An early botulinum toxin A treatment in subacute stroke patients may prevent a disabling finger flexor stiffness six months later: a randomized controlled trial.

OBJECTIVE: The study asked whether an early botulinum toxin A (BTX-A) injection in subacute stroke patients may prevent a disabling finger flexor stiffness six months later. DESIGN: Single-blind, randomized pilot study. SETTING: Inpatient rehabilitation centre. SUBJECTS: Eighteen stroke patients, interval 4-6 weeks, non-functional arm, Fugl-Meyer arm score (0-66) <20, beginning elevated finger flexor tone, randomly allocated to group A or B. INTERVENTIONS: In group A patients 150 units BTX-A (Xeomin) injected into the deep and superficial finger (100 units) and wrist flexors (50 units), no injection in group B patients. Comprehensive rehabilitation in both groups. MAIN MEASURES: Primary variable was the Modified Ashworth Scale score (0-5) of the finger flexors; secondary variables were whole arm muscle tone with REPAS (a summary rating scale for resistance to passive movement), its motor control with the Fugl-Meyer arm score, and a disability scale, blindly assessed at T0 (start), T1 (four weeks) and T6 (six months). RESULTS: Homogeneous groups at T0. Significantly less finger flexor stiffness in the BTX-A group at T1 and T6, the mean (SD) Modified Ashworth Scale scores in group A (B) were: 1.7 ± 0.5 (1.6 ± 0.5) at T0; 0.4 ± 0.5 (1.9 ± 0.7) at T1; and 1.4 ± 0.7 (2.4 ± 0.9) at T6. Among the secondary measures, the disability score, namely the items pain and passive nail trimming, was lower in group A at T1 and T6. CONCLUSIONS: The results indicate an effect of early BTX-A injection on finger flexor stiffness six months later, presumably attributable to a reduced contracture development. Effect size calculation suggests inclusion of at least 17 patients per group excluding drop-outs in a warranted placebo-controlled trial.

Recurrent aphasic status epilepticus after prolonged generalized tonic-clonic seizures versus a special feature of Todd's paralysis.

Postictal aphasia may be a feature of Todd's paralysis or the presentation of aphasic nonconvulsive status epilepticus (NCSE). We describe a 74-year-old woman with three episodes of aphasic status epilepticus after prolonged generalized tonic-clonic seizures. In the first episode, the NCSE was not definitively diagnosed, but an increase in the epileptic medication led to resolution of the epileptic activity within 2 weeks. During the second episode, NCSE was terminated within 7 days under intensified antiepileptic treatment. In the third episode, phenytoin treatment led to intoxication and resulted in further treatment on an intensive care unit. The patient required several months to recover from this episode. NCSE in the elderly is difficult to recognize, especially when it presents as a prolonged postictal deficit like aphasia. Once diagnosed it has to be treated carefully, because in the elderly, aggressive treatment strategies may be associated with a high risk of adverse events.

Molecular epidemiology study of a nosocomial Moraxella catarrhalis outbreak in a neurological rehabilitation unit.

BACKGROUND: Moraxella catarrhalis is a common agent causing upper and lower respiratory tract infections, particularly of ventilated patients. The bacteria are transmitted between humans by direct and indirect contacts. However, reports of nosocomial outbreaks by this pathogen are scarce. AIM: To analyse M. catarrhalis strains isolated during an outbreak in a medical rehabilitation centre to reveal their clonal relationship and to elucidate potential transmission routes. METHODS: Extensive environmental and medical staff sampling was performed. Phenotypic and genotypic analyses of 15 isolates were executed, including repetitive element palindromic polymerase chain reaction (repPCR) and whole-genome sequencing. Furthermore, an intensified hygiene regimen was installed. FINDINGS: The clonal nature of nine patient isolates and a simultaneous presence of separate entities including a strain isolated from a physician during staff screening was confirmed. Although neither asymptomatic carriers among the staff persons nor outbreak strain-contaminated fomites were identified for a specific intervention, the outbreak ceased due to maximum general and specific hygiene precautions. Retrospective analysis showed the increasing prevalence of M. catarrhalis strains over a period of two years before the incidence. Since then and after returning to the regular hygiene regimen, only one patient with a phenotypically diverse M. catarrhalis isolate has been documented. CONCLUSION: The first M. catarrhalis outbreak involving nine patients of a neurological and trauma rehabilitation centre was reported. Potential transmission pathways were discussed. Comprehensive outbreak analyses insinuated the extension of routine laboratory storage time for defined species.

