Polyphenon E: a new treatment for external anogenital warts.

Background External genital warts (EGWs, condylomata acuminata) are a common, highly contagious disease caused by human papillomavirus (HPV), predominantly HPV 6 and HPV 11. Green tea catechins have been identified for their immunostimulatory, antiproliferative and antitumour properties. Two phase III trials evaluated treatment of EGWs with ointment containing a mixture of green tea catechins (Polyphenon E), U.S. adopted name: sinecatechins). Objectives To obtain additional data on the efficacy and safety of Polyphenon E ointment in the treatment of EGWs from two randomized, double-blind, vehicle-controlled trials. Methods Men and women aged > or = 18 years (n = 1005), with two to 30 EGWs (12-600 mm(2) total area) applied vehicle (G(Veh); n = 207), Polyphenon E ointment 10% (G(10%); n = 401) or Polyphenon E ointment 15% (G(15%); n = 397) three times daily until complete clearance of all EGWs (baseline + new EGWs) or for a maximum of 16 weeks. Results A total of 1004 patients were evaluable for safety and 986 for efficacy; 838 completed treatment after 16 weeks. Complete clearance of all EGWs was obtained in 53.6% (G(10%)) and 54.9% (G(15%)) of patients with Polyphenon E vs. vehicle (35.4%) (P < 0.001). Statistically significant differences in clearance rates appeared after 6 weeks of active treatment. Odds ratios vs. G(Veh) for G(10%) [2.10; 95% confidence interval (CI) 1.49-2.98] and G(15%) (2.22; 95% CI 1.57-3.14) indicated about a twofold higher chance of complete clearance under active treatment. Time to complete clearance was shorter with active treatment (hazard ratios 1.57 and 1.87, respectively, for G(10%) and G(15%) vs. G(Veh) groups; P < 0.001). Recurrence rates during follow-up were low and similar across groups: 5.8%, 6.8% and 6.5% (G(Veh), G(10%) and G(15%) groups, respectively). Adverse events were evenly distributed across groups ( approximately 30% of patients). Severe local signs were more frequent but moderate in the active treatment groups (1.5%, 9.2% and 13.5% for G(Veh), G(10%) and G(15%) groups, respectively). Conclusions Polyphenon E ointment is effective and well tolerated in the treatment of EGWs.

Efficacy of a polyvalent bacterial lysate in children with recurrent respiratory tract infections.

Respiratory tract infections (RTIs) are the most frequent infections in humans, particularly in children. In addition to intervention, increasing interest is focusing on immunomodulatory therapy for recurrent RTIs, which indicate a reduced defense capacity of the respiratory mucosa. LW 50020, an oral immunomodulator that contains the antigens of seven bacteria common in RTIs, has reduced the number, duration, and severity of RTIs in children and adults. This 56-week placebo-controlled, double-blind study in 188 children investigated whether the efficacy of the standard schedule (immunization cycle + one booster cycle) would be enhanced by additional booster cycles. Efficacy and safety over the long term were also assessed. The rate of infection was reduced by 50% with the standard schedule and could not be further decreased by two consecutive booster cycles. With both schedules, this reduction was sustained during a 28-week treatment-free observation period that followed the 28-week treatment period. The number of adverse drug reactions was low, and all were transient, expected, and nonserious. These results confirm that LW 50020 is an effective and safe strategy for RTIs.

Efficacy and safety of eltenac gel in the treatment of knee osteoarthritis.

OBJECTIVE: A double-blind, placebo-controlled dose-finding study was performed in 237 patients with predominantly unilateral knee osteoarthritis (OA) evaluating efficacy and safety of a new topical NSAID. DESIGN: The patients applied 3 g tid eltenac gel 0.1%, 0.3%, 1% or placebo gel over a period of 4 weeks. The patients were supplied with paracetamol tablets as an escape analgesic. Primary efficacy end-point was mean global pain in the week preceding the examinatio ns, evaluated on a visual analog scale (VAS). Secondary criteria were Lequesne's score ISK, Jezek score, muscle strength and dolorimeter measurements, walking time, clinical examination results of the knee joint and patient's and investigator's overall efficacy estimates. RESULTS: The graphical depiction of VAS and ISK suggested a dose-related efficacy, but the pre-planned statistical analysis did not show significant differences between treatments. In the patient subgroup with a higher degree of baseline severity of knee OA the ISK showed significant and relevant advantages of eltenac gel 1% to placebo at different examination times. Two patients each of the eltenac gel 1% group and the placebo group showed local intolerance reactions which subsided spontaneously. CONCLUSION: This study did not provide confirmatory proof of an efficacy of topical eltenac in patients with knee OA. Methodological pitfalls and possible responder subgroups are described. Despite the difficulties, dose-finding studies seem to be feasible even with topical NSAIDs.

