Different kinetics of lung clearance of technetium-99m labelled diethylene triamine penta-acetic acid in patients with sarcoidosis and smokers

The rate of clearance from the lungs of inhaled technetium-99m labelled diethylene triamine penta-acetic acid (^99mTc-DTPA) is often increased in interstitial lung disease as well as in smoking. In smokers a bi-exponential clearance course of ⁹⁹mTc-DTPA when measured over 3 h has previously been shown. This study was performed to compare the kinetics of clearance of ^99mTc-DTPA, measured for 3 h, in sarcoid patients and healthy smokers. Forty-one never-smoking patients with sarcoidosis and radiological signs of intrathoracic disease were studied. The results were compared with those of 16 healthy current smokers and of 14 healthy never-smokers reported previously. A mono-exponential clearance equation described the clearance in 22 of the sarcoid patients and all normal never-smokers, but with a shorter average tracer half-life in the patients (P<0.05). In 19 patients and all smokers a bi-exponential equation gave a significantly better curve fit. The rate of clearance of the slow component was higher in patients with sarcoidosis than in smokers (P< 0.05). The fraction of the tracer cleared by the fast clearance component was smaller in patients with sarcoidosis than in smokers (P<0.01). Differences in kinetics of clearance of ^99mTc-DTPA in sarcoidosis and smoking could thus be demonstrated, suggesting that the abnormal clearance is caused by diverging pathophysiological mechanisms.     

Physicochemical aspects of drug release. XV. Investigation of diffusional transport in dissolution of suspended, sparingly soluble drugs

The dissolution rates of sparingly soluble, fine particulate, suspended drugs have been studied using a Coulter Counter Model TAII. For two sieve fractions of oxazepam the dissolution rates were monitored in media with varying viscosities brought about by the addition of glycerol, while for griseofulvin the change in the medium's viscosity was induced by changing the temperature. By calculating the dissolution rate, and compensating for differences in particle surface area and media solubility, it was shown that the dissolution rate was diffusion controlled. After additional normalization for the diffusion coefficient, it was suggested that the so-called apparent diffusional distance decreased substantially with particle size. The effect of particle size was more limited above approx. 15 μm.     

CAG repeat polymorphism within the KCNN3 gene is a significant contributor to susceptibility to anorexia nervosa: a case-control study of female patients and several ethnic groups in the Israeli Jewish population.

The human small-conductance Ca(2+)-activated potassium channel gene KCNN3 has been involved in mechanisms underlying neuronal function and plasticity. A multiallelic CAG repeat polymorphism within the KCNN3 has been associated with schizophrenia and bipolar disorder. We have previously reported in a family-based study that longer CAG repeats are preferentially transmitted to patients with anorexia nervosa (AN). The present study extends the analysis of KCNN3 allele distribution to a larger series of AN female patients and control groups, incorporating information on ethnicity and co-morbidities associated with AN. The data analysis is presented while considering separately the two alleles of each individual, namely a minor (shorter) and a major (longer) allele. This study has found that the KCNN3 allele distribution in the general Israeli population does not differ significantly in at least four Jewish ethnic groups of Ashkenazi, North African, Iraqi, and Yemenite origin. These have been used as control groups in a matched case-control analysis that has demonstrated a significant over-representation of KCNN3 alleles with longer CAG repeats among AN patients (P < 0.001 for the major allele and P = 0.035 for allele sum). Under dichotomization, a significantly higher prevalence of the L allele (>19 repeats) has been observed among AN patients (P < 0.001). While considering AN and co-morbid phenotypes, a tendency towards longer (L) alleles has been observed in the subset of patients with obsessive-compulsive disorder (OCD) co-morbidity. These findings further implicate KCNN3 as a significant contributor to predisposition to AN.     

Induction of antigen-specific isotype switching by in vitro immunization of human naive B lymphocytes

The use of in vitro immunization technology for the generation of human antigen-specific antibodies has essentially resulted in low affinity IgM antibodies, resembling an in vivo primary immune response. We now describe a detailed reproducible protocol for a two-step in vitro immunization, which yields isotype switched, antigen-specific human antibodies. The immunizing antigen was a 30aa synthetic peptide, containing both a B (15aa V3 peptide of the HIV-1) and a T helper cell epitope (15aa peptide from tetanus toxin). The immunization protocol includes: (i) a selection procedure of donors with a memory T cell response against tetatus toxoid; (ii) immunization of mature naive peripheral B lymphocytes in two distinct phases, involving a primary and a secondary step. None of the donors which were examined after primary 7immunization showed at any time an IgG anti-V3 specific antibody response, while all the donors showed an IgM response. After the secondary immunization step, anti-V3 antibodies of both IgM and IgG isotypes were detected. The switch frequency event was high among the tested donors (5/8).     

