Benign metastasizing chondroblastoma: a case report

Treatment of interdigital tinea pedis often involves long-term therapy with topically applied preparations. Effective oral preparations, such as the allylamine terbinafine (Lamisil), taken over a shorter period, could provide a useful therapeutic alternative. A total of 269 patients from five centres with clinically diagnosed interdigital tinea pedis were entered into this double-blind, randomized, double-dummy, parallel-group study comparing oral terbinafine 250 mg once daily for 1 week with 1% clotrimazole (Canesten) cream applied twice daily for 4 weeks. Of these, 137 patients were evaluable for efficacy (confirmed dermatophyte infection by microscopy and culture): 63 terbinafine and 74 clotrimazole. At week 4, the mycological cure rates (negative culture at week 1 and negative results on microscopy and culture at week 4 onwards) were very similar (71% for clotrimazole and 72% for terbinafine). There was a faster response rate in the terbinafine group with respect to signs and symptoms at week 1. Both treatments were equally well tolerated; adverse events occurred equally in the two groups. In conclusion, oral terbinafine in a single daily dose of 250 mg for 1 week is as effective and as well tolerated as 1% clotrimazole cream applied twice daily for 4 weeks in the treatment of interdigital tinea pedis.     

Variability of impedivity in normal and pathological breast tissue

Bite wounds have a special position in traumatology because of their high complication rate compared to similar soft tissue wounds caused by other reasons. The authors report in a retrospective study about the results of 525 patients with bite wounds. In 98 (18.7%) cases the wounds were sutured primarily after surgical revision when there was no sign of infection. Antibiotic therapy (a combination of amoxicillin and clavulan acid) was given to 109 patients (20.8%) who had infected wounds or who were at greater risk for infection (e.g., extremely large wounds, large hematoma). Antibiograms were only made when the wounds had already been infected. The total infection rate came to 11.8%, with 5.2% infected facial bites, 11.3% lower extremity, 18.6% upper extremity and 18.8% hand bite wounds. The infection rate after primary suture was 10.2% (3.2% at the face, 18.8% at the upper extremity and 25% each in the hand and the lower extremity). The average time period from the trauma to the first medical treatment amounted to 11 h in the infected wounds and 2 h in the non-infected ones. Cat bites became infected in 37.5%, dog bites in 14.9%.     

Comparison of ceftibuten once daily and amoxicillin-clavulanate three times daily in the treatment of acute exacerbations of chronic bronchitis

In medical practice, antibiotics are generally given empirically for the treatment of acute exacerbations of chronic bronchitis (AECB). To be effective, antibiotic therapy should be broad in spectrum, and it should also cover the common beta-lactamase-producing pathogens. In this multicenter, randomized, investigator-masked study, 469 patients with AECB were randomized (in a ratio of 2:1) to receive 400-mg oral ceftibuten capsules once daily or 500-mg amoxicillin-clavulanate tablets three times daily for 5 to 15 days. Patients receiving ceftibuten were further divided into those who took the capsule with a meal (fed) and those who took the capsule 1 hour before a meal (fasted). Clinical and microbiologic responses were evaluated after treatment at 0 to 6 days (end of treatment) and 7 to 21 days (follow-up). Overall clinical success was determined by cure/improvement of signs and symptoms of AECB at the end of treatment and at follow-up. Overall microbiologic assessment was graded as eradication, persistence, relapse, reinfection, colonization, superinfection, or unassessable. Tolerability was evaluated by grading observed adverse events. The mean duration of treatment was 10.4 days for patients who received ceftibuten and 10.1 days for patients who received amoxicillin-clavulanate. A total of 252 patients receiving ceftibuten and 117 patients receiving amoxicillin-clavulanate were evaluable for clinical efficacy, and 55 patients were evaluable for microbiologic response. Both treatments improved the signs and symptoms of bronchitis, and overall clinical success rates were equivalent for patients treated with ceftibuten (211 of 252 [84%]) and amoxicillin-clavulanate (93 of 117 [79%]) (95% confidence interval [CI], -4.5% to 13.6%). Overall microbiologic eradication rates were also similar for patients treated with ceftibuten (36 of 37 [97%]) and amoxicillin-clavulanate (12 of 14 [86%]) (95% CI, -5.2% to 21.2%). The most frequently reported treatment-related adverse events were gastrointestinal disturbances, which occurred in 15% (47 of 316) and 24% (36 of 152) of patients treated with ceftibuten and amoxicillin-clavulanate, respectively. No significant difference was observed in the ceftibutenfed and ceftibuten-fasted groups in overall clinical assessments of the clinical efficacy population and safety population. In conclusion, 400 mg oral ceftibuten once daily has a similar clinical success rate to 500 mg amoxicillin-clavulanate three times daily, with a trend toward fewer gastrointestinal side effects, in the treatment of patients with AECB.     

