Cleidocervical muscle: a mini literature survey of a human muscle variation.

Cleidocervical muscles (CCM) or levator claviculae muscles in humans can be found as supernumerary unilaterally or bilaterally on the neck attached proximally to the clavicle and distally to the transverse process of cervical vertebrae at various levels. Altogether 20 case reports from year 1994 till present including 25 subjects related to CCM were found and analysed where parameters such as cervical insertion level, clavicular insertion at the middle vs. lateral third, unilateral vs. bilateral presence of the muscle, study type, reported gender of the subjects were extracted. Our literature survey shows that the prevalence of CCM in male and female was equally presented in radiological studies whereas almost 3-fold higher prevalence of males was found in cadaver reports. Since body donor system worldwide is male dominant, a 1:1 proportion of male and female in radiological studies could show more reality-based distribution of this muscle. Nevertheless, the presentation of this muscle was found in over 90% of the case reports unilaterally with higher left sided dominance. Even though the attachment points of CCM varied from case to case, the proximal attachment was found slightly more frequent on the middle third of the clavicle whereas the distal insertion was present more often on the superior cervical vertebrae than the lower ones. With prevalence of CCM in the population around 2.0-2.5%, the clinical, radiological and surgical relevance of this variation has to be highlighted to avoid potential misleading diagnostics in the neck.

Surgical removal of the index node marked using magnetic seed localization to assess response to neoadjuvant immunotherapy in patients with stage III melanoma.

This pilot study explored the value of localized index node removal after neoadjuvant immunotherapy in patients with stage III melanoma, for use as a response indicator to guide the extent of completion lymph node dissection. Promising technology.

Development and validation of a nomogram to predict recurrence and melanoma-specific mortality in patients with negative sentinel lymph nodes.

BACKGROUND: Patients with melanoma and negative sentinel nodes (SNs) have varying outcomes, dependent on several prognostic factors. Considering all these factors in a prediction model might aid in identifying patients who could benefit from a personalized treatment strategy. The objective was to construct and validate a nomogram for recurrence and melanoma-specific mortality (MSM) in patients with melanoma and negative SNs. METHODS: A total of 3220 patients with negative SNs were identified from a cohort of 4124 patients from four EORTC Melanoma Group centres who underwent sentinel lymph node biopsy. Prognostic factors for recurrence and MSM were studied with Cox regression analysis. Significant factors were incorporated in the models. Performance was assessed by discrimination (c-index) and calibration in cross-validation across the four centres. A nomogram was developed for graphical presentation. RESULTS: There were 3180 eligible patients. The final prediction model for recurrence and the calibrated model for MSM included three independent prognostic factors: ulceration, anatomical location and Breslow thickness. The c-index was 0·74 for recurrence and 0·76 for the calibrated MSM model. Cross-validation across the four centres showed reasonable model performance. A nomogram was developed based on these models. One-third of the patients had a 5-year recurrence probability of 8·2 per cent or less, and one-third had a recurrence probability of 23·0 per cent or more. CONCLUSION: A nomogram for predicting recurrence and MSM in patients with melanoma and negative SNs was constructed and validated. It could provide personalized estimates useful for tailoring surveillance strategies (reduce or increase intensity), and selection of patients for adjuvant therapy or clinical trials.

The Khorana score for the prediction of venous thromboembolism in patients with pancreatic cancer.

BACKGROUND: The Khorana score is a clinical prediction score developed to identify ambulatory cancer patients at high risk of venous thromboembolism (VTE), who may be eligible for thromboprophylaxis. This score has been validated in various populations with cancer, but its performance in patients with pancreatic cancer is less clear. PATIENTS AND METHODS: This is a single center, retrospective cohort study in which consecutive, ambulatory patients with pancreatic adenocarcinoma, who started neoadjuvant or palliative chemotherapy at our center between 2003 and 2014 were included. At baseline, the Khorana score classified patients as 'intermediate risk' (2 points) or 'high risk' (≥3 points) for VTE. The primary outcome was the composite of objectively confirmed symptomatic or incidental lower extremity deep vein thrombosis (DVT) or pulmonary embolism (PE) during 2-year follow-up. RESULTS: The study group comprised 178 patients. The mean age was 62years and 62% had distant metastasis. Overall, 22 of 178 patients (12.4%) developed lower extremity DVT or PE. The estimated cumulative incidence at 6months was 8.2% in 'intermediate risk' patients and 9.5% in the 'high risk' patients (subhazard ratio for first 6months: 1.23; 95% CI: 0.41-3.65). At 2years, the cumulative incidence was higher in 'intermediate risk' patients (15.3%) than in 'high risk' patients (10.1%). CONCLUSIONS: In the present study, the Khorana score was not able to discriminate between pancreatic cancer patients at intermediate risk and high risk of VTE. Physicians should have a low threshold of considering thromboprophylaxis in patients with pancreatic cancer given the high absolute VTE risk.

