Six3, a medaka homologue of the Drosophila homeobox gene sine oculis is expressed in the anterior embryonic shield and the developing eye.

The conserved transcription factor Pax6 is essential for eye development in Drosophila and mammals (Hill, R.E., Favor, J., Hogan, B.L.M., Ton, C.C.T., Saunders, G.F., Hanson, I.M., Prosser, J., Jordan, T., Hastie, N.D., van Heyningen, V., 1991. Mouse small eye results from mutations in a paired-like homeobox containing gene. Nature 354, 522-525; Ton, C., Hirvonen, H., Miwa, H., Weil, M., Monaghan, P., Jordan, T., van Heyningen, V., Hastie, N., Meijers-Heijboer, H., Drechsler, M., Royer-Pokora, B., Collins, F., Swaroop, A., Strong, L.C., Saunders, G.F., 1991. Positional cloning and characterization of a paired box- and homeobox-containing gene from the aniridia region. Cell 6, 1059-1074; Matsuo, T., Osumi-Yamashita, N., Noji, S., Ohuchi, H., Koyama, E., Myokai, F., Matsuo, N., Toniguchi, S., Dari, H., Jseki, S., Ninomiya, Y., Fujiwara, M., Watanabe, T., Eto, K., 1993. A mutation at the Pax-6 gene in rat small eye is associated with impaired migration of midbrain crest cells. Nature genet. 3, 299-304; Quiring, R., Walldorf, U., Kloter, U., Gehring, W.J., 1994. Homology of the eyeless gene of Drosophila to the small eye gene in mice and aniridia in humans. Science 265, 785-789). These findings led to the hypothesis that additional genes involved in invertebrate and vertebrate eye development are structurally and functionally conserved (Halder, G., Callaerts, P., Gehring, W.J., 1995. New perspectives on eye evolution. Curr. Opin. Gen. Dev. 5, 602-609; Quiring, R., Walldorf, U., Kloter, U., Gehring, W.J., 1994. Homology of the eyeless gene of Drosophila to the small eye gene in mice and aniridia in humans. Science 265, 785-789). Candidates for such conserved genes are the Drosophila homeobox gene sine oculis (Cheyette, B.N.R., Green, P.J., Martin, K., Garren, H., Hartenstein, V., Zipursky, S.L., 1994. The Drosophila sine oculis locus encodes a homeodomain-containing protein required for the development of the entire visual system. Neuron l2, 977-996) and its murine homologue Six3 (Oliver, G., Mailhos, A., Wehr, R., Copeland, N.G., Jenkins, N.A., Gruss, P., 1995. Six3, a murine homologue of the sine oculis gene, demarcates the most anterior border of the developing neural plate and is expressed during eye development. Development 121, 4045-4055). sine oculis (so) is essential for the development of the larval and adult visual system (Cheyette, B.N.R., Green, P.J., Martin, K., Garren, H., Hartenstein, V., Zipursky, S.L., 1994. The Drosophila sine oculis locus encodes a homeodomain-containing protein required for the development of the entire visual system. Neuron l2, 977-996). Six3 is expressed in the anterior neural plate and optic vesicles, lens, olfactory placodes and ventral forebrain (Oliver, G., Mailhos, A., Wehr, R., Copeland, N.G., Jenkins, N.A., Gruss, P., 1995. Six3, a murine homologue of the sine oculis gene, demarcates the most anterior border of the developing neural plate and is expressed during eye development. Development 121, 4045-4055). Overexpression of mouse Six3 gene in medaka fish embryos (Orvzias latipes) results in the formation of an ectopic lens, indicating that Six3 activity can trigger the genetic pathway leading to lens formation (Oliver, G., Loosli, F., Koster, R., Wittbrodt, J., Gruss, P., 1996. Ectopic lens induction in fish in response to the murine homeobox gene Six3. Mech. Dev. 60, 233-239). We isolated the medaka Six3 homologue and analyzed its expression pattern in the medaka embryo. It is expressed initially in the anterior embryonic shield and later in the developing eye and prosencephalon. The early localized expression of Six3 suggests a role in the regionalization of the rostral head.

