Current status of physical measurements of the skeleton. An overview is presented of some of the major methods of measuring the skeleton in the past 30 years. These include single photon absorptiometry (SPA), dual photon absorptiometry (DPA), quantitative computed tomography (QCT), and recently dual energy radiographic absorptiometry (DRA), also called DEXA (dual energy x-ray absorptiometry). In addition to these methods, all attempting to measure bone mineral density, regional and total body calcium have been determined by in vivo neutron activation analysis (IVNAA). An attempt to determine bone quality as contrasted with bone quantity has been made using ultrasound, with measurements of speed of sound and of attenuation as useful parameters to characterize bone tissue. While the various methods for measuring bone density have been most useful, no one method includes all the features required to be entirely satisfactory: excellent precision and accuracy and the ability to measure volumetric density in gm/cm3. Least successful has been the ability to predict fracture risk, an essential goal in helping the patient.


[Sudden death caused by freon 22?].

[Sudden death caused by freon 22?]. Case report of a plumber's fatal work accident. Investigations on the causes of death made at post mortem showed that the worker had absorbed a large quantity of freon 22 (chlorodifluoromethane) which is known to be a narcotic agent and capable of inducing cardiac arrhythmia. It is believed freon inhalation was the cause of loss of consciousness with consequent death from drowning in the water issuing from the pipes. It is concluded that preventive measures need to be reinforced by adequate information to the workforce on the risks connected to this type of gas.


Biological effects of the Auger emitter iodine-125: a review. Report No. 1 of AAPM Nuclear Medicine Task Group No. 6. The biological implications of Auger electron cascades following inner shell ionization of atoms have been of interest for over 25 years. By virtue of their decay via orbital electron capture and/or internal conversion, several biomedical radionuclides emit numerous low-energy electrons spontaneously. The biological effects of such radionuclides incorporated into tissues cannot be predicted a priori because of the highly localized patterns of energy deposition by the electrons. Results of extensive research using Iodine-125 as a model Auger electron emitter are now available. This article presents an up-to-date review of the physical and radiobiological data on this Auger emitter. Valuable concepts concerning the action of internal Auger emitters are identified phenomenologically, and questions that need to be answered are indicated. The present understanding provides a scientific basis toward estimation of risk associated with Auger emitters used in diagnosis, and suggests potential applications to therapy.


Radiation spectra for Auger-electron emitting radionuclides: report No. 2 of AAPM Nuclear Medicine Task Group No. 6. Radiation spectra for radionuclides currently provided by the MIRD Committee and ICRP do not include the very low-energy N- and O-shell Auger electrons. These electrons, emitted in large numbers by radionuclides decaying by electron capture and/or internal conversion, are important for determining the absorbed dose in microscopic volumes. Accordingly, the present AAPM Report employs Monte Carlo computational methods to obtain a self-consistent set of complete radiation spectra for a variety of radionuclides including 55Fe, 67Ga, 99mTc, 111In, 113mIn, 115mIn, 123I, 125I, 193mPt, 195mPt, 201Tl, and 203Pb. Although the conventional spectra provided by MIRD and ICRP are adequate for most dosimetry calculations, the Auger electron spectra provided in this report are recommended for calculating the dose to target volumes < 1 microns in diameter.


Analytic microdosimetry for radioimmunotherapeutic alpha emitters. Analytic microdosimetry using Fourier transform techniques has been applied to internal alpha emitters. These techniques need revision and simplification for use with short-lived radionuclides such as those which may be useful for radioimmunotherapy. Analytic methods may have advantages over Monte Carlo methods in some cases (e.g., where time is important). Applications to eight different source geometries show the usefulness of these techniques. Comparisons of some of the results of Monte Carlo calculations prove its accuracy. For a uniform source of 5.867-MeV alphas spread throughout the volume outside a cell surface, the two methods agree well. Results are within 1% both for the average specific energy and for the number of hits. Analytic microdosimetry provides an alternate method to use for the critical evaluation of models that seek to predict the relation between alpha energy deposition and cell survival data. Similarly, it may be helpful to point the way toward the rational interpretation of general biological results for antibodies labeled with alpha emitters.


Microbeam radiation therapy.

