Non-occupational ladder and scaffold fall injuries

In the period 1988–1997 a series of 1462 patients aged 15 years or older with non-occupational fall injuries from ladders or scaffolds were studied. We registered 1402 ladder falls and 60 scaffold falls. The mean age was 50 years, and 1052 were males. The mean annual incidence rate was 1.18 per 1000 inhabitants/year for males and 0.41 per 1000 inhabitants/year for females. A rise in the annual incidence rates with increasing age were observed for both males and females, whereas no trend in the annual incidence rates for each of the ten years studied were observed. About 1/5 of the patients were hospitalized with a median number of 7 days. Two patients died following the injury. Half of the registered injuries were contusions or sprains, whereas about 1/3 were fractures or dislocations. The extremities were most commonly injured as 36% of the injuries were located to the lower extremities and 33% to the upper extremities. The forearm was most commonly fractured or dislocated, whereas the ankle joint was most commonly sprained or contused.     

Providing patients with their diagnostic test results. A vignette study in general practice

The communication of results of HIV tests and chest-X-rays because of persistent coughing are of particular interest because potential life-threatening disease may be disclosed. For HIV tests it is recommended that the result is communicated to the patient in the doctor's office face to face. In this questionnaire study based on two simulated case-stories with a 63 year-old man referred to chest-X-rays because of persistent coughing, and a 27 year-old man, who had been living in Africa for some time, now wanting a HIV test performed, we found that only half (53%) of the general practitioners (GP) did communicate HIV test results in the consultation office. X-ray test results were only communicated in the consultation office by 18% of the GPs. Communication of test results which might have serious implications to the patient should preferably not be done by telephone. Patients should be told of potentially serious results in person by their own physician.     

Solid-state NMR studies of the prion protein H1 fragment

Conformational changes in the prion protein (PrP) seem to be responsible for prion diseases. We have used conformation-dependent chemical-shift measurements and rotational-resonance distance measurements to analyze the conformation of solid-state peptides lacking long-range order, corresponding to a region of PrP designated H1. This region is predicted to undergo a transformation of secondary structure in generating the infectious form of the protein. Solid-state NMR spectra of specifically 13C-enriched samples of H1, residues 109-122 (MKHMAGAAAAGAVV) of Syrian hamster PrP, have been acquired under cross-polarization and magic-angle spinning conditions. Samples lyophilized from 50% acetonitrile/50% water show chemical shifts characteristic of a beta-sheet conformation in the region corresponding to residues 112-121, whereas samples lyophilized from hexafluoroisopropanol display shifts indicative of alpha-helical secondary structure in the region corresponding to residues 113-117. Complete conversion to the helical conformation was not observed and conversion from alpha-helix back to beta-sheet, as inferred from the solid-state NMR spectra, occurred when samples were exposed to water. Rotational-resonance experiments were performed on seven doubly 13C-labeled H1 samples dried from water. Measured distances suggest that the peptide is in an extended, possibly beta-strand, conformation. These results are consistent with the experimental observation that PrP can exist in different conformational states and with structural predictions based on biological data and theoretical modeling that suggest that H1 may play a key role in the conformational transition involved in the development of prion diseases.     

Self-organizing map in recognition of topographic patterns of EEGspectra

The self-organizing map, a neural network algorithm, was applied to the recognition of topographic patterns in clinical 22-channel EEG. Inputs to the map were extracted from short-time power spectra of all channels. Each location on a self-organized map entails a model for a cluster of similar input patterns; the best-matching model determines the location of a sample on the map. Thus, an instantaneous topographic EEG pattern corresponds to the location of the sample, and changes with time correspond to the trajectories of consecutive samples. EEG segments of “alpha”, “alpha attenuation”, “theta of drowsiness”, “eye movements”, “EMG artifact”, and “electrode artifacts” were selected and labeled by visual inspection of the original records. The map locations of the labeled segments were different; the map thus distinguished between them. The locations of individual EEG's on the “alpha-area” of the map were also different. The clustering and easily understandable visualization of topographic EEG patterns are obtainable on a self-organized map in real time     

Structural features of thyroid hormone response elements that increase susceptibility to inhibition by an RTH mutant thyroid hormone receptor

