Selective Cytotoxicity of Manganese Nanoparticles against Human Glioblastoma Cells.

Toxicity of different types of manganese nanoparticles against glioblastoma U-87MG and U-251 cells and normal human cells was studied using MTT test. The selectivity of the toxic effect of nanoparticles was evaluated as the ratio of 50% cytotoxic concentration (СС50) for human embryos fibroblasts (FECh-15) to their СС50 for tumor cells. Five of 6 samples of tested nanoparticles demonstrated selective toxic effect in vitro. Manganese oxide nanoparticles were characterized by maximum selectivity (СС50 6.9 nM and 2.1 nM for U-87MG and U-251 cells, respectively): selectivity index for glioblastoma U-87MG and U-251 cells was 29 and 95.2, respectively. Manganese oxide nanoparticles used for MRI detection of gliomas can be used for designing an oncolytic agent for the treatment of glial tumors in humans.

Clinical challenges in addressing resistance to antimicrobial drugs in the twenty-first century.

It has been more than 60 years since Alexander Fleming discovered the drug that came to be known as penicillin. Antibiotics are now one of the most frequently used medications in the United States and are prescribed by medical professionals in almost every specialty. The past decade has seen an alarming increase in the number of pathogens that are resistant to antimicrobial drugs, in the hospital as well as in the community.(1) Among the gram-positive pathogens, methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus species are the biggest threats. The situation is even more alarming with respect to gram-negative pathogens, especially because there are currently no late clinical trials involving new anti-infective drugs that are active against these pathogens.

[Volumetry of the human tongue by MRI]. / MR-Volumetrie der Zunge zur Abschätzung der individuellen Zungengrösse.

AIM: The purpose of this study was to determine the volume of the tongue using MRI. The correlation of the individual volume of the tongue and the size of the oral cavity was to be investigated. MATERIAL AND METHODS: To analyze the tongue volume we combined coronal and sagittal data acquisition, which divided the tongue virtually into two lateral and one medial part. This procedure helped to decrease artefacts by partial volume effect. In 20 probands (m/f 7/13, average age of 36.3 years) the volume of the tongue was determined. Imaging protocol: Magnetom 63 SP (Siemens, Erlangen), T1-weighted sequences (TR/TE 500 ms/10 ms), slice thickness 5 mm, matrix 256 x 256, FOV 250 mm. RESULTS: There was a significant linear regression between the tongue volume and height of the mouth cavity. This correlation can be used to calculate the normal volume of a patient's tongue. DISCUSSION: Volumetry of the tongue can be carried out by means of MRI without application of injurious X-rays. It can be employed before as well as after tongue reduction surgeries for therapy control. The individual ideal tongue volume can be determined easily by determination of the height of the oral cavity.

[Allogenic heterotopic cartilage transplantation for primary corneal replacement in a rabbit model]. / Allogene heterotope Knorpeltransplantation als primärer Hornhautersatz--eine tierexperimentelle Studie am Kaninchen.

BACKGROUND: Aim of the present study was to investigate woundhealing after allogen heterotopic cartilage transplantation in a rabbit model. MATERIAL AND METHODS: Cartilage discs were transplanted by central lamellar keratoplasty (diameter 5.0 mm) in eleven New Zealand White Rabbits. Cartilage was harvested of the ears of rabbits at the day of transplantation. The cartilage discs 0.5-0.6 mm thick were prepared with 5.2 mm diameter and transplanted within 12 hours. Fixation was performed by eight 10-0 nylon sutures. Postoperatively, dexamethasone ointment containing gentamicin was applied three times a day for three weeks. Clinical course was documented by photographs. For histological examinations the transplanted eyes were enucleated after one day or three days, and after 3, 6 or 12 months. RESULTS: Allogen cartilage healed firmly in the cornea within two months. During the course of observation the cartilage grafts thinned and were replaced by normal appearing collagen fibrills. In one case neovascularisation of the cornea occurred and reached the cartilage graft, but did not invate. Histologically, in all cases no leukocytes could be seen in the cartilage or its neighbourhood. The cartilage grafts did not proliferate and remained avascular. The intraocular structures showed no inflammatory reaction. CONCLUSIONS: Allogen cartilage grafts to a clear corneal pounch do not induce an inflammatory reaction. Therefore, autologous cartilage prepared of ears seems to be useful biological material in ophthalmologic surgical procedures, for example to fill up corneal defects. To investigate if cartilage grafts will be helpful to stop neovascularisation in keratoplasty further studies with vascularisized corneas are necessary.