Microbeam radiation therapy. It is proposed to carry out radiotherapy and radiosurgery for brain lesions by crossfiring an array of parallel, closely spaced microbeams of synchrotron-generated x rays several times through an isocentric target, each microbeam in the array having an approximately 25-microns-wide adjustable-height rectangular cross section. The following inferences from the known tissue sparing of 22-MeV deuteron microbeams in the mouse brain and the following exemplary Monte Carlo computations indicate that endothelial cells in the brain that are lethally irradiated by any microbeam in an array of adequately spaced microbeams outside an isocentric target will be replaced by endothelial cells regenerated from microscopically contiguous, minimally irradiated endothelium in intermicrobeam segments of brain vasculature. Endothelial regeneration will prevent necrosis of the nontargeted parenchymal tissue. However, neoplastic and/or nonneoplastic targeted tissues at the isocenter will be so severely depleted of potentially mitotic endothelial and parenchymal cells by multiple overlapping microbeams that necrosis will ensue. The Monte Carlo computations simulate microbeam irradiations of a 16-cm diameter, 16-cm-long cylindrical human head phantom using 50-, 100-, and 150-keV monochromatic x rays.


A finite-size pencil beam model for photon dose calculations in three dimensions. A three-dimensional dose computation model employing a finite-size, diverging, pencil beam has been developed and is demonstrated for Cobalt-60 gamma rays. The square cross-section pencil beam is simulated in a semi-infinite water phantom by convolving the pencil beam photon fluence with the Monte Carlo point dose kernel for Cobalt-60. This finite-size pencil beam is calculated one time and becomes a new data base with which to build larger beams by two-dimensional superposition. The pencil beam fluence profile, angle correction for beam divergence, the Mayneord inverse square correction, radial and angular sampling rates, error propagation, and computation time have been investigated and are reported. Radial and angular sampling rates have a great effect on accuracy and their appropriate selection is important. Percent depth doses calculated by finite-size pencil beam superposition are within 1% of values calculated by full convolution and the agreement with values from the literature is within 6%. The latter disagreement is shown to be due to a low-energy photon component which is not modeled in other calculations. Computation time measurements show the pencil beam method to be faster than full convolution and one implementation of the differential-scatter-air-ratio (dSAR) method.


A study of interface effects in 60Co beams using a thin-walled parallel plate ionization chamber. A large plane-parallel ionization chamber has been constructed to investigate interface effects in 60Co beam. The designed geometry yields negligible perturbation from the side walls, as opposed to the large effects existing in commercially available plane-parallel chambers. The chamber has been used to investigate interface phenomena in transition zones using a wide range of elements (Z = 4-82) as front- and back-scattering media and a clinically relevant 60Co gamma-ray field size. The effects of varying the chamber height discretely (0.5-11 mm) and increasing the wall thickness (1-9 mg/cm2) have been investigated. The variation of the measured ionization with the experimental setup (air gap between backscatter material and chamber wall, measurements at dmax and at 5-cm depth, varying the material both in front of and behind the chamber, etc.) has also been investigated. The simple geometry of the ion chamber has been found optimum for benchmark studies of Monte Carlo calculations. The ion chamber is suited for investigating experimentally the effects of varying transport parameters used in Monte Carlo simulations. The results presented show that the complex physical mechanisms governing 60Co interface dosimetry still make Monte Carlo condensed-history (macroscopic) techniques uncertain. It has been found that the EGS4 Monte Carlo system, together with the user code DOSRZ V4.0 and the PRESTA algorithm, yields good agreement with experiments for low and medium Z (main interest in dosimetry and radiotherapy), but may underestimate up to 10% the backscatter from high-Z materials even when transport parameters are optimized.


Uncertainty analysis of absorbed dose calculations from thermoluminescence dosimeters. Thermoluminescence dosimeters (TLD) are widely used to verify absorbed doses delivered from radiation therapy beams. Specifically, they are used by the Radiological Physics Center for mailed dosimetry for verification of therapy machine output. The effects of the random experimental uncertainties of various factors on dose calculations from TLD signals are examined, including: fading, dose response nonlinearity, and energy response corrections; reproducibility of TL signal measurements and TLD reader calibration. Individual uncertainties are combined to estimate the total uncertainty due to random fluctuations. The Radiological Physics Center's (RPC) mail out TLD system, utilizing throwaway LiF powder to monitor high-energy photon and electron beam outputs, is analyzed in detail. The technique may also be applicable to other TLD systems. It is shown that statements of +/- 2% dose uncertainty and +/- 5% action criterion for TLD dosimetry are reasonable when related to uncertainties in the dose calculations, provided the standard deviation (s.d.) of TL readings is 1.5% or better.