A genetic screen for mutations affecting embryonic development in medaka fish (Oryzias latipes).

In a pilot screen, we assayed the efficiency of ethylnitrosourea (ENU) as a chemical mutagen to induce mutations that lead to early embryonic and larval lethal phenotypes in the Japanese medaka fish, Oryzias latipes. ENU acts as a very efficient mutagen inducing mutations at high rates in germ cells. Three repeated treatments of male fish in 3 mM ENU for 1 h results in locus specific mutation rates of 1.1-1.95 x10(-3). Mutagenized males were outcrossed to wild type females and the F1 offspring was used to establish F2 families. F2 siblings were intercrossed and the F3 progeny was scored 24, 48 and 72 h after fertilization for morphological alterations affecting eye development. The presented mutant phenotypes were identified using morphological criteria and occur during early developmental stages of medaka. They are stably inherited in a Mendelian fashion. The high efficiency of ENU to induce mutations in this pilot screen indicates that chemical mutagenesis and screening for morphologically visible phenotypes in medaka fish allows the genetic analysis of specific aspects of vertebrate development complementing the screens performed in other vertebrate model systems.

Autonomic dysfunction in polyneuropathies: a report on 106 cases.

Autonomic dysfunction is a common feature in various forms of polyradiculoneuropathy. This study investigated the kinds and frequency of of autonomic dysfunction in 106 cases. Denervation insufficiency of organs associated with supersensitivity of reflex mechanisms was found to be the best explanation of the pathophysiology. Early insertion of a transient cardiac pacemaker is recommended to counteract life-threatening cardiac failure.

Anxiety and anger among abusers of different substances.

The levels of trait anxiety and trait anger were compared for adult clients in residential treatment with primary diagnoses of alcoholism, cannabis dependence, cocaine abuse and opioid dependence. With a sample of 809 clients results suggested each of these groups to have significantly elevated anxiety and anger scores, compared to non-client samples. However, there were no significant differences on either anxiety or anger scores based on drug of choice.

Transcranial color-coded real-time sonography in the evaluation of intracranial neoplasms and arteriovenous malformations.

Transcranial color-coded real-time sonography (TCCS) was performed in 57 patients with primary intracranial brain tumors (n = 49) or arteriovenous malformations (n = 8) to evaluate its diagnostic potential. In 46 patients (81%), lesions could be identified employing this technique. In 7 patients, transcranial ultrasound examination was not feasible because of bone thickness; in the remaining 4 patients, the tumor was indistinguishable from adjacent brain tissue despite sufficient insonation, suggesting that these neoplasms are isoechogenic. The sonographic features of brain tumors were very similar: a hyperechogenic matrix of the lesion was interspersed by hypoechogenic pixels. Larger hypoechogenic areas (0.5-1 cm) gave evidence of tumor necrosis. Differences between the findings of TCCS and computed tomography concerning tumor size were found in 7 patients, in whom TCCS revealed an area of smaller extension within the corresponding hypodense area on the computed tomographic scan. Perifocal brain edema could not be detected by ultrasound examination. In 13 patients, a thin, hypoechogenic peritumoral halo was disclosed that did not correlate with perifocal brain edema identified by computed tomography and that may have been due to compression of adjacent parenchyma. In patients with arteriovenous malformations, TCCS permitted the identification of the main feeders, the nidus, and the draining venous system by color-coded depiction of intravascular blood flow. In conclusion, TCCS is an additional method for initial diagnosis and highly suitable for follow-up in tumor patients and provides valuable information about tissue characteristics and blood flow.

Postoperative neuroimaging of high-grade gliomas: comparison of transcranial sonography, magnetic resonance imaging, and computed tomography.