[Primary pigment epithelial cysts of the iris]. / Primäre Pigmentepithelzysten der Iris.

PURPOSE: We want to present a case of bilateral, unusually large pigment epithelial cysts of the iris. PATIENT: A four-year old girl presented with multiple, un-usually large, bilateral pigment epithelial iris cysts and tags at the pupillary margin. The right eye additionally presented with two adhesions of the cysts at the corneal endothelium. Otherwise, the anterior and posterior segment as well as the intraocular pressure were normal. The visual acuity was at least 0.8 without glasses, and there was no evidence of strabism or other functional impairments. At normal daylight and with non influenced pupils, the visual axis was not covered by the cysts. Since the lesions anamnesti cally appeared to be congenital and the clinical course had been benign, no therapy was initiated. The patient has been checked on at regular intervalls without any functional or morphological change. CONCLUSION: Pigment epithelial cysts of the iris usually do not cause any complications due to their small size and stationary clinical course. In rare cases, the lesions can be so large, that they get into contact with the corneal endothelium and sometimes nearly cause visual impairment by covering the visual axis.

[Atypical non-Hodgkin's lymphoma of the conjunctiva as an incidental finding in lower lid entropion]. / Untypisches Non-Hodgkin-Lymphom der Bindehaut als Zufallsbefund bei Unterlidentropium.

PURPOSE: We want to demonstrate an unusual conjunctival Non-Hodgkin-Lymphoma with bleedings. PATIENT: A 77-year-old female patient presented with an entropion of the left lower eye-lid. Bilaterally reddish, soft tumors showed in the lower fornices with circumscript bleedings. On account of an absolute arrhythmia of the heart the patient has been on a medication of cumarine-derivates since 9 years. Histologically we found underneath the epithelium densely packed lymphocytic cells with small uniform nuclei intermingled with many erythrocytes. The immunohistological investigations revealed a Non-Hodgkin-Lymphoma of B-cell origin. CONCLUSIONS: Bleedings in a conjunctival Non-Hodgkin-Lymphoma can alter the clinical aspect of the tumor. It is necessary to inspect each entropion thoroughly in order to rule out any other pathological lesions.

[Lymphangioma of the conjunctiva]. / Lymphangiom der Bindehaut.

A 23-year-old female presented with a yellow-brownish, asymptomatic tumour of the bulbar conjunctiva in her left eye. The lesion had been detected 5 years previously and had grown since then. Prior to presentation there were 2 episodes of intratumoral hemorrhage. Funduscopy revealed tortuous vessels on the left. Complete tumour excision was performed. Histology showed numerous channels lined by a flat endothelium, and inflammatory cells in the fibrous septae. A diagnosis of a conjunctival lymphangioma was established. The tortuosity of the retinal vessels was probably associated by chance or caused by an undetected orbital lymphangioma.

[Erythema exsudativum multiforme major]. / Erythema exsudativum multiforme major.

UNLABELLED: Erythema exudativum multiforme major (EEMM), also know as Stevens-Johnson syndrome, may cause severe conjunctival and corneal alterations. The etiology remains unknown. The aim of are study was to evaluate the clinical course, therapy and prognosis of ocular involvement. PATIENTS AND METHODS: In a retrospective study, we evaluated ten patients with EEMM who were treated between 1986 and 1994 at the University Eye Clinic Tübingen. RESULTS: The age of the four female and six male patients varied between 5 and 70 years. Drugs as a possible precipitating factor were found in all cases (acetylsalicylicacid, sulfonamide, erythromycin, cotrimoxazole, Valproinicacid, paracetamol). Eight patients experienced an infection at the same time. Clinically, we were able to differentiate two groups regarding severity of the disease. Seven patients were characterized by ocular alterations that only involved the conjunctiva, leading to conjunctival scars. In those cases local treatment with antibiotics and corticosteroids was effective. In the second group severe ocular damage occurred, with symblephara, keratinization and consecutive perforating keratoplasty. Secondary infections became evident in a total of six cases from the two groups. SUMMARY: Drugs as a possible precipitating factor could be identified in all cases. In eight of ten patients previous infection was known. This agrees with literatures reports of viral infections (e.g. herpes simplex) as cofactors causing EEMM, especially for the aggressive form, remains unresolved. The danger of possible superinfection should always be taken into consideration.

Isolated hyperthermic perfusion with mitoxantrone of melphalan in malignant melanoma of the limb.