Characterisation of deep arterio-venous anastomoses within monochorionic placentae by vascular casting.

OBJECTIVE: To characterise arterio-venous anastomoses (AVA) in monochorionic (MC) placentae and determine (i) whether shared cotyledons lie beneath the co-termination of an artery from one twin and a vein to the contralateral twin and (ii) whether all AVA can be detected by visual inspection of the chorionic plate. METHODS: Vascular casts were made of 15 MC placentae. The number of typical AVAs suspected visually before digestion was compared with the number of AVAs identified after acid digestion. RESULTS: Thirty-three of 67 (49%) suspected typical AVAs were confirmed as typical after casting. There were five false positives and no false negatives. The remainder were classified as atypical AVAs, found in > or =90% of MC placentae. Type I (small vascular connections between two apparently normal cotyledons not seen before casting) and Type II (shared cotyledons arising within larger apparently normal cotyledons) atypical AVAs were found in 53% and 73% of placentae, respectively. CONCLUSIONS: Only half the shared cotyledons in MC placentae are characterised by co-termination of an artery and vein on the chorionic plate. We report the existence of deep anastomoses beneath the chorionic plate that cannot be visualised by chorionic plate inspection. These findings have implications for laser treatment of twin-twin transfusion syndrome.

Crystallization of the isobutylphosphocholine-cholesterol-isobutanol (1:3:3) complex and its investigation by X-ray analysis: interaction of phopholipid headgroups with cholesterol.

A crystal complex consisting of the isobutyl analog of phosphatidylcholine (PC) (isobutylphosphocholine), cholesterol, and isobutanol with molecular ratio 1:3:3 was obtained and investigated by means of X-ray analysis. The complex was shown to correspond to the monoclinic system (sp. gr. P2(1)): a=16.994(10), b=11.314(7), c=28.164(15), beta=104.07(3), V=5252.63 A(3), Z=2, D(calc)=1.0273 g/cm(3). The isobutylphosphocholine molecule is the key component of the complex. Pairs of hydrogen bonds are formed between the (-delta)O-P-O(delta-) group of the isobutylphosphocholine molecule and C-OH groups of two cholesterol and two isobutanol molecules. The third molecules of cholesterol and isobutanol are H-bonded with the (-delta)O-P-O(delta-) group of the isobutylphosphocholine molecule via C-OH groups of isobutanol and cholesterol, respectively. The crystal structure is built up by translation of the complex in multiplicate along the two-fold axis in the direction of axis b. It contains bands formed by isobutylphosphocholine molecules alternately changing their direction. They are fixed by virtue of two zones of electrostatic interactions of the type (-delta)O-P-O(delta-)ellipsis(+)N(CH(3))(3) and are more or less parallel to the bc plane. The structure also contains three-layer domains formed by cholesterol molecules perpendicular to isobutylphosphocholine bands. In the direction of the c-axis isobutylphosphocholine bands alternate with the layers of cholesterol molecules herewith reproducing repeated blocks. The obtained structure is compared with that of crystals of phospholipids and cholesterol and its derivatives.

Reconstitution of the zone-block model of biomembranes. 3. Synthesis and investigation of the structure of phosphatidylcholine analog isobutyl-2-(trimethylammonia)ethyl phosphate in its monohydrate crystals and monohydrate complexes with isobutanol.

