Nosocomial postsurgical meningitis in children: a 12-year survey comparing data from 1993-1998 with data from 1999-2004.
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Child↗
Biomedical subjects
I Sulla
Publications and source records attributed to I Sulla.
Diazepam enhances hypericin-induced photocytotoxicity and apoptosis in human glioblastoma cells.
Glioblastoma multiforme (GBM) is neoplasm which is resistant to all currently used treatment modalities including surgery, radiation therapy and chemotherapy. Photodynamic therapy (PDT) has been suggested as a novel therapeutical approach to the treatment of malignant gliomas. Here, we attempted to enhance hypericin-induced photocytotoxicity and apoptosis by diazepam, a non-selective ligand of peripheral benzodiazepine receptors (PBR) which seem to play an important role in apoptosis regulation. For the study, we used U-87 MG and U373 MG glioma cell lines and primary cultures of GBM cells prepared from peroperatively obtained tumor specimens. The patients included 7 histologically confirmed GBMs. Colorimetric MTT assay was employed to study the photocytotoxic effects of hypericin and diazepam. Flow cytometry was used to detect apoptosis and assess the proapoptotic effects of diazepam. We found that hypericin upon photoactivation exerts strong cytotoxic effects against U-87 MG and U373 MG cells as well as primary GBM cell cultures. No cytotoxic effect of hypericin was observed under dark conditions. Diazepam inhibited cell growth in U-87 MG cells and primary cultures whereas proliferation of U373 MG cells remained unaffected. When hypericin was combined with diazepam, photocytotoxicity was increased in U-87 MG cells and primary cultures unlike U373 MG cells. Flow cytometric analysis revealed photoactivated hypericin-induced apoptosis in both cell lines. Apoptosis was significantly enhanced by diazepam in U-87 MG cells. However, no such effect was observed in U373 MG cells. In the present study, we showed that photocytotoxic effect of hypericin in glioma cells can be potentiated by diazepam. This effect is underlied by the ability of diazepam to facilitate hypericin-induced apoptosis. This work provides support to performe clinical studies involving diazepam in the antiglioma treatment regimens as an apoptosis-modulating agent.
Adult↗
[Ischemic-reperfusion paraplegia in the dog and its light microscopy imaging].
Paraplegia, which develops after operation on aorta, represents a real catastrophe for the patient and for the surgeon. The aim of the present work was to investigate the light microscopy picture of this complication and consequently better understand related processes. Twenty one adult dogs, cross breeds of both sexes, weight 18-25 kg, were divided into four groups: 1. Controls (n = 3); 2.30-min ischemia induced by occlusion of thoracic aorta by a tourniquet, followed for 30 min survival (n = 6); 3.30-min ischemia and 72 h of survival (n = 6); 4) 30-min ischemia and 6 days of survival (n = 6). All these manipulations were made in sterile conditions under general anesthesia. As soon as the planned time of survival passed, the animals were flushed out, in deep pentobarbital anesthesia, with 3,000 ml of sodium chloride and fixed with 3,000 ml of 10% neutral formaldehyde. Sections, 30 microns thick, from L3-S1 medulla segments were processed in the laboratory of Neurobiological Institute by the method of Nauta for light microscopy examination. Neurohistological picture was characterized by a marked damage of the medulla neurons. The changes proved to be irreversible and resulted, in the course of six days of survival, to death of the cells, characterized by their disintegration. The results indicate that the only rational procedure in conditions of threatening ischemic-reperfusion injury of medulla is to prevent it.
Animals↗
[Surgical treatment of discogenic compression of the spinal cord in the thoracic region].
