Beta Decay of Molecular Tritium.

The beta decay of tritium in the form of molecular T_{2} is the basis of sensitive experiments to measure neutrino mass. The final-state electronic, vibrational, and rotational excitations modify the beta spectrum significantly and are obtained from theory. We report measurements of the branching ratios to specific ionization states for the isotopolog HT. Two earlier, concordant measurements gave branching ratios of HT to the bound HHe^{+} ion of 89.5% and 93.2%, in sharp disagreement with the theoretical prediction of 55%-57%, raising concerns about the theory's reliability in neutrino mass experiments. Our result, 56.5(6)%, is compatible with the theoretical expectation and disagrees strongly with the previous measurements.

Abdominal actinomycosis after laparoscopic cholecystectomy: a rare complication of bile spillage.

BACKGROUND: Abdominal actinomycosis has not been reported after elective cholecystectomy. METHODS: Case report and review of the pertinent English-language literature. CASE REPORT: A 69-year-old man with abdominal actinomycosis presented with an abdominal mass mimicking a malignant tumor two years after laparoscopic cholecystectomy. Investigation revealed the likely source of infection to be bile spillage during surgery. CONCLUSION: This is the first reported case of abdominal actinomycosis probably attributable to bile spillage during laparoscopic cholecystectomy.

Basal cell carcinoma does metastasize.

Basal cell carcinoma (BCC) rarely metastasizes. However, this unfortunate outcome can occur, usually in neglected tumors. We report a 52-year-old man with a BCC on the left chest that enlarged and then ulcerated over a 6-year period. Metastasis of the tumor to lymph nodes in the left axilla resulted, but the patient remains free of disease 24 months after wide excision, lymph node dissection, and local radiation therapy to the axilla.

Comparative evaluation of the efficacy and safety of two doses of terbinafine (500 and 1000 mg day(-1)) in the treatment of cutaneous or lymphocutaneous sporotrichosis.

The aim of this study was to evaluate the safety and efficacy of oral terbinafine (500 and 1000 mg day(-1)) in the treatment of cutaneous or lymphocutaneous sporotrichosis. A culture for Sporothrix schenckii was required for inclusion into this multicentre, randomized, double-blind, parallel-group study. Patients received either 250 mg b.i.d. or 500 mg b.i.d. oral terbinafine for up to a maximum of 24 weeks and were assessed up to 24 weeks post-treatment. The main efficacy outcome measure was cure, defined as no lesion and absence of adenopathy at the end of follow-up. Adverse events (AEs), laboratory tests, vital signs and ophthalmological examinations were also assessed. Sixty-three patients (14-85 years of age) were treated with 500 mg day(-1) (n = 28) or 1000 mg day(-1) terbinafine (n = 35). The majority of patients were cured after 12-24 weeks of treatment, and the response was dose-dependent throughout the study and at the end of follow-up. The cure rate was significantly higher in patients treated with 1000 mg day(-1) terbinafine compared with those treated with 500 mg day(-1) terbinafine (87% vs. 52%, respectively; P = 0.004). There were no cases of relapse after 24 weeks of follow-up in the 1000 mg day(-1) terbinafine group, compared with six relapses in the terbinafine 500 mg day(-1) group. Terbinafine was well tolerated and the frequency of drug-related AEs was slightly higher in the 1000 mg treatment group. Both doses of terbinafine were well-tolerated and effective for the treatment of sporotrichosis. The 1000 mg day(-1) terbinafine dose was more efficacious than 500 mg day(-1) in the treatment of cutaneous or lymphocutaneous sporotrichosis.

Clinical trial: the safety of terbinafine in patients over the age of 60 years: a multicenter trial in onychomycosis of the feet.

