[Pharmacists graduated in the first twenty years on the medical faculty of Hungarian Royal University]. / A Magyar Királyi Tudományegyetem orvosi karának elsö húsz évében végzett gyógyszerészek.

The present paper, summarizing the results of original archival researches, gives a survey on the beginnings of the pharmaceutical education in Hungary at the end of the 18th century. While analysing the documents the author calls our attention to some stubborn errors and mistakes of the former historical literature as well. The paper-based on the data of the promotional book-presents a list including names, nationality and religion of those 170 students of pharmacy, who completed their studies during the first 20 years of pharmaceutical education in Hungary. Comparing the dates of tirocinial and those of university examinations respectively, the author proves that sometimes even 40 or 59 years old, respected pharmacists were forced to take their exams at the university. Having made a comparison between the register of students and that of promotions the author concludes that until 1788 the studies took three months or a year only in theory, for candidates actually did not attend university courses at all. In the case when one failed, a short preparation for a make-up exam was also available. Data prove, that the requirements of the royal decree, a centrally made regulation, called Normativum Sanitatis - in spite of the difficulties caused e.g. by the lack of handbooks - could be more or less responded. (The circumstances of the courses are going to be analysed in a further paper.)

Adherence of Candida albicans to epithelial cells: studies using fluorescently labelled yeasts and flow cytometry.

Candida albicans adherence to epithelial cells is the first step in the infectious process, but in spite of its importance, current methods for the quantitative measurement of adherence of C. albicans to epithelial cells in vitro have some serious limitations. They are based on filtration assays and either microscopic or radiometric analysis. The adherence reaction is usually carried out with a large excess of yeasts (100-fold) over epithelial cells in order to perform the microscopic analysis, which is slow, subjective and limited to 100-200 cells and thus lacks statistical power. The radiometric analysis fails to measure individual cells. A method for measuring yeast adherence that overcomes these problems has been developed. It is based on labelling the yeasts with the fluorogenic marker 2',7'-bis-(2-carboxyethyl)-5(6)-carboxyfluorescein acetoxymethyl ester (BCECF) prior to the adherence reaction, and analysing 10(4) epithelial cells by flow cytometry, while nonbound yeasts are excluded by gating. Two subpopulations of buccal epithelial cells (BECs) which differ in their mean fluorescence intensities per cell (MFIs) were observed: one with MFI which did not exceed nonspecific fluorescence, and the other with MFI as high or higher than the MFI of labelled yeasts. The two subpopulations represent yeast-free and yeast-binding epithelial cells, respectively, and the MFI increment of the BECs is a quantitative measure of the extent of yeast adherence. Control experiments confirming previously described basic features of adherence, such as enhanced adherence at increasing yeast excess, diminished adherence of trypsin-treated or heat-inactivated yeasts, and the differential adherence of various Candida species, supported the validity of the assay. The possibility of studying adherence reliably at low yeast:epithelial cell ratios, which better mimic adhesion as it occurs in vivo, is an important advantage of the assay. New findings, using this method, included the observation that exfoliated BECs from diabetic patients exhibited the same capacity for C. albicans adherence as cells from healthy controls, and that epithelial cells from early human ontogenic stages had a significantly lower adherence level than those from later stages.

Hereditary leukoencephalopathy and palmoplantar keratoderma: a new disorder with increased skin collagen content.

We report a new neurocutaneous syndrome of apparent autosomal recessive inheritance consisting of early-childhood-onset palmoplantar keratoderma followed in adulthood by progressive tetrapyramidal syndrome and cognitive impairment. Of the four affected siblings, two were available for evaluation. Investigation disclosed cerebral white-matter involvement on MRI and arylsulfatase A pseudodeficiency carrier state, which was also identified in clinically unaffected family members. Since skin biopsies showed dermal connective tissue abnormalities, we studied collagens I, III, and VI biosynthesis. Northern blotting of RNA extracted from cultured skin fibroblasts revealed an increased steady-state messenger RNA (mRNA) level of alpha 1(VI) collagen, whereas no differences were detected for pro alpha 1(I), pro alpha 1(III), and tropoelastin mRNAs. The skin content of collagen and total protein was higher in the patients than in controls. We suggest that an extracellular matrix abnormality may be involved in the pathogenesis of this disorder.

Efficacy of doxycycline and tetracycline in ocular rosacea.

We compared the effects of doxycycline and tetracycline hydrochloride on the subjective symptoms in ocular rosacea. Twenty-four patients with symptomatic ocular rosacea were randomly assigned to two groups and treated with doxycycline 100 mg/day (group 1, 16 patients) or tetracycline hydrochloride 1 g/day (group 2, eight patients). The dosages of each drug were gradually tapered and discontinued according to symptomatic response. At each examination all the manifesting symptoms were scored by the patients. Patients were followed up from six weeks to three years. After six weeks of drug treatment, all patients except one had symptomatic improvement. Although most of the scores of the symptoms were significantly decreased in both groups, greater symptomatic relief occurred in the tetracycline hydrochloride-treated patients (P = .041). However, after three months of treatment there was no significant difference in symptoms between the two groups. Gastrointestinal tract complications occurred in two of the 16 patients (12.5%) in group 1 and in three of the eight patients (37.5%) in group 2. Both tetracycline hydrochloride and doxycycline can control the symptoms of ocular rosacea.