The objective of the submitted work was to draw attention to some problems associated with the diagnosis and treatment of prolapse of sequestra of thoracic intervertebral discs. The investigated group comprised 9 subjects (4 women, 5 men) aged 33 to 67 years operated upon at the Neurosurgical Clinic in Kosice between Jan. 1 1982 and June 30 2001 on account of compression of nervous structures in the thoracic portion of the spine by sequestra of intervertebral discs. This was manifested by back pain, a sensation of stiffening of the muscles of the lower extremities, altered sensitivity and in all by impaired gait. Only one female patient developed urinary retention, another one painless paraparesis of the lower extremities, therefore the condition was evaluated as a demyelinisation process. In three patients as the only imaging examination method perimyelography was used, in another two it was supplemented by CT. Four patients were examined by MRI. This graphic method proved to be the most suitable. In all subjects of the investigated group the clinical picture and examination methods indicated a unilateral predominance of the affection. In five subjects it proved possible to remove the sequestream of the intervertebral disc via laminectomy, in another four a transpedicular approach into the spinal canal was used successfully. In all patients the condition improved after surgery.
Adult↗
Allelic and haplotype frequencies of the p53 polymorphisms in brain tumor patients.
The polymorphisms of the tumor suppressor gene p53 in exon 4 (p53 BstUI) and in intron 6 (p53 MspI) have been suggested to be associated with the genetically determined susceptibility in diverse types of human cancer. In our hospital-based case-control study, we examined the allele and genotype incidence of these polymorphisms as well as their haplotype combinations in 60 brain tumor patients (27 males and 33 females) and 183 controls without malignancies. The genotype characteristics were determined by the PCR-based RFLP method using DNA extracted from peripheral blood. In this study we show that the p53 BstUI and the p53 MspI polymorphisms are not associated with increased risk of brain tumors. Thus, we conclude that the p53 BstUI and the p53 MspI polymorphic sites within the tumor suppressor gene p53 do not represent genetic determinants of susceptibility to brain tumors.
Adult↗
Cauda equina syndrome.
Single or double-level compression of the lumbosacral nerve roots located in the dural sac results in a polyradicular symptomatology clinically diagnosed as cauda equina syndrome. The cauda equina nerve roots provide the sensory and motor innervation of most of the lower extremities, the pelvic floor and the sphincters. Therefore, in a fully developed cauda equina syndrome, multiple signs of sensory disorders may appear. These disorders include low-back pain, saddle anesthesia, bilateral sciatica, then motor weakness of the lower extremities or chronic paraplegia and, bladder dysfunction. Multiple etiologies can cause the cauda equina syndrome. Among them, non-neoplastic compressive etiologies such as herniated lumbosacral discs and spinal stenosis and spinal neoplasms play a significant role in the development of the cauda equina syndrome. Non-compressive etiologies of the cauda equina syndrome include ischemic insults, inflammatory conditions, spinal arachnoiditis and other infectious etiologies. The use of canine, porcine and rat models mimicking the cauda equina syndrome enabled discovery of the effects of the compression on nerve root neural and vascular anatomy, the impairment of impulse propagation and the changes of the neurotransmitters in the spinal cord after compression of cauda equina. The involvement of intrinsic spinal cord neurons in the compression-induced cauda equina syndrome includes anterograde, retrograde and transneuronal degeneration in the lumbosacral segments. Prominent changes of NADPH diaphorase exhibiting, Fos-like immunoreactive and heat shock protein HSP72 were detected in the lumbosacral segments in a short-and long-lasting compression of the cauda equina in the dog. Developments in the diagnosis and treatment of patients with back pain, sciatica and with a herniated lumbar disc are mentioned, including many treatment options available.
Animals↗
Fos protein expression in sacral spinal cord in relation to early phase of cauda equina syndrome in dogs.
1. The aim of the present study is to map the incipient phase of Fos expression in the sacral spinal cord neuronal pools of multiple cauda equina constrictions canine model. 2. Fos-positive neurons were found bilaterally in the lateral portion of superficial dorsal horn layers (Laminae I-III) and along the lateral edge of the dorsal horn accompanied by the lateral collateral pathway, fibers of Lissauer's tract, terminating at the sacral parasympathetic nucleus. Similarly, high Fos expression was detected in the ventral portion of the dorsal sacral commissure and in the dorsomedial portion of the anterior horns at S1-S3 segment level. Finally, a clearly expressed Fos-positivity was disclosed bilaterally in the neuropil of the nucleus Y in the anterior horn. 3. Data from the present study show that continuous stimulation of the central fibers of sacral dorsal root ganglia neurons, i.e., fibers of sacral primary afferents, unlike those using various stimulations of the peripheral fibres offers an unusual pattern of Fos-like immunoreactivity.
