High interindividual variability in LDL-cholesterol reductions after inclisiran administration in a real-world multicenter setting in Germany.

BACKGROUND AND AIMS: Low-density lipoprotein cholesterol (LDL-C) is the main therapeutic target in the treatment of hypercholesterolemia. Small interfering RNA (siRNA) inclisiran is a new drug, which targets PCSK9 mRNA in the liver, reducing concentrations of circulating LDL-C. In randomized trials, inclisiran demonstrated a substantial reduction in LDL-C. The German Inclisiran Network (GIN) aims to evaluate LDL-C reductions in a real-world cohort of patients treated with inclisiran in Germany. METHODS: Patients who received inclisiran in 14 lipid clinics in Germany for elevated LDL-C levels between February 2021 and July 2022 were included in this analysis. We described baseline characteristics, individual LDL-C changes (%) and side effects in 153 patients 3 months (n = 153) and 9 months (n = 79) after inclisiran administration. RESULTS: Since all patients were referred to specialized lipid clinics, only one-third were on statin therapy due to statin intolerance. The median LDL-C reduction was 35.5% at 3 months and 26.5% at 9 months. In patients previously treated with PCSK9 antibody (PCSK9-mAb), LDL-C reductions were less effective than in PCSK9-mAb-naïve patients (23.6% vs. 41.1% at 3 months). Concomitant statin treatment was associated with more effective LDL-C lowering. There was a high interindividual variability in LDL-C changes from baseline. Altogether, inclisiran was well-tolerated, and side effects were rare (5.9%). CONCLUSION: In this real-world patient population referred to German lipid clinics for elevated LDL-C levels, inclisiran demonstrated a high interindividual variability in LDL-C reductions. Further research is warranted to elucidate reasons for the interindividual variability in drug efficacy.

Effects of the COVID-19 pandemic on suicide attempts in a rural region in Germany, a 5-year observational study.

BACKGROUND: The COVID-19 pandemic and public life restrictions may have a negative impact on people's mental health. Therefore, we analyzed whether this condition affected the occurrence of suicide attempts (SA) over 20 months during the pandemic period. METHODS: We included patient records according to DSM-5 criteria for suicidal behavior disorders (n = 825) between Jan 1, 2017, and Dec 31, 2021. We applied interrupted time-series Poisson regression models to investigate the effect of the pandemic on SA occurrence, time trends, and seasonal patterns in the whole group of patients as well as stratified by age and gender. RESULTS: There was no significant effect of the pandemic on the occurrence of SA in the overall group. However, we observed a significant impact of the pandemic on the seasonal pattern of SA, also the variance differed significantly (pre-pandemic mean ± variance: 13.33 ± 15.75, pandemic: mean ± variance: 13.86 ± 7.26), indicating less periodic variation in SA during the pandemic. Male patients and young adults mainly contributed to this overall effect. Subgroup analysis revealed a significant difference in SA trends during the pandemic in older adults (>55 years) compared with younger adults (18-35 years); SA numbers increased in older adults and decreased in younger adults as the pandemic progressed. LIMITATIONS: A few patients may have received initial care in an emergency department after SA without being referred to psychiatry. CONCLUSIONS: In general, the COVID-19 pandemic and related measures did not significantly affect the occurrence of SA but did significantly affect the dynamics. In addition, the pandemic appeared to affect suicidal behavior differently across age groups as it progressed. Particularly for the older adult group, negative long-term effects of the pandemic on suicidal behavior can be derived from the present results, indicating the need to strengthen suicide prevention for the elderly.

Chromosome number and ploidy level of balm (Melissa officinalis).

BACKGROUND: Lemon balm (Melissa officinalis L.) is of increasing importance resulting in rising growth area. Improved knowledge on the genome structure, number of chromosomes in connection with the taxonomical structure of balm is indispensable for improved new varieties. RESULTS: A collection of 40 balm accessions (M. officinalis) was characterized by flow cytometry and FISH (18/25S and 5S rDNA) to determine the chromosome number and ploidy level. Three different types were found: diploid genotypes with 2n = 2× = 32 chromosomes; tetraploid 2n = 4× = 64 chromosomes and triploid 2n = 3× = 48 chromosomes. A haploid base number of × = 16 chromosomes is likely. First time described triploid accessions are sterile but cytologically and morphologically stable for many years. Triploids express better winter hardiness and regeneration after harvesting cuts as well as bigger leaves and internodes. CONCLUSIONS: A basic chromosome number of x = 16 is reported for the first time for the species M. officinalis.

Distinct fluctuations of ammonia levels during asparaginase therapy for childhood acute leukemia.