Thirty patients completed this open-label, multicenter prospective study performed to evaluate the efficacy and safety of terbinafine treatment of onychomycosis of the feet in elderly patients. Inclusion criteria included an age of 60 years or older, a diagnosis of onychomycosis confirmed by positive potassium hydroxide (KOH) preparation at baseline, and toenails capable of regrowth. Patients were excluded from the study if they had received any systemic antifungal therapy within the previous 3 months or topical antifungal therapy within 1 week prior to the start of the study; had psoriasis; had toenail abnormalities interfering with normal toenail appearance; were immunosuppressed or immunodeficient; or had serum hepatic enzyme (serum glutamic-oxaloacetic transaminase, SGOT; serum glutamic-pyruvic transaminase, SGPT) values greater than 1.5 times the upper limit of normal at baseline. Following baseline evaluations, eligible patients received a 12-week supply of oral terbinafine (250 mg/day) for self-administration. Compliance was assessed by tablet counts at each visit and defined as the use of at least 80% of the medication prescribed at the first two visits. Follow-up evaluations were conducted for the next 60 weeks, for a total study period of 72 weeks. These visits occurred at weeks 6, 12, 24, 36, 48, and 72. All follow-up visits included: (i) the reporting of adverse effects; (ii) assessment of efficacy by KOH preparation, mycologic culture, and investigator evaluation; and (iii) physician and patient global assessments of various quality of life parameters (except for the visit at week 36). Safety and tolerance were assessed by physical examination at baseline and week 12, by laboratory evaluations (hematology, blood chemistry, and urinalysis) at baseline, week 6 and week 12, and by reporting and evaluation of adverse events throughout the entire study. Investigators assessed the extent of involvement of the target toenail and recorded global assessments of therapeutic efficacy at all visits. Mycologic evaluation was conducted by KOH preparation and a mycologic culture of the target toenail. Because of discrepancies in KOH results between the investigator sites and the central laboratory in early analyses, we chose to use the mycologic culture results to evaluate efficacy. Because all 30 subjects were treated with terbinafine, the entire group was considered for safety evaluation.

Smooth muscle cell outgrowth stimulated by fibrin degradation products. The potential role of fibrin fragment E in restenosis and atherogenesis.

This study is based on the observation that deposition of thrombus within the arterial wall and on its surface is a consistent response to the vascular injury of angioplasty and of angioplasty lesions at risk of rapid restenosis. Mitogenic activity is stimulated by fibrin degradation products in extracts of human atherosclerotic plaques and plasmin digests of fibrin, and this has been attributed to products that include fibrin fragment E. The effect of human fibrin degradation products on smooth muscle outgrowth from rabbit aortic medial explants now has been explored in culture. Every batch of fibrin degradation products was first tested on the in vivo chick chorioallantoic membrane model for the ability to stimulate cell proliferation, including angiogenesis as shown previously. Increasing concentrations of fibrin degradation products were stimulated significantly earlier and with greater outgrowth of smooth muscle cells than controls, up to an optimum at 92 microg/mL fibrin degradation products. The effect of fibrin degradation products was blocked by the prior admixture of a specific antifragment E antiserum, but not by an antifragment D antiserum. Purified commercial fibrinogen E is inactive, but when treated with thrombin to resemble fibrin E it stimulated smooth muscle cell outgrowth, and this was not seen with comparable dosages of fragment D. We propose that fibrin degradation products, in particular fibrin fragment E, provide an abundant in situ early initiator of smooth muscle cell migration and proliferation in restenosis and atherogenesis.

Fibrin gel induces the migration of smooth muscle cells from rabbit aortic explants.

A major step in the pathogenesis of atherosclerosis is the vectorial migration of smooth muscle cells (SMCs) from the arterial media into the intima. Although subcultured SMCs usually show synthetic phenotype, the behaviour of contractile SMCs may be crucial for the subsequent migration of the cells. In the present study, we utilized an in vitro assay system to evaluate the effects of fibrin gels on the migration of SMCs from explants taken from rabbit aorta. After cultured for 5-7 days in a serum-free condition, SMCs appeared from explants covered with fibrin gel. The cells were positive on immunostaining for SMC specific alpha-actin. No migration of SMCs from the control explants without fibrin gel was observed. Then the percentage of explants showing cell migration and the number of migrating cells increased with time. The migration of SMCs into fibrin gels was not dependent on the concentration of fibrinogen used for the preparation of fibrin gel in the range of 1.5-3 mg/ml. Variations of thrombin concentration in the range of 0.25-1.25 U/ml had no significant effect. However, there was less migration of SMCs with higher concentrations of thrombin. Thrombin inhibitors, hirudin and PPACK had no significant effect on the migration of SMCs. An RGD-containing peptide, GRGDS inhibited the migration of SMCs although a control peptide GRGES at the same concentration had no significant effect. A monoclonal antibody to alphavbeta3, LM609, completely inhibited the migration of SMCs from the explants, suggesting that alphavbeta3 integrin is involved in the migration of SMCs into fibrin gels. SMCs which migrated from the explants showed the positive staining with the monoclonal antibodies against SMC myosin heavy chain isoforms, SMemb, SM1 and SM2, suggesting that they are in an intermediate state changing from contractile to synthetic state. In conclusion, the present study showed that fibrin gel induces the migration of SMCs from explants into itself and the process may not need other growth factors or cytokines.

