Pitfalls in clinical genetics

With the increasing availability of genetic tests, more doctors are offering and ordering such tests for their patients. Ordering a genetic test appears to be a simple process of filling in paperwork, drawing 3 mL of blood in an ethylenediaminetetraacetic acid tube and receiving a test report. This is identical to sending off a full blood count. However, it is far more complex than that. There are many potential pitfalls, as shown by the increasing number of complaints and lawsuits filed against doctors and allied health staff. Furthermore, clinical genetics involves more than just ordering tests; in fact, focusing on genetic tests alone is a potential pitfall. In this review, we discuss the common pitfalls in clinical genetics and how doctors can avoid these pitfalls to ensure patient safety and to safeguard their practice.

Inclusion complexes and self-assembled cyclodextrin aggregates for increasing the solubility of benzimidazoles

Albendazole and fenbendazole are imidazole derivatives that exhibit broad spectrum activity against parasites, but the low solubility of these drugs considerably reduces their effectiveness. Complexation of albendazole and fenbendazole with cyclodextrins (ß-cyclodextrin and hydroxypropyl-ß-cyclodextrin) in both water and an aqueous solution of polyvinylpyrrolidone (PVP-k30) was studied to determine if it could increase the solubility and dissolution rate of the drugs. In an aqueous solution, ß-cyclodextrin increased the solubility of albendazole from 0.4188 to ~93.47 µg mL-1 (223×), and of fenbendazole from 0.1054 to 45.56 µg mL-1 (432×); hydroxypropyl-ß-cyclodextrin, on the other hand, increased solubility to ~443.06 µg mL-1 (1058×) for albendazole and ~159.36 µg mL-1 (1512×) for fenbendazole. The combination of hydroxypropyl-ß-cyclodextrin and polyvinylpyrrolidone enabled a solubility increase of 1412× (~591.22 µg mL-1) for albendazole and 1373× (~144.66 µg mL-1) for fenbendazole. The dissolution rate of the drugs was significantly increased in binary and ternary systems, with hydroxypropyl-ß-cyclodextrin proving to be more effective. The presence of the water-soluble PVP-k30 increased the dissolution rate and amorphization of the complexes. Analysis of the changes in displacement and the profile of the cyclodextrin bands in the 1H NMR spectra revealed a molecular interaction and pointed to an effective complexation in the drug/cyclodextrin systems. Monomeric forms and nanoclusters of cyclodextrins were observed in the drug/cyclodextrin systems, suggesting that the increase in solubility of the drugs in the presence of cyclodextrins should not be attributed only to the formation of inclusion complexes, but also to the formation of cyclodextrin aggregates

Anthelmintic efficiency of doramectin, fenbendazole, and nitroxynil, in combination or individually, in sheep worm control / Eficiência anti-helmíntica da doramectina, fenbendazole e nitroxinil, associados ou utilizados individualmente, no controle da verminose ovina

Abstract The anthelmintic efficiency of doramectin, fenbendazole, and nitroxynil, used individually or in combination, was determined by the Fecal Egg Count Reduction (FECR) test and cultivation of larvae of anthelminthic-treated sheep grouped as follows: G1 (doramectin), G2 (fenbendazole), G3 (nitroxynil), G4 (doramectin + fenbendazole), G5 (doramectin + nitroxynil), G6 (fenbendazole + nitroxynil), G7 (doramectin + nitroxynil + fenbendazole), G8 (untreated). In addition to individually used doramectin and fenbendazole, the helminths were also resistant to the combination of doramectin + fenbendazole; nitroxynil + fenbendazole; and doramectin + nitroxynil + fenbendazole, with their FECR rates ranging from 62-83%. The helminths showed possible nitroxynil-resistance, but had low resistance when the drug was administered in combination with doramectin. The evaluation of individual helminth species revealed that fenbendazole was fully effective against Cooperia; doramectin (G1), moderately effective against Haemonchus and insufficiently active against Cooperia; nitroxynil, effective against Haemonchus and insufficiently active against Cooperia. It was concluded from the results that herd nematodes are resistant to doramectin, fenbendazole, and nitroxynil, and that the combined use of the drugs not only fails to significantly improve the anthelmintic efficiency against Haemonchus and Cooperia, but is also cost-ineffective.