GARDASIL: prophylactic human papillomavirus vaccine development--from bench top to bed-side.

GARDASIL (Merck, Whitehouse Station, NJ) is a non-infectious recombinant, quadrivalent vaccine prepared from the highly purified virus-like particles (VLPs) of the major capsid proteins of human papillomavirus (HPV) types 6, 11, 16, and 18. GARDASIL is the first vaccine approved for use in women aged 9-26 years for the prevention of cervical cancer and genital warts, as well as vulvar and vaginal precancerous lesions. This report describes some of the key preclinical efforts, achievements in pharmaceutical development, in vivo animal evaluation, and clinical trial data.

Efficiency measurement and Monte Carlo simulations of a CeBr3 scintillator.

CeBr3 crystals meet many of the demands of high performance scintillators, due to their excellent timing properties, good effective Z and high photon yield. It is important to characterize their efficiency and to verify whether modern Monte Carlo codes are reliable enough to reproduced the observed values. We report here on the measurement of both total and photopeak efficiency of a 1" diameter×1" height CeBr3 crystal for gamma-ray energies up to 1.4MeV at several distances, using a variety of low energy gamma rays sources. The measured experimental efficiencies are compared with simulations developed in the framework of PENELOPE and GEANT4.

Sucralfate and soluble sucrose octasulfate bind and stabilize acidic fibroblast growth factor.

The actions of the anti-ulcer drug sucralfate have been proposed to be mediated through interaction with fibroblast growth factors (Folkman, J., Szabo, S., Strovroff, M., McNeil, P., Li, W. and Shing, Y. (1991) Ann. Surg. 214, 414-427). We show here that acidic fibroblast growth factor (aFGF; FGF-1) binds in vitro to both the soluble potassium salt and the insoluble aluminum salt of sucrose octasulfate, as demonstrated by a variety of biophysical techniques. Similar to the well-described interaction and stabilization of aFGF by heparin, soluble sucrose octasulfate (SOS) stabilizes aFGF against thermal, urea and acidic pH-induced unfolding as determined by a combination of circular dichroism, fluorescence spectroscopy and differential scanning calorimetry. In addition, SOS also enhances the mitogenic activity of aFGF and partially protects the protein's three cysteine residues from copper-catalyzed oxidation. SOS competes with heparin and suramin for the aFGF polyanion binding site as measured by both fluorescence and light scattering based competitive binding assays. Front-face fluorescence measurements show that the native, folded form of aFGF binds to the insoluble aluminum salt of sucrose octasulfate (sucralfate). Moreover, sucralfate stabilizes aFGF against thermal and acidic pH-induced unfolding to the same extent as observed with SOS. Thus, due to their high charge density, SOS and sucralfate bind and stabilize aFGF via interaction with the aFGF polyanion binding site.

Spectroscopic characterization of tick anticoagulant peptide.

Tick anticoagulant peptide (TAP) is a disulfide rich potent inhibitor of factor Xa. Although this peptide is of potential clinical utility, very little is known about its higher order structure. Therefore, the secondary structure of recombinant TAP (rTAP) has been examined by circular dichroism (CD) and Fourier transform infrared (FTIR) spectroscopy. Both techniques suggest that rTAP is rich in beta-sheet structure. Disulfide bonds play a significant role in the folding and structural stability of rTAP. This is apparent from the resistance of rTAP to fluorescence-detected unfolding by guanidinium chloride (Gdn-HCl), unless disulfides are first reduced. The protein's tryptophan and tyrosine residues exhibit greater solvent exposure upon reduction of the cystines as indicated by fluorescence spectra and second derivative UV spectroscopy. A considerable amount of beta-structure appears to be retained after reduction of disulfides, although the CD spectrum manifests an increased amount of disordered structure in the reduced peptide. While rTAP does not bind the hydrophobic fluorescence probe 2-p-toludinylnaphthalene-6-sulfonate (TNS) at neutral or acidic pH, the reduced peptide binds TNS at pH 2.0 but not at pH 7.0. The secondary structure of the reduced peptide at pH 2 is, however, similar to that at pH 7 as judged by CD spectroscopy. The reduced form of rTAP at acidic pH thus resembles a molten globule-like state.

Structure of synthetic peptide analogues of an eggshell protein of Schistosoma mansoni.

