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Biomedical subjects

H Granlund

Publications and source records attributed to H Granlund.

At least 19 recordsLinked to original sources

Three-year results of a randomized clinical trial of lightweight or standard polypropylene mesh in Lichtenstein repair of primary inguinal hernia.

BACKGROUND: This randomized trial examined whether lightweight (LW) polypropylene mesh (large pore size, partially absorbable) could have long-term benefits in reducing chronic pain and inflammation after inguinal hernia repair. METHODS: Six hundred men with a primary unilateral inguinal hernia were randomized to Lichtenstein repair using a standard polypropylene mesh or a LW mesh in one of six centres. The patients were blinded to which mesh they received. Clinical examination was performed and a pain questionnaire completed 3 years after surgery. RESULTS: Of the 590 men who had surgery, 243 (82.7 percent) of 294 in the standard mesh group and 251 (84.8 percent) of 296 in the LW mesh group were examined in the clinic, a median of 37 (range 30-48) months after hernia repair. There were nine recurrent hernias in each group (3.7 percent with standard mesh and 3.6 per cent with LW mesh). Patients who had LW mesh had less pain on examination, less pain on rising from lying to sitting, fewer miscellaneous groin problems and felt the mesh less often than patients with standard mesh. CONCLUSION: Use of LW mesh for Lichtenstein hernia repair did not affect recurrence rates, but improved some aspects of pain and discomfort 3 years after surgery.

Adult↗

One year results of a randomised controlled multi-centre study comparing Prolene and Vypro II-mesh in Lichtenstein hernioplasty.

A standard polypropylene mesh used in Lichtenstein's operation induces a strong foreign tissue reaction with potential harmful effects. A mesh with less polypropylene could possibly be beneficial. Six hundred men with primary unilateral inguinal hernias were randomised to Lichtenstein's operation using a Prolene- or Vypro II-mesh in six centres. The patients were blinded to which mesh they received. A validated questionnaire assessing recurrence and pain along with SF-36 Health Survey was sent after 1 year to all patients and a selected group was clinically examined. Of the 591 operated patients, 526 (89.0%) returned the questionnaire. 188 patients had some complaints or sensations of which 111 patients were clinically examined. The mean follow-up time was 13.6 (SD. 4.0) months. The incidence of hernia recurrence (four vs. four patients) and neuralgia (three vs. four patients) did not differ between Prolene and Vypro II-groups, respectively. One Vypro II-patient was re-operated due to neuralgia. There was no difference in the SF-36 scores. The results of Lichtenstein's operation with either Prolene or Vypro II do not seem to differ significantly.

Hernia, Inguinal↗

Analysis of Borrelia burgdorferi IgG antibodies with a combination of IgG ELISA and VlsE C6 peptide ELISA.

Enzyme-linked immunosorbent assays (ELISAs) were used to detect antibodies to the C6 peptide of the Borrelia burgdorferi VlsE protein and a selection of B. burgdorferi IgG antigens, separately and as a combination, in 355 serum specimens from blood donors and patients. Western immunoblotting was used as the reference method. The sensitivity of the combined analysis of IgG antigen and C6 peptide analysis was markedly superior to those of the separate analyses. When the C6 peptide and IgG results were concordant, the customary confirmatory Western immunoblotting assay could be omitted, thus reducing the time and cost of analysis.

Antibodies, Bacterial↗

Seasonal variation in the occurrence of late adverse skin reactions to iodine-based contrast media.

PURPOSE: To study the possible seasonal effect in the occurrence of late adverse skin reactions to iodine-based contrast media (CM). MATERIAL AND METHODS: Data on 4,875 adult patients followed for late adverse reactions after i.v. injections of iohexol or iopamidol, or intra-arterial injection of ioxaglate were retrospectively investigated with respect to the amount of global radiation vs. the occurrence of reactions. The information on these reactions was collected from questionnaires that were filled out by the patients (out-patients) or by nurses (in-patients). The follow-up time was 24 h. RESULTS: Fifty-two of 4,875 patients (1.07%) had experienced a late skin reaction (urticaria or rash); this number exceeds the reports on spontaneous occurrence of such reactions by a factor of 300. Most of the reactions in a known location occurred on sun-exposed areas of the body. A 2-month peak in the incidence of reactions (May to June) included 35% of all events (p<0.025) and a 3-month peak (April to June) 46% of all events (p<0.01). There was a significant rank correlation (r = 0.613, p<0.05) between the frequency of reactions and the mean amount of global radiation. CONCLUSION: This study demonstrates a seasonal variation in skin reactions after intravascular injection of iodine-based CM. The possible photosensitising effect of these drugs should be further studied.