A randomized comparative study on the safety and efficacy of clarithromycin and erythromycin in treating community-acquired pneumonia

BACKGROUND: Clarithromycin, a new macrolide, has distinct microbiological and pharmacokinetic advantages compared with erythromycin. This study was designed to compare the safety and efficacy of clarithromycin and erythromycin in the treatment of community-acquired pneumonia. METHODS: Forty adult patients, diagnosed with community-acquired pneumonia, were randomly arranged to received either clarithromycin 250 mg twice daily (20 patients) or erythromycin 500 mg four times daily (20 patients), over a period of 14 days each. RESULTS: There were no statistically significant differences between the two groups in terms of clinical cure (65% for clarithromycin, 65% for erythromycin), clinical success (clinical cure and improvement: 95% for clarithromycin, 90% for erythromycin) and radiological response (95% for clarithromycin, 90% for erythromycin). However, adverse effects, mainly gastrointestinal, were significantly higher among patients treated with erythromycin than among patients treated with clarithromycion (p < 0.05). CONCLUSIONS: These results demonstrate that clarithromycin 250 mg twice daily is at least as effective as erythromycin 500 mg four times daily for the treatment of community-acquired pneumonia, and is much better tolerated.     

Labeling of penicillamine di sulfide with technetium-99m

OBJECTIVE: To compare the safety and efficacy of 1% SDZ ASM 981 cream and a matching placebo cream in the treatment of patients with moderate atopic dermatitis. DESIGN: A randomized, double-blind, placebo-controlled, right-and-left comparison study. SETTING: Academic referral center. PATIENTS: Thirty-four adult patients with moderate atopic dermatitis. INTERVENTION: Topical 1% SDZ ASM 981 cream was applied twice daily (n=16) or once daily (n=18) and compared with a corresponding placebo cream base. MAIN OUTCOME MEASURES: Efficacy was measured using a 4-point (0-3) scale for erythema, pruritus, exudation, excoriation, and lichenification (Atopic Dermatitis Severity Index [ADSI]). The ADSI score was defined as the sum of these 5 ratings (range, 0-15) and was determined on the pretreatment day (1 to 14 days before day 0) and on days 0, 2, 4, 7, 9, 11, 14, 16, 18, and 21. The percentage change from baseline (day 0) in the ADSI score was calculated on each of these days. Safety was evaluated by monitoring of adverse events, physical examination, hematologic examination, clinical chemistry studies, urinalysis, and measurement of blood levels of SDZ ASM 981. RESULTS: Of the 38 patients recruited, 34 started and 28 completed treatment according to the protocol. Sixteen patients used the cream twice daily, with significant improvement after 2 days of treatment. Within 3 weeks of topical therapy with 1% SDZ ASM 981 cream twice daily, a mean reduction of 71.9% in the ADSI score was observed at the actively treated test sites compared with a mean reduction of 10.3% at the placebo-treated test sites (P<.001). Efficacy was significantly less in the group treated once daily (n=18), with mean reductions of 37.7% and 6.2%, respectively. The efficacy was especially apparent for pruritus and excoriation. There were no clinically relevant drug-related adverse effects. CONCLUSIONS: Treatment with 1% SDZ ASM 981 cream was well tolerated. Twice-daily application of 1% SDZ ASM 981 cream was significantly more effective than use of the corresponding placebo and more effective than once-daily treatment. The new macrolactam ascomycin derivative SDZ ASM 981 is a promising agent for the treatment of patients with atopic dermatitis. More elaborate phase 2 and 3 trials are under way to fully investigate the potential of this medication.     

