Biting deterrent activity of a deet analog, two DEPA analogs, and SS220 applied topically to human volunteers compared with deet against three species of blood-feeding flies

An earlier in vitro screening of N,N-diethyl-3-methylbenzamide (Deet) and N,N-diethylphenylacetamide (DEPA) analogs showed that two DEPA analogs, N,N-diethyl(3-bromophenyl) acetamide and N,N-diethyl[(alpha,alpha,alpha-trifluoro-m-tolyl)]acetamide, and one Deet analog, N,N,diethyl[3-(trifluoromethyl)]benzamide, had biting-deterrent activities that were superior to Deet against Aedes aegypti (L.) and Anopheles stephensi Liston. In the current study, the three analogs and (1S,2'S)-methylpiperidinyl-3-cyclohexene-1-carboxamide (SS220) were applied topically to the skin of human volunteers at 24 nmol compound/cm2 skin and compared with the activity of Deet at the same dose against biting by Ae. aegypti, An. stephensi, and Phlebotomus papatasi Scopoli females. SS220 proved to be as effective as Deet against Ae. aegypti and P. papatasi but more effective than Deet against An. stephensi. Contrary to the earlier in vitro tests, results with humans (in vivo testing) showed that neither of the DEPA analogs nor the Deet analog performed more effectively than Deet against the insects. The in vivo results showed that the analogs were not sufficiently effective to warrant further development. Notably, in vivo and in vitro methods used in discovery of personal protection chemicals for human use against blood-feeding flies can both be effective discriminating tools, but results obtained with the respective methods may not always agree. Ultimately, we surmise that in vivo testing methods with humans must be used to discriminate among compounds that superficially seem effective when screened using an in vitro method.     

Survivors of childhood cancer lost to follow-up can be re-engaged into active long-term follow-up by a postal health questionnaire intervention

Lifelong long-term follow-up (LTFU) is recommended for all survivors of childhood cancer. National guidelines recommend risk-stratified levels of follow-up by a multidisciplinary team, in an age-appropriate environment. Many survivors do not participate in long-term follow-up.ObjectiveTo re-engage childhood cancer survivors lost to follow-up in late effects programmes by means of postal questionnaire.Population and methodsRetrospective cohort study of all children (<19 years) diagnosed with cancer in a single institution in the UK between 1971 and 2003. All lost to follow-up survivors (not seen in clinic >2 years) were sent a postal health and well-being questionnaire.Results831 patients were diagnosed with childhood cancer between 1971 and 2003, with 575 long-term survivors (overall survival rate 69%). Information was available on 550 survivors (males 290 (53%), median age (range) at review 18.8 (5.4–44.2) years and at diagnosis 5.0 (0.0–18.8) years, and disease free survival (range) was 10.8 (1.0–37.4) years. Of the 550 survivors, 256 (46%) were lost to follow-up. 99 (39%) of lost to follow-up survivors returned completed postal questionnaires (58% female). 45% of responders reported at least one late effect, 36% mild-moderate, and 8% severe-life threatening. 19% reported two or more late effects. 74% of all childhood cancer survivors are now in active follow-up.ConclusionsAlmost half (46%) of all long-term survivors of childhood cancer are lost to follow-up, Postal follow-up is an effective means of re-engaging more than one third of survivors of childhood cancer in active long-term follow-up, half of whom had at least one late effect.     

Bisphosphonate-associated osteonecrosis. A clinician's reference to patient management

Bisphosphonates, as inhibitors of osteoclasts, are widely used in the management of metastatic bone disease and in the prevention of osteomalacia and osteoporosis. Recent cases of bone necrosis of the jaws have been associated with the use of bisphosphonate therapy. A case is presented of a patient with osteonecrosis of the maxilla with a history of long-term bisphosphonate therapy for metastatic breast cancer. The authors treated the patient and suggest appropriate patient management guidelines with reference to current knowledge. Although a definitive treatment for bisphosphonate-associated osteonecrosis has not yet been established, clinicians must be aware of the pharmacologic properties of several bisphosphonates currently available and their indications, susceptible risk factors in the development of osteonecrosis of the jaws, the clinical signs and symptoms, and recommendations for patient management, including prevention and early recognition.     

Assistance for customers with sexually transmitted diseases at pharmacies in the Federal District, Brazil: an intervention study

A quantitative survey was conducted to analyze the type of assistance provided by pharmacy employees for cases of STDs. Simulated customer visits and interviews were conducted in 70 pharmacies in Brasilia and Taguatinga, Brazil, randomly assigned to two groups, one of which participated in educational activities on STDs. There were 411 simulated client visits to the pharmacies, with the following results: recommendation to seek medical care in 30% of cases, while in 70% of cases the pharmacy employees themselves recommended some drug treatment (although only 16.4% admitted to such practice). None of these suggested treatments was appropriate, based on the syndromic approach. Recommendations for prevention and treatment of partners were rare. Pharmacists recommended consulting a physician more frequently than attendants, and the latter recommended medicines more frequently than the former. Pharmacy workers had only superficial knowledge of STDs. After an educational intervention, none of the indicators showed a significant improvement in either group. The observations point to the need for regulation and intervention to publicize educational practices for the control of diseases like STDs and for the rational use of medicines in pharmacies.     