Adolescent↗

hu1124 (Genentech).

Genentech and XOMA are collaborating in the development of a humanized monoclonal antibody, hu1124 (anti-CD11a), which has the potential to treat psoriasis and prevent organ transplant rejection. It is currently undergoing phase III clinical trials for psoriasis and phase I/II trials for transplant rejection. A phase II trial in moderate-to severe psoriasis patients was completed in January 1999 and data were initially presented at the Canadian Dermatology Association meeting in Vancouver, BC in July 1999. Following positive results from this trial, a phase III trial in moderate-to-severe psoriasis patients was initiated in December 1999. In August 1999, Genentech and XOMA expanded their collaboration to include organ transplant rejection. In March 2000, XOMA and Genentech initiated a phase I/II study of hu1124 in kidney transplant patients. In February 1999, Lehman Brothers predicted the drug had a 30% probability of reaching market. Assuming a successful launch, Lehman Brothers analysts estimated peak sales would occur in 2009 with sales at that time of 100 million USD.

Journal Article↗

Evaluation of treatment responses in late Lyme borreliosis on the basis of antibody decrease during the follow-up period.

The purpose of this study was to identify a serological marker of successful treatment as distinct from treatment failure in late Lyme borreliosis. Consecutive serum samples from 68 treated patients with late Lyme borreliosis were analyzed during a 1-2 year follow-up period after the start of treatment. End-point enzyme immunoassay titres of IgG1, IgG2, IgG3, and combined IgG1+3 subclasses against a sonicate antigen of Borrelia burgdorferi were determined and compared to the IgG antibody response against Borrelia burgdorferi flagella. Individual half-lives of the antibody levels were calculated for each patient. The half-life values were compared to the patients' clinical outcome in order to find a serological marker of remaining disease activity or relapse. The levels of combined IgG1+3 subclass antibodies against the sonicate antigen and the individual levels of IgG1, IgG2, and IgG3 antibodies did not change significantly after treatment. In contrast, antibodies to flagella decreased markedly after successful treatment, with a half-life of 112+/-92 days (arithmetic mean value +/- SD). This was significantly shorter than the half-life after unsuccessful treatment (271+/-151 days), (P<0.0001). The decrease was observed mainly in IgG1 and IgG4 responses to flagella, less so for IgG2 or IgG3. The results suggest that a rapid decrease in flagella antibodies can serve as a marker for a successful treatment of Lyme borreliosis.

Animals↗

Tacrolimus ointment improves psoriasis in a microplaque assay.

Tacrolimus (FK506) is an effective and well tolerated immunosuppressant used to prevent allograft rejection. We describe the evaluation of two tacrolimus ointment formulations for treatment of chronic plaque-type psoriasis. This was a microplaque assay with randomized, double-blind design. Sixteen patients (15 men, one woman, all white and 28-69 years old) with chronic plaque-type psoriasis participated. Six different ointments were applied to discrete microplaques, 17 mm in diameter, on a descaled psoriasis lesion: these were tacrolimus ointment with diisopropyl adipate as penetration enhancer, tacrolimus ointment without diisopropyl adipate, 0.1% betamethasone 17alpha-valerate ointment, 0.005% calcipotriol ointment and, as controls, the ointment bases for tacrolimus and betamethasone. Ointments were reapplied and the area was sealed every 2-3 days during the 14-day treatment period. After 7 and 14 days, erythema and infiltration were graded on a scale of 0-4, and superficial blood flow was measured with a laser Doppler flowmeter. Epidermal thickness was measured histologically at the end of treatment. Compared with the vehicle controls, sites treated with tacrolimus ointment (with or without penetration enhancer) showed a significant reduction in erythema and infiltration (P < 0. 001), a significant reduction in superficial blood flow (P < 0.01) and a significant decrease in epidermal thickness (P < or = 0.001). Results for betamethasone and calcipotriol, when compared with the vehicle controls, were similar. These results suggest that, under conditions of descaling and occlusion, tacrolimus ointment is effective in the treatment of psoriasis.

