Mothers' perceptions of and feelings towards their babies' crying

The frequency and type of crying and the parents' perceptions of it were evaluated in 281 Finnish infants underthe age of 1 year. Not many mothers [14#pc] claimed that their babies cried often or very often. The infants less than three months old cried significantly more in the evening than the older ones. Most mothers [94#pc] reported that the crying aroused feelings of tenderness, but 4#pc found it irritating. The most common response to the cry [97#pc] was to pick the baby up. Additional help was wanted by 49 mothers because of their babies' disturbing crying spells. These mothers reorted that their infants cried more and they stated that the cry made them feel more irritated and more often gave them a feeling of failure than the mothers not in need of help. The majority of these mothers would have been glad to help, including advice, whent the infants were under 3 months of age.     

Pilocarpine release from hydroxypropyl-cellulose-polyvinylpyrrolidone matrices

Characteristics of pilocarpine release from cast plasticized hydroxypropylcellulose (HPC) and HPC-polyvinylpyrrolidone (PVP) matrices were studied using tritiated pilocarpine. Increased concentration of PVP and decreased molecular weight of HPC accelerated release of pilocarpine from the matrices. The aqueous solution penetrated rapidly into the matrices, which swelled rapidly to their equilibrium volumes. With increased molecular weight and concentration of HPC in the matrices, the rate of solvent penetration decreased and swollen volume of the matrix increased. Pilocarpine concentration also decreased in the ungelled cores of the matrices, indicating that the solvent had penetrated these cores. Solvent penetration alone did not control the rate of drug release, because penetration was at least twice as rapid as pilocarpine release. In the matrices without polymer dissolution, the best fits of the release data were obtained with diffusional square-root of time dependence, although relaxation of the polymers caused slight deviations from the Fickian diffusion. Thus the rate-limiting step of pilocarpine release was the diffusion of the drug from the matrix. The decreased rate of pilocarpine release with increased molecular weight and concentration of HPC was due to the decreased rate of drug diffusion from the matrix. Retardation of this diffusion was caused by the increased swelling of the matrix and decreased diffusivity of the drug. High initial concentration of PVP resulted in substantial deformation and attrition of the matrices.     

Nandrolone decanoate added to tamoxifen in the treatment of advanced breast cancer

Summary Since 1980 we have been carrying out a prospective randomized trial comparing tamoxifen with the combination of tamoxifen plus nandrolone decanoate in advanced breast cancer. The tamoxifen dose is 30 mg daily and the nandrolone decanoate dose 100 mg i.m. once a week for four weeks and thereafter every other week. 98 post-menopausal patients have been evaluated for the response. The number of patients is 49 in both groups.The overall response rates (CR +PR) to tamoxifen and tamoxifen plus nandrolone decanoate were not significantly different; in the tamoxifen group the response rate was 49% and in the combination group 45%. The mean time to progression in tamoxifen group is over 13 months and in tamoxifen plus nandrolone decanoate group over 12 months. Our results do not suggest a synergistic effect from combining tamoxifen and nandrolone decanoate treatments. The response rates to tamoxifen at different sites of metastases were as follows: bones 47%, soft tissues 56%, and viscera 48%. The respective figures with the combination therapy were 36%, 64%, and 40%.Both treatments were well tolerated and in no patient was withdrawal of the therapy necessary. Mild virilization and hoarseness were experienced by all patients treated with nandrolone decanoate. Side-effects associated with tamoxifen were rare, although five patients experienced nausea and two had hot flushes.     

Papillary thyroid carcinoma: The new,age-related TNM classification system in a retrospective analysis of 199 patients

The new, age-related TNM classification system of papillary thyroid carcinoma was applied in a retrospective analysis of 199 patients operated on during the 24-year period from 1956 through 1979 at the Second Department of Surgery, Helsinki University Central Hospital. According to the new staging system, 103 patients (under 45 years of age) and 96 T1 patients (45 years of age and older) were categorized into stage I. The incidence of carcinoma-positive cervical lymph nodes was highest among patients under 30 years of age at primary surgery. During the follow-up period of 6–29 years, cervical lymph node involvement was verified at reoperation in 20 patients (10%). Distant metastases (bone or lung) developed in 11 patients (5.5%). thirty-one patients (16%) died from carcinoma. The prognostic value of stage grouping, in terms of metastatic tendency and cancer mortality, was clearly demonstrated in the present material, suggesting the suitability of this simplified, new, age-related staging system in clinical practice.

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Resumen La nueva clasificación TNM relacionada con la edad, del carcinoma papilar de la tiroides fue aplicada en un análisis retrospectivo de 199 pacientes operados en un período de 24 anos entre 1956 y 1979 en el Segundo Departamento de Cirugía del Hospital Central de la Universidad de Helsinki. De acuerdo con el nuevo sistema de estadificación, 103 pacientes menores de 45 años y 96 pacientes T1 de 45 años o más, fueron categorizados como estado I. La incidencia de ganglios cervicales positivos fue maxima entre los pacientes menores de 30 anos en el momento de la primera cirugía. En el curso del seguimiento de 6–29 años, se verificó invasión glanglionar cervical en reoperación en 20 pacientes (10%). Metástasis distantes (hueso o pulmón) aparecieron en 11 pacientes (5.5%). Treinta y un pacientes (16%) murieron por carcinoma. El valor pronóstico de la agrupación por estadificación, en términos de metastásis y mortalidad por cáncer, fue bien demostrada en este material chínico, lo cual sugiere la confiabilidad del nuevo y simplicado método de clasificación segÚn la edad, en la cual todo paciente menor de 45 años, no importa cuales sean las categorias T y N, son clasificados como estado I.