Bacterial prostatitis: treatment with carbenicillin indanyl sodium

The efficacy and safety of carbenicillin indanyl sodium were evaluated in 16 patients with acute or chronic bacterial prostatitis. Each patient received carbenicillin indanyl sodium (Geocillin) tablets, at a dosage of two 500 mg tablets (each tablet equivalent to 382 mg of carbenicillin) four times daily for either 14 days (acute patients) or 28 days (chronic patients). Clinical and bacteriologic success rates, based upon 4 week post therapy followup, were 93 per cent and 75 per cent respectively. There were no adverse reactions. Results with cephalexin in a concurrently treated alternative therapy group were generally unsatisfactory. Further evaluations of carbenicillin indanyl sodium in this treatment of resistant populations are clearly warranted.     

Late recurrence of a large post-infarction left ventricular pseudo-aneurysm. A case report

OBJECTIVE: To evaluate effects of treatment with a pulsed electromagnetic field (PEMF) on healing of open and sutured wounds, clinicopathologic variables, and CNS activity of dogs. ANIMALS: 12 adult female Beagles. PROCEDURE: Open and sutured wounds were created in the skin of the trunk of the dogs. Dogs were divided into 2 groups. One group received PEMF treatment and 1 group served as untreated (control) dogs. The PEMF-treated dogs received treatment twice a day starting the day before surgery and lasting through day 21 after surgery. Wounds were evaluated by use of tensiometry, planimetry, laser Doppler perfusion imaging, and histologic examination. Clinicopathologic variables and electroencephalographic tracings were also evaluated. RESULTS: Use of PEMF treatment resulted in significantly enhanced epithelialization of open wounds 10 and 15 days after surgery. Five days after surgery, wounds of control dogs had a negative value for wound contraction, whereas PEMF-treated wounds had a positive value. The PEMF treatment did not cause significant changes in short-term planimetric, perfusion, tensiometric, histologic, clinicopathologic, or electroencephalographic results. CONCLUSIONS: The PEMF treatment enhanced wound epithelialization in open cutaneous wounds and provided indications of early contraction without significant short-term changes in other variables.     

Dimensions of schizophrenia in the elderly. Correlations with cognitive and motor symptoms

Wound contraction is thought to be independent of site, and circular full-thickness skin wounds are though not to contract completely. To verify these statements four circular full-thickness skin wounds were created on each side of eight pigs and randomised to treatment with either split-thickness skin grafts, or healing by secondary intention under a hydrocolloid dressing. Time to healing, contraction, and final scar shape were evaluated. The median healing time was 12 days (range 6-18) in the grafted wounds and 30 days (range 15-45) in the secondarily healing wounds. There were significant differences in healing time between the different sites on the pigs. In the secondarily healing group, medial-caudal wounds healed in 21 (15-21) days compared with lateral wounds which healed in 36 (21-45) days (p < 0.005), while no differences were found in the grafted group. There was a clear relationship between site and contractility and shape of the scars in both treatment groups. Scars located on the lateral-caudal aspect of the pig were predominantly round and contracted only slightly. Scars located on the lateral aspect of the pig tended to be oval. Contraction was greatest in the medial scars and least in the lateral scars. Median contraction was 33% (range -2-63) in skin grafted wounds and 64% (range 42-82) in secondarily healed wounds. This randomised experiment showed that extent of wound contraction is dependent of site, and that circular wounds do heal with contraction.     