Administration, Topical↗

Double-blind placebo-controlled study of long-term low-dose cyclosporin in the treatment of palmoplantar pustulosis.

We previously showed in a double-blind, placebo-controlled study that cyclosporin at a dose of 2.5 mg/kg per day is an effective treatment for palmoplantar pustulosis (PPP). In the present randomized, double-blind, placebo-controlled multicentre study we treated 58 PPP patients with placebo or cyclosporin at an initial dose of 1 mg/kg per day. Disease activity was calculated from the number of fresh pustules. Treatment success was defined as the number of fresh pustules not exceeding 50% of the patients' own baseline pustule number. In cases of treatment success the dose of the test medication was not increased and the treatment was kept blinded for a maximum of 12 months. Blinding was broken only on treatment failure of the initial test medication dose. The mean blinded treatment time was 5.1 months for the patients receiving cyclosporin and 2.1 months for placebo (P < 0.01). Treatment was kept blinded for 12 months for seven patients in the cyclosporin and two in the placebo group (P < 0.05). Patients whose treatment code was broken continued in an open dose-finding part of the study with dose adjustments of cyclosporin every second month. In cases of treatment failure the dose of cyclosporin was increased in steps of 1 mg/kg per day; in cases of treatment success the cyclosporin dose was decreased by 1 mg/kg per day. The minimum and maximum doses were 1 and 4 mg/kg per day, respectively. The mean effective dose during the dose-finding part was between 1.2 and 1.7 mg/kg per day. Two patients did not respond to the highest dose of 4 mg/kg per day. In two patients serum creatinine levels increased by > 30% of their own baseline. The other main adverse events were hypertension (seven patients) and hypertrichosis (six patients). After stopping cyclosporin treatment the mean number of fresh pustules showed a maximum after 2 weeks with a continuous decline after that. Twelve months after completing the treatment the mean number of pustules was reduced to 20.0 compared with 63.6 at baseline (P < 0.001); 11 patients were free from pustules and two of these were totally cleared. We conclude that cyclosporin at 1-2 mg/kg per day is an effective and well tolerated treatment for PPP in most patients.

Adolescent↗

Tacrolimus ointment does not affect collagen synthesis: results of a single-center randomized trial.

We conducted a randomized, double-blind, placebo-controlled trial to assess the atrophogenicity of tacrolimus ointment. In a combined group of atopic dermatitis patients (n = 14) and healthy volunteers (n = 12), 0.3% tacrolimus, 0.1% tacrolimus, betamethasone-valerate, and a vehicle control were applied in a randomized order to nonsymptomatic, 4 cm x 4 cm regions of abdominal skin. After 7 d of treatment under occlusion, the carboxy- and amino-terminal propeptides of procollagen I (PICP, PINP) and the amino-terminal propeptide of procollagen III (PIIINP) were measured from suction blister fluid with specific radioimmunoassays. In addition, ultrasound measurements of skin thickness were taken. Betamethasone-treated areas showed median PICP, PINP, and PIIINP concentrations of 17.0%, 17.6%, and 39.5% of the vehicle control at the end of the treatment period, respectively, whereas the 0.1% and 0.3% tacrolimus-treated areas showed median concentrations of approximately 100% of the vehicle control (p < 0.001). Betamethasone was also the only treatment to reduce skin thickness; the median decrease in skin thickness was 7.4% relative to 0.1% tacrolimus, 7.1% relative to 0.3% tacrolimus, and 8.8% relative to the vehicle control (p < 0.01). Results for atopic dermatitis patients and healthy volunteers were similar. These findings suggest that tacrolimus does not cause skin atrophy.

Adolescent↗

Long-term follow-up of eczema patients treated with cyclosporine.

Cyclosporine is efficacious in short-term treatment of various eczematous disorders. In a follow-up study we have evaluated the long-term efficacy of cyclosporine in 75 patients, who in previous studies had been treated with cyclosporine for chronic actinic dermatitis (6 patients), atopic dermatitis (42 patients) and chronic hand eczema (27 patients), 4, 2 and 1 year after the initial treatment, respectively. Three out of 6 patients with chronic actinic dermatitis showed long-term efficacy. Two years after the initial treatment with cyclosporine (5 mg/kg/day for 1-2 treatment periods of 6 weeks) for atopic dermatitis the mean disease activity was significantly lower compared to baseline (58% decrease), and compared to the time of treatment stop no significant change had occurred. Of 37 evaluable patients 35 were still in remission. One year after the initial treatment with cyclosporine (3 mg/kg/day for 6 weeks) for chronic hand eczema the mean disease activity was significantly lower than at baseline (54% decrease), and compared to the time of treatment stop no significant change had occurred. Of 27 evaluable patients 21 patients were still in remission. The study suggests that long-term remissions are possible in eczematous diseases treated with cyclosporine, even for a relatively short treatment period. It must be stressed, however, that we did not have control groups for any of the studied patient groups.

