Prophylactic nimodipine treatment improves hearing outcome after vestibular schwannoma surgery in men: a subgroup analysis of a randomized multicenter phase III trial.

A 2016 published randomized multicenter phase III trial of prophylactic nimodipine treatment in vestibular schwannoma surgery showed only a tendency for higher hearing preservation rates in the treatment group. Gender was not included in statistical analysis at that time. A retrospective analysis of the trial considering gender, preoperative hearing, and nimodipine treatment was performed. The treatment group received parenteral nimodipine from the day before surgery until the seventh postoperative day. The control group was not treated prophylactically. Cochlear nerve function was determined by pure-tone audiometry with speech discrimination preoperatively, during in-patient care, and 1 year after surgery and classified according to the Gardner-Robertson grading scale (GR). Logistic regression analysis showed a statistically significant effect for higher hearing preservation rates (pre- and postoperative GR 1-4) in 40 men comparing the treatment (n = 21) and the control (n = 19) groups (p = 0.028), but not in 54 women comparing 27 women in both groups (p = 0.077). The results were also statistically significant for preservation of postoperative hearing with pre- and postoperative GR 1-3 (p = 0.024). There were no differences in tumor sizes between the treatment and the control groups in men, whereas statistically significant larger tumors were observed in the female treatment group compared with the female control group. Prophylactic nimodipine is safe, and an effect for hearing preservation in 40 men with preoperative hearing ability of GR 1-4 was shown in this retrospective investigation. The imbalance in tumor size with larger tumors in females of the treatment group may falsely suggest a gender-related effect. Further investigations are recommended to clarify whether gender has impact on nimodipine's efficacy.

Interobserver variability of the House-Brackmann facial nerve grading system for the analysis of a randomized multi-center phase III trial.

BACKGROUND: Evidence of a high interobserver variability of the subjective House-Brackmann facial nerve grading system (HBGS) would justify cost- and time-consuming technological enhancements of objective classifications for facial nerve paresis. METHOD: A total of 112 patients were recruited for a randomized multi-center trial to investigate the efficacy of prophylactic nimodipine treatment in vestibular schwannoma (VS) surgery. For the present investigation both treatment groups were pooled for the assessment of facial nerve function preoperatively, in the early postoperative course and 1 year after the surgery. Facial nerve function was documented photographically at rest and in motion and classified according to the HBGS by three independent observers (neurosurgeon, neurologist, ENT) and by the investigator of each center. RESULTS: Interobserver variability was considerably different with respect to the three time points depending upon the severity of facial nerve paresis. Preoperative facial nerve function was normal or only mildly impaired (HB grade I or II) and was assessed consistently in 97%. Facial nerve function deteriorated during the early postoperative course and was subsequently documented without dissent in only 36%, with one grade difference in 45%, two grade difference in 17% and three grade difference in 2%. One year after surgery, facial nerve function predominantly improved resulting in a consistent assessment in 66%. Differing ratings were observed in 34% with one grade deviation in 88% and of two grades in 12%. Patients with differing ratings of two or more grades exhibited considerably worse facial nerve function (p < 0.001). CONCLUSIONS: The HBGS produced comparable results between different observers in patients with normal or only mildly impaired facial nerve function. Interobserver variability increased depending on the severity of facial nerve paresis. The results suggest that the HBGS does not promote uniformity of reporting and comparison of outcomes in patients with moderate or severe facial nerve paresis.

Transoral, retromolar, para-tonsillar approach to the styloid process in 6 patients with Eagle's syndrome.

