A unique variation of a four-bellied digastric muscle named "real quadrigastric muscle": a case report and literature review.

From a topographical standpoint, the digastric muscle is key to the formation of several triangles of the neck, which are of the utmost clinical significance. Herein, we present a previously unrecognised variation of the digastric muscle: a quadrigastric muscle with two accessory bellies originating from the body and angle of the mandible and inserting to the intermediate tendon. Three new triangles are demarcated between the four bellies of the aberrant muscle. Detailed knowledge of variations of the digastric muscle, changing the borders and relationships of the topographic triangles, is paramount for radiologists and surgeons operating on the anterior region of the neck.

Evaluation of the food effect on a drospirenone only contraceptive containing 4 mg administered with and without high-fat breakfast in a randomised trial.

BACKGROUND: The objective of the present trial was to assess the difference in pharmacokinetics (PK) of an oral test preparation containing 4 mg drospirenone (DRSP) under fasting conditions compared to PK upon food intake after single dose administration. METHODS: Open label, single centre, two-treatment, two-sequence, crossover study in 24 healthy female volunteers, with duration of 1 day per sequence and with a real wash-out period of 14 days to investigate the relative bioavailability of DRSP with both forms of administration. The 90% confidence intervals (CI) were calculated for the intra-individual ratio (test with food vs. without food) of the PK endpoints Area under the curve; 0-72 h [AUC(0-72 h)] and maximal plasma concentration [Cmax] of DRSP. RESULTS: The 90% CI calculated by analysis of variance using logistic transformation (ANOVA-log) for the endpoint, intra-individual ratio (Test 'A' = with food intake) vs. Test 'B' = without food intake) of AUC(0-72 h) of drospirenone was between 104.72 and 111.36%. The 90% CI calculated by means of ANOVA- log for the endpoint intra-individual ratio (Test 'A' vs. Test 'B') of Cmax of DRSP was between 118.58 and 141.10%. The mean relative bioavailability of the test with food 'A' compared to the Test without food 'B' after single dose administration based on the endpoints AUC(0-72 h) was 107.99%; for the endpoint Cmax it was 129.35%. CONCLUSIONS: The rate of absorption, based on the endpoint Cmax of DRSP was increased by about 30% under fed conditions. With respect to consumer habits, this may represent a relevant benefit for contraceptive safety, as the time span between food consumption and pill intake does not play a role. IMPLICATIONS: Our results suggest that the food intake has no impact on the absorption of 4 mg DRSP in the management of contraception. This increases the contraceptive efficacy as no interference with food is expected when consuming the oral formulation under real life conditions. TRAIL REGISTRATION: Trial registration number: EudraCT-No: 2012-004,309-28.

Variations in the origin of the superior laryngeal artery and their clinical significance: a case report with a proposal for a new classification / Variaciones en el origen de la arteria laríngea superior y su significado clínico: reporte de un caso con una nueva propuesta de clasificación

SUMMARY: The superior laryngeal artery is the primary vessel providing the blood supply to the larynx. Commonly, it is derived from the superior thyroid artery. Different variations in the origin have been described in the current literature; knowledge of such variations is crucial for various surgical interventions of the larynx and surgical procedures in the lateral region of the neck regarding the carotid triangle. It should be noted that radiological studies, such as selective angiography of the thyroid gland, can also be misleading in cases of variations. Herein, we describe a case of bilateral superior laryngeal artery originating directly from the external carotid artery of the neck. The arteries at first have a transverse course and then pierce through the thyrohyoid membrane alongside internal laryngeal nerves. Moreover, we also review the known variations in the origin of the superior laryngeal artery and propose a new classification of all known variations.

RESUMEN: La arteria laríngea superior es el vaso principal que proporciona el suministro de sangre a la laringe. Comúnmente, se deriva de la arteria tiroidea superior. Han sido descritas diferentes variaciones en su origen y el conocimiento de éstas resulta crucial para las intervenciones quirúrgicas realizadas en la laringe, como también en los procedimientos quirúrgicos que se llevan a cabo en la región lateral del cuello, respecto al triángulo carotídeo. Cabe señalar que los estudios radiológicos, como la angiografía selectiva de la glándula tiroides, también pueden ser engañosos en casos de variaciones anatómicas. Aquí, describimos un caso de arteria laríngea superior bilateral que se originaba directamente de la arteria carótida externa. Las arterias al inicio tenían un curso transversal y luego atravezaban la membrana tirohioidea junto con los nervios laríngeos internos. Revisamos también las variaciones conocidas en el origen de la arteria laríngea superior y proponemos una nueva clasificación de todas las variaciones conocidas.

Differential collagen expression in kidney and heart during hypertension.