High-energy x-ray beam characterization using photonuclear reaction. Spectral changes in the primary photon beam of a high-energy medical electron accelerator have been monitored using photonuclear reactions. The beam across the radiation field was measured using induced activity in Teflon cylinder and copper foil samples at several off-axis angles, at different SSDs in air and in a solid water phantom. The induced activities of the positron emitters were measured using a coincidence detection system. The experimental results are in agreement with Monte Carlo calculations and Schiff's theory.


Simple calculation of the electron-backscatter factor. The authors have studied the dependence of the electron-backscatter factor (EBF) on mean electron energy and on backscatterer atomic number by using the semiempirical depth-dose code EDMULT. A plane-parallel electron beam is assumed to be normally incident on a polystyrene slab, which is backed with a layer (backscatterer) of different materials of effectively semi-infinite thickness. A small air cavity to measure ionization is embedded in the polystyrene slab at the boundary facing the backscatterer. The EBF is defined as the ratio of the ionization with the backscatterer to the ionization with a full polystyrene medium, and is approximated by the ratio of the doses computed at the depth of the cavity. Values of EBF obtained show trends similar to the experimental data of Klevenhagen et al. [Phys. Med. Biol. 27, 263-373 (1982)], although the former are generally lower than the latter. When the typical energy spread of clinical electron beams is taken into account, the difference between the experimental and the calculated values is reduced. The present results also show the same trend of increase of the backscatter factor with increasing energy as observed by Klevenhagen et al. in some series of measurements for the lead backscatterer at the lowest energies. This is explained by the rapid buildup of the dose with depth for electrons of low initial energies incident on the full polystyrene medium.


On the field-size dependence of relative output from a linear accelerator. The radiation output in air on the central axis of a linac photon beam has been modeled as the sum of two components. These are a point source representing radiation direct from the target and a distributed source representing scatter in the flattening filter and primary collimator. By fitting only two parameters, the ratio of the two components for a 20 x 20 field and a width parameter for the distributed source this semi-empirical model describes the relative outputs of square, symmetric rectangular, and asymmetric rectangular fields with an average error of 0.25% for the field sizes studied.


Wedge factor dependence on depth and field size for various beam energies using symmetric and half-collimated asymmetric jaw settings. The depth- and field-size dependence of the in-phantom wedge factor have been determined for a Cobalt-60 (Co-60) teletherapy unit and four medical linear accelerators with 4-, 6-, 10-, and 18-MV x-ray beams containing 15 degrees-60 degrees (nominal) lead, brass, and steel wedge filters. Measurements were made with ionization chambers in solid water or water with a source-skin distance of 80 or 100 cm. Field sizes varied from 4 x 4 cm up to a maximum allowable size for each wedge filter. Measurements were performed for symmetric and half-collimated asymmetric fields at depth of maximum dose, 5- and 10-cm depths. For half-collimated fields, wedge factor reference points were located at a fixed off-axis distance from the collimator's rotational axis. These systematic measurements on wedges indicate that the wedge factor dependence on depth and field size is a function of beam energy as well as the design of the treatment head and wedge filters. Significance of the results reported herein are discussed for the most commonly used treatment depths and field sizes with various beam energies and wedge filters.


A rapid method for electron beam energy check. Assessment of electron beam energy and its long term stability is part of standard quality assurance practice in radiation oncology. Conventional depth-ionization or depth-film density measurements are time consuming both in terms of data acquisition and analysis. A procedure is described utilizing ionization measurements at two energy specific depths. It is based on a linear relationship between electron beam energy and its practical range. Energy shifts within the range covered by the two measurement depths are easily resolved. Within a range of +/- 0.50 MeV (+/- 1.30 MeV) around the established mean incident energy of 5.48 MeV (20.39 MeV), the method accuracy is better than 0.10 MeV.