The use of doxycycline and tetracycline in ocular rosacea.

The authors compared the effects of doxycycline and tetracycline hydrochloride on subjective symptoms in ocular rosacea. Twenty-four patients with symptomatic ocular rosacea were prospectively treated with doxycycline 100 mg/day (group 1, n=16) or tetracycline hydrochloride 1g/day (group 2, n=8). The dosages of each drug were gradually tapered and discontinued according to symptomatic response. Patients were followed from six weeks to three years. In group 1, 15 patients (94%) had symptomatic improvement (12 patients were asymptomatic and three symptomatically improved), and two patients (13%) had gastrointestinal tract (GIT) complications followed by discontinuation of medication. In group 2, seven of the eight patients (87%) were asymptomatic and one patient (13%) had symptomatic improvement; three patients discontinued the use of tetracycline as a result of GIT complaints. This study indicates that both tetracycline hydrochloride and doxycycline can control the symptoms of ocular rosacea.

Binding modes of IgG from pemphigus autoimmune sera onto guinea pig keratinocytes and the fate of bound IgGs.

Pemphigus is an intraepidermal autoimmune blistering disease of humans caused by circulating IgGs. We have investigated the binding mode and the fate of bound antibodies from Pemphigus sera (P-IgG) on guinea pig keratinocytes in suspension in order to find clues to the loss of cell adhesion in vivo (acantholysis). Flow cytometry, following indirect immunofluorescent labeling of the keratinocytes, and dead cells' staining with ethidium bromide, demonstrated the specific surface binding of P-IgG onto living keratinocytes only. This was shown with several Pemphigus sera or purified P-IgG. This technique, used with various Pemphigus sera, showed that the specific binding is increased when the serum titer is higher, and "Km" values for P-IgG were roughly and inversely correlated to the titers. Upon saturation the same average number of Pemphigus IgG sites per cell were found for the sera of different patients. Analysis of the specific binding of [125I]-P-IgG onto Percoll-separated (living) keratinocytes showed the existence of two classes of sites: 2 x 10(6) sites/cell high-affinity sites (Kd = 1.5 x 10(-6) M total IgG) and 25 x 10(6) sites/cell low-affinity sites (Kd = 6 x 10(-5) M total IgG). Cell sorting and flow cytometry of individual cells allowed us to correlate the light-scattering signal, the RNA content, the size and morphology, and the P-IgG binding to the cells. The results indicated that P-IgG binding is homogeneous within the living keratinocytes and increases with cell size (cell maturity). Cell-sorter analysis of cells with membrane-bound P-IgG, coupled to direct determination of P-IgG released in the medium, revealed the fate of bound P-IgG: 40-60% of the P-IgGs were released in the medium within 30 minutes at 37 degrees C. This was accompanied and followed by a much slower, metabolic energy-dependent, internalization process of the membrane-bound P-IgG. The internalization has been confirmed by electron microscopy of bound P-IgG labeled with protein A-gold. Internalized IgGs were seen in the cells in coated membranous vesicles and other endocytic compartments. Similar behavior was also observed with two other membrane ligands: i.e., concanavalin A and multispecific rabbit "antisurface" antibodies.

Seasonal variation of UV radiation at the Dead Sea.

Pilot measurements were made of natural UV radiation (UVA and UVB, broad-band and erythemogenic) on the Dead Sea (400 m below sea level) and in Spain at sea level, both at approximately the same geographical latitude. Measurements were made at different times of single days during the 1985/1986 season. The preponderance of UVA over UVB was more pronounced in winter.

Papular acrodermatitis of childhood associated with hepatitis A virus infection.

A 2-year-old girl developed an erythematous papular eruption on her face and extremities a week after an epidemic of hepatitis A had occurred in her school. Clinical and laboratory signs of acute hepatitis, together with serologic verification, confirmed hepatitis A infection. That diagnosis should be considered in the etiology of papular acrodermatitis of childhood.

Aminophylline versus doxapram in idiopathic apnea of prematurity: a double-blind controlled study.

A double-blind controlled study, in two parts, was undertaken to compare the effectiveness of aminophylline and doxapram therapy in idiopathic apnea of prematurity. In the first part of this study, eight of 15 infants responded to doxapram therapy with complete cessation of apneic spells and six of 11 infants responded similarly to administration of aminophylline. These differences were statistically insignificant. In the second part of the study, assessment was made of whether the addition of doxapram to aminophylline therapy was effective in treatment of apnea of prematurity that had been unresponsive to aminophylline alone. Of ten infants who continued to have apneic spells during treatment with aminophylline, eight responded to the addition of doxapram with complete cessation of apnea. Nine infants received placebo in addition to aminophylline, and none had a reduction in frequency of apnea.

Aminophylline versus doxapram in weaning premature infants from mechanical ventilation: preliminary report.

A small, double-blind crossover study compared the efficacy of aminophylline and doxapram in ventilator weaning of eight premature infants recovering from respiratory distress syndrome (RDS). Although neither drug was significantly better than the other, four infants were weaned from mechanical ventilation after drug administration. It is suggested that drugs stimulating the respiratory center may aid in shortening the duration of mechanical ventilation in premature infants recovering from RDS.