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Résumé Le nouveau système TNM de classification du carcinome papillaire de la thyroÏde en fonction de l'âge a été appliqué dans l'analyse rétrospective de 199 patients opérés sur une période de 24 ans, de 1956 à 1979, dans le 2ème Département de Chirurgie de l'Hôpital Central de l'Université d'Helsinki. Selon cette nouvelle classification, 103 patients T1 âgés de moins d 45 ans et 96 patients T1 de 45 ans et plus ont été répertoriés dans le stade I. L'incidence des adénopathies cervicales était plus fréquente chez les patients âgés de moins de 30 ans lors de la première intervention. Pendant la période de suivi allant de 6 à 29 ans, l'état des ganglions du cou a été contrôlé par réopération chez 20 patients (10%). Des métastases à distance (os ou poumon) se sont développées chez 11 patients (5.5%). Trenteet-un patients (16%) sont morts du cancer. La valeur pronostique du regroupement par âge, en terme de tendance métastasique et de mortalité, a été clairement démontrée dans cette étude, suggérant l'emploi de ce nouveau système de classification simplifié en fonction de l'âge dans la pratique clinique.

     

Challenges and obstacles of ocular pharmacokinetics and drug delivery

Modern biological research has produced increasing number of promising therapeutic possibilities for medical treatment. These include for example growth factors, monoclonal antibodies, gene knockdown methods, gene therapy, surgical transplantations and tissue engineering. Ocular application of these possibilities involves drug delivery in many forms. Ocular drug delivery is hampered by the barriers protecting the eye. This review presents an overview of the essential factors in ocular pharmacokinetics and selected pharmacological future challenges in ophthalmology.     

Safety profile of plasmid/liposomes and virus vectors in clinical gene therapy

Despite of more than 500 gene therapy trials worldwide very little systematic safety information is available from gene therapy. Safety information was collected from 146 consecutive patients who participated in three randomized, controlled phase II gene therapy trials in cardiovascular diseases and malignant glioma using adenoviruses, plasmid/liposomes and retrovirus packaging cells. Total follow-up time of the patients was 78794 days which equals 1.5 years per patient. The main outcome measures were serious adverse events, other adverse events and changes in general laboratory parameters. Except fever and increases in CRP values plasmid/liposomes were safe and well tolerated. The incidence of serious adverse events in adenovirus-treated patients was 0.9 and 4.0/10000 patient days in cardiovascular and malignant glioma trials as compared to 0.5 and 2.1 in randomized control patients, respectively. Transient fever, leukopenia and increases in CRP and liver enzymes were detected in virus-treated patients. No deaths from side effects or no new cancers were associated with gene therapy. It is concluded that gene therapy, like any other therapy, is associated with side effects which depend on the administered vector, dose, and route of delivery and properties of the transgene. However, given the limitations of this study and length of the follow-up, the safety profile of gene therapy seems to be acceptable for the treatment of severe human diseases.     

Ultrastructure of the corneal nerves after fixation with potassium permanganate

The innervation of the rat cornea was investigated electron microscopically after KMnO₄ fixation. Myelinated nerve fibres were observed only in the limbal margin of the cornea, whereas the axons located in the stroma of the avascular cornea were surrounded by the Schwann cell cytoplasm. Axon profiles with small (300-500 A) granular vesicles and another type with agranular vesicles were seen among the non-vesiculated fibres in all parts of the cornea. After superior cervical ganglionectomy it was not possible to find any axons with small granular vesicles. On the other hand, some degenerating axon profiles were observed in the stromal nerve trunks after ganglionectomy. In the epithelium-naked axons with an occasional mitochondrion and a few agranular vesicles penetrated between the epithelial cells. Moreover, axons filled with several mito-chondria were rarely observed in the epithelium, but these were difficult to differentiate from the surrounding epithelial cells. The role of the different nerve types observed in the cornea is discussed. The results suggest that the rat cornea has a dual vegetative innervation.     

Use of cancer‐specific genomic rearrangements to quantify disease burden in plasma from patients with solid tumors

Detection of recurrent somatic rearrangements routinely allows monitoring of residual disease burden in leukemias, but is not used for most solid tumors. However, next‐generation sequencing now allows rapid identification of patient‐specific rearrangements in solid tumors. We mapped genomic rearrangements in three cancers and showed that PCR assays for rearrangements could detect a single copy of the tumor genome in plasma without false positives. Disease status, drug responsiveness, and incipient relapse could be serially assessed. In future, this strategy could be readily established in diagnostic laboratories, with major impact on monitoring of disease status and personalizing treatment of solid tumors. © 2010 Wiley‐Liss, Inc.