An isobutyl analog of phosphatidylcholine--isobutyl-2-(trimethylammonia)ethyl-phosphate (IPC)--was synthesized to accomplish the physical reconstitution of the zone-block model of biomembranes. X-ray analysis was used to study the IPC monohydrate (IPC.H2O) crystals grown from water or dimethylformamide with 2% water and the IPC.H2O complex with isobutanol (IPC.H2O.IB) formed by IPC crystallization from isobutanol with 0.5% water. The two compounds were shown to belong to the monoclinic syngony (Sp. gr. P2(l)/a): IPC.H2O-a = 11.075(4), b = 9.679(3), c = 13.921(5) A; beta = 110.61(4) degrees, Z = 4; IPC.H2O.IB-a = 11.370(6), b = 9.397(5), c = 18.12(1) A, beta = 99.42(5) degrees, Z = 4. In IPC.H2O crystals, IPC molecules formed chains due to the system of hydrogen bonds between water molecules and IPC phosphate groups. In turn, ionic bonds between trimethylammonium and phosphate groups of the bipolar heads made these chains to form layers. Another system of ionic bonds (also between -N+(CH3)3 and -O-P = O groups) arranged the layers in a bilayer structure. The bonds were formed between the pairs of molecules oppositely directed and located in neighbouring monolayers. The structure of the bilayer in IPC.H2O.IB crystals was similar. The only difference was the presence of isobutanol molecules between the IPC isobutyl radicals. C-OH groups of isobutanol formed hydrogen bonds with water molecules. However, the interlayer gaps in these two cases differed significantly. In IPC.H2O, the bilayers partially overlapped, whereas in IPC.H2O.IB, they were located at a considerable distance. The structures of the investigated compounds confirm in principle the possibility of the formation of ionic bonds between trimethylammonium and phosphate groups within the bilayer as well as in the interzonal region with apolar radicals that was predicted by the zone-block model of biomembrane. However, the phosphocholine heads were parallel but not perpendicular (as presumed in the model) to the bilayer plane.

Do anaesthetics and surgical stress increase the risk of post-exposure rabies treatment failure?

Rabies is fatal in humans and, after exposure, only correct postexposure treatment as outlined in World Health Organization guidelines can prevent the disease. Analysis of case reports of treatment failures has shown that recommendations have not been followed and that patients presenting risk factors should receive additional care. Known risk factors are delay of more than 24 h in starting postexposure treatment, multiple wounds (especially on head, neck, arm or fingers), incorrect initial wound treatment, immunodepression and non-application of anti-rabies immunoglobulins or serum. We present a case, recently reported from India to Drug Surveillance Behringwerke AG, Marburg, Germany, in which surgery under ketamine anaesthesia might have been an additional risk factor for postexposure treatment failure.

[Itching following therapy with hydroxyethyl starch (HES) in otoneurological diseases]. / Juckreiz nach Therapie mit Hydroxyäthylstärke (HES) bei otoneurologischen Erkrankungen.

It is generally assumed, that a disturbance of microcirculation is the common pathogenetic end factor in various cochleovestibular disorders of different etiology. Therefore improvement of microcirculation is an important therapeutic goal. Several studies demonstrated, that hydroxyethylstarch (HES) has better haemorheological effects than Dextran and less side effects. For this reason we have changed the therapy with Dextran since 1987 to hydroxyethylstarch in several oto-neurological disorders (as sudden hearing loss, neuronopathia vestibularis, idiopathic facial palsy). As after the therapy with HES--generally after dismissal from the ENT-department--some patients complained of general pruritus, so we performed a retrospective study with a standardized interview-protocol. Of 481 treated patients we investigated 237 (49%): of 149 patients treated with HES 200/0.5, 43 patients (28.8%) complained of pruritus; from 88 patients treated with Dextran 40, only 5 patients (5.7%) reported pruritus. The difference is significant (p less than 0.0001). In nearly half of the patients (more than 40%) the pruritus started in normal skin 1 to 3 weeks after the HES-therapy and lasted for 6 weeks to 6 months; the itching was very resistant to therapy (f.e. with antihistaminics). We want to draw the attention to this possible, in the literature until now quite neglected, for some patients extremely uncomfortable and socially embarrassing side effects after HES-therapy when given in relatively high doses. It is therefore suggested therapeutic recommendations should be developed to prevent this undesired side effect.

[Experiences with a new cat coryza-panleukopenia-rabies combined vaccine]. / Erfahrungen mit einem neuen Katzenschnupfen-Panleukopenie-Tollwut-Kombinationsimpfstoff.

The development of a new combined vaccine against cat flu, panleukopenia and rabies should lead to a simplification of the vaccination calendar in small animal practice. In order to judge the suitability of the new vaccine, its efficacy, local tolerability, and safety were evaluated. All vaccinated cats developed high antibody titres against herpes-, calici-, panleukopenia- and rabies virus that persisted well during the trial of 18 months. In comparison to other vaccines containing a smaller number of antigens the suitability of the vaccine on trial could be shown.

Purified chick-embryo-cell (PCEC) rabies vaccine: its potency performance in different test systems and in humans.

