Intense self-compressed, self-phase-stabilized few-cycle pulses at 2 microm from an optical filament.

We report the compression of intense, carrier-envelope phase stable mid-IR pulses down to few-cycle duration using an optical filament. A filament in xenon gas is formed by using self-phase stabilized 330 microJ 55 fs pulses at 2 microm produced via difference-frequency generation in a Ti:sapphire-pumped optical parametric amplifier. The ultrabroadband 2 microm carrier-wavelength output is self-compressed below 3 optical cycles and has a 270 microJ pulse energy. The self-locked phase offset of the 2 microm difference-frequency field is preserved after filamentation. This is to our knowledge the first experimental realization of pulse compression in optical filaments at mid-IR wavelengths (lambda>0.8 microm).

High-energy cutoff in the spectrum of strong-field nonsequential double ionization.

Electron energy distributions of singly and doubly ionized helium in an intense 390 nm laser field have been measured at two intensities (0.8 PW/cm2 and 1.1 PW/cm2, where PW is defined as 10(15) W/cm2). Numerical solutions of the full-dimensional time-dependent helium Schrödinger equation show excellent agreement with the experimental measurements. The high-energy portion of the two-electron energy distributions reveals an unexpected 5U(p) cutoff for the double ionization (DI) process and leads to a proposed model for DI below the quasiclassical threshold.

Technical note. Pyogenic spinal epidural abscess: a minimally invasive technique for multisegmental decompression.

Spontaneous spinal epidural abscess is a rare condition that is devastating and often fatal. Traditionally, surgery and antibiotics have been the treatment of choice; however, there has been some debate on the indications for their use. This technical note discusses a method for decompressing an acute multisegmental pyogenic spinal epidural abscess, thereby avoiding multilevel laminectomies.

Pediatric occipitocervical arthrodesis. A review of current options and early evaluation of rigid internal fixation techniques.

OBJECT: Few reports exist on the options and effectiveness of craniocervical stabilization in the pediatric population compared with the adult literature. Traditional options in children include onlay grafting and semi-rigid occipitocervical wiring. Recently, reports on the use of rigid internal fixation devices such as occipitocervical plates and contoured loops have provided excellent results in adults, and their use has often obviated the need for external orthosis. The purpose of this article is to report our experience with both traditional and newer rigid internal fixation methods for occipitocervical fusion in children. METHODS: During the past 4.5 years, 14 children (ages 4 months to 16 years) have undergone occipitocervical fusion. Indications for fusion included trauma (n = 4), congenital instability/stenosis (n = 6), postinfectious instability (n = 1) and basilar invagination (n = 3). Techniques using onlay grafting (n = 3) as well as rigid internal fixation using plates (n = 1) and contoured craniocervical titanium loops (n = 10) were used. Postoperative orthosis included halo vests (n = 7), minerva jackets (n = 3), sterno-occipital mandibular immobilizer (n = 1), and a cervical collar (n = 3). Long-term follow-up (range 13-58 months) was available for 13 of the 14 children. CONCLUSIONS: While each occipitocervical fusion in pediatric patients requires a customized treatment plan, we believe children older than 12 months of age should be considered candidates for rigid internal fixation methods. The rigidity afforded by this method may eliminate the need for rigid external orthotic support in selected individuals. In our experience, anatomic constraints in children less than 1 year old usually require fusion with more traditional onlay techniques. Long-term follow-up studies are still required to assess the effects of rigid internal fixation in the skeletally immature spine.

Single-stage anterior-posterior decompression and stabilization for complex cervical spine disorders.

