 2, 4, 24 and 72h after start of drug infusion in week 1, 4, 8 and 12. No tumor regressions were seen. Tumors progressed in 11 patients, in 4 of them within 2 months; 3 patients had stable disease. The intensity and frequency of side effects (fever and nausea) diminished from week 1 to 12. The rate of disappearance of total and free MTP-PE from blood was rapid and mean serum concentration-time curves remained unchanged throughout 12 study weeks. MTP-PE caused a marked increase of serum TNFa, IL-1 receptor antagonist (IL-1ra) and IL-6 in week 1, but not thereafter. In contrast, MTP-PE caused a persistent, 2-fold increase in serum neopterin and young forms of granulocytes (bands) during week 1 to 12. Before therapy, monocyte tumor cytotoxicity and in-vitro monocyte derived TNFa, IL-1 beta and IL-6 production were low in 9 patients (group L, < 15%) and high in 5 patients (group H, > 40%). Monocyte cytotoxicity and in-vitro cytokine production was transiently enhanced in week 1 in group L, it declined under therapy in group H. In conclusion, MTP-PE induced marked initial immunomodulation; the extent of the ex vivo monocyte cytokine and tumor cytotoxic response was dependent on pre-therapy cell activity. A decrease of the cytokine and IL-1ra response during prolonged therapy contrasted with a persistent increase of neopterin and juvenile blood granulocytes. The long lasting biologic effects may be relevant to direct future clinical studies with liposomal MTP-PE in an adjuvant setting.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1992

MTP-PE in liposomes as a biological response modifier in the treatment of cancer: current status.

MTP-PE in liposomes is a BRM which can be given relatively safely to patients with cancer. The maximum tolerated dose appears to be higher than the optimal dose inducing immunomodulatory effects such as cytokine induction and monocyte/macrophage activation. The most consistently induced cytokines measured in the plasma of patients a few hours after MTP-PE are TNF and IL-6. Indirect evidence supports the assumption that increased levels of TNF and IL-6 are signs of macrophage activation occurring in situ in tissues taking up liposomal MTP-PE shortly after injection. These tissues are mainly lungs, liver and spleen, as shown in 4 patients injected with radiolabelled liposomes containing MTP-PE. Assuming that activated monocytes and macrophages cannot eliminate gross tumor load, the main targets for MTP-PE are micrometastases after removal of the primary tumor. Thus, adjuvant treatment using liposomal MTP-PE in combination with chemotherapy is a major goal for the future.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1991

Phase I study of liposomal MTP-PE-activated autologous monocytes administered intraperitoneally to patients with peritoneal carcinomatosis.

We have conducted a phase I study with autologous monocytes activated ex vivo and administered intraperitoneally in nine patients with peritoneal carcinomatosis. Blood monocytes were collected by leukapheresis and then purified by counterflow elutriation (up to 10(9) cells, with a purity of greater than 90%). Ex vivo activation was obtained by incubating these cells with 1 micrograms liposomal MTP-PE/10(6) monocytes for 18 hours in hydrophobic culture bags at 37 degrees C in 5% carbon dioxide humidified air. The activated monocytes were then infused in the peritoneal cavity once a week for 5 consecutive weeks through an implanted peritoneal infusion system, Port-A-Cath (Pharmacia Deltec, St Paul, MN), on an intrapatient dose-escalating schedule (10(7) to 10(9) monocytes). No severe adverse reactions occurred. Toxicity was mild, the chief acute reactions being fever (27%), chills (13%), and abdominal pain (25%). None of the side effects led to dose reduction. No consistent change in hemostatic function, liver function, or renal function was observed. Significant increases in granulocyte counts, neopterine, and acute phase reactants (fibrinogen, C-reactive protein) occurred in the peripheral blood. In vitro monocyte activation was demonstrated by the relapse of procoagulant activity and monokines (interleukin-1 [IL-1], IL-6, and tumor necrosis factor-alpha [TNF alpha]) in the supernatants of cultured monocytes. Evidence for in vivo monocyte activation was provided by the increase of these monokines in the peritoneal fluids. Kinetic studies with indium-111 (111In)-labeled activated autologous monocytes in five patients suggest that these infused monocytes may remain in the peritoneal cavity for up to 7 days. This locoregional immunotherapeutic approach seems to be encouraging in view of adjuvant therapeutic modality in ovarian cancer patients with minimal residual intraabdominal disease following second-look laparotomy.

Aged↗
PubMed1990

Initial clinical trial of the macrophage activator muramyl tripeptide-phosphatidylethanolamine encapsulated in liposomes in patients with advanced cancer.