BACKGROUND: A precise and comprehensive knowledge of tumor burden and its extent and growth pattern in the pre- and postsurgical states is required to optimize tumor therapy and to determine treatment success and failure. This prospective study compares the diagnostic potential of computed tomography (CT), magnetic resonance imaging (MRI), and transcranial sonography (TCS) in the postoperative follow-up of brain tumors. METHOD: Twenty-six patients with high-grade gliomas were included in the study. After tumor debulking, a total of 31 biopsy specimens were obtained from the resection margin in 21 patients and histological findings were compared with the findings of early postoperative TCS, CT, and MRI. Findings indicating residual tumor tissue were nonlinear contrast enhancement at the resection site revealed by CT or MRI or hyperechogenic lesions revealed by TCS. Follow-up examinations using all three imaging techniques were performed every 3 months. The end points of the follow-up were tumor recurrence as defined by CT and MRI, death, or severe clinical deterioration. RESULTS: On the basis of the above criteria, TCS identified residual tumor more often than did CT or MRI. In the group of 19 patients with histologically proven tumor remnants, residual tumor tissue was identified by TCS in all patients, whereas MRI and CT failed to show contrast enhancement in three and eight patients, respectively. However, the results of the TCS were false positive for one patient because of hemorrhage into the resection site. The average time to identification of tumor regrowth was 27 weeks using TCS, 29 weeks using CT, and 33 weeks using MRI. Only the differences between TCS and MRI reached statistical significance. For one patient, multicentric tumor recurrence was not detected using TCS. CONCLUSION: TCS may complement CT and MRI in the postoperative follow-up of patients with high-grade gliomas. Because none of these modalities alone is both sensitive and specific, an integrated analysis of imaging findings is recommended.

Epi-arachnoidal drug deposit: a rare complication of intrathecal drug therapy.

Intrathecal (i.t.) drug application is accepted as a highly effective treatment option for various neurological conditions. Technical risks and potentially dangerous complications require appreciation. We present the case of a patient treated with i.t. recombinant, human brain-derived neurotrophic factor (rhBDNF) as an experimental therapy for amyotrophic lateral sclerosis (ALS). Five days after starting the i.t. drug infusion, she complained of severe headache and nausea. Radiological studies suggested the catheter was located within the epi-arachnoidal space. A deposit of more than 10 ml secluded from the subarachnoidal space was found within this space. I.t. contained a high concentration of the applied drug. Revision of the catheter resulted in complete recovery from symptoms and i.t. infusion could be continued. The epi-arachnoidal positioning of a spinal catheter is a potential cause for treatment failure. If the membrane around the fluid deposit ruptures, the drug could be released into the subarachnoidal space, with the consequence of a potentially life-threatening complication.

New ultrasound techniques and their application in neurosurgical intra-operative sonography.

We describe a variety of new ultrasound techniques by their physical background, potentials and applications regarding usefulness during intra-operative neurosurgical procedures. Transducers like high-frequency and small rotating probes fitting into neuroendoscopes, imaging techniques as extended field-of-view technique, harmonic imaging, echo-enhancers, 3-D imaging and the real-time integration of neurosonography with pre-operative CT- or MR-data are mentioned. The technical or physical principles are explained, followed by a discussion of these techniques from available literature dealing with their intra-operative neurosurgical applications and the experience of the authors with the techniques. With higher frequencies micromillimeter imaging is possible and small probe allows endoneurosonography. Echo-enhancers and harmonic imaging improve the signal-to-noise ratio and 3-D imaging and extended field-of-view techniques allows a better understanding of the pathoanatomy. With the real-time integration of intra-operative ultrasound images and pre-operative CT or MR images additional information, like hemodynamic pattern, are available for the neurosurgeon. Although until now only a limited number of reports about new sonographic techniques during intra-operative application in neurosurgery exist, the methods seem to be promising in creating images easier to understand, incorporating more information about pathoanatomy and supplying the neurosurgeon with information additional to that provided by CT and MRI.

Intraoperative color duplex sonography of basal arteries during aneurysm surgery.