OBJECT: To evaluate the applicability and safety of single-stage combined anterior-posterior decompression and fusion for complex cervical spine disorders, the authors retrospectively reviewed 72 consecutive procedures of this type performed using a uniform technique at a single center. METHODS: The indications for decompression and stabilization included: postlaminectomy kyphosis (15 patients), trauma (19 patients), spondylosis and congenital stenosis (32 patients), and ossification of the posterior longitudinal ligament (six patients). All patients underwent anterior cervical corpectomies in which allograft fibula and plates were placed, with 89% of patients undergoing two- or three-level procedures (range one-four levels). Lateral mass plating with autograft (morselized iliac crest) fusion was performed in all patients while the same anesthetic agent was still in effect. A hard cervical collar was used postoperatively in all patients (mean 13 weeks). All patients were followed for a minimum of 2 years (mean 29 months). Fusion was determined to be successful in all 72 patients (100%). Although the short-term morbidity rate reached 32%, the significant long-term morbidity rate was only 5%. At the 2-year follow-up examination, anterior cervical plate dislodgment was seen in one patient, and 16 of the 516 lateral mass screws implanted were observed to have partially backed out. However, there were no cases of nerve root injury, strut graft extrusion, or anterior plate or screw fracture. There were no clinically significant hardware complications and no patient required repeated operation. CONCLUSIONS: The combined single-stage anterior-posterior decompression, reconstruction, and instrumentation procedure represents a viable option in the treatment of a select group of patients with complex cervical spinal disorders. The technique provides immediate rigid stabilization of the cervical spine, prevents anterior plate failure or strut graft extrusion, and eliminates the need for halo immobilization postoperatively. Furthermore, a higher rate of fusion is achieved with this combined approach than with the anterior approach alone.

Solitary intracerebral juvenile xanthogranuloma. Case report and review of the literature.

A case of an intracerebral juvenile xanthogranuloma (JXG) producing complex-partial seizures in a 13-year-old boy is presented. Although the child had no history of JXGs or a systemic histiocytic proliferative disorder, the histopathological and immunocytochemical studies of this lesion were identical to that of a cutaneous JXG. This represents the first description of an isolated intracerebral JXG. On extensive review of the literature, this case comprises only the second reported intracranial lesion and the fourth CNS lesion in a child without cutaneous manifestations of JXG. In contrast to cerebral xanthogranulomas of adulthood, all reported cases of isolated CNS JXG presented with focal symptoms referable to the neuroanatomic localization of the lesion. In this limited series, the magnetic resonance imaging appearance was predictable and consistent, although spinal and intracranial lesions differ with respect to their enhancement with paramagnetic contrast media. While complete surgical excision, if feasible, has been the most utilized form of therapy for symptomatic or progressive lesions, external beam irradiation and cytotoxic chemotherapy have been utilized for unresectable or recurrent disease. Given their rare occurrence and uncertain natural history, it remains unclear whether these solitary CNS lesions represent a distinct clinical entity with a potentially more aggressive clinical course or merely a variant of the systemic non-Langerhans cell histiocytoses.

Substance P is generated in vivo following nasal challenge of allergic individuals with bradykinin.

BACKGROUND: Bradykinin, a potent inflammatory mediator, is released during allergic and non-allergic rhinitis and asthma in man. Nasal bradykinin challenge induces a dose-dependent plasma leakage into the nasal cavity and relevant symptoms of rhinitis. OBJECTIVE: We now report on substance P generation during nasal bradykinin challenge in vivo. METHODS: The effect of locally applied bradykinin on substance P generation was studied in nine individuals, allergic to grass pollen and six non-allergic controls. In the allergics TAME-esterase activity, histamine and substance P concentrations were measured in nasal lavages and correlated to the clinical symptoms. RESULTS: Substance P concentrations in nasal lavages increased in a dose-dependent fashion during nasal bradykinin challenge in both groups. In the allergic group Substance P-increases correlated with the production of TAME-esterase activity (r = 0.9, P < 0.05) whereas these allergic individuals did not produce any histamine increases. The generation of substance P and the increase of TAME-esterase activity was associated with the onset of clinical symptoms. Correlation of oedema and hypersecretion to substance P were significant by linear regression analysis (r = 0.88, P < 0.005 and r = 0.89, P < 0.02, respectively). Bradykinin induced irritations like burning and itching were short-term and rare. Serial dilutions of nasal washes produced Substance P-RIA displacement curves that paralleled the standard curve and recovery of standard substance P that was added to nasal washes was 76 +/- 4% (mean +/- SEM), n = 8. CONCLUSION: Bradykinin induces in vivo a dose-dependent plasma leakage into the nasal cavity without affecting mast cells, but stimulates nerve endings resulting in the release of the neuropeptide substance P.