Pattern of breast cancer among white-American, African-American, and nonimmigrant west-African women.

This study reviews the current understanding of the pattern of breast cancer among whites, African Americans, and West Africans who have never immigrated to the US to find better ways of improving the prevention, early detection, and care of breast cancer world-wide. In the United States, the behavior pattern of breast cancer in African-American women differs from that of white women. Among the three populations, breast cancer appears to be least common in nonimmigrant West-African women. The peak incidence in African Americans and West Africans occurs around the premenopausal period while it occurs postmenopausal period in whites. Also, unlike white women, West-African and African-American women present late for treatment with a greater cancer burden and consequently lower survival rates. The predominant histological type is infiltrating ductal carcinoma in the three groups but the highest percentage (33%) of infiltrating poorly differentiated anaplastic carcinoma occurs in West Africans. Menstrual and obstetric history, obesity, and high body mass index status appear to be greater specific risk factors among African Americans than among West Africans. African Americans and West Africans have three "Ls" in common: late stage in seeking treatment, lower age at peak incidence with severe tumor burden, and consequently lower survival rates. There is a need for more detailed population-based research at molecular levels to elucidate the basis for some of these features.

Effect of crosslinking by factor XIIIa on the migration of vascular smooth muscle cells into fibrin gels.

We evaluated the migration of vascular smooth muscle cells into crosslinked fibrin gels, using an in vitro assay system. Vascular smooth muscle cells from bovine fetal aorta migrated into non-crosslinked and crosslinked fibrin gels and showed a characteristic elongated spindle-shaped appearance with long cytoplasmic processes. The cells displayed two-fold increase in migration into crosslinked fibrin gels compared to non-crosslinked gels, suggesting the importance of fibrin crosslinking by factor XIIIa on its three-dimensional structure for the migration of smooth muscle cells.

Once-weekly fluconazole (150, 300, or 450 mg) in the treatment of distal subungual onychomycosis of the toenail.

BACKGROUND: Onychomycosis is a prevalent infection of the nail caused primarily by dermatophytes. Fluconazole is active in vitro against the most common pathogens of onychomycosis, penetrates into the nail bed, and is clinically effective in the treatment of a wide variety of superficial fungal infections. OBJECTIVE: The purpose of this study was to compare the efficacy and safety of three different doses of fluconazole (150, 300, and 450 mg) given orally once weekly to that of placebo in the treatment of distal subungual onychomycosis of the toenail caused by dermatophytes. METHODS: In this multicenter, double-blind study, 362 patients with mycologically confirmed onychomycosis were randomized to treatment with fluconazole, 150, 300, or 450 mg once weekly, or placebo once weekly for a maximum of 12 months. To enter the study, patients were required to have at least 25% involvement of the target nail with at least 2 mm of healthy nail from the nail fold to the proximal onychomycotic border. Patients who were clinically cured or improved at the end of treatment were further evaluated over a 6 month follow-up period. At both the end of therapy and the end of follow-up, clinical success of the target nail was defined as reduction of the affected area to less than 25% or cure. RESULTS: At the end of therapy, 86% to 89% of patients in the fluconazole treatment groups were judged clinical successes as defined above compared with 8% of placebo-treated patients. Clinical cure (completely healthy nail) was achieved in 28% to 36% of fluconazole-treated patients compared with 3% of placebo-treated patients. Fluconazole demonstrated mycologic eradication rates of 47% to 62% at the end of therapy compared with 14% for placebo. The rates at the end of follow-up were very similar, indicating that eradication of the dermatophyte was maintained over the 6-month period. All efficacy measures for the fluconazole groups were significantly superior to placebo (p=0.0001); there were no significant differences between the fluconazole groups on these efficacy measures. The clinical relapse rate among cured patients over 6 months of follow-up was low at 4%. Fluconazole was well tolerated at all doses over the 12-month treatment period, with the incidence and severity of adverse events being similar between the fluconazole and placebo treatment groups. Mean time to clinical success in the fluconazole treatment groups was 6 to 7 months. This time frame may be used as a guideline for fluconazole treatment duration. CONCLUSION: The results of this study support the use of fluconazole in the treatment of distal subungual onychomycosis of the toenail caused by dermatophytes. Doses between 150 to 450 mg weekly for 6 months were clinically and mycologically effective as well as safe and well tolerated.