BACKGROUND: Melphalan administered by isolated hyperthermic perfusion of the affected limb is an accepted treatment for malignant melanoma of the extremities. In contrast, pharmacologic and phase I studies suggest that, because of its high uptake, mitoxantrone may give even better local control, but data on survival, onset of metastases, and local and systemic toxicities have not yet been reported. METHODS: A matched-pairs comparison was performed to examine differences in the tolerability and effectiveness of isolated hyperthermic extremity perfusion with mitoxantrone (n = 44) and melphalan (n = 44) in high risk and locoregionally (P < 0.41) metastatic malignant melanoma. Criteria evaluated were local and systemic complications, and recurrence-free and overall survival. RESULTS: Local complications, such as delayed wound healing, were more frequent in the mitoxantrone (27.9%) than in the melphalan group (9.8%) (P < 0.05). Systemic toxicity, in particular bone marrow toxicity, was also more severe with mitoxantrone (78.6% versus 15.4%, P < 0.001). Hepatotoxic effects were more frequent among patients in the melphalan group who were older and has lower tissue perfusion temperatures (P < 0.05). There was no difference between the two groups in overall or recurrence-free survival (P < 0.41). CONCLUSIONS: Local and systemic toxicity seem to be higher with mitoxantrone. Survival rates were similar with both drugs. The data obtained suggest a randomized phase II study with an appropriate number of patients.

Antisocial behavior, somatization, and sensation-seeking behavior in mothers of clinic-referred children.

OBJECTIVE: The relationship between antisocial behavior and somatization was studied in a sample of mothers of clinic-referred, school-age children. The goal was to overcome some of the methodological limitations of past research in this area and to provide a preliminary test of the theory that these disorders share a common substrate: a tendency toward behavioral disinhibition. METHOD: Structured diagnostic interviews and an objective personality measure were used to assess antisocial behavior and somatization in a sample of 90 biological mothers (mean age 34 years) of children referred to an outpatient mental health clinic. A rating scale measure of sensation-seeking behavior was used as a measure of behavioral disinhibition. Structured interviews were used to assess a history of antisocial behavior in the children and their biological fathers. RESULTS: Results indicated a link between somatization and antisocial behavior both within individuals and across generations. This intergenerational link could not be solely accounted for by assortative mating between women with somatization and antisocial men. Both somatization and antisocial behavior were correlated with scores on the sensation seeking scale. CONCLUSIONS: These findings are consistent with the theory that antisocial behavior and somatization are related syndromes and that behavioral disinhibition may be a common predisposition that underlies both.

[Diffuse xanthogranuloma as a cause of infantile heterochromia]. / Diffuses Xanthogranulom als Ursache einer infantilen Heterochromie.

A 7-month-old female infant presented with a heterochromia and an anisocoria. A spontaneous hyphema and a secondary glaucoma had developed. Under topical and systemic steroid therapy the eye improved continuously. At the time of the last ocular examination the hyphema had resorbed, and the intraocular pressure was normal. Heterochromia had almost completely vanished, and dilation of the pupil was much better. Since even a massive juvenile xanthogranuloma of the iris responds well to steroids, operative and radiation treatment should be limited to cases refractory to antiinflammatory drug therapy.

Spin-echo methods for the determination of 31P transverse relaxation times of the ATP NMR signals in vivo.

31P magnetic resonance spectroscopy (MRS) examinations of the calf muscles of healthy volunteers were performed to determine T2 of the coupled ATP signals by use of the Hahn spin-echo and the frequency-selective spin-echo method. Additional measurements with the J-coupling refocused double echo are presented. The most reliable determination of T2 relaxation times is possible with the frequency-selective spin echo. The other methods yield substantially wrong results. Theoretical explanations are given how J-coupling and pulse-angle deviations affect the signals and therefore the T2 determinations. The calculations for a weakly coupled homonuclear AX spin system are shown because they demonstrate most of the relevant facts. In addition, some important results for a homonuclear AMX spin system, which the ATP is considered to be, are given.

31P transverse relaxation times of ATP in human brain in vivo.

31P MRS examinations of the brain of 10 healthy volunteers were performed to determine T2 of the coupled ATP signals by use of the localized 90 degrees-TE/2-2662-TE/2-acq frequency selective spin echo sequence for elimination of phase and intensity distortions. The T2 relaxation times obtained are much longer than usually assumed: gamma-ATP: 89 +/- 9 ms; alpha-ATP: 84 +/- 6 ms; beta-ATP: 62 +/- 3 ms.