Demonstration of megavoltage and diagnostic x-ray imaging with hydrogenated amorphous silicon arrays. Flat-panel imagers consisting of the first large area, self-scanning, pixelated, solid-state arrays made with hydrogenated amorphous silicon (a-Si:H) are under development by the authors for applications in diagnostic x-ray and megavoltage radiotherapy imaging. The arrays, designated by the acronym MASDA for multi-element amorphous silicon detector array, consist of a two-dimensional array of a-Si:H photodiodes and thin-film transistors and are used in conjunction with scintillating materials. Imagers utilizing MASDA arrays offer a variety of advantages over existing technologies. This article presents initial megavoltage and diagnostic-quality x-ray images taken with several such arrays including the first examples of anatomical-phantom images. The external readout electronics and imaging techniques required to obtain such images are outlined, the construction, operation, and advantages of the arrays briefly reviewed, and the future potential of this new technology discussed.


Parametrized x-ray absorption in diagnostic radiology from Monte Carlo calculations: implications for x-ray detector design. The integral dose to the patient and image signal to noise ratio (SNR) are inexorably coupled in x-ray-based diagnostic imaging. Advancements and optimal design of imaging devices need to consider the SNR as well as patient dose. The figure of merit, FOM = (SNR)2/(integral dose), is a useful parameter in optimizing detector designs because it is independent of input exposure, and therefore eliminates exposure as a design consideration. Although numerical calculation of the SNR is relatively straightforward in most cases, the integral dose calculation is made complex due to its scatter component's high dependency on both x-ray energy and patient thickness. Monte Carlo calculations over a range of monoenergetic x-ray energies were used to calculate total energy absorption, and the results are parametrized using polynomial expressions. The results are shown to be applicable to any arbitrary polyenergetic spectrum. An example using the above FOM is given to illustrate the utility of the parametrized results. The parametrized results may prove useful in the computer simulations of x-ray detector systems where the above FOM is utilized.


[New perspectives in oncology: is selective destruction of tumor cells with immunotoxins in Hodgkin's disease an additional therapeutic alternative?]. In the present paper, the authors describe the production and testing of immunotoxins for clinical application in Hodgkin's disease. The immunotoxins were constructed by chemical coupling of deglycolysated ricin-A to monoclonal antibodies against antigens on Hodgkin's and Reed-Sternberg cells (CD25, CD30, IRac). The cytotoxic effect of the immunotoxins was investigated in vitro against Hodgkin's and Reed-Sternberg cells (H-RS) and in vivo against solid Hodgkin's tumors in nude mice and disseminated Hodgkin's tumors in SCID mice. Cross-reactivity with normal tissue and the staining behaviour observed in sections of Hodgkin's tissue of various subtypes proved important parameters for the assessment of clinical applicability. Of more than 30 evaluated MoAb's, eight immunotoxins were produced, of which six showed both, cytotoxic effects of considerable potency against Hodgkin's tumor cells and low cross-reactivity with vital human organs. The most effective immunotoxin, RFT5 gamma 1.dgA, (CD25) inhibits the growth of H-RS cells at concentrations of 7 pMol and destroys about 60% of solid Hodgkin's tumors of 0.5 cm in diameter in nude mice. This immunotoxin binds to virtually all tumor cells in more than 90% of patients with Hodgkin's disease. Sufficient quantities of RFT5 gamma 1.dgA were produced for the treatment of patients with refractory Hodgkin's disease. These patients are currently being treated in a phase I clinical trial.


Improvement in specificity of ultrasonography for diagnosis of breast tumors by means of artificial intelligence. A set of ultrasonograms of lesions from 200 patients between the ages of 14 and 93 years who underwent mammography followed by ultrasonographic examination and excisional biopsy has been studied with computer vision techniques to improve the ultrasonographic specificity of the diagnosis. Selected features representing the texture of the lesion were calculated and then classified by an artificial neural network. This network was biased toward correctly classifying all the malignant cases at the expense of some misclassification of the benign cases. The network diagnosed the malignant cases with 100% sensitivity and 40% specificity (compared with 0% specificity for the radiologists diagnosing the same set of cases in the breast imaging setting), and tests performed with a leave-one-out technique indicate that the network will generalize well to new cases. This suggests that methods based on neural network classification of texture features show promise for potentially decreasing the number of unnecessary biopsies by a significant amount in patients with sonographically identifiable lesions.