The peptide (Gly-L-Tyr-L-Asp-L-Lys-L-Tyr)6, referred to as F4-6, was synthesized as a model for a schistosome eggshell protein in which the Gly-Tyr-Asp-Lys-Tyr consensus sequence is repeated over 40 times. Analysis by CD, Fourier transform infrared spectroscopy, potentiometric and spectrophotomertric titrations, NMR, and molecular modeling suggests that F4-6 forms some type of left-handed structure. A likely possibility appears to be a left-handed alpha-helix stabilized by Lysi-Aspi +4 salt bridges and possibly Aspi-Tyri +4 hydrogen bonding and Tyr-Tyr interactions. Spectroscopic studies of a number of F4-6 analogues support this conclusion. For example, substitution of D-Ala for Gly produces a peptide with enhanced left-handed helical spectral characteristics, whereas an L-Ala substitution results in a peptide with minimal structure. These studies suggest that the F4 protein from Schistosoma mansoni may be the first example of a naturally occurring protein devoid of proline and carbohydrate that forms a left-handed helix composed of L-amino acids, although alternative forms of other left-handed structures have yet to be rigorously excluded.

Degradative covalent reactions important to protein stability.

Commonly observed chemical modifications that occur in proteins during their in vitro purification, storage, and handling are discussed. Covalent modifications described include deamidation and isoaspartate formation, cleavage of peptide bonds at aspartic acid residues, cystine destruction and thiol-disulfide interchange, oxidation of cysteine and methionine residues, and the glycation and carbamylation of amino groups.

Experimental ruthenium plaque therapy of amelanotic and melanotic melanomas in the hamster eye.

The effects of beta-radiation on melanoma implanted into the hamster's eye were investigated. Two Bomirski hamster melanomas (BHMs), differing in their melanin content, were compared with regard to their radiosensitivity to ruthenium-106 (106Ru) radiation. Tumours growing in the iris were irradiated with 3, 6 or 10 Gy of 106Ru given as a single dose or in four fractions at 24 h Intervals. Tumour growth kinetics and distant metastases were studied, and the eyeballs were examined histologically. Dose-dependent delay of tumour growth was observed in both melanomas. After treatment with a dose of 6 Gy, the Ab amelanotic tumours grew 2.6 times slower, and the Ma melanotic tumours 1.4 times slower than untreated ones. The location of metastases differed in the two tested lines--pigmented metastases were found mainly in the lungs, while unpigmented metastases were found mainly in the kidneys. Histopathological analysis showed signs of blood vessel damage such as endothelial cells swelling, erythrocyte extravasation and tumour necrosis. This last finding increased with the rising dose of beta-radiation. Pigmented tumours were found to be two times more resistant to beta-radiation than amelanotic ones. The pattern of metastases of BHMs is determined by the type of melanoma (Ab or Ma). Exposure to beta-radiation from 106Ru did not significantly affect either the number or size of metastases except at a dose of 10 Gy. This dose caused a statistically significant decrease in the number of metastases in the Ma melanotic subline.

Angiomorphology of the pigmented Bomirski melanoma growing in hamster eye.

An melanotic line of Bomirski Hamster Melanoma (BHM Ma) was implanted into the anterior chamber of the hamster eye and the ensuring vascular system was studied using scanning electron microscopy (SEM) of vascular corrosion casts. The tumor vasculature, induced mainly from the host iris vessels, showed generally disorganized and irregular patterns. Tortuous tumor capillaries of uneven contour with local dilatations and constrictions were drained by markedly dilated, thin-walled, venous vessels connected with the eye veins. Vascular sprouting and, less frequently, intussusceptive formation of new vessels were observed at the periphery and also within the tumor mass. The presence of numerous nodular outgrowths, varying in size, on the surface of dilated venules and venous vessels represent morphological evidence for continuous remodeling of the tumor vasculature. The observed features of the vascular system seem to provide a pathway for further tumor expansion. Our study showed that BHM Ma line, originating from an aggressive skin melanotic melanoma, implanted to the eye anterior chamber gave rise to rapidly growing tumors with the capability of inducing abundant vasculature which allows metastasis to the lungs, kidneys and regional lymph-nodes.

[Physiologic significance of "stringent control" in Escherichia coli under extreme starvation]. / Physiologische Bedeutung der "Stringent Control" bei Escherichia coli unter extremen Hungerbedingungen.

The viability of three isogenic relA+/relA strain pairs of Escherichia coli (CP78/CP79; NF161/NF162; CP107/CP143) was studied during prolonged starvation for amino acids, glucose or phosphate. After amino acid limitation we found a prolonged viability of all relA+ strains which synthesized ppGpp. We suggest that some ppGpp-mediated pleiotropic effects of the stringent response (e.g. glykogen accumulation, enhanced protein turnover) might be involved in this prolongation of survival. After glucose or phosphate starvation there was no difference in the relA+/relA strains either in the ppGpp content or in the survival.