Determination of substance P in human nasal lavage fluid.

The determination of substance P (SP) concentrations in human nasal lavages can be used to monitor physiological and certain pathophysiological processes in human airway mucosa. But, because of the low concentrations, immunoassays of high sensitivity are needed. Two approaches to improve the sensitivity of the radioimmunological determinations of SP are compared: increasing the sample volume and miniaturizing the assay design. The characterization of SP-like immunoreactivity (SP-LIR) in human nasal lavage was performed by investigating the immunological specificity of the antibody used in the radioimmunoassays and by reversed-phase high-performance liquid chromatography separation of the SP-LIR. SP concentrations in nasal lavages can be reliably measured by each of the two introduced RIA methods. Despite the lower detection limit of the miniaturized immunoassay (0.2 in comparison to 1.3 fmol/incubate) it is advisable to increase the sample volume in order to improve the sensitivity because of the higher precision of the determinations. SP-LIR was found in nasal lavage specimens in concentrations between 2 and 10 fmol/ml and consisted of authentic SP and, to a less extent, SP-sulfoxide.

Clinical and pathophysiological aspects of hydroxyethyl starch-induced pruritus: evaluation of 96 cases.

BACKGROUND: It has been recently recognized that long-term infusions of hydroxyethyl starch (HES) as a substitute of human plasma may lead to deposits within the human skin and clinically induces severe pruritus in approximately one-third of the patients treated. OBJECTIVE: To analyze the clinical features and pathophysiology of HES-induced itching. METHODS: Clinical data of 86 patients were analyzed retrospectively. Furthermore, 10 patients were followed prospectively, in whom we also performed routine laboratory tests, skin biopsies, allergological investigations (skin prick, basophil degranulation test), and substance P measurements in stimulated macrophages. RESULTS: Special features of HES-induced pruritus included long latency of onset and persistence. Noteworthy, itching is not always generalized. 30% of patients present with localized pruritus. Symptoms were not relieved by antihistaminics. Accordingly, the basophil degranulation test after HES exposure was negative. Also, substance P release from macrophages was not increased following HES stimulation. Deposits were found mainly in macrophages and endothelial cells. CONCLUSIONS: Our findings indicate that pruritus in HES-infused patients is most likely not triggered by pruritogenic mediators. We support data from the recent literature, suggesting a direct stimulation of cutaneous nerves by HES deposits. In patients suffering from long-standing itching it seems important to consider previous HES exposure as a possible cause not only in generalized pruritus but also in localized symptoms.

Substance-P-induced histamine release from human nasal mucosa in vitro.

There is growing evidence that substance P (SP) is one of the main neuropeptides involved in neurogenic inflammation of the airways. However, a number of studies were not able to demonstrate histamine release from human mucosal mast cells after SP administration. Since cultures of isolated cell systems provide only a partial picture of the inflammatory processes in vivo, organ culture models promise to offer physiologically relevant assay systems for studying tissue interactions. Thus, we examined the influence of SP on histamine release and its morphological effects on human nasal mucosa using a previously described histoculture technique. Compared to controls, the histamine content in the culture bath was significantly elevated after SP stimulation (p < 0.05). Histomorphometry showed a decreased density of mast cells and an increased percentage of degranulated mast cells. These findings were dose and time dependent and support the hypothesis of a close interaction between C-sensory nerves and mast cells implying that these interactions are of pathogenetic importance in nasal mucosa inflammation.

Gelatin sponge-supported histoculture of human nasal mucosa.