OBJECTIVES: Eagle's syndrome is caused by an elongated or mineralised styloid process and characterised by facial and pharyngeal pain, odynophagia and dysphagia. Diagnosis is based on clinical findings. However radiologic imaging, like panoramic radiograph, helps to confirm the diagnosis. There are different treatments of the Eagle's syndrome. Anti-inflammatory medication (carbamazepime, corticosteroids) and/or surgical interventions are established. The aim of the different surgical techniques is to resect the elongated styloid process near the skull base. STUDY DESIGN: A transoral, retromolar, para-tonsillar approach was performed to expose and resect the elongated calcified styloid process in a consecutive series of six patients. The use of different angled ring curettes, generally used in hypophysis surgery, facilitated the preparation of the styloid process through the surrounding tissue to the skull base, without a compromise to the surrounding tissue. Clinical examinations were performed pre- and postoperatively (3 month and after 1 year after surgery) in all patients. RESULTS: No intra- or postoperative complications were observed. The hypophysis ring curettes facilitated the preparation of the styloid process to the skull base. CONCLUSIONS: The transoral, retromolar, para-tonsillar approach is a secure and fast method to resect an elongated symptomatic styloid process. Side effects of the classical transoral trans-tonsillar approach did not occur.

Vitamin B-complex application promotes secondary palate development in a palate organ model of the A/WySnJ mouse.

PURPOSE: This study analyzed the direct influence of vitamin B-complex supplements (Polybion N, Merck Pharma GmbH, Germany) in medium on secondary palatal development in palatal organ cultures of A/WySnJ mice. Because of positive clinical experiences with prophylactic vitamin B substitution in mothers of cleft-related families, the direct influence of the vitamin B-complex on palatal tissue was analyzed. MATERIALS AND METHODS: The inbred A/WySnJ mouse strain shows a highly spontaneous, genetically determined clefting rate of 20% to 44%. One hundred seventy-seven A/WySnJ fetuses were microdissected on gestational day 14.3 before the occurrence of palatal fusion. Palatal organ cultures were prepared and incubated in chemically defined serum-free medium with different concentrations (0.1% and 1.0%) of the vitamin B-complex Polybion N for 72 hours. Palatal development was analyzed microscopically according to the 6-step visual scale that describes the approximation of palatal shelves during development. RESULTS: At the beginning of the experiment (gestational day 14.3), the palatal development of all specimens used for in vitro organ culture showed a clear approach of the palatal shelves at stage II (2.25±0.78). Seventy-two hours after in vitro cultivation, the palatal shelves of the organ cultures supplemented with the vitamin B-complex showed significant growth (0.1%, P=.00017; 1.0%, P=.00078), whereas the untreated control group remained at initial developmental stage II (P=.291). CONCLUSIONS: The results of this in vitro study suggest a significant positive influence of vitamin B supplementation on palatal shelf development in organ culture. Further studies will focus on the vitamin B concentration in the amniotic fluid of dams with or without cleft in their offspring.

Lower concentrations of B-vitamin subgroups in the serum and amniotic fluid correlate to cleft lip and palate appearance in the offspring of A/WySn mice.

PURPOSE: The pathogenesis and prevention of cleft lip and palate (CL/P) have been studied mainly in clinical and animal experiments. A prophylactic poly-B-vitamin substitution during the first months of pregnancy has provided the most encouraging results for the prevention of CL/P recurrence in families at risk. In vitro studies of the palatal organ in an A/WySn mouse model have confirmed the positive influence of B-vitamins on palatal development. The present animal study was performed to analyze different B-vitamin concentrations in the serum and amniotic fluid of A/WySn mice according to the appearance of CL/P in their offspring. MATERIAL AND METHODS: Concentrations of different B-vitamins (B1, B2, B3, B5, B6, and folic acid) in serum and amniotic fluid were analyzed by high-performance liquid chromatographic detection. Immunohistochemical staining against thiamin-1 receptor was performed on histologic midface sections of A/WySn fetuses with (n = 12) and without (n = 14) CL/P. RESULTS: Vitamin B5 (P < .001) and folic acid (P < .004) concentrations in the amniotic fluid of dams with CL/P were significantly lower than in dams without CL/P. Serum concentrations of folic acid (P = .5) and B5 (P = .4) showed no difference between the 2 groups. Dams with CL/P had significantly lower thiamine concentrations in serum (P = .01) and amniotic fluid (P < .001). Histologic midface sections presented high thiamin-1 receptor expression in the palatal shelf of fetuses with CL/P. CONCLUSION: A decreased use or uptake of some B-vitamin subgroups (B1, B5, and folic acid) in amniotic fluid and serum (vitamin B1) was correlated to an increased cleft appearance in A/WySn mice. The high thiamin-1 receptor expression in the palatal tissue of mouse fetuses with CL/P may be caused by a decreased availability of vitamin B1.

