Challenges in obtaining adequate genetic sample sets in clinical trials: the perspective of the industry pharmacogenomics working group.

Collection of DNA samples from subjects participating in clinical trials is vital to understanding variability in drug response. The purpose of this study was to assess pharmacogenetic sample-collection practices in the industry and to gather information on issues affecting collection. A survey questionnaire was developed and distributed to 20 pharmaceutical companies; 15 provided responses. Assessments included rate of DNA sample collection, reasons for low collection rates, reasons for rejection by health authorities (HAs) and institutional review boards/ethics committees (IRBs/ECs), and country-specific hurdles to sample collection. The results indicated that, although DNA samples are frequently collected, sample-acquisition rates remain lower than expected. Overall, the companies' experience has been that restrictions on sample usage are not consistently applied by regulatory bodies. This may reflect changing opinions/interpretations of HAs/IRBs/ECs. Collection of DNA samples in industry trials is still a challenge. Harmonization of sample-collection practices may facilitate the process.

Efeito de diferentes meios de cultivo no desenvolvimento e proporção do sexo de embriões bovinos produzidos in vitro / Effect of different culture media on development and sex ratio of bovine embryos fertilized in vitro

Avaliou-se o efeito da suplementação de meios de cultivo sobre o desenvolvimento e proporção do sexo de embriões bovinos fertilizados in vitro. Complexos cumulus-oócitos obtidos de ovários de matadouro foram maturados e fertilizados in vitro. Os zigotos (n= 484) foram distribuídos aleatoriamente em meio CR2aa, contendo soro fetal bovino (SFB) (T1), albumina sérica bovina (BSA) (T2) ou BSA mais insulina:transferrina:selênio e vitaminas (BSA+) (T3), no cultivo embrionário in vitro, a uma atmosfera de 5 por cento CO2 a 38,8ºC em ar. A taxa de clivagem foi observada 72-76 horas pós-fertilização (PF) e a taxa de blastocistos com sete e oito dias PF. Os blastocistos (n= 63) foram sexados pela técnica de reação em cadeia de polimerase. A taxa de clivagem em T2 foi maior (P<0,05) do que em T1 e T3. A taxa de blastocistos foi similar (P>0,05) entre T2 e T3, porém menor (P<0,01) do que em T1. A proporção do sexo dos embriões não diferiu (P>0,05) entre os tratamentos. O T1 influenciou o desenvolvimento de blastocistos, mas não teve efeito sobre a proporção do sexo.

A primary cutaneous non-T, non-B CD4+, CD56+ lymphoma.

BACKGROUND: Cutaneous lymphomas are heterogeneous clonal lymphoproliferative disorders originating from B or T lymphocytes. OBSERVATION: We describe a patient with a unique primary cutaneous lymphoma characterized by a bruise-like aspect of the skin lesions, a CD4+, CD43+, CD56+, CD2-, CD3-, CD8-, T-cell receptor-negative phenotype of the medium-sized to large lymphoid tumor cells and an undetermined genotype (T-cell receptor beta and immunoglobulin heavy chain in germline configuration, no clonal T-cell receptor gamma population as detected after analysis with polymerase chain reaction combined with denaturing gradient gel electrophoresis) and fast relapse after radiotherapy. CONCLUSIONS: This non-B, non-T cutaneous lymphoma cannot be classified by any current lymphoma classification. It seems to represent a new disease entity with peculiar clinical, histologic, and molecular features.

[Pollinosis in Canton Ticino. A prospective study in Locarno]. / Pollinose im Kanton Tessin. Eine prospektive Studie in Locarno 1990-1993.

A study was carried out in the southern part of Switzerland (Canton Ticino) in 1990-1993 to determine the spectrum of cutaneous sensitivity to a large amount of pollens and several perennial allergens (50), using skin prick tests in a sample of 503 consecutive patients suffering from hay fever. The Canton Ticino is a very specific geographical and botanical area which includes several plants of the alpine and Mediterranean flora as well as representatives of the tropical flora, forming a unique pattern from a botanical and allergological point of view. The results of the study indicate that in this region the patients have symptoms of hay fever almost 10 months a year (from December until October) with a peak in May and June (88% and 73% of the patients respectively have symptoms in these months). The symptoms are mainly localized in the upper respiratory tract and eyes. Asthmatic symptoms were found in about 23% of the patients. At the top of the allergen list were grass-pollens (72% of the patients had sensitivity); rye (69%); olive tree (54%); birch (46%); chestnut (37%); ash tree (36%); alder tree (33%); ragweed (17%); parietaria (18%). Of real interest in this study area are, besides the classical allergy-inducing pollens, those of chestnut, parietaria, olive tree, ash tree and cupressaceae (for example cypress). Chestnut pollens represent about 30% of the airborne pollens in this region. 30% of the patients had sensitivity against dust mites (Dermatophagoides pteronissimus und D. farinae), and 20% against cats. Sensitivity against 8 mould spores was 2-9%.

A prospective study of skeletal changes during short-term acitretin therapy.

We prospectively analyzed skeletal changes of 16 patients who were treated with acitretin for various disorders of keratinization at doses of 10-50 mg/day (overall mean 0.4 mg/kg/day) for 7-12 months (mean 11.4 months). Skeletal changes from pretherapy findings were observed in 5 patients. In 4 of 5 patients they appeared to be linked to a preexisting degenerative pathology and could not be attributed to acitretin therapy. However, in 1 patient a spinal osseous side effect could not be excluded. No retinoid-induced extraspinal tendon or ligament calcifications were observed.

Mastocytosis and atopy: a study of 33 patients with urticaria pigmentosa.