A pitfall associated with determination of transverse relaxation times of the 31P NMR signals of ATP using the Hahn spin-echo.

T2 measurements of 31P NMR signals of ATP using the Hahn 90 degrees-180 degrees spin-echo sequence imply difficulties whenever the 180 degrees pulse angle is not completely perfect. The reason for this finding is the crucial influence of the J-couplings of the ATP signals which result in intensity modulations and consequently in false T2 values even when the echo times are chosen to TE = n/J. Examinations on the calf muscles of healthy volunteers were performed to demonstrate this effect and its influence on in vivo T2 determinations. The T2 relaxation times evaluated with the Hahn spin-echo in combination with a Helmholtz coil are far shorter than the true T2 values.

Imaging of the human cardiovascular system using the rapid echo flow-rephased spin-echo technique.

Using a flow-rephased spin-echo technique with a short echo time of TE = 9.7 msec, "white blood" multislice and single slice first echo images of the human heart were acquired using standard 1.5 T whole-body imagers. The technique almost completely eliminates phase shifts for flow with constant velocity and constant acceleration, so the investigations with healthy volunteers show images which are almost free of the artifacts often found in ECG-gated standard spin-echo imaging of the heart. T1-weighted images with good contrast between tissue and blood are achieved at any time during the whole heart cycle. The results obtained indicate that the technique might be helpful for imaging small vessels, vessels which contain slowly flowing blood, and vessels located in regions with static field inhomogeneities, for example, lung vessels.

31P transverse relaxation times of the ATP NMR signals of human skeletal muscle in vivo.

31P MRS examinations of the calf muscles of 12 healthy volunteers were performed to determine T2 of the coupled ATP signals by using the 90 degrees-TE/2-2662-TE/2-acq selective spin-echo sequence for elimination of phase and intensity distortions. The T2 relaxation times obtained are much longer than those usually assumed: gamma-ATP, 93 ms; alpha-ATP, 74 ms; beta-ATP, 75 ms.

Localized phosphorus NMR spectroscopy: a comparison of the FID, DRESS, CRISIS/CODEX, and STEAM methods in vitro and in vivo using a surface-coil.

The FID, DRESS, CRISIS/CODEX, and STEAM techniques for localized 31P NMR spectroscopy were compared using a Siemens Magnetom SP63 1.5 T whole-body imager and a surface-coil, 80 mm in diameter, acting as transmitter and receiver coil. The comparison was performed with phantom experiments and human in vivo investigations on the calf muscle. The phantom experiments which used the same volume size showed a comparable signal-to-noise ratio for FID and DRESS, while the two fully localized techniques showed a reduction in signal-to-noise ratio to 76% for CRISIS/CODEX and 31% for STEAM. The in vivo measurements confirm the phantom results and reveal that CRISIS/CODEX gains a 2.5 fold higher signal-to-noise ratio than STEAM under the same conditions.

Subdiaphragmatic extralobar pulmonary sequestration.

A 21-day-old girl presented with a left subdiaphragmatic retroperitoneal mass discovered on maternal ultrasound at 23 weeks' gestation. The clinical impression was neuroblastoma, and preoperative workup showed no for metastatic disease. Histologically, the lesion proved to be an extralobar pulmonary sequestration. We present this case to remind pathologists of the occurrence of subdiaphragmatic pulmonary sequestration and its potential clinical confusion with other more familiar lesions that may occur in this location in a neonate.

[T2*-weighted MR images of gynecologic tumors with the FLASH sequence: the initial experiences at 1.5 T]. / T2*-betonte MR-Bilder gynäkologischer Tumoren mit der FLASH-Sequenz: Erste Erfahrungen bei 1,5 T.

To speed up the time taken for MR examinations, 20 patients with malignant gynaecological lesions (carcinoma of the cervix, uterus or ovary) and two operative specimen (carcinoma of the cervix) were examined by T2*-weighted flash sequences; the results were compared with T2-weighted spin echo sequences. In ten out of 20 in vivo examinations, the flash method produced a similar contrast range between tumour and normal tissues, cystic lesions being particularly well seen in gradient echo sequences. In the remaining patients, and in the surgical specimen, demarcation of the tumour was significantly poorer on the flash sequences. There was also loss of anatomic detail and an increased susceptibility to artifacts. The flash sequence as used here can therefore not be regarded as of the same diagnostic value as T2-weighted spin echo sequences in the diagnosis of gynaecological malignancies.