Single horizontal Y-V vermilion plasty including orbicularis oris muscle repair for secondary correction of the whistling defect: a universal technique.

OBJECTIVES: The present prospective study aimed at objectively evaluating the relevance of a single horizontal Y-V vermilion plasty including orbicularis oris muscle repair for secondary correction of whistling deformities in unilateral as well as bilateral cleft lip cases. STUDY DESIGN: Ten patients were included in the study (mean age 20.2 ± 6.2 years). The size of the whistling defects was determined on photographs before and 12 months after surgery. Additional surgical procedures like columella lengthening and rhinoplasty were documented. RESULTS: Seven minor and 3 moderate whistling defects were corrected. In 7 patients additional procedures were carried out. The data of the 12 months follow-up showed that the whistling defect was significantly reduced in size (p < 0005). In 7 out of 10 patients the result of surgery was rated "good" and in 3 patients "moderate". CONCLUSIONS: The present prospective study is the first one to show on an objective basis that the presented technique allows reducing whistling deformities significantly with good overall results in the majority of the cases. Moreover, the technique can be combined with other corrective procedures like columella lengthening without problems. As a consequence, it is a relevant and universal surgical technique for the correction of whistling defects.

Comparison of different fabrication techniques for human adipose tissue engineering in severe combined immunodeficient mice.

Adipose tissue engineering has been advocated for soft-tissue augmentation and for the treatment of soft tissue defects. The efficacy in terms of persistence of the engineered fat is, however, not yet understood and could depend on the nature of fabrication and application. The high metabolic demand of adipose tissue also points to the problem of vascularization. Endothelial cell (EC) cotransplantation could be a solution. Human adipose tissue-derived stromal cells were seeded on collagen microcarriers and submitted to adipogenic differentiation ("microparticles"). In a first run of experiments, these microparticles were implanted under the skin of severe combined immunodeficient (SCID) mice (n = 45) with and without the addition of human umbilical vein ECs (HUVECs). A group of carriers without any cells served as control. In a second run, adipose tissue constructs were fabricated by embedding microparticles in fibrin matrix with and without the addition of HUVEC, and were also implanted in SCID mice (n = 30). The mice were sacrificed after 12 days, 4 weeks, and 4 months. Mature adipose tissue, fibrous tissue, and acellular regions were quantified on whole-specimen histological sections. The implantation of microparticles showed a better sustainment of tissue volume and a higher degree of mature adipose tissue compared with adipose tissue constructs. Immunohistology proved obviously perfused human tissue-engineered vessels. There was a limited but not significant advantage in EC cotransplantation after 4 weeks in terms of tissue volume. In groups with EC cotransplantation, there were significantly fewer acellular/necrotic areas after 4 weeks and 4 months. In conclusion, the size of the implanted tissue equivalents is a crucial parameter, affecting volume maintenance and the gain of mature adipose tissue. EC cotransplantation leads to functional stable vascular networks connecting in part to the host vasculature and contributing to tissue perfusion; however, the long-term benefit depends on additional basic conditions that need further research.

Superficial skin sensitivity impairment and skeletal stability after sagittal split ramus osteotomy.