Traumatic duodenal haematoma in children

A clinical study of 96 patients compared a new hydrocolloid dressing (Granuflex Extra Thin) with a non-adherent dressing (perforated film absorbent dressing) in the management of lacerations, abrasions and minor operation incisions at the Accident and Emergency (A&E) Department of the University College Hospital, Galway. While time to heal was similar for both groups, the patients using Granuflex Extra Thin experienced less pain (P < 0.001), required less analgesia (P = 0.0154) and were able to carry out their normal daily activities including bathing or showering without affecting the dressing or the wound. Patient satisfaction with the new dressing appeared to be very high especially in those patients who pursued an active lifestyle.     

Ocular toxicity following topical application of anesthetic cream to the eyelid skin

BACKGROUND AND OBJECTIVE: The use of topical anesthetic cream in the periorbital region may be of clinical value. The potential for toxic effects from such use has not been studied in a controlled manner. This study was performed to evaluate the potential ocular toxicity of anesthetic cream topically applied to the eyelid in an animal model. MATERIALS AND METHODS: Ten rabbits underwent periorbital eutectic mixture of local anesthetics (EMLA) (2.5 percent lidocaine and 2.5 percent prilocaine) application and were observed for evidence of gross or microscopic ocular toxicity. Baseline external and anterior segment examinations were performed, including biomicroscopy and fluorescein staining, after which a standard quantity of EMLA cream (0.75 g) was applied along the upper eyelid and covered with an occlusive dressing. After 1 hour of treatment, the eyelid and anterior segment were examined for evidence of adverse reaction. The eyelids were excised and examined histopathologically. RESULTS: No significant adverse effects were noted on external lid and anterior segment examination. The histopathologic findings were within normal limits. CONCLUSIONS: This study suggests that external application of EMLA cream to the eyelid does not induce local toxicity in the rabbit model. The external application of EMLA cream may be safe in the periorbital region.     

A new silver sulfadiazine water soluble gel

Silver sulfadiazine is the most commonly used topical antibacterial agent for the treatment of burn wounds. It has many clinical advantages, including a broad spectrum of antimicrobial activity, low toxicity, and minimal pain on application. The current formulation of silver sulfadiazine contains a lipid soluble carrier, polypropylene glycol, that has certain disadvantages, including pseudo-eschar formation and the need for twice daily application. The purpose of this investigation was to describe a new formulation of silver sulfadiazine in a water soluble gel, poloxamer 188. The antibacterial activity of this new gel has been compared to that of the commercially available silver sulfadiazine cream by in vitro and in vivo testing. The results of the in vitro antibacterial testing of these two different agents demonstrated the superiority of the new gel formulation. In experimental wounds, the antibacterial activity of the gel and the commercially available silver sulfadiazine cream were not significantly different when applied once a day. The antibacterial activity of the gel when applied once a day was comparable to that encountered by twice daily applications of the silver sulfadiazine cream by experimental wounds. The major advantage of this gel was its ease of application and removal that is attributed to its water solubility.     

A comparison of pressure patching versus no patching for corneal abrasions due to trauma or foreign body removal. Corneal Abrasion Patching Study Group

PURPOSE: To evaluate the effectiveness of pressure patching in the treatment of noninfected, noncontact lens-related traumatic corneal abrasions and abrasions secondary to removal of corneal foreign bodies. METHODS: Two hundred twenty-three patients with noninfected, noncontact lens-related traumatic or foreign body removal-related corneal abrasions were followed daily after receiving topical antibiotics and mydriatics and after being randomized to receive either a pressure patch or no patch. RESULTS: Twenty-two patients were excluded from the study. For data analysis, the remaining patients were split into two sections: those with traumatic corneal abrasions (120 patients) and those with corneal abrasions secondary to removal of corneal foreign bodies (81 patients). Patients with traumatic corneal abrasions healed significantly faster, had less pain, and had fewer reports of blurred vision" when they were not wearing a patch. The amount of photophobia, tearing, and foreign body sensation were similar between the patch and no-patch groups. Similarly, for corneal abrasions due to removal of foreign bodies, patients healed significantly faster and had less pain when they were not wearing a patch. There was no difference in the amount of photophobia, tearing, foreign body sensation, or blurred vision. Finally, there was better compliance in the no-patch group. CONCLUSIONS: Noninfected, noncontact lens-related traumatic corneal abrasions as well as abrasions secondary to foreign body removal can be treated with antibiotic ointment and mydriatics alone without the need for a pressure patch.     