Considerable progress has recently been made in the understanding of airway inflammation by cell culture assays and in vivo provocation studies. Inasmuch as ethical considerations limit experimental work in humans, physiologically relevant in vitro models are required to better understand cellular and molecular tissue interactions in human nasal mucosa. Here we describe a human nasal mucosa culture model utilizing a simple gelatin sponge-supported histoculture system at the air-liquid interface. Viable mucosa was preserved for at least 48 h, as shown by morphology and immunohistochemical staining with Ki-67 as marker for proliferation. Pro-inflammatory mediators (kinins, histamine, thromboxane B2, prostaglandin F2 alpha, and substance P) are detectable in serum-containing as well as serum-free culture medium. Incubation with 10(-8) M substance P increases the number of degranulated mast cells after 48 h by 26% (P < 0.01). In this model, biochemical responses can be correlated with histologic alterations of the target tissue. Inflammatory parameters can be examined and compared in various patient groups and different stimulators/inhibitors. This culture method provides a valuable research tool for analyzing all compartments present in nasal mucosa under physiologically relevant conditions, and for studying complex interactions and responses of mucosal cell populations in their natural tissue environment.

Hair growth induction by substance P.

BACKGROUND: In vitro, some neuropeptides, including the tachykinin, substance P (SP), act as growth factors. The cyclic growth of the richly innervated hair follicle offers a model for probing such functions in a complex, developmentally regulated tissue interaction system under physiologic conditions. Dissecting the role of neuropeptides in this system may also reveal as yet obscure neural mechanisms of hair growth control. EXPERIMENTAL DESIGN: The neuropeptide-releasing neurotoxin, capsaicin was injected intradermally, or SP slow-release formulations were implanted subcutaneously in the back skin of C57BL/6 mice with all follicles in the resting stage of the hair cycle (telogen) in order to see whether this induced hair growth (anagen). In addition, the endogenous SP skin concentration and the activity of the main SP-degrading enzyme, neutral endopeptidase, were determined during the induced murine hair cycle by high performance liquid chromatography-controlled radioimmuno-assay (SP) or by fluorometry (neutral endopeptidase). RESULTS: Both capsaicin and SP induced significant hair growth (anagen) in the back skin of telogen mice. This was associated with substantial mast cell degranulation. The endogenous SP skin concentration showed significant, hair cycle-dependent fluctuations during the induced murine hair cycle, which were largely independent of the activity of neutral endopeptidase. CONCLUSIONS: SP may play a role in the neural control of hair growth. Whereas this pilot study does not address the underlying mechanisms of action, it demonstrates that SP has potential as a hair growth-stimulatory agent in vivo, and serves as a basis for exploring the role of tachykinins in epithelial-mesenchymal-neuroectodermal interaction systems like the hair follicle.

ELISA for the neuropeptide degrading endopeptidase 3.4.24.11 in human serum and leukocytes.

We describe the development of a new ELISA for the detection of neural endopeptidase 3.4.24.11 (NEP). Neutral endopeptidase 3.4.24.11 was determined in preparations of human granulocytes, mononuclear cells (MNC), and in serum. Human recombinant NEP was used as reference. Specificity of the mAbs was tested using APAAP, FACS analysis, and Western blot analysis. Lysis of the blood cells was performed by incubating the cells with 0.4% Tween-20 and repeated freezing cycles. The minimal detectable dose for recombinant NEP was 15 pg/ml. The recovery was 94 +/- 9%. The NEP was detectable in 15 out of 20 serum samples of 20 volunteers (mean +/- SEM, 245 +/- 88 pg/ml, n = 20)) and in all granulocyte preparations (1176 +/- 138 pg/10(7) cells, n = 20)). The results were reproducible among replicates (CV = 3 +/- 1%, n = 40), dilutions (CV = 8 +/- 2%, n = 5), and assays (CV = 12 +/- 4%, n = 5). With this new ELISA, a simple and reproducible method for the measurement of NEP 3.4.24.11 is described.

Increased forskolin stimulation of lymphocyte-adenylate cyclase in normotensive subjects predisposed to essential hypertension.