A phase I clinical trial of the macrophage activator, muramyl tripeptide-phosphatidylethanolamine has been carried out in 37 patients (47 courses) at doses of 0.01-6.0 mg/m2 intravenously twice weekly for 4 weeks. Activation of peripheral blood monocytes and drug toxicity were used as the parameters to monitor the trial. Toxicity was acute systemic responses of fever, chills, and hypertension without a clear dose response. No major organ-related toxicity was seen. A dose of 4.0 mg/m2 biweekly produced activation of blood monocytes; a dose of 6.0 mg/m2 produced inhibition. There was one complete response of 3 months duration in a patient with renal cell carcinoma with pulmonary metastases. The optimum dose for phase II studies is in the range of 1-4 mg/m2 twice weekly for 4 weeks, a dose that is well tolerated.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1990

Interleukin-6 induction by a muramyltripeptide derivative in cancer patients.

Interleukin-6 (IL-6) was measured in sera from 26 patients with advanced malignancies before and after an I.V. infusion of muramyltripeptide-phosphatidylethanolamine (MPT-PE) in liposomes. Significantly elevated IL-6 could be measured 2 and 4 h after medium (0.25-0.5 mg/m2) and high (1.0-6.0 mg/m2) doses of the drug accompanied by a rise in body temperature. The biological activity of IL-6 in sera could be inhibited in vitro by monoclonal antibodies against IL-6. Other biological effects of MTP-PE in vivo such as leukocytosis and elevated acute phase reactants are discussed in view of increased IL-6 levels. It is concluded that MTP-PE in liposomes generates increased amounts of IL-6 measurable in serum several hours after administration. IL-6 could therefore play an important role in the biological response modification induced by the drug.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1989

Human Fc epsilon R II and IgE-binding factors.

The low-affinity receptor for IgE (Fc epsilon R II) is mainly expressed on B lymphocytes, although it may also be found on some monocytes, eosinophils, and platelets. The presence of Fc epsilon R II on T cells is still controversial, but our results demonstrate that it is expressed on some HTLV-I-transformed T lymphocytes, and they strongly suggest that it may be found on a small proportion of normal T cells. Fc epsilon R II is a 45-KD glycoprotein containing one N-linked carbohydrate of complex type, O-linked carbohydrates, and sialic acid residues. Fc II is cleaved into soluble fragments with molecular weights of 37, 33, 25, and 12 KD, the first three retain the ability of binding to IgE, i.e., they are IgE-binding factors (IgE-BFs). The enzymes involved in their proteolytic cleavage are cell bound. The cDNA coding for Fc epsilon R II was cloned and functionally expressed. The predicted sequence has no homology with that of murine IgE-BFs which are of T cell origin. However, there is a striking homology with several animal lectins, and since the IgE-binding site is located in the homology region, it is possible that it binds to IgE via the carbohydrates expressed on the Fc region of this immunoglobulin. The expression of Fc epsilon R II on B cells and the release of IgE-BFs are upregulated by interleukin 4 and suppressed by gamma and alpha interferons.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, Differentiation, B-Lymphocyte↗
PubMed1989

Phase I trial of liposomal muramyl tripeptide phosphatidylethanolamine in cancer patients.

Twenty-eight evaluable patients with metastatic cancer refractory to standard therapy received escalating doses of muramyl tripeptide phosphatidylethanolamine (MTP-PE) (.05 to 12 mg/m2) in phosphatidylserine (PC):phosphatidylcholine (PS) liposomes (lipid:MTP-PE) ratio 250:1). Liposomal MTP-PE (L-MTP-PE) was infused over 1 hour twice weekly; doses were escalated within individual patients every 3 weeks as tolerated for a total treatment duration of 9 weeks. Routine clinical laboratory parameters, acute phase reactants and various immunologic tests were monitored at various time points during treatment. Toxicity was moderate (less than or equal to grade II) in 24 patients with chief side effects being chills (80% of patients), fever (70%), malaise (60%), and nausea (55%). In four patients L-MTP-PE treatment was deescalated due to severe malaise and recurrent fever higher than 38.8 degrees C. The maximum-tolerated dose (MTD) was 6 mg/m2. Significant (P less than .05) increases in WBC count, absolute granulocyte count, ceruloplasmin, beta 2-microglobulin, c-reactive protein, monocyte tumoricidal activity, and serum IL-1 beta were found. Significant decreases in serum cholesterol were also observed. Clearance of intravenously (iv)-infused technetium-99 (99mTc)-labeled liposomes containing MTP-PE in four patients was biphasic; gamma camera scans revealed uptake of radiolabel in liver, spleen, lung, nasopharynx, thyroid gland, and tumor (two patients). No objective tumor regression was seen. In view of its definite immunobiologic activity and lack of major toxicity, additional phase II and adjuvant trials of L-MTP-PE are warranted.

Acetylmuramyl-Alanyl-Isoglutamine↗