The chicken lysozyme silencer F2 (F2) thyroid hormone response element (TRE) contains an unusual everted palindromic arrangement, has a high affinity for thyroid hormone receptor (TR) homodimers, and is especially sensitive to dominant negative inhibition by, the T3 resistance (RTH) mutant TR beta P453H. We used various TREs and TR mutations to determine the mechanisms for this sensitivity. Changing the F2 orientation from an everted palindrome to a direct repeat with a 4-bp gap (DR+4) (F2-DR) decreased the sensitivity to inhibition at high T3 concentrations, while a loss of this sensitivity occurred with a palindromic arrangement of these same half-sites. F2 contains the dinucleotide TG 5' to each consensus half-site conforming to the optimal TR-binding octamer, YRRGGTCA. A T to A change in position 1 of both F2 half-sites markedly reduced T3-induction, yet only slightly reduced TR homodimer or TR-retinoid X receptor (RXR) heterodimer binding. The TR beta ninth heptad mutation, L428R, prevents TR heterodimerization with RXR and eliminates the inhibitory effect of the P453H mutant TR on the F2-DR, but not the F2 element. Structural features of a TRE that favor strong TR binding of both TR homodimers and TR-RXR heterodimers containing the mutant TR, such as the everted palindromic conformation or the optimal TR-binding consensus octamer, enhance the sensitivity of a TRE to inhibition by the mutant TR. Thus, both half-site orientation and sequence contribute to the sensitivity of a given TRE to dominant negative inhibition by a mutant TR.     

Novel monoclonal antibodies to putative selectin carbohydrate ligands that inhibit selectin binding to myeloid cells

Four newly developed monoclonal antibodies (MAbs) are characterized using flowcytometry, enzyme-linked immunoadsorbent assay (ELISA), immunoprecipitation and Western blots, carbohydrate epitope mapping, glycosidase cleavage, and competition binding assays. Their effects on selectin binding to myeloid cells was tested. These MAbs react only with myeloid cells. MAbs CI-1, BU60, and HIM95 recognize epitopes expressed by CD11/CD18 (beta2) integrins, while HI247 and CSLEX1 do not. The epitopes require Lewis x [Galbeta1-4 (Fucalpha1-3)GlcNAc] based on reactivity with oligosaccharide-polyacrylamide-biotin or oligosaccharide-BSA conjugates. MAb HI247 recognizes a related structure, sialyl-Lewis x, NeuAcalpha2-3GaLbeta1-4(Fucalpha1-3)GlcNAc. The three MAbs against Lewis x show some minor differences in their reactivity such as recognizing their antigens on CD11/CD18 integrins after endo-beta-galactosidase treatment and recognizing free Lewis x. The hydroxyl group on C-3 of the terminal galactose is important for recognition by MAb CI-1, BU60, and HIM95 as its substitution with sulfo group of sialic acid abolishes the binding of these MAbs. The C-3 sialic acid is crucial for the binding of MAb HI247. Its replacement by sulphate or its cleavage by sialidase eliminates recognition by this MAb. MAbs HI247 and CSLEX-1 did not react in ELISA with immobilized CD11/CD18, suggesting that the majority of sialyl Lewis x on CD11/CD18 molecules may have sialic acid 6-linked rather than 3-linked to galactose. Unexpectedly, MAb BU60 inhibited binding of P-selectin mu chain chimera to HL-60 or U937 cells, while CI-1, HIM95 and three other defined anti-Lewis x MAbs (6C7, M6-1 and LeuM1) did not. MAb HI247 inhibited binding of both E- and P-selectin chimeras to these cell lines more effectively than several characterized MAbs (CSLEX-1, FH6, HECA-452) to sialyl Lewis x and related oligosaccharides. Certain combinations of these anticarbohydrate MAbs had additive inhibitory effects on selectin binding, suggesting a potential application of these new MAbs in cell adhesion/migration and tumor metastasis studies.     

Primary lung cancer in patients under 40 years of age

There seems to be a resistance of patients and physicians towards aggressive diagnostic evaluation of the symptoms of lung cancer in young people. We here review nine series of young patients with primary lung cancer. Patients below 40 years of age represent between 1.2 and 5% of the total lung cancer population. The distribution of sex and histopathologic findings is different, there being more women, fewer cases of squamous cell and more cases of small anaplastic and adenocarcinoma in the young group. Between 87 and 96% are smokers. There is a delay from the debut of symptoms to the first contact with a general physician of 2.4 to 10.8 months. There is a wide variation concerning tendency to operate with a frequency of curative resection of between 15 and 57%. Based on the survival of young patients who are treated by curative surgical resection, the outcome of surgical treatment for young patients does not differ from the general experience concerning resection in patients of all ages. Young patients who are found inoperable have worse survival than the older patients. Seventy to 90%, more than in the group of patients of all ages, have stadium II or III at the time of diagnosis. In conclusion, physicians should be aggressive with respect to the diagnostic evaluation even of young patients with symptoms suggestive of lung cancer.