Radiologic long-term results after cervical vertebral interbody fusion with Polymethyl Methacrylat (PMMA)

Long-term results of cervical interbody fusion with PMMA were evaluated in a retrospective study. X-ray films of 83 patients were obtainable. Post-operative follow-up in this series was between 15 and 20 years. The results show that PMMA is engrafted after about 2 years. Stable vertebral interbody fusion is obtained in about 90% of cases. Development of malignoma was not observed. Resorptive bone alterations, which can be seen in about 2% of cases one to two years after operation are shown not to be progressive. This process heals and stable fusion develops.     

Testing for skin sensitization according to the notification procedure for new chemicals: the Magnusson and Kligman test

The notification procedure for new chemicals in the European Union (called the Chemicals Act in Germany) requires a skin sensitization test when the amount of a new chemical produced exceeds 100 kg/year. The preferred test is that of Magnusson and Kligman; more than 90% of the tests submitted are performed with it. Though the Magnusson and Kligman test is described in the literature, and in the test guidelines of the European Union and of the OECD, discrepancies do occur in the performance of the test between test laboratories. In this paper, recommendations are given for standardized performance of the Magnusson and Kligman test.     

Ruminative Response Style and Vulnerability to Episodes of Dysphoria: Gender, Neuroticism, and Episode Duration

A number of recent laboratory and prospectivefield studies suggest that the tendency to ruminateabout dysphoric moods is associated with more severe andpersistent negative emotional experiences (e.g., Morrow & Nolen-Hoeksema, 1990;Nolen-Hoeksema & Morrow, 1991). The current paperreports two studies that tested the hypotheses that (a)ruminative response styles act as a trait vulnerabilityto dysphoria, particularly to relativelypersistent episodes of dysphoria; (b) aspects ofrumination that are not likely to be contaminated withthe presence and severity of previous symptomatology(introspection/self-isolation, self-blame) demonstrate vulnerability effects;and (c) rumination mediates the effects of gender andneuroticism on vulnerability to dysphoria. Consistentsupport was found for each of these hypotheses. Overall, our data suggest that rumination mightreflect an important cognitive manifestation ofneuroticism that increases vulnerability to episodes ofpersistent dysphoria.     

PDGF AA as mediator in nicotine-dependent carcinogenesis

Effect of nicotine on PDGF AA and PDGF BB interaction with cervicalcancer SiHa cells was tested. [¹²⁵I]PDGF AA was internalizedby cells and accumulated in the cytoplasm and nucleus (chromatin).In the absence of nicotine, maximal accumulation of [¹²⁵I]PDGFAA inside the cells occurred after 1 day of incubation, whichwas followed by a progressive degradation of the growth factorduring the next 2, 3 and 5 days of cell exposure. In the presenceof 0.001 or 0.01% nicotine, accumulation of [¹²⁵I]PDGF AA wasslightly higher than in the absence of nicotine, and maximalaccumulation occurred after 2 days of incubation. In the presenceof 0.1% nicotine, maximal accumulation occurred after 5 daysof incubation and was 20 and 14 times higher in the cytoplasmand chromatin, respectively. Nicotine-postponed degradationand increased nuclear accumulation of PDGF AA resulted in activationof RNA synthesis and cell proliferation. PDGF BB, which wasnot internalized by cells did not respond to nicotine treatment.The proposed mechanism of nicotine-PDGF AA co-carcinogenesismay involve inhibition of growth factor degradation at the lysosomallevel and an increased chromatin accumulation of the non-degradedPDGF.     