[Coronary stent implantation: a procedure for treatment of acute dissections after percutaneous transluminal coronary angioplasty]. The development of percutaneous wire-guided endoprostheses (stents) has expanded the possibilities for treating acute vascular occlusion within the field of coronary angioplasty (PTCA). A balloon-expandable Palmaz-Schatz stent was implanted in a total of 14 patients. The coronary arteries involved were the right coronary artery (seven cases), the anterior interventricular branch (five cases), and the circumflex branch (two cases). In seven cases the stent was inserted on an emergency basis to deal with treatening occlusion during PTCA, in one case of occlusion following coronary angiography, and in three cases to recanalize the infarcted vessel. Seven of these eleven patients were submitted to a follow-up angiography three months later, when none was shown to have a restenosis of more than 50%. Stent placement was followed by anticoagulation therapy comprising coumarin combined with acetylsalicylic acid. The Palmaz-Schatz stent represents an alternative to emergency bypass surgery in the treatment of acute dissection during PTCA.


A MRI gradient waveform model for automated sequence calibration. In order to set up magnetic resonance imaging (MRI) procedures of arbitrary voxel dimensions, slice orientation, and sequence timing in a reasonable time, some form of automatic gradient pulse calibration is required. One such method, involving simulation of gradient waveforms, is presented. Waveforms are modeled based on measurements of the step response. The model used divides each transition into three time regions: a "start" region in the first 0.3 ms, a "slew" region, and a "tail" region representing decay of the eddy current compensation error. In the "slew" region, the time derivative of the gradient, G' (t), is expressed as a function of G(t). The first two regions are nonlinear with respect to demand. The mean error in the simulated gradient is generally less than 0.04 mT m-1 in spin echo sequences. Image signal/noise ratios resulting from sequences calibrated using the model are within 5% of those of empirically calibrated sequences.


Testing mammography equipment: evolution over a 4-year period. The results of quality control (QC) tests on 70 mammography units in Southern California from 1986 to 1990 are reported. Thirteen facilities, selected because they housed all of the mammography units in three communities involved in a National Institutes of Health research project, had their units tested twice at an interval of 1 year. Fourteen self-selected units were also tested twice at intervals ranging from 1-3 years. Forty-three self-selected units in 31 additional facilities had testing only once. All 70 units underwent measurement of focal spot size or resolution, tube output, half-value layer (HVL), automatic exposure control (AEC) accuracy, relative kVp accuracy, mean glandular dose, and imaging of several test objects. The test results for the units tested once showed no significant differences compared to those tested twice. For the latter, once the units were tested and determined to be acceptable, retesting showed differences only in overall film optical density, dose, and AEC performance.


[Determinants of serum pentamidine concentration in the human]. By means of serial measurements of pentamidine in plasma, urine and feces the significance of biologically available dose, volume of distribution, elimination and dose interval for serum concentration is investigated in patients with AIDS and bone marrow transplantation after inhaled and intravenous application. Aerosolisation of the drug yields to serum concentration mostly below the detection limit (HPLC). In urine only 0.15 to 0.8% of the substance biologically available in the lung are measured as unaltered pentamidine-base. After i.v. infusion the dose dependent low serum concentrations of 30 to 100 ng/ml indicate a fast distribution in peripheral compartments from which a very slow deliberation is seen. The half-life of the drug is also dose dependent and amounts under clinical conditions at minimum four days. The fecal excretion is found to be only one third of that measured in urine. A difference in the kinetic of elimination between bone marrow transplantated and AIDS-patients could not be evaluated. For clinical therapy the most important pharmacokinetic variable seems to be the terminal elimination constant which would implicate a prolongation of the common dose interval.