Pharmacokinetics of three doses of once-weekly fluconazole (150, 300, and 450 mg) in distal subungual onychomycosis of the toenail.

BACKGROUND: Preliminary clinical data suggest that fluconazole is effective in the treatment of patients with onychomycosis. To design optimum dosage regimens, a better understanding of fluconazole's distribution into and elimination from nails is needed. OBJECTIVE: The purpose of this study was to determine plasma and toenail concentrations of fluconazole. METHODS: In this multicenter, randomized, double-blind investigation, fluconazole (150 mg, 300 mg, or 450 mg) or matching placebo was administered once a week for a maximum of 12 months to patients with onychomycosis of the toenail. A total of 151 subjects participated in the pharmacokinetic assessment. Blood samples and distal toenail clippings from both affected and healthy nails were obtained for fluconazole concentration determinations at baseline, at the 2-week visit, at each monthly visit until the end of treatment, and then at 2, 4, and 6 months (nail samples only at the latter two) after fluconazole was discontinued. RESULTS: Fluconazole was detected in healthy and affected nails at the 2-week assessment in nearly all subjects. The median time to reach steady-state fluconazole concentrations in healthy nails was 4 to 5 months in the three fluconazole dose groups. In affected nails, steady-state fluconazole concentrations were achieved more slowly, with a median time of 6 to 7 months. At the 8-month assessment, affected toenail fluconazole concentrations were higher than corresponding plasma fluconazole concentrations, with ratios of 1.31 to 1.50 in the three active treatment groups. Toenail concentrations of fluconazole declined slowly after treatment was discontinued, with elimination half-lives of 2.5, 2.4, and 3.7 months for the 150, 300, and 450 mg doses, respectively. Measurable fluconazole concentrations were still present in toenails at 6 months after treatment in most subjects. CONCLUSION: Fluconazole penetrates healthy and diseased nails rapidly, yielding detectable concentrations after two weekly doses. Once it penetrates nail, fluconazole persists for up to 6 months or longer after therapy is stopped. These favorable pharmacokinetic characteristics support a once-weekly fluconazole dosage regimen for the treatment of patients with onychomycosis.

Patient consultation in a managed care setting: guiding pharmacy into the future.

Managed care organizations are excellent environments for pharmaceutical care programs to demonstrate their impact on patient care outcomes and to decrease costs. Patient consultation is the cornerstone in implementing pharmaceutical care because it increases patient contact with the pharmacists while improving patient compliance with drug therapy (adherence). Implementation of a patient consultation program that verifies patients' understanding of their disease and therapy gives the pharmacist information necessary to monitor drug therapy. Use of strategic planning to overcome barriers, followed by the development of local standards of practice, will refocus the practice philosophy to one of improving patient outcomes. Pharmacy managers must demonstrate and document the value that patient consultation brings to the patient and the healthcare system. Then, they must integrate their counseling effort with other health education efforts of the managed care system. Pharmacists will gain the support of other disciplines by reinforcing their efforts. Together they can work to decrease the problems that are inherent with drug therapy. These goals can be accomplished with minimal expense and have the potential to produce significant savings in healthcare costs.