Corticosteroid-induced cutaneous atrophy and telangiectasia. Experimental production associated with weight loss in rats

A bioassay for the evaluation of certain adverse effects of various corticosteroids was performed. Twenty-eight daily topical applications of corticosteroids to young rats produced reduction in body-weight gain, atrophy of the skin as determined by double skin-fold thickness micrometer measurement, and mild to severe telangiectasia. This animal model demonstrates corticosteroid-induced skin atrophy and telangiectasia and the correlation of the degree of atrophy and telangiectasia to body-weight change. Nine corticosteroids were evaluated by this method and are listed in terms of increasing severity of side-effects as follows: 1.0% hydrocortisone cream, 0.1% betamethasone valerate cream, 0.025% betamethasone benzoate cream, 0.05% flurandrenolide cream, 0.05% fluocinonide cream, 0.1% dexamethasone cream, and 0.03% flumethasone pivalate cream. Triamcinolone acetonide cream, 0.5%, and 0.2% fluocinolone acetonide cream resulted in death of the animals prior to completion of 28 days of topical application.     

Chronic otitis media treated topically with ciprofloxacin or tobramycin

OBJECTIVE: To evaluate the efficacy of ciprofloxacin compared with tobramycin and placebo ear drops in the treatment of chronic suppurative otitis media without cholesteatoma. DESIGN: Sixty ears (in 51 patients) were randomly divided into 3 treatment groups: ciprofloxacin hydrochloride, tobramycin, and placebo interventions. SETTING: The otolaryngology department of a university teaching hospital. INTERVENTION: All ears were treated topically for 3 weeks. MAIN OUTCOME MEASURES: Each patient received a small, numbered bottle and was instructed to instill 5 drops 3 times daily for 3 weeks. The final clinical and bacteriologic assessment was made after 3 weeks. RESULTS: The organism most commonly isolated from the ear discharge was Pseudomonas aeruginosa. Its sensitivity to ciprofloxacin and tobramycin was 94.2% and 70.6%, respectively. The clinical response was 78.9%, 72.2%, and 41.2% in the ciprofloxacin, tobramycin, and placebo groups, respectively. The bacteriologic response rate was 66.7% for the ciprofloxacin and tobramycin groups and 20% for the placebo group. Treatment with ciprofloxacin ear drops seemed to be as effective as treatment with tobramycin. CONCLUSION: While the lack of ototoxicity of ciprofloxacin was not tested in our study, this treatment may be considered as a potential topical therapy for cases of chronic suppurative otitis media.     

Cloning, sequencing and functional analysis of a truncated cDNA encoding red deer prolactin receptor: an alternative tyrosine residue mediates beta-casein promoter activation

The purpose of these studies was to compare directly the percutaneous absorption,excretion and metabolism of all-trans-retinoyl beta-glucuronide (RAG), a nontoxic retinoid, with all-trans-retinoic acid (RA) in the rat. Previously, it was demonstrated that topical treatment of human acne with either RAG or RA in cream resulted in a significant reduction of lesions. Whereas 0.1% RA showed adverse effects, concentrations of RAG up to 2.4% did not cause any adverse reactions. In the present studies, radiolabeled RAG or RA, dispersed in a water-based cream, was applied to the shaved dorsal skin of vitamin A-sufficient rats. Both RAG and RA were absorbed from the skin in a similar way. In both cases, radioactivity peaked in the plasma within 2-4 h and within the liver at 4-12 h. During a 7-day period, the overall excretion of radioactivity derived from RA and RAG in the feces and urine were similar, e.g. 17 and 12%, respectively. it is concluded that: (1) the transport, metabolism and excretion of topically applied radioactive RA and RAG are similar, although not identical, in the rat and (2) the toxic skin manifestations induced by RA but not by RAG cannot be attributed to major differences in their overall absorption, metabolism and excretion.     