[Risk factors and prevention of pneumocystis carinii pneumonia after bone marrow transplantation]. For six months after bone marrow transplantation (BMT) there is a risk of 5 to 15% to suffer from interstitial pneumonia due to pneumocystis carinii (PcP). Prophylaxis with trimethoprim/sulfamethoxazol is therefore routinely and successfully applied. However myelotoxicity, allergic reactions, augmentation of the risk of nephrotoxicity with cyclosporine A and noncompliance may be serious problems. Since the prophylaxis of PcP with pentamidine-aerosol proved to be effective in patients with AIDS, we conducted a prospective trial with regular inhalations of pentamidine. The aim of this study was to evaluate the toxicity, safety, practicability and possible resorption of pentamidine when applied as aerosol. The first of 43 patients were treated with 60 mg pentamidine on two days before, at the day of BMT and 14 days after BMT. Starting four weeks after BMT, 300 mg pentamidine were given every four weeks up to six months. After the study, the four 60 mg inhalations were replaced by two 300 mg inhalations before BMT, because this proved to be more convenient for the patients. There was no pneumonia due to pneumocystis carinii. The only noteworthy side effects observed were cough (19.8%), salivation (9.6%) and sore throat (5.7%). In general pentamidine was well tolerated and well accepted by the patients. Pentamidine could only be detected in the serum of 40 to 60% of all patients. In those patients the serum levels were 7.5 to 9 ng/ml and similar to concentrations found in comparable patients with AIDS. We conclude, that pentamidine-aerosol has only minor side effects, is well tolerated and safe and is therefore an attractive alternative for PcP-prophylaxis after BMT.


[Pneumocystis carinii pneumonia: a life threatening complication after kidney transplantation]. Aggressive immunosuppression in kidney transplantation increases the risk of opportunistic infections. We report ten cases of pneumocystis carinii pneumonia in a group of 420 kidney recipients (2.1%). All patients showed a severe--hyperacute--course of the infection. One patient required mechanical ventilation. In all cases the diagnosis could be established applying fibreoptic bronchoscopy with lavage and partly using transbronchial biopsy. The therapy consisted of intravenous cotrimoxazole and inhalation of pentamidine. All patients survived even after severe course of the disease. Graft explantation for saving patients was not necessary.


[Pentamidine inhalation in prevention of pneumocystis carinii pneumonia in treatment of rejection with monoclonal antibody Orthoclone (OKT-3)]. The use of the monoclonal antibody OKT-3 (Orthoclone) is associated with an increased risk of pneumocystis carinii pneumonia. In a retrospective study, the efficiency of a prophylactic inhalation of pentamidine during acute renal allograft rejection therapy with OKT-3 was investigated. From July 1988 until October 1989 32 renal transplanted patients with acute rejection refractory to steroids had been treated with OKT-3. Twelve of the patients developed a pneumonia (four pneumococcus, one klebsiella, one cytomegalovirus), in six cases, a pneumocystis carinii infection was diagnosed in the bronchial lavage. Four of these patients with pneumocystis carinii pneumonia died despite high dose treatment with cotrimoxazole. From November 1989, a prophylactic inhalation of pentamidine was performed during acute renal allograft rejection therapy with OKT-3. From 33 patients, in eleven cases, a pneumonia was diagnosed (three pneumococcus, one klebsiella, two legionella, three cytomegalovirus, one candida), one patient developed a pneumocystis carinii pneumonia, which was successfully treated with cotrimoxazole. No patient in this group died because of pulmonary infection. The results suggest, that a prophylactic inhalation of pentamidine in severely immunosuppressed solid organ transplant recipients can prevent pneumocystis carinii pneumonia.


[The effect of rigid fixation on bone growth: a radiologic study in the rabbit]. The rigid fixation with plates represents an useful aid in the treatment of the maxillofacial diseases. To the best of our knowledge no studies on the effects of the plates placed across the growing fronto-nasal suture are available. We have therefore examined these effects in an experimental model represented by the suture of eight rabbits. The surgical procedure consists of placing one microplate and four screws across the frontonasal suture of each rabbit, one month old. Radiographies were made both at the moment of the operation and after thirty days. Our results demonstrate a decrease of the normal growth of the suture stressed by plates.


[Lingual thyroid].

[Lingual thyroid]. Lingual thyroid is a rare occurrence in oral surgical practice. A case is reported accompanied by a current view of the presions literature. A brief resumé of methods of treatment is given and the importance of investigations before excision is emphasised.