Resumo Eficiências da doramectina, fenbendazole e nitroxynil, utilizados individualmente ou associadamente, foram determinadas através do Teste de Redução na Contagem de Ovos nas Fezes (RCOF) e cultivo de larvas. Os grupos experimentais foram os seguintes: G1 (ovinos tratados com doramectina), G2 (fenbendazole), G3 (nitroxynil), G4 (doramectina + fenbendazole), G5 (doramectina + nitroxynil), G6 (fenbendazole + nitroxynil), G7 (doramectina + fenbendazole + nitroxynil) e G8, não tratados. Os helmintos foram considerados resistentes a doramectina e ao fenbendazole isoladamente e às associações doramectina + fenbendazole, fenbendazole + nitroxynil, e doramectina + fenbendazole + nitroxynil, com taxas de RCOF variando de 62-83%. Helmintos foram considerados suspeitos de resistência ao nitroxynil e apresentaram baixa resistência, quando esta droga foi associada à doramectina. Dos tratamentos isolados, o fenbendazole demonstrou total eficácia (100%) contra Cooperia. Doramectina (G1) foi moderadamente efetiva contra Haemonchus e insuficientemente ativa contra Cooperia, e o nitroxynil efetivo contra Haemonchus (93,2%) e insuficientemente ativo contra Cooperia (0%). Concluiu-se neste estudo que os nematódeos do rebanho são resistentes à doramectina, fenbendazole e nitroxynil, e que, ainda que associadas, não devem ser utilizadas no rebanho por não melhorarem a eficiência anti-helmíntica nem a efetividade contra Haemonchus e Cooperia e por não apresentarem custo-benefício justificado.

Eficacia del fenbendazol por vía tópica contra nematodos gastrointestinales y pulmonares de ganado bovino en clima cálido húmedo / Efficacy of fenbendazole Pour-on againts gastrointestinal and lungworm nematodes in bovines in Mexico

Se hicieron dos experimentos para valorar la reducción en el número de huevos por gramo de heces (hpgh) de nematodos gastrointestinales y larvas de vermes pulmonares en bovinos, localizados en el Centro experimental Pecuario del Estado de Puebla, México. En el primer experimento se utilizaron cinco lotes de 11 a 13 becerros cada uno, parasitados de manera natural con nematodos gastrointestinales. Los animales de los lotes 1, 2 y 3 se trataron por vía tópica, con dosis de 5, 7.5 y 10 mg/kg de fenbendazol preparado para su aplicación por vía tópica; los del lote 4 recibieron una dosis oral de 5 mg/kg y los del lote 5 se mantuvieron como testigos. La eficacia en la reducción de huevos en los lotes tratados, a los 7 día postratamiento, fue de 82.01 por ciento, 98.35 por ciento, 96.42 por ciento y 93.40 por ciento, respectivamante. El segundo experimento se realizó en cuatro lotes de 12 becerros parasitados con nematodos gastrointestinales y positivos a larvas de Dictyocaulus viviparus. Tres lotes se trataron con 5, 7.5 y 10 mg/kg de fenbendazol por vía tópica y el 4º se dejó como testigo. La eficacia de dichas dosis en la reducción de hpgh de nematodos gastrointestinales, fue 99.33 por ciento, 99.16 por ciento y 100 por ciento, respectivamente, y en la reducción de las muestras positivas a larvas del D. viviparus fue de 100 por ciento, 91.66 por ciento y 100 por ciento, respectivamante. El moderado descenso observado en la eficacia del fenbendazol aplicado por vía tópica en el Experimento 1, pudo ser debido al deslave del antihelmíntico producido por el fuerte aguacero que cayó al finalizar la aplicación del tratamiento. Mediante el análisis de varianza de una vía y el test LSD se detectaron diferencias estadísticamente significativas en la eficacia del fenbendazol, en la reducción de huevos de nematodos gastrointestinales, ante el lote del primer experimento tratado con 5 mg/kg y cada uno de los restantes lotes tratados, de ambos experimentos, por la misma vía. Los géneros de dichos nematodos identificados en los coprocultivos a través de larvas III, en ambos experimentos, fueron: Haemonchus, Trichostrongylus, Cooperia, Oesophagostomum y Bunostomum