AIM: The aim of the present study was to investigate the immunohistochemical expression of selected collagen types, namely collagen types I and V and procollagen type III in the renal parenchyma and interstitium and in the myocardium of spontaneously hypertensive rats. MATERIAL AND METHODS: For the present study, we used two age groups of 6- and 12-month-old spontaneously hypertensive rats. An immunohistochemical analysis was conducted with monoclonal antibodies against collagen types I and V and procollagen type III. A semi-quantitative analysis of immunostaining intensity was conducted with the Image J software. RESULTS: In the kidney, all three molecules showed higher expression at the age of 12 months, which was particularly notable for procollagen type III and collagen type V, which stained as highly-positive. In the myocardium, the immunoreactivity of collagen types I and V was stronger in 12-month-old animals, while that of procollagen type III did not change substantially. CONCLUSION: The present study suggests a role of collagen types III and V in hypertensive kidney disease, while also establishing the role of increased expression of collagen types I and V in adverse myocardial remodeling (Tab. 1, Fig. 2, Ref. 48).

Comparative pharmacokinetic estimates of drospirenone alone and in combination with ethinyl estradiol after single and repeated oral administration in healthy females.

OBJECTIVE: To determine the pharmacokinetics (PK) of drospirenone (DRSP), alone versus in combination with ethinyl estradiol (EE), after single and repeated administration. STUDY DESIGN: We conducted a single-centre, open-label, crossover, 2-treatment, 2-period, 2-sequence study in which non-micronized DRSP 4 mg or a combination of DRSP 3 mg and EE 0.02 mg were administered to healthy female subjects on day 1 to obtain a single-dose kinetic profile, and from day 4 to day 15 to obtain a repeated-dose kinetic profile. The maximum observed concentration (Cmax) and area under the concentration/time curve (AUC) were determined in a model-independent way using non dose corrected data. Statistical analysis was based on a parametric method (ANOVA-log). RESULTS: A total of 24 healthy female subjects were randomized 1:1 into the study. The mean relative, non-dose-corrected PK estimates after single-dose administration for the endpoints AUC(0-72h), AUC(0-24h) and Cmax were 543.5 ng*h/mL, 296.1 ng*h/mL and 27.3 ng/mL for DRSP alone, and 442.0 ng*h/mL, 264.7 ng*h/mL and 37.5 ng/mL for the DRSP/EE combination; p < 0.001. The mean relative, non-dose-corrected PK estimates after repeated dose administration for the endpoints AUC(0-72h), AUC(0-24h) and Cmax were 1066.8 ng*h/ml, 570.2 ng*h/mL and 41.0 ng/mL for DRSP alone, and 1394.5 ng*h/mL, 732.8 ng*h/mL and 61.4 ng/mL for the DRSP/EE combination; p < 0.001. CONCLUSIONS: DRSP alone exhibits a lower accumulation ratio than together with EE. The extent of systemic exposure at steady-state is about 32% less with the new formulation (AUC(0-24h), steady-state geometric mean ratio: 77.8%; 90% confidence interval: 74.6%-81.1%). This PK profile may be caused by EE. IMPLICATIONS: Our results suggest that metabolic pathways of DRSP can be inhibited by EE resulting in higher DRSP plasma concentrations in DRSP/EE formulations than in a DRSP-alone formulation. The enzymes CYP3A4 and SULT1A1 may play a role. Additional drug-drug-interaction studies are needed to better understand these metabolic pathways and their future clinical implications.

A comparative morphometric study of the myocardium during the postnatal development in normotensive and spontaneously hypertensive rats.

BACKGROUND: Differences in the size of cardiac muscle cells observed in normal and hypertrophic hearts have been assessed through different methodologies. Spontaneously hypertensive rats are often used as an experimental model of essential hypertension in humans, which allows researchers to study the relation between hypertension and cardiac hypertrophy. It has been shown that ventricular hypertrophy in mammals progresses and ventricular failure develops in the end stage of hypertrophy. The aim of the present study was to analyse a number of morphometric markers and compare them between male normotensive Wistar rats (WR) and male spontaneously hypertensive rats (SHR). MATERIALS AND METHODS: The total number of male WR was 15, distributed in five age groups, each containing three animals: 2-week-old; 1-month-old; 3-month--old; 6-month-old; 12-month-old. The male SHR were distributed in two age groups, each containing three animals: 1-month-old (young) and 6-month-old (adult). RESULTS: As aging progressed, both in male normotensive WR and in male SHR we noted a statistically significant increase in the morphometric parameters thickness of the free wall and the cross-sectional area of the cardiomyocytes and their nuclei and a decrease in the cardiomyocytic density in both ventricles. These changes were more pronounced and occurred at an earlier age in SHR. CONCLUSIONS: The present study analyses in detail the alterations in the myocardium of the left and right ventricle, initiated by age-related hypertrophy, as well as hy-pertrophy induced by arterial hypertension. (Folia Morphol 2018; 77, 2: 253-265).