Wound irrigation with tap water

OBJECTIVE: The study hypothesis was that irrigation with tap water is as efficacious as irrigation with sterile saline in removing bacteria from simple lacerations in preparation for wound closure. METHODS: The study was conducted in a laboratory rat model previously described in the literature for evaluating wound irrigation techniques. The study used a randomized, blinded crossover design using 10 animals. Two full-thickness skin lacerations were made on each animal and each wound was inoculated with standardized concentrations of a Staphylococcus aureus broth. Wounds were irrigated for 4 minutes with normal saline from a syringe or 4 minutes with tap water from a faucet. Tissue specimens were sampled from each laceration prior to and following irrigation. Bacterial counts per gram of tissue were determined for each specimen and compared pre- and postirrigation. RESULTS: Preirrigation bacterial counts were not significantly different for saline vs tap water specimens. The wounds irrigated with saline had a mean reduction in bacterial count of 54.7% (SD=+/-28%), while the wounds irrigated with tap water had a mean reduction in bacterial count of 80.6% (SD=+/-20%) (p < 0.05, 2-tailed, paired t-test). CONCLUSIONS: In this animal model, bacterial decontamination of simple lacerations was not compromised, and was actually improved using tap water irrigation. This is most likely due to the mechanical differences in the types of irrigation. In certain instances, such as with upper-extremity lacerations, tap water irrigation would likely be cheaper and less labor-intensive than irrigation with normal saline from a syringe.     

Human leukocyte interferon-alpha in a hydrophilic cream versus in a gel for the treatment of genital herpes in males: a placebo-controlled, double-blind, comparative study

The aim of this double-blind, placebo-controlled, comparative study was to differentiate the clinical efficacy and tolerability of human leukocyte interferon-alpha incorporated (2 x 10(6) IU/g) in a hydrophilic cream and in a gel to heal males afflicted with first episodes of genital herpes. Patients (n = 60), aged 18-40 years (mean 23.2) with culture-confirmed diagnosis of herpes genitalis were randomized to three parallel groups. Each patient was allocated a precoded 40-g tube, containing either preparation or placebo. Cream or gel was applied three times daily for 5 consecutive days. The duration of the active treatment was two weeks. Patients were examined after 48 hours in initial treatment, and thereafter two times a week. A reepithelialized lesion with some residual erythema was recorded as healed. The study demonstrated that patients treated with leukocyte interferon-alpha cream had both significantly shorter mean duration of lesions than gel and placebo recipients (5.3 days vs. 8 days, 13 days respectively; p < 0.001) and a higher number of healed patients (80% vs. 55%, 20% respectively; p < 0.001). Of the 60 patients, 49 (82%) complained of no drug-related side effects. Eleven patients predominantly in the cream/gel groups reported non-objective transitory increase in their body temperature (> 38 degrees C) with moderate headache, malaise and myalgia. The study was followed-up for 24 months after the first day of the treatment, and out of 31/60 cured patients, 4 had a relapse after 18 months. In conclusion the study affirmed that human leukocyte interferon-alpha (2 x 10(6) IU/g) in a hydrophilic cream is more efficacious than its incorporation in gel or placebo, thus suggesting that leukocyte interferon-alpha in a hydrophilic cream, with a profile of non-objective mild to moderate drug-induced indications, may be considered an alternative and effective treatment modality to cure male patients afflicted with first episodes of genital herpes.     