Animals↗
Diazepam enhances etoposide-induced cytotoxicity in U-87 MG human glioma cell line.
Various approaches might be employed in an effort to increase efficacy of the chemotherapeutic treatment of cancer. Recently, various modulators of anticancer therapy effectiveness have been studied. Antiproliferative effects of peripheral benzodiazepine receptor (PBR) ligands might be exploited to enhance cytotoxic effect of a chemotherapeutic drug towards cancer cells. In this work, we sought to enhance cytotoxic effect of etoposide (VP-16) by a PBR ligand, diazepam (DZ) in U-87 MG human glioma cells. Cytotoxicity of VP-16, DZ and their combinations was assessed by using the microculture MTT assay. Cell survival, effective concentrations (EC) and the onset of cytotoxic effect were determined. After 72 h of cultivation, survival of U-87 MG cells was reduced to 57 +/- 7% in the presence of VP-16 at 12.5 microg/mL alone, whereas DZ at 10-4 mol/L alone caused 28 +/- 6% reduction in cell survival. Coincubation of VP-16 at 12.5 microg/mL with DZ at 10-4 mol/L led to a further decrease in cell survival to 45 +/- 6%. Furthermore, DZ at 10-4 mol/L significantly decreased effective concentrations, EC10, EC30 and EC50, of VP-16 and the dose-response curves were shifted to the left. Addition of DZ at 10-4 mol/L to VP-16 also facilitated the onset of its cytotoxic effect. The same decrease in survival was thus achieved approximately 30 h earlier in comparison with VP-16 alone. However, DZ at 10-9 mol/L failed both to exert any effect on glioma cells survival and enhance cytotoxic effect of VP-16. DZ at 10-4 mol/L was capable of both reducing U-87 MG glioma cells survival when applied alone and also enhancing the cytotoxic effect of VP-16. No such observation was made for the lower concentrations of DZ. Potential implementation of diazepam in the antiglioma/anticancer armamentarium awaits further experimentation but phase I and phase II clinical trials could be suggested.
Anticonvulsants↗
[A patient with spontaneous healing of traumatic spondylolisthesis of the cervical vertebrae].
The authors submit a report on a patient with traumatic spondyloptosis of the sixth cervical vertebra which occurred in an adult man when he bumped his head against a standing lorry. The injury of the cervical spine was diagnosed only four weeks after the accident when the patient regained consciousness and the vertebrae were already fixed in a pathological position. Seven years after the injury the patient is satisfied with his health, works in his original occupation, is engaged in sports and leads an active life.
Cervical Vertebrae↗
Incipient cauda equina syndrome as a model of somatovisceral pain in dogs: spinal cord structures involved as revealed by the expression of c-fos and NADPH diaphorase activity.