Use of a polyvalent bacterial lysate in patients with recurrent respiratory tract infections: results of a prospective, placebo-controlled, randomized, double-blind study.

Respiratory tract infections (RTIs) are the most common infections in humans, and it is difficult to effectively treat patients with increased susceptibility to these ailments. LW 50020 (Luivac; Paspat oral), an oral immunomodulator consisting of the antigens of seven bacteria commonly involved in RTIs, has been developed for the induction of specific and nonspecific immune responses of the mucosa-associated lymphoid tissue. In this placebo-controlled study, the efficacy and safety of the tablet formulation of LW 50020 were evaluated in children and adults with recurrent RTIs. Tablets were taken once daily during two periods of 4 weeks each, interrupted by a treatment-free interval of 4 weeks. The main endpoint of the study, a clinical severity score that evaluated treatment benefits, was significantly lower in the second study period in patients treated with the bacterial lysate compared to patients given placebo. A comparison of the infection rates in the first and second study periods of patients treated with LW 50020 revealed a placebo-corrected reduction of 39% in children and a placebo-corrected reduction of 44% in adolescents and adults. The placebo-corrected duration of infections was shortened by 47% in children and by 55% in older patients. No serious drug-related side effects occurred. This study demonstrated that the oral bacterial immunomodulator LW 50020 is efficacious in treating patients with recurrent RTIs.

Glycosaminoglycan polysulfate injections in lateral humeral epicondylalgia: a placebo-controlled double-blind trial.

The purpose of this study was to investigate the therapeutic benefit of local Glycosaminoglycan polysulfate (GAGPS) injections in the treatment of chronic epicondylalgia. The study was conducted as a prospective, placebo-controlled double-blind trial. Sixty patients with a typical history of pain for at least 3 months who attended two private orthopaedic clinics in Stockholm received 50 mg GAGPS or placebo injections, one injection a week, for five weeks. The main outcome measures were the patients' evaluation of pain in connection with daily activities with a visual analogue scale and the number of treatment failures. The follow-up period was six months. The difference in reduction of painscore (VAS) ranging between 11.1 percentage units at the half-year follow-up and 20.9 percentage units 2 weeks after the treatment period is clinically good. The number of treatment failures in the GAGPS treatment groups at the 6 week follow-up was only 4 (13%) compared with 12 (40%) of the placebo treated patients. At the half-year follow-up 5 of those who received GAGPS had experienced a recurrency. The recurrency rate is thus smaller than most of those reported in controlled studies with corticosteroids. In the GAGPS treated group 13 patients reported on local pain after some injections, 2 cases combined with local haematomas, compared with 5 cases of local pain in the placebo group. The results confirm previous good results of GAGPS injection therapy in subchronic and chronic peritendinitis.

Topical treatment of acute sprains.

In a randomised, placebo-controlled, double-blind study with parallel group comparison, the efficacy and tolerability of topical treatment with a mucopolysaccharide polysulphate/salicylic acid cream was investigated in 156 patients with acute sprains of the knee or ankle joint. There was a more rapid reduction in pain on movement (the main parameter) in the active drug group compared with the placebo group. On day 9 after randomisation the difference was highly significant. There were no adverse events in the active drug group.

Idiopathic osteoporosis in a three-year-old girl. Follow-up over a period of 6 years by computed tomography bone densitometry (CT).

In a girl suffering from idiopathic transient osteoporosis the development of vertebral deformation and recovery could be followed from the age of 3.4 to 9.3 years. Computed bone densitometry (CT) revealed values below normal for trabecular bone density (-2.6 SD at 4.3 years and -2.8 SD at 5.3 years) during the clinically symptomatic phase of the disease and normalization after the age of 6 years (-0.2 SD at 6.7 and 9.3 years). Cortical bone mineral parameters measured by CT and metacarpal bone measurements from conventional X-rays showed values at the lower range of normal and only a weak correlation with clinical symptoms, vertebral deformation and recovery, respectively. CT may probably allow to diagnose osteoporosis before the appearance of deformities or fractures; in milder forms of osteoporosis the diagnosis may be possible by CT only.