BACKGROUND: The enzyme asparaginase (L-Asp) catalyses the hydrolysis of the non-essential amino acids asparagine and glutamine to aspartic and glutamic acid and ammonia. Ammonia therefore represents a direct metabolite of the biochemical reaction induced by this enzyme. However, data regarding the dynamics and clinical relevance of ammonia levels during L-Asp therapy are lacking. PROCEDURE: We prospectively followed the dynamics of ammonia levels during L-Asp containing induction therapy according to the ALL-BFM 2000 protocol in 10 pediatric patients with acute lymphoblastic leukemia (ALL), in order to assess the possible relevance of ammonia levels for clinical practice and its use as a possible surrogate parameter of L-Asp enzyme activity. RESULTS: We observed a significant elevation of ammonia levels 1 day after intravenous L-Asp administration with ammonia levels reaching up to the seventh fold of normal values, followed by a steep decline to basal values within another 2 days, resulting in an undulating course of ammonia concentrations during L-Asp containing induction treatment. CONCLUSIONS: Although there are potential neurotoxic properties of ammonia, central nervous system (CNS) toxicity has not been observed in our study and is generally not seen as a common side effect of L-Asp therapy. Furthermore, due to the characteristic fluctuation profile, ammonia levels may represent a suitable surrogate parameter of L-Asp enzyme activity and may enable the monitoring of silent inactivation of L-Asp.

[Cryosurgery--the last resort or a surgical alternative in the treatment of lichen sclerosus et atrophicus of the vulva (LSAV)?]. / Kryochirurgie--ultima ratio oder chirurgische Alternative beim vulvären Lichen sclerosus et atrophicus (LSAV)?

BACKGROUND: The treatment of LSAV consists mainly of topical corticosteroids, progesterone or testosterone. Often these approaches neither improve the clinical findings nor relieve the symptoms. We evaluated cryotherapy as a possible therapeutic option. PATIENTS AND METHODS: Nine girls (age between 5 and 15 years, mean 9 years) and 22 women (age between 33 to 74 years, mean 54 years) with clinically and histologically confirmed LSAV were treated with cryotherapy. RESULTS: All patients experienced improvement of their clinical signs and symptoms. Five patients had a second cycle of cryotherapy after an average of 10,6 months; 2 women were treated a third time. CONCLUSIONS: Cryotherapy is an effective therapeutic option for LSAV. It has few side effects and seems to be an attractive alternative especially in children.

[Acid oligosaccharides as the active principle of aqueous carrot extracts for prevention and therapy of gastrointestinal infections]. / Saure Oligosaccharide als Wirkprinzip von wässrigen Zubereitungen aus der Karotte in der Prophylaxe und Therapie von gastrointestinalen Infektionen.

Adherence of microorganisms to the intestinal mucosa is an important and initial step in the pathogenesis of gastrointestinal infections and mediated by carbohydrate structures on the cell surface. Adherence can be blocked by carbohydrate receptor analogues. Aqueous extracts from carrots (carrot soup) contain acidic oligosaccharides, which are able to block adherence of various enteropathogenic microorganisms to HEp-2 cells and human intestinal mucosa in vitro. Dependent on the grade of polymerisation the most potent blocking ability was seen for trigalacturonic acid. Clinical studies revealed, that aqueous carrot extracts are significantly superior to the basic glucose-electrolyt-solution for oral rehydration in acute gastrointestional infections of children.

Influence of macrolide antibiotics on promotion of resistance in the oral flora of children.

BACKGROUND: The long elimination half-life of azithromycin allows subinhibitory serum and epithelial lining fluid (ELF) concentrations over a period of several weeks post treatment, which may have an impact on the emergence of macrolide resistance. In this prospective, open-label, randomized study, four macrolides and the azalide azithromycin were studied for their likelihood to promote resistance in the oral flora of children with respiratory tract infections. PATIENTS AND METHODS: Children were randomly assigned to receive azithromycin, clarithromycin, erythromycin, roxithromycin and josamycin. Throat swabs were obtained prior to treatment and weekly for 6 weeks. Minimum inhibitory concentrations (MICs) for resistant strains were assessed by E-test and National Committee for Clinical laboratory Standards (NCClS) broth microdilution. RESULTS: One week post treatment, up to 90% of children harbored macrolide-resistant strains in their oral flora. Except for azithromycin, the percentage of patients colonized by resistant organisms decreased to a rate of 17% for clarithromycin (10/60), erythromycin (2/12) and josamycin (2/12) and 33% for roxithromycin (4/12) after 6 weeks. In the azithromycin group, 85% (51/60) of patients were colonized by macrolide-resistant organisms after 6 weeks, 11.6% (7/60) of children suffered from reinfection. CONCLUSION: Azithromycin therapy appears to put selective pressure on the infective and native flora of children, promoting the carriage of macrolide-resistant strains.