The potency of purified chick embryo cell rabies vaccine Rabipur was evaluated by four different in vivo test systems: (1) NIH test with homologous strain LEP challenge; (2) intramuscular challenge of vaccinated laboratory animals; (3) postexposure vaccine treatment trials in laboratory animals; and (4) antibody induction tests in laboratory animals. These different test systems were compared with the Standard NIH test and an in vitro test, the modified ABT. Each of the four in vivo methods chosen demonstrated potency values superior to that of the Standard NIH test in which challenge was with CVS strain. Potency relations were: Standard NIH test versus alternative methods versus modified ABT 1.0-2.2-1.85 respectively. There was good correlation between alternative in vivo methods and the ABT. In addition examples of antibody induction in man following administration of various postexposure treatment regimens are presented which lead to the conclusion that postexposure vaccination method and composition of the study group play a more important role in achieving optimum treatment results than vaccine potency, provided that it corresponds to WHO requirements (minimum 2.5 IU per dose).

Production of antibodies to canine distemper virus in chicken eggs for immunohistochemistry.

The present study describes the application of egg yolk antibodies in immunohistochemistry. In order to obtain specific antibodies against canine distemper virus (CDV), chickens were immunized with attenuated virus. Distinct antibody titres in serum and yolk could be detected by means of a modified plaque/focus immunoassay (ELISA) two weeks after a second immunization. The lower concentrations in corresponding yolk globulin preparations are attributed to the loss of antibodies caused by the isolation procedure (dextran and ammonium sulfate precipitation). After verification of the antibody specificity by indirect immunofluorescence technique high titred globulin fractions were employed in immunohistochemistry using the Avidin-Biotin-Complex method. A specific and distinct immunostaining in formalin fixed and paraffin embedded brain sections of CDV-infected dogs was obtained. The advantages of egg yolk antibodies for immunological purposes are discussed in detail.

Preclinical investigations of the safety, immunogenicity and efficacy of a purified, inactivated tick-borne encephalitis vaccine.

A new tick-borne encephalitis (TBE) vaccine for human use has been developed. TBE virus (TBEV) was propagated in primary chick embryo cells, inactivated by formalin and purified by continuous-flow density gradient centrifugation. The TBE vaccine was tested for innocuity, immunogenicity and protective capacity in a series of laboratory tests. The results indicated that the vaccine is outstandingly well tolerated, highly immunogenic in various laboratory animals, and induces protective immunity in mice. These data suggest that this new vaccine should be studied in clinical trials.

[The prevention of distemper in zoo animals]. / Prophylaxe der Staupe bei Zootieren.

The distemper virus infection of different non-domestic carnivorous zoo animals is known since long. All species involved belonged to the suborder Fissipedia. In 1988 a distemper or morbillivirus-like infection occurred in harbour seals, a member of the suborder pinnipedia. For the prophylaxis of distemper in dogs attenuated live vaccines are commonly used. In zoo animals, however, these vaccines caused distemper several times. In contrast, an inactivated virus vaccine proved both its safety and efficacy in more than hundred zoo animals of various species.

[Occurrence and identification of enterotoxin-producing E. coli strains in milk and dairy products]. / Vorkommen und Nachweis von Enterotoxin-bildenden E. coli-Stämmen in Milch und Milchprodukten.

Enteric diseases caused by enterotoxigenic E. coli strains (ETEC) become more and more important all over the world. Frequently food is implicated as a vector. --From this the necessity arises to identify ETEC strains and/or their heatlabile (LT) and heat-stable enterotoxins (ST). The examinations carried out for the presented paper showed the following results: Detection of LT by coagglutination is a simple and rapid test and may be helpful for screening. Most suitable, however, is the application of ELISA which enables the detection of 1 ng/ml LT with a good reproducibility. For identification of ST the suckling mouse assay (SMA) yields reliable results. ELISA and SMA have proved to be useful in practice for examination of food samples. By means of these methods 157 E. coli strains predominantly isolated from milk and milk products were examined. Hereby, five ETEC strains could be identified (3.2%). For the purpose of food examination a procedure was developed which ensures a reliable and efficient identification of E. coli enterotoxin. The essential steps are enrichment in E.E.-broth, subcultivation in CAYE-2-broth, identification of LT by ELISA resp. coagglutination and the detection of ST with aid of the SMA. So, isolation of single colonies can be omitted, which is an essential advantage.

[Conservative complete restoration of the apical-ostitis foci]. / Uber die konservative Ausheilungsmöglichkeit apikal-ostitischer Herde

Histological pictures on the initial and further development of periapical inflammations show that they may develop after the formation of an abscess as well as primary solid granulation starting at the apex. It depends on the surrounding connective tissue interpreted as sclerosed edema whether in the case of an abscess, the abscess cavity will be organized or whether a cyst will be developing.