Adjustable osteosynthesis miniplates are used to facilitate positioning of the mandible after bilateral sagittal split osteotomy (BSSO) to avoid skeletal relapse and occlusal discrepancies. The short Obwegeser BSSO reduces neurosensory disturbances. Adjustable osteosynthesis plates suited for the Obwegeser BSSO are not commercially available. This study tested adjustable miniplates for the short Obwegeser BSSO in advancement of the mandible and correction of facial asymmetry, assessing (1) sensitivity impairment of the lower lip and (2) skeletal stability.A prototype of L-shaped, 6-hole, 2.0-mm miniplate with 2 sliding holes was used. Five patients with facial asymmetry (group 1) and 10 patients with mandibular hypoplasia (group 2) were operated on. Sensitivity of the lower lip was quantified using the pain and thermal sensitivity test before the surgery (T0), 1 week after the surgery (T1), and 12 months after the surgery (T2). The length of the ascending ramus (group 1) and the corpus (group 2) was determined at T1 and T2 using cone beam computed tomographic scans and lateral skull radiographs, respectively.After the surgery, occlusion was adequate. There was no need for revisional surgery. At T2, no patient showed a pathologically reduced sensitivity of the lower lip. The length of the ascending ramus in group 1 and the length of the corpus in group 2 did not have statistically significant changes between T1 and T2.The current study revealed that the adjustable osteosynthesis plates especially designed for the short Obwegeser BSSO can be safely used for the advancement of the mandible and the correction of facial asymmetry, with a minimum risk for neurosensory disturbance and a high skeletal stability.

Closure of cleft lips with Pfeifer's wave line technique does not inhibit upper lip growth: A retrospective study.

The aim of this study is to describe the growth of the upper lip after reconstruction with a Pfeifer wave-line incision in patients with unilateral and bilateral cleft lip and palate (CL/P) in the long term. This was a longitudinal, monocentric, retrospective study. Metric standardized lip length measurements were taken annually from the age of 6 months to the age of 16 years. Defined anatomical points were determined which describe the lip length from the nasal entrance to the highest point of the Cupid's bow. The lip length of the unaffected side in unilateral cleft patients was taken as control. A total of 234 patients with cleft lip with/without cleft palate (CL/P) were included in the study. At the time of the primary surgery, the medial sides in unilateral clefts were 2-4 mm and the lateral sides 1.5-2 mm shorter than the normal unaffected side (p≤0.001). Two main periods of growth, one during childhood (first to sixth years) and one during adolescence (12th-16th years) were seen. At the age of 16 years, the end of the observation period, the lip length in unilateral clefts resulted in a clinically not noticeable shortening of the cleft side (0.37±0.26 mm). There was no correlation between lip length development and primary cleft width at the time of primary cleft lip surgery at 6 months. The upper lip in patients with bilateral clefts developed symmetrically without any obvious asymmetry. Both sides showed a lip length difference of 0.1±0.05 mm at the age of 16 years (p=0.1). Compared to the upper lip length of the control group, bilateral clefts showed a slight tendency toward a longer upper lip (p=0.52). Within the limitations of the study it seems that when lip length development is a priority in cleft lip surgery, Pfeifer wave-line procedure is good option to achieve symmetric results in unilateral and bilateral cleft lip surgery and, therefore, is a relevant option among a variety of other techniques.

[The Pierre Robin sequence from an anesthesiologic perspective : Presentation of the procedure based on a retrospective analysis at a university hospital]. / Die Pierre-Robin-Sequenz aus anästhesiologischer Sicht : Darstellung des Vorgehens anhand einer retrospektiven Analyse an einem Universitätsklinikum.

INTRODUCTION: As part of surgical interventions in pediatric patients, children with craniofacial malformations and syndromes are presented in the field of oral and maxillofacial surgery, anesthesia and also in all other clinical disciplines. In particular, the Pierre Robin sequence in the clinical context leads to a situation albeit a rare one, which should be given high attention in preoperative, intraoperative and postoperative care. MATERIAL AND METHODS: In a retrospective analysis from 1993 to 2020 in the Department of Oral and Maxillofacial Surgery at the University Hospital Halle (Saale), a total of 54 patients were identified with syndromic changes and a need for surgical treatment. During this period, 12 patients with a Pierre Robin sequence were genetically confirmed, who received a total of 20 surgical interventions under general anesthesia at different times. Statistical analysis was performed using SPSS 17.0. RESULTS: In 12 patients with a Pierre Robin sequence, 20 surgical procedures were performed with the patient under general anesthesia. The youngest patients had an average age of 6 months, the oldest 16 years at the time of the operation. The average age was 5.7 years. In addition to the genetic component, all children were assigned to the ASA I classification. The surgical indication was initially an isolated cleft palate in all patients, followed by further interventions such as dental restorations, corrective surgery in the area of the palate or ear nose throat (ENT) examinations. Drug induction of general anesthesia was weight-adapted using propofol 1%, fentanyl or remifentanil and rocuronium. In our study, out of 18 orotracheal intubations, only 2 patients had to be intubated by video laryngoscopy. One patient required nasal intubation and another was fitted with a laryngeal mask. The success rate of conventional intubation was 89.5%. Postoperatively, one infant had recurrent drops in saturation, so that reintubation was necessary.