Adult↗

IgG seroprevalence of Lyme borreliosis in the population of the Aland Islands in Finland.

This is a study of people living in Aland, a group of islands in the Baltic Sea between Finland and Sweden. 500 blood donors and 3,248 health service clients who did not have Lyme borreliosis were examined for Borrelia burgdorferi IgG antibodies. The method used was an ELISA containing a selection of diagnostic antigens to a Borrelia burgdorferi PKo strain. It was found that the distribution according to sex, age and titre values was identical in the 2 groups, which were therefore treated as one. 19.7% of all the sera was positive. The prevalence in men was 23.6%, and in women 16.7%. The prevalence rises with age, the highest prevalence being seen in men (44.7%) and women (37.0%) over 70 y of age. The data show that the Aland islands are strongly endemic for Lyme borreliosis compared with international levels of infection.

Antibodies, Bacterial↗

Comparison of the influence of cyclosporine and topical betamethasone-17,21-dipropionate treatment on quality of life in chronic hand eczema.

In a randomized, controlled parallel group study we have shown that cyclosporine at 3 mg/kg/day is as effective as topical betamethasone-17,21-dipropionate in the treatment of chronic hand eczema. In this study we compared the influence of these therapies on the quality of life. Forty-one patients were treated with either treatment for 6 weeks, after which patients with failure were switched to the other treatment for another 6 weeks. Quality of life was assessed with the Eczema Disability Index (EDI) at baseline and at the end of both treatment periods. The total EDI score decreased significantly and to the same degree in both groups, i.e. from the mean value of 30.5 to 20.9 in the cyclosporine group and from 27.2 to 18.9 in the betamethasone-17,21-dipropionate group. Irrespective of the dimension of the EDI (daily activity, school/work, personal relationship, leisure, treatment), the difference between the treatment groups at the end of the first treatment period was not significant. In the second part of the study a slight further decrease in total score was observed, but without any difference between the groups. There was a significant correlation between changes in the total EDI score and changes in all the clinical assessments, i.e. disease activity, extent of the disease, itch, sleep disturbances and use of emollients. Though the significant correlation between the total EDI and clinical assessments makes quality of life assessments in hand eczema questionable, the missing correlation between some clinical assessments and dimensions of the EDI suggests that EDI views aspects of the disease not covered by clinical measures.

Administration, Topical↗

Comparison of cyclosporin A pharmacokinetics of a new microemulsion formulation and standard oral preparation in patients with psoriasis.

Cyclosporin A (CyA) is a potent immunosuppressive drug which has shown efficacy in various skin disorders. The bioavailability of the oral CyA formulation (Sandimmun) is approximately 30%, showing high interpatient and intrapatient variability. The steady-state pharmacokinetics, efficacy and tolerability of CyA in two formulations: commercial Sandimmun soft gelatin capsules (CyA-SGC) and a newer oral formulation (Sandimmun Neoral: CyA-NOF), were compared in an open prospective study with a crossover between the two treatments in 19 patients with psoriasis. Each patient received a twice-daily treatment of CyA with a clinically effective dose of 2-5 mg/kg per day. The individual dosages were kept unchanged for at least 2 weeks before study entry and over the 42-day course of the study. At entry, patients were switched to CyA-NOF for 4 weeks and then back to CyA-SGC for another 2 weeks. Pharmacokinetic profiles were assessed at steady-state on day 14 while the patients were on CyA-NOF, and on day 42 while on CyA-SGC. Switching from CyA-SGC to CyA-NOF using 1:1 dose conversion resulted in an increased absorption of the drug. On average there was a 61% increase in maximum drug concentration (Cmax) and a 32% increase in the area under the steady-state blood concentration-time curve (AUC): Cmin was comparable in the two formulations. The increases in Cmax and AUC were associated with some increase in the clinical efficacy of the treatment. The number of adverse events reported by the patients and observed by the investigators were increased during CyA-NOF; the mean serum creatinine levels were not affected. An increased and a more consistent and predictable absorption of CyA is achieved with the new oral microemulsion formulation.