Influence of the cytochrome P4502D6*4 allele on the pharmacokinetics of controlled-release metoprolol.

AIM: The aim of the present paper was to compare the pharmacokinetics of metoprolol in homozygous Caucasian volunteers for the wild-type CYP2D6 allele (CYP2D6*1/CYP2D6*1) and heterozygous (CYP2D6*1/CYP2D6*4) Caucasians. METHODS: Thirty-six unrelated healthy male Caucasians were screened for two of the most frequently occurring mutant alleles (CYP2D6*3 and CYP2D6*4) using polymerase chain reaction (PCR). Twenty-four volunteers with a genotype suggesting a rapid hydroxylator phenotype were enrolled in a bioequivalence trial and each received in a randomized, cross-over fashion one of the three formulations compared. Each formulation contained 200 mg metoprolol tartrate/(tablet). In each of the three periods of the trial, one of the formulations was administered under fasting conditions in the morning on 4 consecutive days. Blood for quantification of metoprolol was drawn immediately before the last dose and in selected time intervals thereafter. A sensitive and specific high-performance liquid chromatography (HPLC) method with fluorescence detection was applied for the quantification of metoprolol. Pharmacokinetic parameters were determined for each subject and statistically compared in two groups of 16 homozygous (CYP2D6*1/CYP2D6*1) and six heterozygous (CYP2D6*1/CYP2D6*4) volunteers. RESULTS: Significant differences between homozygous and heterozygous individuals were observed for all pharmacokinetic parameters. The AUC in the course of one those interval of 24 h (AUCtau), minium steady-state concentration (C(min)ss) and average steady-state concentration (C(av)ss) values for heterozygous individuals were more than twice those of individuals. Significantly higher values for C(max)ss, t1/2, half-value duration (HVD) and mean residence time (MRT) were also observed in heterozygous volunteers. The higher concentrations of metoprolol in heterozygous individuals also had pharmacodynamic consequences, namely, greater heart rate and blood pressure reduction.

[Absolute bioavailability of chlorpromazine, promazine and promethazine]. / Absolute Bioverfügbarkeit von Chlorpromazin, Promazin und Promethazin.

The absolute bioavailability of the three phenothiazine neuroleptics, promazine (Sinophenin, CAS 58-40-2), chlorpromazine (Propaphenin, CAS 50-53-3) and promethazine (Prothazin, CAS 60-87-7) was tested in three single-dose cross-over studies. In each trial 12 to 14 healthy volunteers were enrolled. The single doses for promazine, promethazine and chlorpromazine were 100, 75 and 150 mg (orally) and 20, 50 and 50 mg (intravenously), resp. The serum concentrations of the three neuroleptics were measured by means of a selective HPLC-method. the distribution-free confidence intervals for the absolute bioavailability of the three phenothiazines were within 10.5 to 24.7% for chlorpromazine, 7.8 to 24.9% for promazine and 12.3 to 40% for promethazine. Promazine and chlorpromazine are pharmacokinetically very similar and differ substantially from promethazine.

Differences in the bioavailability of dihydrotachysterol preparations.

The bioavailability of four preparations containing dihydrotachysterol (DHT2) was tested in two separate trials with administration of single, oral doses of 1 mg per individual. The relative bioavailability of corresponding preparations (capsules vs capsules and oral solution vs oral solution) was tested in a randomised, cross-over pattern within the same group of volunteers. Two different groups of 24 healthy volunteers took part in each trial. Solution and capsule bioavailability was also compared inter-individually. A new sensitive HPLC-method (quantification limit 0.5 ng.ml-1) was used for the measurement of DHT2 concentration in serum. Three of the preparations tested had a similar bioavailability (mean AUC values of 195.5-223 ng.h.ml-1); the bioavailability of the fourth preparation (A.T.10 oral solution) was considerably lower (mean AUC value 111.5 ng.h.ml-1). The present dosage recommendations of all four preparations are identical. A new dosage recommendation is thus required for the oral solution with low bioavailability (A.T.10).

Protective effect of rioprostil on indomethacin-induced lesions of gastric and duodenal mucosa in healthy volunteers.