This prospective study aimed at (1) characterizing the duplex sonographic appearance of cerebral aneurysms, (2) visualizing their location, and (3) ensuring the complete occlusion of the aneurysm as well as the patency of the basal arteries during aneurysm surgery. During 9 months 30 craniotomies for aneurysm clipping in 29 patients were monitored intraoperatively by B-mode and color-coded duplex sonography. Following craniotomy the aneurysm and the preaneurysmatic and postaneurysmatic arteries were sonographically visualized before and after clipping and removal of the spatulas. Twenty-seven (90%) of 30 aneurysms appeared as a hypoechoic structure. Together with the typical dichromatic picture in the color mode and the characteristic bidirectional flow pattern in the duplex mode, 29 (97%) of 30 aneurysms were identified and localized anatomically correctly. Eighty (99%) of 81 relevant vessels were visualized and measured with the Doppler mode. After clipping, flow was detectable in all major arteries except 3 middle cerebral artery (MCA) branches. In 1, occlusion was confirmed by postoperative angiography. In the other 2, early postoperative computed tomography showed an infarction of the corresponding MCA territories. This study demonstrated the potential of color duplex sonography to visualize and characterize cerebral aneurysms and adjacent basal arteries before and after clipping. It offers a noninvasive intraoperative method to control the patency of basal arteries and complete occlusion of the aneurysm.

Preoperative and postoperative follow-up in high-grade gliomas: comparison of transcranial color-coded real-time sonography and computed tomography findings.

Twenty patients with high-grade gliomas were prospectively studied by pre- and postoperative transcranial color-coded real-time sonography (TCCS) and CT, to determine the sensitivity of TCCS in the identification of residual tumor and tumor regrowth. Each patient was subjected to preoperative and early postoperative CT (postoperative day 1) and TCCS examinations (postoperative days 6 to 8) and subsequent CT and TCCS follow-up examinations within a time interval of 6 weeks to 3 months. In eight patients, a total of 15 biopsy specimens were intraoperatively obtained from the wall of the resection cavity. Histological findings of intraoperative biopsy specimens showed that hyperechogenic areas adjacent to the resection cavity always contained residual tumor tissue. Early postoperative TCCS identified these hyperechogenic areas in 19 of 20 patients. In 12 patients, postoperative CT revealed contrast enhancement at the resection margin, indicating residual tumor. In these patients the extension of these hyperechogenic areas on TCCS exceeded the contrast-enhancing areas on CT by a mean of 58%. In eight patients, postoperative CT displayed no contrast enhancement along the border of resection. TCCS and histological findings indicated residual tumor in seven of these eight patients. The size of the hyperechogenic lesions identified by postoperative TCCS increased in time and follow-up examinations revealed that tumor regrowth arose from these hyperechogenic areas in all patients. In four patients, tumor regrowth was identified, on average 0.7 months earlier by TCCS than by CT. From these data we conclude that the sensitivity of TCCS in detection of residual tumor and tumor regrowth seems to be superior to CT. The value of TCCS requires further clarification by comparative studies including histology and MRI.

MMPI profiles of cocaine-addicted individuals in residential treatment: implications for practical treatment planning.

The MMPI profiles of 268 clients presenting for residential treatment of cocaine addiction were examined. The results revealed clinically significant elevations on the Pd and Ma scales of this instrument. In addition, elevations approaching clinical significance were found on the D, Pa, and Pt scales. These results are discussed in terms of conducting treatment within the context of an Alcoholics Anonymous/Narcotics Anonymous framework, as well as the implications for relapse prevention planning.

MMPI profiles of adolescent substance abusers in treatment.

The non-K-corrected MMPI profiles of 243 adolescents presenting themselves for chemical dependency treatment in a residential setting were examined. Results suggested a general lack of psychopathology in this population, although a significant elevation on the Pd scale did emerge. These data are compared to the findings of previous studies with both adolescent and adult populations.

Traumatic tetraparesis in craniocervical dysplasia. Case report.

Case report of traumatic induced tetraplegia due to multiple cranio-cervical abnormalities with cord compression at the level of C4/C5. Diagnostic and operative procedure.

Ureteral injury in lumbar disc surgery.

Among retroperitoneal injuries in lumbar disc surgery ureteral transection is a rare complication and only 8 cases have been reported so far. They are analysed and a ninth case is added and described. In this case the complication was recognized immediately and successfully treated by end-to-end anastomosis of the ureter with an internal stent. Usually the diagnosis was delayed due to uncharacteristic symptoms (fever, haematuria, abdominal pain and distension, ileus, palpable mass etc.) which led to septic courses and nephrectomy in 3 cases. The anatomical relationship of the lumbar spine and retroperitoneal structures is illustrated by CT scans. Factors contributing to these injuries and ways of recognizing and preventing complications are discussed.