Comparison of the efficacy, safety and tolerability of azithromycin and co-amoxiclav in the treatment of acute periapical abscesses

The activity, safety and tolerability of the azalide azithromycin were compared with those of co-amoxiclav in the treatment of acute periapical abscesses in adults in an open, randomized, multicentre comparative study. Patients of either sex, recruited from 106 dental practices in Belgium, were aged between 18 and 75 years and had acute periapical abscesses not requiring drainage, confirmed by radiology. Azithromycin was administered as a 500-mg tablet orally once daily for 3 days (n = 150) and co-amoxiclav as a 625-mg capsule three times daily, for 5-10 days (n = 153). Both before and after treatment, masticatory pain, percussion pain, headache, and oedema and redness of soft tissue were graded on a four-point scale. Overall clinical success (cure plus improvement) was seen in 131/144 (91%) evaluable patients receiving azithromycin and in 142/148 (96%) receiving co-amoxiclav (difference not significant). There was no significant difference between the two groups in the incidence or severity of adverse events or in the number of discontinuations because of adverse events.     

Controlled study of brodimoprim and cephalexin in the treatment of patients with acute sinusitis in general practice

Brodimoprim, a new dehydrofolate reductase inhibitor, was compared with cephalexin in the treatment of patients with acute sinusitis. A total of 49 patients were randomly assigned to receive either brodimoprim 200-mg tablets once a day (400 mg on the first day as a loading dose) or cephalexin 500-mg tablets three times a day for 8 to 12 days. Nearly all patients treated were judged clinically cured/improved; in fact, only one failure (in the cephalexin group) was noted. In the 45 assessable patients, the time until disappearance of the symptoms and the duration of treatment did not differ significantly between the two groups. A bacteriologic examination was performed in all patients at baseline as well as at the end of therapy. Bacteriologic eradication was obtained in 88% of the patients treated with brodimoprim and in 76% of those receiving cephalexin. Both compounds were generally well tolerated (one patient in the brodimoprim group complained of skin reactions). These results suggest that once-daily treatment with brodimoprim represents safe and effective therapy for adults with acute bacterial sinusitis.     

The efficacy and safety of the dorzolamide-timolol combination versus the concomitant administration of its components. Dorzolamide-Timolol Study Group

OBJECTIVE: To evaluate whether a fixed combination of 2% dorzolamide and 0.5% timolol given twice daily showed equivalent efficacy to the concomitant administration of 2% dorzolamide given three times daily and 0.5% timolol given twice daily in patients whose intraocular pressure (IOP) remained elevated during monotherapy with 0.5% timolol twice daily. DESIGN: Multicenter, parallel, randomized, double-masked clinical trial with an open-label extension. PARTICIPANTS AND INTERVENTION: In the masked phase, 242 patients received either the dorzolamide-timolol combination twice daily and placebo three times daily or dorzolamide three times daily and timolol twice daily for up to 3 months. In the open-label extension, 220 patients received the dorzolamide-timolol combination twice daily for up to 9 months. MAIN OUTCOME MEASURES: The criterion for establishing treatment equivalency was a 95% or greater confidence that the absolute difference in the mean change in IOP from baseline was less than 1.5 mmHg between treatments. RESULTS: During 3 months of treatment, the dorzolamide-timolol combination reduced IOP relative to the 0.5% timolol baseline by approximately 14% at hour 0 (just before the morning dose), 20% at hour 2, and 15% at hour 8. The IOP-lowering effect of concomitant therapy with dorzolamide and timolol was approximately 16% at hour 0.20% at hour 2, and 17% at hour 8. At hours 0, 2, and 8, there was greater than 97% confidence that the treatments were equivalent. During the open-label extension, the mean IOP reduction ranged from 14% to 15% at hour 0 and from 20% to 21% at hour 2. The treatment groups were generally comparable in terms of adverse events, symptoms, ocular signs, visual acuity, visual fields, physical examination, and laboratory measures. CONCLUSIONS: The IOP-lowering effect of the dorzolamide-timolol combination is comparable to that of dorzolamide three times daily plus timolol twice daily and is maintained for up to 1 year. The dorzolamide-timolol combination provides clinically important reduction in IOP relative to baseline treatment with timolol alone and is generally well-tolerated for up to 1 year.