Thirty-three patients with histologically verified urticaria pigmentosa were studied for coexisting atopic disease by means of history, skin prick testing with five common inhalants and serological investigation for total IgE and specific IgE antibodies to five common inhalants. The prevalence of atopy in urticaria pigmentosa was similar to that observed in the normal Swiss population, both on the basis of history (7/33 = 21%) and of positive skin prick tests to common inhalants (12/33 = 36%). However, total serum IgE levels were significantly lower (geometric mean value 16.8 kU/l) than in a control group of 52 Swiss blood donors of comparable age and sex distribution (geometric mean value 43.0 kU/l, t = 2.93, P less than 0.005). Specific IgE antibodies to common inhalants were also observed less frequently in urticaria pigmentosa patients than in controls, although this difference was not statistically significant. Low total and specific IgE values in patients with urticaria pigmentosa may be explained by increased absorption of circulating IgE to abundant tissue mast cells.

Acitretin in the symptomatic therapy for severe recessive x-linked ichthyosis.

Eight men with severe recessive x-linked ichthyosis were treated with acitretin, the main metabolite of etretinate, during four months. All of the patients showed marked clinical improvement of scaling during therapy. Hypervitaminosis A-type adverse reactions were observed in all patients. Although the overall tolerance was good, therapy was interrupted in one atopic patient because of pruritus. There were no undesirable laboratory changes in values. Thirty-five milligrams of acitretin daily provided the best efficacy, with minimal side effects. The beneficial effect of this retinoid lasted between four and six weeks after therapy was stopped. These results suggest that acitretin is a useful agent in the symptomatic therapy of severe recessive x-linked ichthyosis resistant to topical therapeutic modalities. Good results with this agent can be achieved with interval therapy adjusted to seasonal variations of the skin symptoms.

[Andrologic studies in patients with X-chromosome recessive ichthyosis]. / Andrologische Untersuchungen bei Patienten mit X-chromosomal rezessiver Ichthyose.

In the past there have been several reports of testicular abnormalities (hypogonadism, cryptorchidism and so-called atypical germ cells) in patients with recessive X-linked ichthyosis. Anamnestic interviews, clinical as well as chemical investigations in ten patients (aged 25-52 years) with recessive X-linked ichthyosis have been undertaken in order to examine their endocrine and exocrine testicular function. Normal serum levels of gonadotropins were observed in nine of ten patients, while four of ten men had decreased levels of dehydroepiandrosterone. In addition, in eight of these ten patients spermatological alterations were found: two patients suffered from oligozoospermia, while asthenozzospermia occurred in seven patients and teratozoospermia was registered in three men. Although andrological abnormalities were found in five out of ten patients (cryptorchidism, varicocele), the high incidence of spermatological alterations is remarkable. Further investigations will be necessary to clarify whether steroid sulphatase is responsible for some of these alterations, especially for the pronounced asthenozoospermia.

[Biochemical diagnosis of X chromosomal ichthyosis]. / Biochemische Diagnose der X-chromosomalen Ichthyose.

Steroid sulfatase (STS) and aryl sulfatase C (ASC) in leucocytes, as well as the electrophoretic mobility of the beta-lipoproteins, were analyzed in 34 patients with autosomal dominant ichthyosis (ADI), 18 patients with X-linked recessive ichthyosis (XRI), 7 patients with congenital nonbullous ichthyosis (CNBI), and 48 controls. The geometric means of both STS and ASC were significantly lower in the group of XRI by a factor of approximately 10. Analysis of ASC showed a clear separation of the whole group of XRI patients opposed to patients with ADI and CNBI and the controls, whereas an overlapping was observed for STS. With one exception, the clinical and biochemical diagnosis (sulfatase) was confirmed by the results of the lipoprotein electrophoresis (LPE). This case, clinically and biochemically diagnosed as XRI, exhibited normal electrophoretic mobility of beta-lipoproteins. We conclude: if the electrophoretic mobility of beta-lipoproteins is enhanced, XRI can be diagnosed; if the LPE is normal, XRI cannot be excluded; in this case, the diagnosis of XRI can be confirmed or rejected by analysis of the microsomal sulfatases.

KID syndrome (keratitis, ichthyosis, and deafness) and chronic mucocutaneous candidiasis: case report and review of the literature.

In 1981 Skinner et al (1) proposed the term KID syndrome for a previously disparate group of congenital disorders principally made up of keratitis (K), ichthyosis (I), and deafness (D). The coexistence of congenital deafness associated with ichthyosis had been previously recognized (2,3), yet similarities among affected patients were overlooked because of both the paucity of cases and their seeming diversity. The patient reported by Skinner is similar to one whom we have been following at the Clinique Universitaire de Dermatologie in Geneva since 1978. After having reviewed the literature, we believe that KID syndrome is a useful, unifying clinical term.

Sister chromatid exchange in patients affected by severe psoriasis.

An analysis of the sister chromatid exchanges has been carried out in lymphocytes from patients suffering from a severe form of psoriasis--pustular psoriasis (von Zumbusch), eruptive psoriasis vulgaris (more than 30% of the skin surface), severe arthropathic psoriasis and psoriatic erythroderma. These patients had never received treatment for their disorder. Our results, which show a normal level of sister chromatid exchanges in their blood cells, argue against the presence of a mutagenic factor in such patients.

[Thalidomide in the treatment of chronic lupus erythematosus]. / La thalidomide dans le traitement du lupus érythémateux chronique.

The effect of thalidomide was investigated in 12 patients with chronic lupus erythematosus resistant to classical treatment (antimalarial drugs, topical steroids). 10 patients were improved and 2 were not sensitive to the treatment. The doses were 100 mg/day for a minimum period of 2 months. With the exception of 1 case, the treatment was well tolerated. The indications of thalidomide in dermatology and the mechanism of action of the drug are briefly discussed.