Effect of onychomycosis on quality of life.

BACKGROUND: Onychomycosis impairs normal nail functions, causes considerable pain, interferes with daily activities, and has negative psychosocial effects. OBJECTIVE: Our purpose was to determine patients' perception of onychomycosis on the quality of life. METHODS: A total of 258 patients with confirmed onychomycosis were surveyed by telephone at three centers. Responses to a standardized quality-of-life questionnaire were analyzed for patient demographics, physical and functional impact, psychosocial impact, and economic impact. RESULTS: Highest positive responses were nail-trimming problems (76%), embarrassment (74%), pain (48%), nail pressure (40%), and discomfort wearing shoes (38%). Ability to pick up small objects was impaired in 41% of subjects with fingernail involvement. More than 58 onychomycosis-related sick days and 468 medical visits (1.8 per subject) were reported during a 6-month period. CONCLUSION: Onychomycosis has significant social, psychologic, health, and occupational effects. Relevance of quality-of-life issues to overall health, earning potential, and social functioning should prompt reconsideration of the value of aggressive treatment of and financial coverage for onychomycosis.

In vitro metabolism of ceftiofur in bovine tissues.

The metabolism of ceftiofur in bovine kidney, liver, muscle and lung, and the effects of the presence of cystine and glutathione in the media were evaluated using S-9 and microsomal tissue fractions. Conversion of ceftiofur to desfuroylceftiofur (DFC) was catalyzed by an esterase which was most active in kidney, followed by liver. It was not very active in muscle and lung. After DFC was liberated, it rapidly bound primarily to tissue proteins (> 56%), and was also conjugated to cysteine and glutathione. Production of DFC-cysteine by disulfide exchange of DFC with cystine and production of DFC-glutathione by conjugation of DFC to glutathione occurred in buffer if glutathione and cystine were present in the medium. These conjugations were also observed in incubations with tissue fractions, indicating that they were not inhibited by the tissues endogenous molecules. In addition, the metabolism of DFC-glutathione to DFC-cysteine was observed when tissue proteins were present. The metabolism of DFC-glutathione to DFC-cysteine was faster in kidney than in liver. Metabolites devoid of an intact beta-lactam ring were not observed in these in vitro studies.

Bacteriology of inflamed and uninflamed epidermal inclusion cysts.

OBJECTIVE: To determine whether inflamed and uninflamed epidermoid cysts differ in the number and/or type of bacteria inhabiting them. DESIGN: A controlled study. We obtained aerobic and anaerobic bacterial culture specimens from 25 inflamed and 25 uninflamed epidermoid cysts. SETTING: A university medical center. PATIENTS: Nonimmunocompromised adults without recent systemic use of antibiotics. RESULTS: The 2 groups did not differ significantly with respect to number of bacterial isolates, "no growth" cultures, and aerobic, anaerobic, or potential pathogens cultured. CONCLUSIONS: The microbiological milieu of inflamed epidermoid cysts is similar to that of uninflamed cysts. Possible mechanisms for inflammation are discussed.

Comparison of adapalene 0.1% solution and tretinoin 0.025% gel in the topical treatment of acne vulgaris.

A multicentre study was conducted to compare clinical safety and efficacy of adapalene 0.1% solution and tretinoin 0.025% gel, both topical treatments for acne, in a once-daily dosage regimen for 12 weeks. A total of 297 patients were enrolled by eight investigators in this randomized, investigator-masked study in a parallel group design. An open label period using adapalene followed this study to assess the long-term safety of adapalene solution. Adapalene and tretinoin proved to be clinically and statistically effective in treating acne by reducing inflammatory (47% and 50%, respectively) and non-inflammatory lesions (57% and 54%) as compared to baseline. When comparing patients who had 75% or greater improvement in open comedones, adapalene was shown to be significantly more effective than tretinoin. No serious adverse event was reported during this study, including during the long-term period. The reactions that occurred were similar between treatments, i.e. burning, pruritus, scaling, dryness and erythema.