The protective effect of rioprostil against gastroduodenal mucosal lesions induced by indomethacin is investigated in a double-blind controlled trial on 36 healthy adult volunteers, divided into three groups. All the volunteers are treated with indomethacin, 50 mg t.d.s. during a period of 5 days. The first group is treated with placebo, the second with rioprostil, 300 micrograms, and the third with rioprostil, 600 micrograms. Endoscopies are performed before and after treatment. Blood samples for high performance liquid chromatography determination of indomethacin plasma concentrations are taken on the 6th day, before the last dose of indomethacin is administered, and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12 and 24 h after the last dose of indomethacin. It is found that in both doses rioprostil exerts a protective effect against indomethacin-induced lesions, reducing the appearance rate of erosions from 67% to 17% statistically significant in the 600 micrograms group. The bioavailability of indomethacin in the three groups does not differ significantly.

[Effect of wide-band modulated electromagnetic fields on the workers of high-frequency telephone exchanges]. / Izsledvane vliianieto na shirokolentovi modulirani elektromagnitni poleta vurkhu raboteshchi vuv visokochestotni telefonni uredbi.

Physiological examinations of 63 subjects were performed as well as clinical, functional, paraclinical, etc. examinations of 82 subjects working under the effect of wide-band modulated electromagnetic fields in HFA of telephone exchanges. Some physiological changes were found as regards the level of blood pressure and auditory threshold. Though the intensity of EMF were within the allowable limits, changes in the neuro-vegetological state, genital sphere, were found in some of the examined workers as well as in immunologic reactivity and some paraclinical indices, described to develop under electromagnetic effect, attributed to the specificity of EMF-wide-band, modulated.

[Autonomic nervous changes in combined exposure to lead and arsenic]. / Prouchvane nevro-vegetativnite promeni pri kombiniranoto vuzdeistvie na olovo i arsen.

The characteristic features of the clinical and functional indicators in the early stages are outlined. The impression is that the subjective feelings are being overlapped and objectified by the neurologic status. A considerable number of non-specific reactions with a tendency for generalization are established. It is presumed that in the latent period, the functional changes in the nervous system forerun those in the clinical course and blood. Emphasis is laid on the significance of the astheno-vegetative syndrome and some neurological signs for the early diagnosis.

[Skin mediator reactivity in workers in contact with lead]. / Vurkhu koxhnomediatornata reaktivnost pri rabotnitsi v kontakt s olovo.

The intracutaneous adrenomimetic test is discussed against the background of overall neurovascular reactivity. The skin-mediator test is recommended as a reference of the functional condition of vegetovasal substrates. A certain degree of synchronization between dermal reaction and degree of clinical syndromes and their stages is sought for. Emphasis is laid on parasympathetic excitation in the initial stage. Adrenergic reactivity considered in a constellation with the other indicators, has a definite diagnostic-prognostic value.

[Autonomic nervous manifestations in combined exposure to lead and manganese]. / Vurkhu niakoi nevro-vegetativni proiavi pri kombiniranoto vuzdeistvie na olovo i mangan.

An increased reactivity of the vegetative nervous system under manganese-lead effect is established in practically healthy workers during the latent stage. The dynamics of the combined toxic invasion is characterized by sympathetic-adrenergic manifestations mainly. A number of vegetative disturbances showing a tendency for generalization, and involving various levels of the nervous system, are also outlined.

[17-ketosteroids in the 24-hour urine of miners with vibration disease from local vibration exposure]. / Vurkhu 17-ketosteroidite v 24-chasova urina pri min'ori s vibratsionna bolest ot lokalno vibratsionno vuzdeistvie.

The 17-ketosteroid level in the urine secreted in 24 hours s studied in miners with vibration disease. The case material is analyzed according to age, working service, clinical syndromes and stage. It is demonstrated that the continuous effect of local vibrations lead to inhibition of the adrenal function, manifested by a 17-ketosteroids fall. Such a lowering is assumed as one of the adaptational syndrome-manifestations. Regulation of corticosteroid secretion is discussed in the light of complex interrelations--neuroendocrine, biochemical and homeostatic. The role played by oxidation processes is also emphasized. 17-ketosteroids content in the urine has certain diagnostical value, irrespective of the fact that its lowering is by no means a specific manifestation of the vibration disease.

[Neurovascular reactivity in vibration disease]. / Vurkhu nevro-vaskularnata reaktivnost pri vibratsionna bolest.

It is pointed out that neurovascular derangements are among the earliest and primary changes in individuals exposed to the effect of vibrations. The manifestations of vasoconstriction with a tendency for generalization prevail. Angiospasm associated with hypopallesthesia, hypalgesia and hypothermy in miners with continuous service in hard rocks processing, using high-frequency drilling hammers, constitute in many aspects the complex of symptoms, typical of the vibration disease. It is emphasized that neurovascular reactivity might be assumed as having certain diagnostic-prognostic significance provided it is estimated against the background of the other clinical data and indicators.