Topical anti-inflammatory activity of a new germacrane derivative from Achillea pannonica.

The topical anti-inflammatory activity of a germacrane derivative [1,4-dihydroxy-germacra-5E-10(14)-diene; DHGD] isolated from Achillea pannonica Scheele (Asteraceae) was investigated employing the Croton oil-induced dermatitis in the mouse ear. Its effects on the oedematous response and on leukocytes infiltration are described. The germacrane derivative significantly inhibited ear oedema in a dose-dependent manner, with an ID(50) of 0.40 micromol/cm(2). DHGD (0.75 micromol/cm(2)) provoked a global inhibition of the oedematous response (61 %) higher than that induced by an equimolar dose of indomethacin (43 %) within 24 hours; the reduction induced by hydrocortisone (0.10 micromol/cm(2)) was 68 %. The effect of DHGD (61 % inhibition) was higher than that of the equimolar dose of indomethacin (51 % inhibition) also on granulocytes recruitment at the site of inflammation. Hydrocortisone (0.10 micromol/cm(2)) reduced the cellular infiltrate by 44 %.

Pediatric visceral leishmaniasis in Austria: diagnostic difficulties in a non-endemic region.

Visceral leishmaniasis is usually fatal if left untreated. In Europe it is mainly caused by Leishmania infantum which is endemic in the whole Mediterranean region. While visceral leishmaniasis classically affects children, adults increasingly suffer infections in regions which are known to be endemic for HIV. Nowadays up to 70% of the patients with visceral leishmaniasis in southern Europe are HIV-infected adults. The diagnosis is known to be especially difficult to establish in this group of patients because of a frequently atypical clinical presentation, but even in non-HIV-infected patients visceral leishmaniasis often represents a diagnostic challenge particularly when the patient is living in a non-endemic region. We report on four children with visceral leishmaniasis diagnosed at St. Anna Children's Hospital, Vienna, in the last decade. Diagnostic difficulties arose (1) from inexperience with this rare disease, (2) from a long incubation period (6 to 8 months) and (3) from a travel history apparently unsuspicious for the contraction of what is considered a 'tropical' disease. In one case, specific problems resulted (4) from clinical appearance and laboratory data mimicking hemophagocytic lymphohistiocytosis. Consequently even in regions where leishmaniasis is not endemic, diagnostic efforts should be undertaken to rule out this disease especially in patients with the presumptive diagnosis of hemophagocytic lymphohistiocytosis.

Rosacea-like demodicidosis associated with acquired immunodeficiency syndrome.

We present a 35-year-old patient with acquired immunodeficiency syndrome who had demodicidosis on his face, characterized by multiple papules and papulopustules, associated pruritus, numerous mites on skin-surface biopsy and in biopsy specimens, and rapid response to topical treatment with permethrin. It seems likely that Demodex infestation does not manifest unless local or systemic immune function is altered, leading to the proliferation of the organism and subsequent disease.

Formation of onion bulblets in vitro and viability during medium-term storage.

The influences of light conditions, sucrose and ethylene on in vitro formation and storability of onion (Allium cepa L.) bulblets were studied in various accessions. Light, sucrose and ethylene influenced bulb formation. Storability was primarily enhanced by a high sucrose concentration (100 g/l) in the culture medium. The bulbing process was characterised by changes in bulbing ratio, leaf length, number of leaves and leaf development time. The viability of bulbs after 1 year of in vitro storage at low temperatures was determined by their growth reaction in subsequent subcultures, growth after transfer into the greenhouse and tetrazolium staining. Sufficient sprouting of bulblets previously stored at -1  °C demonstrated the possibility of storing them in a low-temperature, slow-growth culture.

Expression of adhesion receptors on rat limb bud cells and results of treatment with a thalidomide derivative.

The expression of several adhesion surface receptors was studied on cells of early limb bud development of 58 Wistar rats treated orally with two daily doses of the thalidomide derivative EM12 (2 x 50 mg/kg body weight) from day 7 to 10 of pregnancy. EM12 is a more potent teratogen than thalidomide. Limb bud cells of 56 untreated animals served as controls. The studies revealed that the integrins CD11a, CD11b, CD18, CD49d, and CD61, as well as the additional adhesion receptors CD54, CD62L, and the transferrin receptor CD71 were expressed on day 11 of gestation to various degrees on these embryonic cells. In contrast to results of previous studies with a non-human primate (Callithrix jacchus) there was no down-regulation of any of these receptors on the surface of limb bud cells of the rat embryos after treatment with EM12. This result is in accordance with the lack of teratogenicity in this rodent species.