Peripheral and axial measurements of trabecular bone density in patients suspected of idiopathic vertebral osteoporosis.

In 18 patients with idiopathic crush fracture syndrome, iliac trabecular bone volume measured in 8 mm trephine biopsies correlated well with trabecular bone density as estimated in low thoracic or high lumbar vertebrae by computed tomography (CT). The CT of trabecular bone in the radius correlated poorly with the other two measurements, but it discriminated fairly well between patients and age-matched controls. These results suggest that abnormally low trabecular bone density values in the radius may be useful in predicting some patients at risk for crush fractures, but ranking patients in order of severity of axial bone loss after they have acquired a fracture requires measurements on the spine or iliac crest.

Long-term treatment of osteoporosis with 24,25 dihydroxycholecalciferol.

Five patients with involutional osteoporosis were treated with 24,25 dihydroxycholecalciferol (24,25-(OH)2D3) for 6 months, in doses sufficient to double plasma levels at that time. Dietary calcium absorption transiently improved by nearly 2 mmol Ca per day at 2 weeks, but this effect was lost by 6 months. The calcium and phosphate balances followed the trends in calcium absorption. Only twenty-five dihydroxyvitamin D levels changed little. Histomorphometric and kinetic indices of new bone formation and bone blood flow remained stable but there was an increase in urine hydroxyproline at 6 months, which was of borderline statistical significance. Treatment at this dosage of 24,25(OH)2D3, which increased plasma levels within the physiological range, conferred no measurable long-term benefit on our patients. Larger doses, or combination therapy, may warrant further clinical evaluation in osteoporosis.

Risk factors for fractured neck of femur in the elderly.

During a 15-month period, 47 elderly female patients admitted to hospital with a fractured neck of femur were studied immediately prior to discharge, in comparison with 34 elderly female control patients undergoing elective surgery who had been admitted over the same period to the same orthopaedic wards. The principal differences between the two populations were that the fracture patients had a lower forearm trabecular bone density, with lower bodyweight (both lower muscle mass and lower fat content), increased body sway, worse eyesight and reduced mental acuity. The serum biochemistry of the two groups was almost indistinguishable except that the fracture patients tended to have slightly lower concentrations of proteins. There was no evidence to implicate dietary vitamin D deficiency, osteomalacia, oestrogen deficiency or alcoholism in the aetiology of the fracture, nor was there evidence to suggest alterations in endocrine function with respect to cacitonin or parathyroid hormone.

Bone rarefaction and crush fractures in juvenile chronic arthritis.

Seventy children with juvenile chronic arthritis have had measurements of cortical and trabecular bone density in one or both radii. In 7 children with unilateral disease of one wrist, there was a substantial reduction in growth on the affected side. Trabecular bone density in the distal radius was reduced in the main group of 63 patients compared with controls, and this deficit was appreciably worse if the wrist was clinically affected by disease or if the child was being treated with steroids. Cortical bone density in the midshaft was less affected. Crush fractures of the spine were associated with more prolonged periods of bed rest, steroid therapy, radial trabecular bone density more than 2 standard deviations below normal, and subnormal 25-hydroxycholecalciferol concentrations in the serum. Since steroid therapy is often mandatory the main therapeutic implications are that the more severely affected child often needs vitamin D supplementation in "physiological" dosage, and that early mobilisation and reduction of steroid dosage should be constant aims.

Regional bone density measurements compared to total body calcium in osteoporosis.

In 21 women with crush fracture osteoporosis quantities related to trabecular bone density in lumbar vertebrae and in the distal radius were significantly correlated (r = 0.50, P less than 0.05). When the group was enlarged to include data from other patients without osteoporosis, a higher coefficient of correlation was obtained (r = 0.69, P less than 0.001). Total body calcium, measured by in vivo neutron activation analysis, was significantly correlated to quantities related to cortical bone mass in the radius and femur. Thus, these quantities could be used to make estimates of total body calcium in osteoporotic patients. There was no significant correlation between total body calcium and quantities related to trabecular bone density, measured by computed tomography, in vertebrae or in the distal radius.