Nocardial cerebral abscess cured with imipenem/amikacin and enucleation.

A 72 year old female with cerebral abscess due to Nocardia farcinica is reported. Needle aspiration, antimicrobial therapy using a new combination of imipenem and amikacin, and, finally, surgical excision led to prompt and complete recovery. This is the oldest patient to survive cerebral nocardiosis reported in the literature. This infection, is usually regarded as opportunistic and is encountered with increasing frequency in immunocompromised conditions (organ transplantation, chemotherapy, underlying disabling disorder, acquired immunodeficiency syndrome, etc.). The literature is extensively reviewed for various aspects of this disease including prognostic factors, recent developments in antibiotic therapy (imipenem, amikacin, minocycline etc.) and the essential role of surgery in the treatment strategy.

Ultrasound-guided neuronavigation of deep-seated cavernous haemangiomas: clinical results and navigation techniques.

The aim of this study was to evaluate guidance techniques and patient outcomes of ultrasound-guided neuronavigation of deep-seated intracerebral cavernous hemangiomas (CAs). Thirty-five patients with deep-seated intracerebral CAs with sizes ranging between 7 and 45 mm were operated upon only with ultrasound-guidance. Twenty-seven were located in or near eloquent regions. In 30 patients dissection to the lesion was performed through sulci and fissures. The best approach to a lesion based on surface anatomy and depth was determined using sonographic information. Navigation was done sonographically. In five patients the shortest approach via a corticotomy was determined sonographically. Twenty-six patients had no neurological deficit postoperatively. Preoperative deficits improved in seven of nine patients. Fifteen of 19 patients suffering epileptic seizures had no seizures postoperatively. Intraoperative sonography revealed residual CA tissue after microsurgical extirpation in two cases. This report shows that intraoperative sonographic navigation provides safe guidance to deep-seated CAs with good clinical outcome independent of size.

Reservoir systems for intraventricular chemotherapy.

This paper describes the current techniques for intraventricular drug administration in patients with meningiosis. Advantages and disadvantages of different reservoir systems, the standard implantation procedure and more recently developed image-guided techniques are discussed. In patients with slit ventricles, the CT-based stereotactic approach is recommended for reservoir implantation.

Reliability of transcranial colour-coded real-time sonography in assessment of brain tumours: correlation of ultrasound, computed tomography and biopsy findings.

Transcranial colour-coded real-time sonography (TCCS) was carried out in 25 patients with brain tumours to determine whether this noninvasive method provides additional information about the extent of solid tumour, its differentiation from oedema, and its tissue components. All 25 patients had serial computed tomography (CT)-guided stereotactic biopsies. Comparison of ultrasound, CT and histological findings revealed that the vast majority of contrast enhancing areas on CT were hyperechogenic (32/33; 97%) and contained tumour tissue (29/32; 91%). Hyperechogenic areas always represented solid tumour (23/23 patients), even when CT showed low density non-enhancing lesions. In lesions hypoechogenic on TCCS and low density on CT, histology consistently revealed necrotic tumour (7/7). Biopsies obtained from parenchyma with normal echogenicity revealed tumour in only 3 of 16 specimens. Despite the high specificity of TCCS in the differentiation of tumour components, its sensitivity to tumour was inferior to that of CT (24/25; 96%). TCCS thus allows noninvasive preoperative identification of tumour tissue and its extent setting.

MMPI profiles of impaired nurses.

The MMPI profiles of 42 nurses presenting themselves for treatment of alcoholism or opiate addiction in a residential setting were examined. When comparisons were made, no significant differences in this sample emerged based on sex, level of professional training, or drug of choice. Results suggested that a significant elevation emerged on the Pd scale, and the D scale approached clinical significance. The clinical implications of these data as they impact the treatment of impaired nurses are discussed.