Administration, Oral↗

Comparison of cyclosporine and topical betamethasone-17,21-dipropionate in the treatment of severe chronic hand eczema.

Topical corticosteroids are the standard treatment for hand eczema. However, in chronic forms of the disease they are often ineffective or lose their efficacy due to tachyphylaxis. In a previous open study cyclosporine showed efficacy in chronic hand eczema. The aim of this study was to compare oral cyclosporine at 3 mg/kg/day with topical 0.05% beta-methasone-17,21-dipropionate (BDP) cream in the treatment of chronic hand eczema. In a randomized, double-blind study 41 patients with chronic hand eczema resistant to conventional treatment were assigned to either cyclosporine or BDP for 6 weeks. Both cyclosporine and BDP improved the eczema. The total disease activity score decreased to 57% of baseline in the cyclosporine group (mean change -6, SD 4.3; p < 0.001) and to 58% of baseline in the BDP group (mean change -5.7, SD 4; p < 0.001) at the end of treatment. However, between the groups there was no significant difference. Adverse events occurred in 68% of the patients during cyclosporine and in 56% during BDP treatment. With cyclosporine no case of hypertension or increase in serum creatinine above normal levels was recorded. In two patients the serum creatinine levels increased to values 30% above their own baseline values. Relapses occurred to the same extent in both groups. Cyclosporine at 3 mg/kg/day is as effective as topical BDP in the treatment of chronic hand eczema. Low-dose cyclosporine could be useful as an alternative treatment for severe chronic hand eczema in patients unresponsive to conventional treatment.

Administration, Oral↗

Cyclosporin in atopic dermatitis: time to relapse and effect of intermittent therapy.

The efficacy of cyclosporin (CyA) in the induction of remission in atopic dermatitis has been documented in controlled studies. However, little information is available on the duration of remission after CyA treatment. We studied the length of remission in 43 patients with severe atopic dermatitis after a 6-week treatment period with CyA at 5 mg/kg per day. After a follow-up of 6-26 weeks, depending on the time-point of relapse, a second treatment period with CyA, identical to the first, was performed. Disease activity was evaluated bi-weekly, using six different parameters: 1, a total body disease activity score; 2, the extent of the disease; 3, the occurrence of itch; 4, the occurrence of sleep disturbance; 5, the use of topical emollients; and 6, the use of topical hydrocortisone. A significant decrease in disease activity was observed. The total body disease activity score decreased from the baseline score of 31 to 11.6 at the end of the first part and to 13.4 at the end of the second part of the study. An almost maximal response to treatment was already apparent after 2 weeks of treatment. All the other efficacy parameters studied also showed a significant response to CyA treatment. A similar response to CyA was seen when the patients were re-treated. After both treatment periods, approximately half of the patients relapsed after 2 weeks (42% first part; 54% second part). After 6 weeks follow-up, the relapse rates were 71 and 90%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Occupational allergy caused by spathe flower (Spathiphyllum wallisii).

Occupational allergy caused by plants is seldom reported although it is probably relatively common. We report on a 22-year-old male atopic caretaker of plants who developed IgE-mediated allergic rhinitis, laryngitis, pharyngitis, and contact and generalized urticaria caused by exposure to spathe flower (Spathiphyllum wallisii) while he was working for a firm that supplied plants to offices. He also had an asthmatic attack at work, but in bronchial provocation tests conducted 8 months after he had stopped doing the work in question, he developed rhinoconjunctivitis, pharyngitis, and laryngitis, but exhibited neither bronchial reaction nor fall in PEF values. Prick tests with spathe flower gave 3+ reactions for exudates from the flower, pollen, stem, and leaves. He also had several positive reactions to fruits, vegetables, and spices, but not to natural rubber latex. The radioallergosorbent test with spathe flower was positive (3.4 PRU/ml, close to class 3). In protein staining with SDS-PAGE, one heavy band was detected at about 14 kDa, and other faint bands were visible on both sides. Six faint bands were detected at the mol. mass range of 30-67 kDa. In IgE immunoblotting, one heavy band was detected at about 14 kDa. The patient became symptomless after he had ceased working with plants.

Adult↗