Reproductive factors and breast cancer: An overview

Summary Despite extensive research, there is still uncertainty on the separate effects of parity and age at first birth on breast cancer risk. Thus, information on these variables from formal epidemiological articles published in English since 1970 is reviewed in the present article. Among 26 studies considered, one found no significant association with either variable, seven showed an association between age at first birth but not parity and breast cancer risk, six an association with parity but not age at first birth, and in twelve studies both variables appeared to be independently related with breast cancer risk. Various reasons for these apparent differences can be considered, including heterogeneity between various populations (for instance, the proportion of multiparous women in studies showing no association with parity tended to be higher than in studies finding an inverse relation with parity), criteria for selection of cases and controls, influence of age and other covariates (among which the interval between pregnancies is of particular interest) and, of course, the role of chance. The data reviewed suggest, from an aetiological viewpoint, that both parity and age at first birth have some independent effect on breast carcinogenesis. From a public health viewpoint, however, it appears that the importance of age at first birth is greater, since the trend is linear across subsequent age levels, while the protection of parity seems to be quantitatively relevant only for women with four or five births or more.

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Fortpflanzungsfaktoren und Brustkrebs: eine Übersicht

Zusammenfassung Trotz intensiver Forschung bestehen immer noch Zweifel über die einzelnen Auswirkungen von Parität und Alter bei der Erstgeburt auf das Brustkrebsrisiko. Deshalb werden in diesem Artikel die Arbeiten, welche seit 1970 in Englisch veröffentlicht worden sind, analysiert. Von den 26 berücksichtigten Studien fand eine keine eindeutige Beziehung zu diesen beiden Variablen. Sieben wiesen eine Beziehung mit dem Alter bei der Erstgeburt nach, jedoch nicht mit der Parität. Sechs fanden einen Zusammenhang mit der Parität, aber nicht mit Alter bei Erstgeburt und aus 12 Studien ging hervor, dass beide Faktoren unabhängig voneinander mit dem Brustkrebsrisiko verbunden sind. Es gibt verschiedene Hypothesen, diese Diskrepanzen zu erklären, darunter auch die Verschiedenartigkeit in den untersuchten Bevölkerungen (so lag z.B. die Proportion der Frauen mit mehreren Geburten in jenen Studien, die nicht mit Parität verbunden sind höher, als in jenen, welche eine Verbindung zur Parität fanden), die Auswahlkriterien für Fälle und Kontrollen, der Einfluss des Alters und von anderen Variablen (wobei der Zeitabstand zwischen den Schwangerschaften besonders interessant ist) und natürlich die Rolle des Zufalls. Die gesichteten Resultate deuten vom ätiologischen Sichtpunkt darauf hin, dass Parität und Alter bei der Erstgeburt unabhängig voneinander das Brustkrebsrisiko beeinflussen. Die Beziehung zwischen dem Alter bei der Erstgeburt und der Brustkrebshäufigkeit scheint, vom Standpunkt der Sozialmedizin aus, jedoch von grösserer Bedeutung zu sein, da das Risiko in jeder Altersklasse linear ansteigt. Der Schutzeffekt der Parität hingegen ist erst von der vierten oder fünften Geburt an nachzuweisen.

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Les facteurs reproductifs et le cancer du sein: un résumé

Résumé Malgré des recherches approfondies, des doutes subsistent quant aux effets de parité et d'âge à la première naissance sur le risque du cancer du sein. Différents travaux parus en anglais depuis 1970 sont analysés dans cet article. Des 26 études analysées, une seule ne démontrait pas d'association. Sept ont montré une association avec l'âge à la première naissance mais pas avec la parité. Six ont démontré une association avec la parité mais non avec l'âge à la première naissance et 12 études ont montré une influence indépendante de ces deux facteurs sur le risque de cancer du sein. Différentes hypothèses peuvent être considérées pour ces différences apparentes, y compris l'hétérogénéité entre les populations étudiées (par exemple la proportion de femmes multipares est plus élevée dans les études démontrant une association avec la parité que dans celles avec une relation inverse), la sélection des cas et des témoins, la structure de l'âge, ainsi que d'autres facteurs comme par exemple l'intervalle entre les grossesses et bien sûr le hasard. Ces données laissent apparaître que la parité, ainsi que l'âge à la première naissance, peuvent influencer d'une manière indépendante le risque du cancer du sein. La corrélation entre l'âge à la première naissance et le cancer du sein est très importante pour la santé publique, étant donné que le risque augmente avec chaque classe d'âge, tandis que la parité n'a un effet protecteur qu'à partir de la quatrième ou de la cinquième naissance.