[Results of surgical treatment for anterior uveal malignant melanoma]. / Wyniki leczenia operacyjnego czerniaków przedniej jagodówki.

The authors observed for 5 to 18 years 41 patients (22 women and 19 men) with malignant iris melanoma and/or malignant melanoma of ciliary body. The age of the patients was 20 to 80 years. All patients underwent surgical treatment with preservation of the eye ball. In 21 cases iridectomy, in 18 cases iridocyclectomy, and in the remaining cases iridocyclectomy-choroidectomy was performed. In 25 eyes the tumour occupied less than 1/4, and in 16 eyes between 1/4 and 1/2 of the iris circumference. During the period of observation 7 eye balls were enucleated, and in 6 recidivation of the tumour was diagnosed. These patients belonged to the group of 18 people with the tumour occupying the iris and the ciliary body, or the ciliary body only. Mortality in this group was 28%. Among 5 patients who died, in 3 the tumour occupied more than 1/4 of the iris circumference. In 3 patients from this group recidivation was diagnosed, in 4 enucleation was necessary. In 4 eyes secondary glaucoma was diagnosed. Therefore, among risk factors one ought to list size of the tumour, recidivation, and secondary glaucoma. On the other hand infiltration of the sclera and of the optic nerve was found only in one deceased person. The authors have not been able to obtain current information about 2 patients. In the whole studied group mortality was 5 out of 39, that is 12.8%. The most common complication during the surgery was hemorrhages. Two other complications: complicated cataract, usually stationary, and secondary glaucoma occurred both before and after treatment. Despite of complications 68.3% of patients maintained good visual acuity.

[Analysis of complications in patients with malignant choroidal melanoma treated with Co60 and xenon-arc photocoagulation]. / Analiza powiklan u chorych z czerniakiem zlosliwym naczyniówki, leczonych kobaltem radioaktywnym i fotokoagulacja ksenonowa.

The authors observed for 5-18 years 157 patients with malignant choroidal melanoma, age 19-80. Among them there were 57.96% men and 42.04% women. The treatment consisted in irradiation of the tumours with Co60 plaques according to Stallard's methods, and additionally, in the majority of patients, in xenon-arc photocoagulation. Complications developed after treatment were diagnosed. The most common complication was cataract, which occurred in 118 eyes (75.2%), average 2.5 years after irradiation, most commonly in the eyes where the tumour was located between the optic disc and the equator. Second most common complication were various lesions of vessels in retina and hemorrhages, which occurred in 105 eyes (66.9), average one year after irradiation, most often in the eyes with tumours of medium size. Another type of complications, retinopathy or maculopathy, was found in 99 eyes (63%), average 14 months after the beginning of the treatment. These lesions occurred more often in younger patients. The fourth complication was consecutive glaucoma. It was diagnosed in 71 eyes (45.2%), most often 1 to 5 years after irradiation. In many cases glaucoma was combined with other complications, which resulted in enucleation of 62% of ill eyes. The fifth complication were hemorrhages to vitreous. They occurred in 35 eyes (22.29%), much more often in the cases where photocoagulation was performed. The authors found glaucoma to be the most dangerous complication of the conservative treatment of choroidal melanoma, often leading to the loss of the eye. Other complications have negative influence on visual acuity. One should expect that application of other methods of irradiation and lower doses will limit the number of complications.

[Nitrate and nitrite levels in daily food rations of children from the rural Pulawy regions]. / Zawartosc azotanów i azotynów w calodziennych racjach pokarmowych dzieci wiejskich z rejonu Pulaw.

In the region of Pulawy where the operation of the Nitrogen-Compound Manufacturing Plant has lead to an increase in nitrogen compound emission to the environment, nitrate and nitrite contents in daily food rations of children were determined. Daily food rations of children aged 8-9 and 12-13 years were collected from individual farms in four villages situated in the vicinity of the Nitrogen Plant, as well as--for control--from individual farms in Janowiec, a village distant from this Plant. Nitrate and nitrite contents were assayed in 300 daily food rations taken in spring and autumn. Nitrate was reduced to nitrite on a cadmium column whereupon it was determined colorimetrically using sulphanilic acid and N-1-napthyl-ethylenediamine. It was found that in the group of younger children as many as 70%, on the average, of the examined food rations displayed nitrate contents exceeding the admissible levels. In the group of the 12-13 years old children, the percentage of daily food rations whose nitrate content exceeded the admissible level was lower, averaging ca. 30% of all rations examined. The percentage of the daily food rations in which the nitrite content was higher than admissible level was closely similar in both groups of children, averaging ca. 30% of all rations examined. Food rations collected in spring, as compared with those taken in autumn, contained significantly greater amount of nitrate. In both periods of studies, nitrate contents were greater in the food rations from the farms situated near the Nitrogen Plant than in the food rations from farms in Janowiec.(ABSTRACT TRUNCATED AT 250 WORDS)

[Results of treating malignant conjunctival melanoma]. / Wyniki leczenia czerniaków zlosliwych spojówki.