Psychosocial and socioeconomically aspects of mothers having a child with cleft lip and/or palate (CL/P): a pilot-study during the first year of life.

BACKGROUND: The emotional impact on parents at the birth of their new-born with cleft lip and/or palate (CL/P) can be traumatic for parents, especially mothers, and affect the sensitive early parent-child relationship. Unlike many other congenital malformations facial deformities are visible to all. The uncommon facial appearance creates feelings and reactions in the mother, families and other people. Only few studies deal with this psychosocial burden of these mothers. MATERIAL AND METHODS: This pilot-study deals with mothers' early experiences (n=84) having a child with CL/P. Mothers were asked to complete a questionnaire at diagnosis, birth and after lip surgery. The questions were focused on the social background of the mother (educational degree, marital status, lifestyle and prenatal care), the medical information at diagnosis and the following reaction. The surveys were administrated from 01/2014 - 12/2016. RESULTS: 84 mothers of affected children (CL/P) replied the completed questionnaire (84/103, 81.5%). At diagnosis 65 mothers (77%) lived in a solid partnership and 44% worked full-time (40h). The diagnosis caused fear among the mothers (60.7%, p≤0.01), despair (27.4%, p≤0.01), grief (17.9%, p≤0.01) and guilt (16.7%, p≤0.01). Despite the emotional stress after the diagnosis only 5 mothers asked for psychological support (6.0%). The medical information by the gynecologist (41.6%) or maxillofacial surgeon (32.2%) was rated as "good" (n=26) or "very good" (n=26) in 60.2%. A lack of medical information and care was rated with "insufficient" (11.9%) or "poor" (14.3%). CONCLUSIONS: There are only few studies about mothers' early feelings and emotions having a child with a CL/P. We found high parental stress, physical and emotional strain among the mothers after diagnosis, mostly caused due to insufficient information's. This stress was not correlated with the educational level and CLP appearance showed no relation about the socioeconomic status. Key words:Cleft lip/palate, mother's emotional experience, psychosocial aspects.

Impact of cleft lip closure on the perception of the child by the mother and the social environment - A retrospective, self-reported, standardized pretest.

The aim of the study was to describe the attractiveness of a newborn with CL/P and the maternal reaction in relation to the child. Another purpose was to explore and describe the experience and subjectively perceived reaction of the mother and the social environment to the child before and after cleft lip surgery. MATERIAL AND METHODS: A study to describe and evaluate mothers' experiences, feelings and emotions (n = 84) regarding having a child with CL/P was performed. Therefore mothers were asked to complete a self-reported, standardized Likert-scale questionnaire. The questions were focused on the mother's own experiences, and the reaction of close family members and the social environment (friends, unknown people) to the child. Therefore two essential situations during the first year of life were analyzed: the first contact with the child, and a second one after lip surgery. The influence of lip reconstruction on the attractiveness of the child and the following reactions were analyzed. The timeline includes surveys from 01/2014 to 12/2016. RESULTS: 84 mothers of affected children (CL/P) replied to the questionnaire (84/103). Most mothers (n = 64) described the attractiveness of their child at birth as "very good" (n = 37) and "good" (n = 27). After lip reconstruction the subjective attractiveness in the mothers' opinions increased to 90.5% (n = 76): 24 "good" (p = 0.23) and 52 "very good" (p = 0.73). 50 mothers defined the postoperative surgical result as "very good", 21 did not see any improvement (p = 0.001). Poor postoperative evaluations like "very poor" (n = 0), "insufficient" (n = 1) or "sufficient" (n = 1) were found two times. The majority of mothers (n = 78) reported negative reactions of the social environment to the child before lip surgery. Friends reacted in general more positively to the child with the visible deformity than did the social environment. 41 mothers described that their life partner or husband reacted "always" more positively to the child (p = 0.018). After surgical lip closure, strangers (n = 22) and even friends (n = 27) did not change their reactions obviously. CONCLUSION: For the mother, the attractiveness of a child with CL/P is not significantly affected by the visible facial malformation. Even if the lip reconstruction increases the child's attractiveness from the mother's perspective, the often negative reactions of the family and social environment did not change.