Interactions between Quaternary Ammonium Surfactant Oligomers and Water-Soluble Modified Guars.

The interaction between hydroxypropylguar (HPG) and its dodecyl-modified derivative (HMHPG) and cationic surfactant oligomers has been investigated by measurements of the solution viscosity at constant shear rate, microviscosity of the aggregates (dipyrenylpropane fluorescence emission spectra), and aggregation number of the polymer hydrophobe and of the surfactant (time-resolved fluorescence quenching). The surfactants are dodecyltrimethylammonium bromide (DTAB, monomeric surfactant) and some of its dimers and trimers which differed by the carbon number s of the polymethylene spacer connecting the surfactant moieties (2

Qualitative and quantitative determination of sesquiterpenoids in Achillea species by reversed-phase high-performance liquid chromatography, mass-spectrometry and thin-layer chromatography.

A reversed-phase high-performance liquid chromatographic method was developed as a universal analysis system in order to determine and quantify antiphlogistic sesquiterpenoids in different Achillea species. Identification was performed by HPLC and diode array detection as well as by monitoring the HPLC fractions by TLC and MS. Using santonin as internal standard, HPLC separations were achieved with a methanol-water gradient system using RP 8 LiChrospher 100 (5 microm) as stationary phase. For validation, sample analyses were performed, using the two tetraploid species A. collina and A. pratensis. The method allows the identification and quantification of the main compounds achillicin, 8alpha-tigloxy-artabsin, 8alpha-angeloxy-artabsin, arglanin and santamarin with variation coefficients between 3.4 and 4.7% (total content) using santonin as internal standard. For the different compounds recovery was found between 81 and 107% performing multiple analyses of A. collina and A. pratensis.

[Bleomycin-induced PSS-like pseudoscleroderma. Case report and review of the literature]. / Bleomycin-induzierte PSS-artige Pseudosklerodermie. Fallbericht und Revision der Literatur.

Although the association between administration of the antitumor agent bleomycin and the development of cutaneous fibrosis is established, there are only a small number of cases of bleomycin-induced scleroderma described in the literature. We report the development of generalised scleroderma with wide spread hyperpigmentation in a 52-year-old male patient, who received a total dose of 360 mg bleomycin in combination with cisplatin and etoposid for therapy of a malignant testicular seminoma. The clinical cutaneous alterations as well as the histological findings were indistinguishable from those encountered in progressive systemic sclerosis (PSS). In contrast to PSS however, Raynaud's phenomenon, cutaneous calcinosis, teleangiectasia, arthritis and involvement of additional organs were all absent. PSS-typical auto-antibodies were negative. Even 18 months after discontinuation of the drug and treatment with UVA1 phototherapy (3-4 times per week with 20 J/cm2) as well as physiotherapy, the skin changes had still not resolved. Based on our case and a detailed review of the literature, we discuss characteristics of bleomycin-induced scleroderma including pathogenesis, treatment modalities and course.

[Balanitis/balanoposthitis chronica circumscripta benigna plasmacellularis--entity or fiction?]. / Die Balanitis/Balanoposthitis chronica circumscripta benigna plasmacellularis--Entität oder Fiktion?

During the years 1985 up to 1995 53 patients between 18 and 80 years of age (mean age 54.7 years) with histologically and clinically proven Zoon's balanitis were treated by circumcision. The majority of patients had symptoms for more than 12 months. In five cases they had lasted for 8, 10, 16, 17 and 47 (!) years. 30 patients were investigated by means of physical examination and questionnaire in this retrospective study. Lesions involved glans in all patients, while in 17 of 30 patients both glans and prepuce were involved. None of the patients showed lesions of the prepuce only. In most cases Zoon's balanitis was successfully treated by circumcision in a period of two to four weeks. In four cases, psoriatic lesions, and in one case lichen ruber was diagnosed. In the remaining patient, whose circumcision was inadequate, a small area of balanitis persisted in the sulcus coronarius still covered by the foreskin. The curative effect of adequate circumcision in 100% of patients suggests that Zoon's balanitis is a relatively non-specific reactive balanitis caused by a disturbed "preputial-ecology". It is remarkable that other distinct inflammatory diseases of glans and prepuce can show features which are identical to those Zoon's balanitis.

Guaianolide-endoperoxide and monoterpene-hydroperoxides from Achillea nobilis.

From flower heads of Achillea nobilis two chrysanthemol derivatives (1, 2), tanaparthin-beta-peroxide (3), and 5-hydroxy-3,6,7,4'-tetramethoxyflavone (4) were isolated by repeated column chromatography and HPLC. Structure elucidation has been performed by means of MS, 1H-NMR, 13C-NMR, and 2D-NMR experiments.