Fulminant puerperal sepsis due to anaplastic large-cell lymphoma (ALCL) with therapy-refractory cerebral edema

Introduction

Lymphoma is among the five most frequent malignancies during pregnancy while anaplastic large-cell lymphoma (ALCL) is rare, accounting only for 2–3 % of all adult-onset non-Hodgkin lymphomas.

Case report

A 23-year-old gravida 1, para 1 presented with puerperal mastitis and septicemia following secondary cesarean section. Mastitis had been present for a week prior to delivery. A CT scan for further diagnostics revealed numerous prominent lymph nodes. Cerebrospinal fluid testing, bone marrow and lymph node biopsy confirmed diagnosis of ALCL. Systemic and intrathecal chemotherapy was initiated, stabilizing the patient’s clinical situation. 30 days postpartum (pp.), a cerebral edema was diagnosed responsible for cerebro-venous hypoperfusion. Immediate ventricle drainage and further therapeutic measures revealed no improvement. The patient died 33 days pp.

Conclusion

Puerperal septicemia seemingly caused by mastitis still needs rapid further evaluation if the patient’s clinical presentation quickly declines despite antibiotic therapy. Immediate initiation of chemotherapy after confirmation of ALCL is required to increase the therapeutic benefit due to the poor prognosis of ALCL.     

Platinum-resistant ovarian cancer: Prematurely stopped phase II Austrian AGO chemotherapy studies

AIM: To report the results of two phase II studies of chemotherapy in patients with platinum-resistant and platinum-refractory ovarian cancer and discuss the current status of systemic therapy in this disease. METHODS: Two subsequent Austrian Arbeitsgemeinschaft für Gynäkologische Onkologie (AGO) phase II studies have been carried out. Patients either had platinum-refractory or platinum-resistant disease, i.e., disease progression during first line platinum-based therapy or recurrence within 6 mo following the last platinum-containing chemotherapy, respectively. In the first study, 6 cycles of irinotecan at 55 mg/m² and docetaxel 25 mg/m² were both administered on days 1, 8 and 15 of a 4 wk cycle. In the second phase II study, either non-pegylated (PEG) liposomal doxorubicin (L-DXR) 60 mg/m² monotherapy on day 1 and PEG filgrastim on day 2 (arm A) or L-DXR at 50 mg/m² and gemcitabine (GEM) at 650 mg/m² on day 1 and GEM on day 8 (arm B) were administered every 4 wk. Patients in arm B received prophylactic filgrastim 5 μg/kg per day from days 3 to 6 and from days 9 to 12, respectively. RESULTS: Response rates in studies were 14% and 17%, respectively. The progression-free survival was less than 3 mo. Diarrhea was most prevalent in patients treated with irinotecan + docetaxel, while stomatitis/mucositis occurred in a quarter of patients treated with L-DXR +/- GEM + granulocyte colony stimulating factor, respectively. Following treatment with the latter regimen, a total of 11 serious adverse events were recorded among the 12 patients included. The rate of remissions of the regimens used in these two Austrian AGO studies was low and their toxicity significant. Due to their low therapeutic index, neither of these regimens can be recommended in this heavily pretreated patient population with platinum-resistant ovarian cancer exhibiting a high tumor-associated symptom burden. CONCLUSION: The two reported phase II studies of the Austrian AGO in platinum-resistant disease had to be terminated prematurely due to a low therapeutic index. Treatment of this disease remains a clinical dilemma. Bevacizumab seems to be active at this late-stage disease but may be associated with significant bowel toxicity.     

Effect of the vehicle on the topical itraconazole efficacy for treating corneal ulcers caused by Aspergillus fumigatus

Background:  The clinical behaviour of mycotic keratitis is aggressive, and the options for treating it are limited. This poses a need to explore new options for efficacious, low-cost treatment. Recent evidence suggests that topical itraconazole may be useful for treating this entity and that it may be possible to improve its efficacy using a suitable vehicle.
Methods:  We included 12 New Zealand white (NZW) rabbits (24 eyes). The rabbits were infected with pathogenic strains of Aspergillus fumigatus and subsequently randomized to receive every 2 h for 5 weeks two different preparations of topical itraconazole 1%. In group 1 (12 eyes), ricinus oil and in group 2 (12 eyes), Systane were used as vehicle. Rabbits were evaluated every week by a masked ophthalmologist to determine the treatment response.
Results:  The size of the ulcers was similar in the two groups at the baseline: group 1: 12.7 ± 2.7 mm (median 12.8, range 9.8–15.5 mm); and group 2: 12.3 ± 3.1 mm (median 12.1, range 9.8–20.8; P  = 0.67). Although both groups responded well to the treatment, the response was better in the group 2, especially in weeks 2 and 3: week 1: 12.7 ± 2.7 vs. 9.3 ± 4.61 mm ( P  = 0.1); week 2: 9.4 ± 3.4 vs. 4.1 ± 2.9 mm ( P  = 0.004); week 3: 5.0 ± 3.4 vs. 1.7 ± 1.0 mm ( P  = 0.004); week 4: 1.9 ± 1.9 vs. 1.0 ± 1.2 mm ( P  = 0.1); and week 5: 0.68 ± 1.2 vs. 0.0 ± 0.0 mm ( P  = 0.3).
Conclusion:  Topical itraconazole may be useful for treating corneal ulcers caused by Aspergillus fumigatus , and its efficacy seems to be related with the vehicle solubility.