Objective evaluation of vertical Z-plasty with double transposition vermillion flaps for secondary whistling deformity correction: A method for uni- and bilateral correction.

OBJECTIVES: This study describes a modified method for secondary correction of whistling deformities in patients with unilateral and bilateral cleft lip/palate (CL/P), using a horizontal double transposition vermilion flap, including parts of the orbicularis oris muscle. The pre- and postoperative results were objectively evaluated. STUDY DESIGN: 34 patients with a whistling deformity who underwent secondary reconstruction between 07/2013 and 11/2018 were included in this study (mean age 20.2 ± 11.6 years). 24 patients were male and 10 female. 30 patients presented with cleft lip and palate (CLP) - 15 bilateral, nine on the left side and six on the right. Four patients had only a left-side cleft lip (CL). The whistling deformity reconstruction was carried out using two triangular transposition vermilion flaps with muscle parts, for a vertical Z-plasty. The surgical procedure is normally performed under local anesthesia in all patients older than 10 years. For statistical evaluation, the size of the whistling defect in the vermilion was determined on photographs before and 6-9 months after surgery. The individual defect score (DS) was evaluated pre- and postoperatively. In all patients, no additional surgical procedures, such as rhinoplasty or scar correction in the upper lip, were carried out simultaneously. RESULTS: Minor (DS < 400), moderate (DS 400-1400), and severe (DS > 1400) whistling defects were surgically corrected. The whistling defect score was significantly reduced in all patient groups (p < 0.001). In six patients the result of surgery was rated as 'acceptable' (DS > 30), in five patients as 'good' (DS 10-30), and in 23 patients as 'very good' (DS 0-10). CONCLUSIONS: This study describes a modified method for whistling deformity reconstruction in uni- and bilateral clefts. The aesthetic results are based on a reconstruction of the subcutaneous muscle layers and the creation of a symmetrical lip contour and prolabium using transposition flaps from the lateral side of the cleft. The great advantage is the uncomplicated performance under local anesthesia, even for all children over 10 years, and the short operation time. Postoperative complications did not occur.

New molecular aspects in the mechanism of oromaxillofacial cleft prevention by B-vitamins.

Clinical and experimental studies show a clear positive effect of B-vitamins in the prevention of oromaxillofacial clefts, especially cleft lip and palate (CL/P). Hereby the local effect of thiamin (B1) in the amniotic fluid is very important for the embryonic facial development as seen in palatal organ models stimulated by topical B-vitamin application (Scheller et al., 2013a). Moreover a low B1 concentration in the serum and amniotic fluid was found in pregnant mice with clefts in their offspring (Scheller et al., 2013b). Immunochemical analyses of midface sections (ThTr-1 transporter) and the placenta (ThTr-2 transporter) of cleft fetuses with orofacial clefts showed an atypical cytoplasmatic localization (Scheller et al., 2017). mRNA nalyses of different B-vitamin transporters (B1, B2, B5, B7, B9) were performed and showed ThTr2 transporter in a short splice variant in all cleft fetuses. This splice variant may cause a functional loss of the transport capacity through the placenta barrier and result in a low amniotic fluid concentration of vitamin B1. All other analyzed transport proteins showed no functional change. These findings confirm the hypothesis that cleft prevention by high vitamin B1 substitution fails in genetically determined cleft mice, caused by an insufficient B1 uptake and missing local effect.