Segmental and laminar distribution of Fos-like immunoreactive, reduced nicotinamide adenine dinucleotide phosphate diaphorase (NADPHd)-exhibiting and double-labeled (Fos-like immunoreactive and NADPHd-exhibiting) neurons was examined in lower lumbar and sacral segments of the dog spinal cord using the model of multiple cauda equina constrictions. NADPHd histochemistry was used as marker of nitric oxide synthase-containing neurons. The appearance and the time-course of Fos-like immunoreactive, NADPHd and double-labeled neurons was studied at 2 h and 8 h postconstriction characterized as the incipient phase of cauda equina syndrome. The occurrence of Fos-like immunoreactive and NADPHd-exhibiting neurons in fully developed cauda equina syndrome was studied at five days postconstriction. An increase in Fos-like immunoreactivity in superficial laminae (I-II) and an enhanced NADPHd staining of lamina VIII neurons were found. A statistically significant increase in Fos-like immunoreactive neurons was found in laminae I-II and VIII-X 8 h postconstriction, and in contrast, a prominent decrease in Fos-like immunoreactive neurons was found in laminae I-II, accompanied by a statistically significant increase in Fos-like immunoreactive neurons in more ventrally located laminae VII-X at five days postconstriction. Quantitative analysis of laminar distribution of constriction-induced NADPHd-exhibiting neurons revealed a considerable increase in these neurons in laminae VIII-IX 8 h postconstriction and a statistically highly significant increase in NADPHd-exhibiting neurons in laminae VII-X five days postconstriction. Concurrently, the number of NADPHd-exhibiting neurons in laminae I-II was greatly reduced. While a low number of double-labeled neurons was found throughout the gray matter of lower lumbar and sacral segments at 2 h postconstriction, a statistically significant number of double-labeled neurons was found in lamina X 8 h and in laminae VII-X five days postconstriction. The course and distribution of anterograde degeneration resulting five days after multiple cauda equina constrictions are compared with segmental and laminar distribution of Fos-like immunoreactive and NADPHd-exhibiting neurons. Prominent involvement of the spinal cord neurons appearing in the lumbosacral segments at the early beginning and in fully developed cauda equina syndrome results in a Fos-like immunoreactivity and strongly enhanced NADPHd staining of some neuronal pools. Under such circumstances, an early cauda equina decompression surgery is advisable aimed at decreasing or preventing the derangement of the neural circuits in the lumbosacral segments.
Animals↗
Effect of midthoracic spinal cord constriction on catalytic nitric oxide synthase activity in the white matter columns of rabbit.
The distribution and changes of catalytic nitric oxid synthase (cNOS) activity in the dorsal, lateral and ventral white matter columns at midthoracic level of the rabbit's spinal cord were studied in a model of surgically-induced spinal cord constriction performed at Th7 segment level and compared with the occurrence of nicotinamide adenine dinucleotide phosphate diaphorase expressing and neuronal nitric oxide synthase immunoreactive axons in the white matter of the control thoracic segments. Segmental and white-column dependent differences of cNOS activity were found in the dorsal (141.5 +/- 4.2 dpm/microm protein), lateral (87.3 +/- 11.5 dpm/microm protein) and ventral (117.1 +/- 7.6 dpm/microm protein) white matter columns in the Th5-Th6 segments and in the dorsal (103.3 +/- 15.5 dpm/microm protein), lateral (54.9 +/- 4.9 dpm/microm protein), and ventral (86.1 +/- 6.8 dpm/microm protein) white matter columns in the Th8-Th9 segments. A surgically-induced constriction of Th7 segment caused a disproportionate response of cNOS activity in the rostrally (Th5-Th6) and caudally (Th8-Th9) located segments in both lateral and ventral white matter columns. While a statistically significant decrease of cNOS activity was detected above the constriction site in the ventral columns, a considerable, statistically significant increase of cNOS activity was noted in the white lateral columns below the site of constriction. It is reasoned that the changes of cNOS activity may have adverse effects on nitric oxide (NO) production in the white matter close to the site of constriction injury, thus broadening the scope of the secondary mechanisms that play a role in neuronal trauma.
Animals↗
[Injuries of the intracranial part of the carotid artery].
The objective of the submitted work was to draw attention to different types of injuries of the intracranial portion of the carotid artery and some problems associated with its solution. The investigated group comprised 7 subjects (2 women, 5 men) aged 19 to 76 years who attended between Jan. 1, 1995 and Feb. 29 2000 the Neurosurgical Clinic in Kosice with sequelae of injuries of the intracranial carotid artery. Two patients developed a pseudoaneurysm. In one case it was manifested by subarachnoid haemorrhage on the 24th day after a crash, in one instance by diplopia six weeks after a retrobulbar injection. Injury of the intracavernous portion of the artery was manifested in one instance by profuse epistaxis on the 17th day after a fall from a bicycle, four times by the development of a carotid-cavernous fistula several days to 3 years after the head injury. In the diagnosis classical as well as MR and digital subtraction angiography were used. In the patient with epistaxis classical carotid angiography was 3 times negative. The results are comparable with data in the literature. In three patients the problem was resolved by ligature of the common carotid artery on the neck. In another three it was necessary to use extra-intracranial trapping. One patient will be subjected to endovascular surgery. Two patients died (a 76-year-old woman from bronchopneumonia, a 19-year-old man from meningitis, despite a liquor fistula treated correctly by a patch).