Since a significant heritability has been shown for forskolin stimulation of lymphocyte adenylate cyclase activity in twins, we evaluated lymphocyte forskolin-stimulated adenylate cyclase activity with respect to a familial predisposition towards essential hypertension. Lymphocyte adenylate cyclase activity was measured in broken cell preparations of 32 male normotensive volunteers with (n = 15) and without (n = 17) a positive family history of hypertension. The maximal forskolin stimulation of adenylate cyclase activity was significantly higher in the positive compared with the negative group (maximal stimulation of activity 53.5 +/- 3.4 versus 41.2 +/- 1.9 pmol cyclic AMP (cAMP)/mg protein per min; P less than 0.01). Dose-response curves showed a significantly greater stimulation of adenylate cyclase activity in the positive group at forskolin concentrations of 10(-7) to 2 x 10(-4) mol/l. The median effective dose (ED50) and adenylate cyclase activity in the absence of forskolin were similar in both groups. We conclude that lymphocyte forskolin-stimulated adenylate cyclase activity may depend in part on hereditary factors associated with a familial predisposition to essential hypertension.

Alpha 2- and beta 2-adrenoceptor downregulation in marathon runners.

The regulation of platelet alpha 2- and lymphocyte beta 2-adrenoceptor densities by alterations in endogenous catecholamines was examined. In order to activate the sympathetic nervous system eight trained male normotensive subjects carried out a marathon run. Adrenoceptor densities and plasma catecholamine concentrations were measured before and immediately after the run. Platelet alpha 2-adrenoceptor density and lymphocyte beta-adrenoceptor density decreased after the run (P less than 0.05), whereas both plasma noradrenaline and adrenaline concentrations increased (P less than 0.01). Mean arterial pressure decreased (P less than 0.05), and the heart rate increased (P less than 0.001). The data suggest that increases in endogenous catecholamine concentrations cause downregulation of both alpha- and beta-adrenoceptor densities on human blood cells.

[Absorption and excretion of g-strophanthin after intravenous or sublingual administration (author's transl)]. / Resorption und Ausscheidung von g-Strophanthin nach intravenöser und perlingualer Gabe.

Tritiated g-strophanthin was administered to six volunteer patients in a dose of 0.25 mg intravenously and 6.0 mg sublingually 1-3 weeks apart. Radioactivity in plasma and urine was measured afterwards for 48 or 96 hours, respectively. Plasma concentration fell to about a fifth of the maximal concentration within 6 min after intravenous administration, total excretion within three days being about 50%, with a half-time of 11 hours. Measurable plasma concentration after sublingual administration was demonstrable only after 15 min in some and after 2 hours in all the six patients. Radioactivity counts increased up to the 24th hour, in three patients up to the 48th hour. Maximal plasma concentration ranged from 4.7 to 0.7 ng/ml, corresponding to levels reached 15 min or 4 hours, respectively, after intravenous administration. Urinary radioactivity reached its maximum after 24-48 hours and then decreased. Within three days 0.6 and 2.5% of the administered radioactivity was recovered, corresponding to the g-strophanthin doses of 0.072 to 0.3 mg. The findings once again confirm the low and irregular absorption of g-strophanthin when administered sublingually or orally.

Overinclusion and transactional thinking on the Object Sorting Test of schizophrenic and nonschizophrenic patients.

Two aspects of "disordered thinking", overinclusion and transactional thinking were studied on the Object Sorting Test responses of 20 young schizophrenic patients and 20 comparable nonschizophrenic patients. Patients' parents were also studied for comparison. In addition, idiosyncratic responses from WAIS Comprehension items were assessed for comparison of another measure on another test. Transactional thinking and idiosyncratic responses were greater in schizophrenic patients. Conceptual overinclusion and bizarre responses also tended to be more frequent in schizophrenics, but behavioral overinclusion showed no differences. Conceptual overinclusion was consistently correlated with transactional thinking and idiosyncratic responses, while behavioral overinclusion showed an inconsistent pattern. The differences were attributed to the differences in the specificity of measures of disordered thinking.