Deficit of trabecular and cortical bone in elderly women with fracture of the femoral neck.

1. The mean attenuation coefficients of trabecular and cortical bone in the radius were measured in 32 female patients with fractured proximal femur, and in 28 age-matched female controls, with a special-purpose computed tomography-scanner. 2. The largest difference between the two groups was in the mean attenuation coefficients for trabecular bone in the distal radius. The mean value for fracture patients (0.53 cm-1) was significantly lower (P < 0.02) than the mean value for the controls (0.62 cm-1). These results are consistent with the view that a loss of trabecular bone predisposes to fractures of the proximal femur.

Effects of high dose oestrogen and testosterone treatment in adolescents upon trabecular and compact bone measured by 125I computed tomography. A preliminary study.

125I Computed Tomography (CT) allows for the selective determination of trabecular and compact bone mineral parameters in the radius. Using this technique the effects of high dose oestrogen treatment in 11 tall girls, and of high dose testosterone treatment in 5 tall boys were monitored. In both groups trabecular bone density (TBD) increased steadily during treatment at a rate of about 1% per month. Also in both groups the compact bone mineral increased steadily. These results are compared with those from a cross sectional study on 49 normal children and 36 normal adults, in whom TBD was found to be independent of age and sex, so that the increases in TBD in both treatment groups can be attributed directly to the influence of the sex hormones. Since the compact bone mineral is higher in adults than in children it cannot yet be decided whether the increases seen in the treated patients are related to the sex hormone treatment, or reflect only the normal development of the bone during adolescence.

Hypophosphatemic vitamin D resistant rickets (phosphate diabetes): bone mineral problems studied by 125I-computed tomography and microradiography.

125I-computed tomography (CT) for the bone mineral analysis of the radius was performed on 9 children with vitamin D resistant hypophosphatemic rickets (VDRR) treated with vitamin D in pharmacological doses. Trabecular bone density was increased in 1 patient and normal in all others. The cortical width of the diaphysis of the radius was decreased, and the cross sectional area of the bone increased, but the total amount of compat bone mineral in the cross section was normal. Measurements of the second metacarpal bone on X-rays of the hand revealed similar findings. Microradiographic and histological examinations of the fibula on 9 different patients also treated with vitamin D showed grossly abnormal mineralization of bone tissue with a perilacunar mineral deficit. It is concluded, that the amount of compact bone and trabecular bone is not decreased in children with VDRR. The normal mineral content determined by CT and the impaired mineralization of the bone material examined by microradiography indicate an over-abundance of incompletely mineralized bone.

Loss and recovery of trabecular bone in the distal radius following fracture--immobilization of the upper limb in children.

Computed tomography of the human radius is performed using a special purpose scanning device which incorporates a radionuclide (125I) as radiation source. Parameters decribing the trabecular bone and the compact bone are determined at a distal and a diaphyseal measuring site respectively. Using this measurement technique changes in bone mineralization in the radius were studied in a group of 23 children following immobilization of an upper limb for fracture healing. An immobilization period of between three to six weeks resulted in a reduction of the relevant parameter value of up to 44% (mean 16%) in the distal part of the radius, whereas no significant change could be seen in the diaphyseal part of the same bone. Rapid remineralization of trabecular bone is indicated by the increase of the corresponding parameter value at a rate of up to several percent per week. However, in some of the patients studied complete normalization was not attained during the first six months following cast removal.

Bone densitometry using computed tomography. Part I: selective determination of trabecular bone density and other bone mineral parameters. Normal values in children and adults.

Gamma-ray computed tomography (gamma-ray CT), using a special purpose scanner, enables in-vivo quantitative analysis of bone mineralization. Trabecular bone density (TBD), the relative amount of compact bone (bone density, BD) and the total absorption (TA) for a cross-section of the radius are determined from measurements of local linear absorption coefficients. A preliminary study of normal children (n = 49) and adults (n = 34) indicated that TBD is independent of age and sex in the age range 4 to 40 years. DB remains constant throughout childhood but increases after puberty in both women and men. TA is higher for adults than for children, and also higher for men than for women. A correlation between TA and parameters relating to body size indicates a relationship between body weight and bone mass.