Oral vitamin B1-substitution does not decrease genetically determined cleft rate in mice (A/WySn).

PURPOSE: Cleft lip and palate (CL/P) are one of the most common human birth defects. Animal experiments and clinical investigations show a clear reduction of teratogenic clefts by a high-dose vitamin B supplementation during early pregnancy, especially in families at risk (reduction of recurrence). The aim of this work was to examine the influence of thiamine (vitamin B1) on CL/P appearance in genetically determined A/WySn mice within different supplementation starting points. MATERIALS AND METHODS: A total of 24 A/WySn female mice were orally supplemented with high doses (80 mg/kg) of thiamine at different times of pregnancy (5 groups, n = 90). The influence of thiamine on the abortion rate and CL/P appearance in the offspring was analyzed with respect to the concentration of thiamine in the serum and amniotic fluid (HPLC-chromatography). Immunochemical analyses of the ThTr-1 und ThTr-2 receptor-status were performed in midface sections of A/WySn-fetuses and the corresponding placenta, with and without CL/P. RESULTS: High doses of orally supplemented thiamine did not reduce the CL/P appearance in A/WySn mice. However, the different starting points of vitamin B1 substitution had some influence. Additionally, an obvious decrease in aborted fetuses was noticed in all supplemented groups. The oral substitution caused a clear increase of the serum concentration in all mothers, but showed no increase of the amniotic fluid concentration. Then immunohistochemistry detected an overexpression of ThTr-1 in the midface and an irregular localization of ThTr-2 in the placenta of fetuses with clefts. CONCLUSION: Our results suggest a time-dependent influence of thiamine on CL/P appearance in female mice. The prophylactic/periconceptional, but not the therapeutic supplementation, starting point can be proposed as a crucial step for regular facial and palatal fusion in embryonic development. The absolute rate of CL/P was not reduced, and the concentration of the water-soluble thiamine could not increase in the amniotic fluid. Thus the proposed local effect of thiamine failed in the development of genetically determined mice.

Sex distribution is a factor in teratogenically induced clefts and in the anti-teratogenic effect of thiamine in mice, but not in genetically determined cleft appearance.

PURPOSE: Cleft lip and/or palate (CL/P) shows a gender-related distribution in human beings. The reason is unknown. This study analyzed the gender-related cleft appearance with respect to teratogenically and genetically determined cleft appearance and the response to thiamine (vitamin B1) supplementation. MATERIAL AND METHODS: Cyclophosphamide (CPA; 0.6 mg) and dexamethasone (0.25 mg) were injected intraperitoneally to A/B-Jena mice on different days of pregnancy. The abortion and malformation rate in the A/B-Jena and A/WySn mice with genetically determined clefting was documented to be gender-specific. Vitamin B1 was given to A/B-Jena dams at different times during pregnancy before, simultaneously and after the teratogenic agent was given to the pregnant mothers. A/WySn mice received oral supplementation at different times during embryonic/fetal development. RESULTS: There were significantly more living female fetuses when mothers were treated with teratogens, and the embryo lethality and malformation affected more male individuals. However, the survival and malformation rate in A/WySn mice was not gender-specific. Especially in male fetuses, vitamin B1 decreased the teratogenic cleft rate (CPA: p < 0.001, dexamethasone: p = 0.6), whereas there was no effect in the A/WySn mice. CONCLUSION: There was a strong anti-teratogenic effect of vitamin B1, especially in the male fetuses. Genetically determined cleft appearance was not positively influenced. These findings confirm observations about cleft appearance in human beings.

Unspecific, idiopathic isolated osteolysis (Gorham-Stout syndrome) of the mandibular condylar process with its radiological, histological and clinical features: a case report and review of literature.