Adult↗
[Spinal root compression and results of treatment of discogenic cauda equina syndrome].
Several experimental and clinical studies suggest an important role of the quality and quantity of the material compressing the lumbosacral spinal cord radices in the development of cauda equina syndrome. These facts inspired the author to find out if the repair of neurological functions depends also on these factors. Clinical investigations of 81 persons (30 women and 51 men) were performed at minimum time of two years after the operation of the cauda equina discogenic syndrome. Mathematical analysis of the acquired data (chi-quadrate) revealed that so-called soft compression of neural structures (intervertebral disc hernia, sequester liber) negatively influenced the restoration of lower extremities motor functions (p = 0.01), sexual functions in men (p = 0.05) and radicular pain persistence (p = 0.01). On the other hand, the so-called hard compression (spondylosis deformans and protrusion of intervertebral disc) negatively influenced the restoration of sensitive innervation (p = 0.01) and voluntary control of urinary bladder emptying (p = 0.01). (Tab. 7, Ref. 24.)
Cauda Equina↗
[The time factor in cauda equina syndrome].
Cauda equina syndrome is a rare but potentially catastrophic complication of lumbar disc disease. In spite of properly performed surgical decompression, the outcome is mostly unsatisfactory. One of the important factors influencing the recovery of motor function of the lower extremities, sensation, bladder and rectum control, sexual function, as well as working ability is thought to be the duration of cauda equina compression. The evaluation of data obtained in a group of 58 persons (21 women and 37 men) operated upon for discogenic cauda equina syndrome in the period of time from January 1, 1982 to December 31, 1991 did not confirm this opinion. (Tab. 7, Ref. 23.).
Adult↗
Multiple protracted cauda equina constrictions cause deep derangement in the lumbosacral spinal cord circuitry in the dog.
Neuropathological changes of the neuronal pools and spinal cord circuitry in the lumbosacral segments were studied in a canine model of multiple protracted cauda equina constrictions. Anterograde degeneration of all sacrococcygeal and L7 dorsal root fibers was detected in S1-S3 and lower lumbar segments. A narrow degenerated gracile fascicle was found in all thoracic and cervical segments terminating in the gracile nucleus. Transneuronal degeneration of middle-sized and large neurons, located in S1-S3 and sporadically in L7 segments, was noted. Identical transneuronal degeneration was seen in a group of small neurons located in the ventralmost part of lamina VII in S1-S3 segments. Simultaneously, a terminal degeneration was detected in the lateral cervical nucleus and in the ventral posterior lateral nucleus of the ventrobasal thalamic complex. Concomitantly, a fully developed retrograde degeneration affecting motoneurons in the ventrolateral portion of the anterior horn in S1-S3 segments appeared.
Animals↗
Ischemia-induced delayed-onset paraplegia is accompanied by an unusual form of synaptic degeneration in the lumbosacral segments: an experimental light and electron microscopic study in dogs.