28 patients with histologically confirmed conjunctival melanoma were treated between 1968 and 1987. In all the cases, the lesion was excised and in 15 cases, it was secondarily irradiated with 60Co or 27Sr. In 9 cases, recurrence appeared and, among them, twice as often in the group treated only surgically. 6 patients with the recurrence of conjunctival melanoma died because of metastases, 2 are alive and there is no information about 1.

[Cadmium content in daily food rations of rural school-age children]. / Zawartosc kadmu w calodziennych racjach pokarmowych dzieci wiejskich w wieku szkolnym.

Cadmium was determined in 230 daily food rations of children aged 8-9 years and 12-13 years. The study was carried out in spring and in autumn during three successive days. Daily meals were collected from the households selected in the area of five villages. Cadmium was determined by the extraction ASA method, after dry mineralization at about 450 degrees C. The level of cadmium in the examined food rations varied from 6 to 569 micrograms/person/day, with the mean value of 43.5 +/- 52.6 micrograms/person/day, and the median of 31.3 micrograms. In 93% of food rations the amount of cadmium was below the upper limit--the dose permitted by the WHO for adults i.e. 57-71 micrograms/day. Considering the children's smaller body weight the daily cadmium intake in food rations was converted into the daily cadmium intake per 1 kilogram body weight. In the group of children aged 8-9 years cadmium intake was 0.3-15 micrograms, with the mean value of 1.7 micrograms, and in the group of 12-13-years-old children it was 0.1-13.9 micrograms, with the mean of 1.3 micrograms. Only 36% of food rations in the group of younger children and 58% of food rations in the older group contained the amount of cadmium below the tolerable value of 1 microgram/kg body weight/day. The weekly cadmium intake was calculated for each child based on its amount in daily food rations during the successive three days. The mean value was 12.3 micrograms/kg body weight, with the median of 8.1 micrograms, within the range of values 2.1-58.8 micrograms.(ABSTRACT TRUNCATED AT 250 WORDS)

[Trabeculotomy and goniotomy in congenital glaucoma]. / Trabekulotomia i goniotomia w jaskrze wrodzonej.

The authors evaluated efficiency of antiglaucomatous surgery in 73 eyes of 50 children, staying under clinical control in the years 1969-1991. It was showed that after trabeculectomy, as the primary procedure, intraocular pressure was normalized much more often (40.9%) than after goniotomy (20.2%). In cases operated many times using different technics, more effective was goniotomy. Better visual acuity was found in cases with intraocular pressure well controlled after one surgical procedure. The most common complications connected with surgery were discussed.

[The fate of children after bilateral enucleation of the eyeball because of retinoblastoma]. / Losy dzieci po obustronnym usunieciu galek ocznych z powodu siatkówczaka.

The authors present the fate of children with particularly severe form of retinoblastoma, in whom despite of treatment both eye balls had to be enucleated. In Ophthalmological Clinic in Kraków there were 70 such cases in the last 30 years, but information was obtained only about 52 children observed for at least 5 years. From among those children 23 (45%) died because of metastases of the tumour. Among the surviving 29, 3 are deeply mentally retarded and remain in nursing homes. The further 22 children maintain average or normal level of mental development, despite the loss of both eyes, they attend schools for the blind and find their place in the society. The remaining four children are talented above average, surprisingly independent, and two among them are university graduate. Owing to the enucleation of the second eye with an advanced tumour the children survived and found their places in the society.

[6 cases of bilateral melanoma of the uvea]. / Szesc przypadków obuocznego czerniaka blony naczyniowej.

Six patients with bilateral ocular melanoma were treated in the period 1967-1989. In one case both eyes were enucleated, in 4 one eye only, the other eye was treated. In all enucleated eyes the clinical diagnosis of melanoma was confirmed histopathologically. Two patients died because of metastases to the lungs and liver, one is alive and remains in a periodical control; there are no informations on the remaining 3 patients.