BACKGROUND: The unspecific, idiopathic isolated osteolysis is a rare condition in the various known osteopathies and better known as Gorham-Stout syndrome (Gorham's disease, GD). It belongs to the primary idiopathic osteolysis, and its aetiology is poorly understood. Many different localisations have been described, but there are only 48 cases affecting the maxillofacial region until now. CASE REPORT: A 76-year-old patient with the singular localisation of GD in the left condylar process is presented. After radical resection of the condylar process, the clinical, radiological and pathological examinations made the diagnosis of GD. Until now, there is no recurrence for two and a half years. DISCUSSION: The unspecific and inconsistent clinical and radiological symptoms complicate the diagnosis of GD. Clinical, pathological and radiological correlation is essential to make the diagnosis. The different therapeutical options and the specific outcome are discussed.

Enteral or parenteral nimodipine treatment: a comparative pharmacokinetic study.

UNLABELLED: BACKGROUND AND STUDY AIMS/OBJECT: Oral nimodipine is recommended to reduce poor outcome related to aneurysmal subarachnoid hemorrhage (SAH). In addition, animal experiments and clinical trails revealed a beneficial effect of enteral and parenteral nimodipine for the regeneration of cranial nerves following skull base, laryngeal, and maxillofacial surgery. Despite these findings there is a lack of pharmacokinetic data in the literature, especially concerning its distribution in nerve tissue. PATIENTS/MATERIAL AND METHODS: Samples were taken from a consecutive series of 57 patients suffering from skull base lesions and treated with nimodipine prophylaxis from the day before surgery until the seventh postoperative day. Both groups received standard dosages for enteral (n = 25) and parenteral (n = 32) nimodipine . Nimodipine levels were measured in serum, cerebrospinal fluid (CSF), and tissue samples, including vestibular nerves. RESULTS: Nimodipine levels were significantly higher following parenteral as compared with enteral administration for intraoperative serum (p < 0.001), intraoperative CSF (p < 0.001), tumor tissues (p = 0.01), and postoperative serum (p < 0.001). In addition, nimodipine was significantly more frequently detected in nerve tissue following parenteral administration (Fisher's exact test, p = 0.015). CONCLUSIONS: From a pharmacokinetic point of view, parenteral nimodipine medication leads to higher levels in serum and CSF. Furthermore, traces are more frequently found in nerve tissue following parenteral as compared with enteral nimodipine administration, at least in the early course.

Neuroprotective efficacy of prophylactic enteral and parenteral nimodipine treatment in vestibular schwannoma surgery: a comparative study.

UNLABELLED: BACKGROUND AND STUDY AIMS/OBJECT: Oral nimodipine improves neurologic outcome after aneurysmal subarachnoid hemorrhage. In addition, the neuroprotective efficacy of nimodipine has been revealed following skull base, laryngeal, and maxillofacial surgery. Pharmacokinetic investigations showed nimodipine to reach higher serum levels following parenteral versus enteral administration. Furthermore, a correlation between nimodipine levels in serum, cerebrospinal fluid, and nerve tissue could be quantified. These observations raise the question whether the proven neuroprotective effect of nimodipine is related to its serum level. PATIENTS/MATERIAL AND METHODS: A consecutive series of 37 patients with vestibular schwannoma treated with nimodipine from the day before surgery until the seventh postoperative day was analyzed retrospectively. Both groups received standard dosages for enteral (n = 17) and parenteral (n = 20) nimodipine medication. Nimodipine levels were measured in pre- and postoperative serum and cerebrospinal fluid samples. Cochlear and facial nerve functions were documented before surgery, in the early postoperative course, and 1 year after surgery. RESULTS: Facial nerve outcome was significantly better in the group with parenteral nimodipine medication (p = 0.038). Logistical regression analysis revealed a seven times smaller risk for a deterioration of facial nerve function in the group with parenteral treatment. There was no difference in hearing preservation between both groups despite tumor size tending to be larger in the parenteral group. Intraoperative (p = 0.004), postoperative (p = 0.001), and serum and cerebrospinal fluid (p = 0.024) nimodipine levels were significantly higher following parenteral administration as compared with enteral administration. Both groups were comparable regarding tumor size and extent of resection. CONCLUSIONS: These results support a dependency of nimodipine's neuroprotective efficacy on its serum levels. Parenteral nimodipine treatment produces higher serum levels and has a higher neuroprotective potency in vestibular schwannoma surgery compared with enteral treatment.