Estudo comparativo da eficiência de Ivermectina, de Fenbendazole, de Mebendazole e de Mebendazole associado ao Citrato de Piperazina no controle de ciatostomíneos de eqüinos da raça Mangalarga Paulista / Efficacy of Ivermectin, Fenbendazole, Mebendazole and Mebendazole combined with piperazine citrate, in the control of cyathostomes of Mangalarga Paulista equids

Através de estudo comparativo, objetivou-se avaliar a eficiência anti-helmíntica de Ivermectina, de Fenbendazole, de Mebendazole e de Mebendazole associado ao Citrato de Piperazina no controle de ciatostomíneos de eqüinos da raça Mangalarga Paulista. As coproculturas realizadas antes e após os tratamentos levaram consistentemente ao encontro de populaçöes puras de ciatostomíneos com oito células intestinais. Os percentuais de eficácia foram avaliados do 7§ ao 72§ dias do pós-tratamento

Efecto del fenbendazol sobre la eliminación de huevos de nematodos gastrointestinales en las heces de caprinos infestados en condiciones naturales / Efect of fenbendazole against gastrointestinal nematode eggs output in goats under natural conditions

El Fenbendazol a la dosis de 5 mg/kg de peso vivo en caprinos infestados en condiciones naturales, ocasionó una drástica reducción de la producción de huevos por gramo de heces de estrongilos digestivos, sin embargo, dicho efecto fue mucho menos intenso sobre Strongiles spp. En los controles coproscópicos postratamiento se observó un incremento en el número de ooquistes de Eimeria spp por gramo de heces. No se encontraron diferencias estadísticamente significativas entre el peso de los caprinos antes y después del tratamiento

Anthelmintic effects of single doses of fenbendazole and oxantel-pyrantel pamoate to the intestinal nematodes

The present study was undertaken to evaluate the anthelmintic effects of fenbendazole against intestinal nematode; Ascaris lumbricoides, hookworm and Trichuris trichiura, and to compare the efficacy in fenbendazole, oxantel-pyrantel pamoate and placebo by means of double blind method. Out of 114 subjects harbouring Ascaris lumbricoides, hookworm and Trichuris trichiura, 36 cases were treated with single dose of fenbendazole, 38 cases with oxantel-pyrantel pamoate, and the remaining 40 cases had received the placebo. The results were as follows: In the group treated with fenbendazole (30-50 mg/kg), the cure rates were 83.9 percent in 31 subjects with Ascaris lumbricoides and 83.3 percent in 18 subjects with hookworm, and only 28.6 percent in 28 subjects with T. trichiura respectively. In the group treated with a single dose of oxantel-pyrantel pamoate (10 mg/mg), the cure rates were 96.7 percent in 30 subjects with A. lumbricoides, 95.2 percent in 21 subjects with hookworm, and 54.6 percent in 33 subjects with T. trichiura. Egg reduction rate was 85.7 percent in T. trichiura cases. On the other hand, the egg negative conversion rates in placebo group were 9.7, 8.3 and 33.3 percent in Ascaris, Trichuris and hookworm infections respectively. The above results showed that fenbendazole was highly effective against Ascaris and hookworm. However, incomparisom with oxantel-pyrantel pamoate, fenbendazole was less effective in regards of A. lumbricoides, hookworm and T. trichiura infections.