We studied the effect of high thoracic aorta cross-clamping, complete transverse section of the spinal cord at Th6 level, and combined hemisection at Th6 level followed later by high thoracic aorta cross-clamping upon the morphology and number of identified presynaptic knobs in lumbosacral segments in dogs. In animals surviving 48-72 hours after high thoracic aorta cross-clamping the occurrence of an unusual form of boutons accompanied by periboutonal halo in L3-S1 segments was found. According to the bouton size and light as well as electron microscopic appearance, four types, i.e., light giant (T1), dark enlarged (T2), light giant with periboutonal halo (T3), and giant disintegrating (T4) boutons were detected after 48 and 72 hour reperfusion. The appearance of four boutonal types in the lumbosacral segments is caused by spinal cord ischemia secondary to high thoracic aorta cross-clamping followed by 48 or 72 hour reperfusion. At the end of the sixth reperfusion day no signs of enlarged and giant boutons were detected in L3-S1 segments. A statistically significant increase of enlarged and giant boutons was noted at the end of the third reperfusion day in comparison with 48 hour survival. After spinal cord transection at midthoracic (Th6) level, followed by 72 hour survival, no such unusual synaptic knobs could be found in L3-S1 segments. The laminar distribution pattern of T1-T4 types based on light microscopic analysis and confirmed electron microscopically is characteristic and strictly bound to those spinal cord gray matter layers which serve as main termination sites of the descending cortical, brain stem, as well as long propriospinal projections in the lumbosacral segments (laminae V-VII). A statistically significant increase of enlarged and giant boutons was found in the intermediate zone (lamina VII). Hemisection at midthoracic level (Th6) followed later by 30 minute high thoracic aorta cross-clamping and 48 hour reperfusion caused a marked decrease of enlarged and giant boutons in L3-S1 segments on the hemisectioned side in comparison with the contralateral one. Large amounts of irregularly arranged round vesicles and tubular profiles were disclosed in the boutonal matrix of T1, T3, and T4 types in L3-S1 segments of animals subjected to 30 minute high thoracic aorta cross-clamping followed by 72 hour reperfusion. Accumulation of tubular and membranous materials was invariably seen in the bulbous enlargement of the terminal axonal branch.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
Patients age and results of treatment in discogenic cauda equina syndrome.
Cauda equina syndrome is a feared complication of lumbar disc disease. Despite of early surgery it frequently leaves persistent effects. Localisation, type, and duration of spinal nerve roots compression are quoted as the most important factors influencing the results of treatment. Statistical evaluation of data acquired by examinations of 58 persons operated on for this disease et the Department of Neurosurgery in Kosice within the period from January 1st, 1982 to December 31st, 1991 has shown that the further important facts are ageing of tissues and impairment of microcirculation. In patients over the age of 45 the recovery of motor and sexual functions, as well as the voluntary control of rectal sphincters, and the working ability were significantly worse. It is suggested thereby that in elderly persons with a proven intervertebral disc disease an early surgical intervention is indicated. (Tab. 7, Ref. 23.)
Adult↗
Central hypothyroidism--various types of TSH responses to TRH stimulation.
Thyrotropin (TSH) levels in serum before and 20 and 60 min after the administration of 0.2 mg TRH i.v. as well as thyroid hormone (T3, T4) levels were studied in 39 patients with organic diencephalo-pituitary lesions and 27 healthy subjects. All participants gave their informed consent with the study. By the type of TSH response to TRH stimulation all patients were divided into 4 groups: 1. Normal response (n = 10): basal TSH 2.31 +/- 1.51, peak TSH 20 min after TRH 12.17 +/- 6.53, TSH 60 min after TRH 8.43 +/- 4.65 microU/ml; T3 2.02 +/- 0.48 and T4 95.9 +/- 27.73 nmol/l; 2. Blunted or absent TSH response (n = 8): basal TSH 0.82 +/- 0.42, peak TSH 20 min after TRH 1.51 +/- 0.66, TSH 60 min after TRH 1.35 +/- 0.51 microU/ml; T3 1.6 +/- 0.49 and T4 86.63 +/- 16.49 nmol/l; 3. Delayed ("diencephalic") TSH response (n = 16): basal TSH 2.69 +/- 1.27, peak TSH 20 min after TRH 7.96 +/- 3.35, TSH 60 min after TRH 10.0 +/- 3.97 microU/ml; T3 1.30 +/- 0.63 and T4 65.85 +/- 21.13 nmol/l; 4. Higher basal or stimulated TSH (n = 10): basal TSH > 10 mU/ml or stimulated values above 25 mU/ml. Mean T3 and T4 values in patients with normal or blunted TSH response did not differ significantly from the controls. Mean T3 and T4 in the group with delayed TSH response were significantly lower (P < 0.01). High TSH and low T3 and T4 levels were found in the patient with large meningioma sellae.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