[A parotid arteriovenous fistula of nontraumatic origin. A case report]. The authors report their experience of a case of non traumatic arteriovenous communication of the parotid region in an adult subject. They confirm that its manifestations in grown-ups are to be linked with an inactive angiodysplastic field. The diagnostic approaches in the face of a hybrid symptomatology and the therapeutic choices are described. Moreover, an aesthetically and functionally efficient surgical correction is proposed.


[A spindle-cell carcinoma of the oral mucosa. A case report]. Spindle cell carcinoma is a relatively rare tumor which occurs often in the upper respiratory tract, the oral cavity, and in the esophagus and skin. In this paper a patient who presented a tumor mass of the lover gingiva which was subsequently diagnosed as a spindle cell carcinoma is reported. The clinicopathologic aspects and diagnostic problems of this unusual tumor of the oral mucosa are discussed.


[Prosthetic rehabilitation in patients with malignant tumors of the soft palate. A clinical case report]. Soft palate neoplasms are relatively rare and their care requires not only an adequate surgical removal but also a post-treatment rehabilitation. In this article the authors after having considered the importance of the soft palate function on the individual's ability to shallow and speak, describe one case of squamous cell carcinoma of the soft palate and treated with surgery followed by prosthetic rehabilitation. Especially it is pointed out the utility of a palatal obturator in the care of deleterious esthetic and psychological aspect of the residual anatomical defect, considering the possibility of the re-establishment the integrity of the tissues and structures in the oral cavity by hand-made prosthesis more and more exact and functional.


[Myelolipomatosis. A report of a case located in the mandible]. Myelolipoma is a rare benign tumour involving, in the majority of cases, the adrenal gland. Given the absolute predominance of this localisation, in this report of extra-adrenal localisations of these tumours the authors considered it worthwhile and necessary to refer to the former, relatively more complete series of data, with the exception of the supposed or real differences which exist between the two groups. Myelolipomatosis should not be considered an example of dysplasia, but on the contrary benign metaplasia/hamartoma. It is therefore obvious that, faced with an expansive process of this type, it is vital to obtain a precise diagnosis on which to base the choice of clinical and therapeutic management since this is also influenced by the anatomical site of the tumour. On the basis of a series of pathophysiological parameters, the authors have formulated a diagnostic protocol followed by a therapeutic approach since, in this context, there is no point resorting to a so-called "wait and see" strategy. In addition, the analysis of the above parameters convinced the authors of the possibility that these tumours should be regarded as bodies which should not be separated from the reaction of the organism as a whole to and appropriate stressigenic event persisting over time.


[A weight and surface analysis of glass ionomer cements in the presence of acid solutions]. The surface and solubility of some glass ionomer cements have been assessed after exposure to four acids (acetic, formic, lactic and propionic), that are usually present in the bacterial plaque. Therefore, we prepared 80 samples--20 for earl of 4 commercial products; after 7 days and, then after 30 other days, the samples were examined by microscope and weighed. Finally, those showing the most significant modifications were photographed.


[Total atrophy of the mandibular alveolar crest. A new therapeutic proposal (the use of a tissue expander) and a clinical case report]. Atrophy of the alveolar crest, meant as a syndrome due to a certain variety of pathogenetic episodes developing in a more or less marked framework of resorption of the alveolar to the maxillary processes, represents an issue of debated and uncertain solution, especially in a view of the extreme degrees of the phenomenon. Various kinds of surgical approach have been suggested over time: among them mention should be made of the onlay graft technique, the osteotomy intervention visor type, the osseous interposition sandwich type, and other methods, which were often the result of a pontered mediation of the above mentioned, and which should have therefore enjoyed their single advantages. In consideration of the different techniques, the results were more or less noteworthy and it was clear, however, that a certain "gap" was still existing between the results aimed to and the results reached. Today, thanks to the tissue-expander technique, combined with the use of alloplasty materials (hydroxylapatite), we can give a new contribution to the solution of this invalidating pathology, thus reaching more complete and lasting results in the plastic reconstruction of the alveolar crest, and avoiding at the same time the disadvantages, even of iatrogenic kind, of an osteotomy intervention.


[Oral lichen planus and liver pathology. I. The prevalence of liver damage in a case load of 96 patients with oral lichen planus]. In order to evaluate if oral lichen planus (OLP) may be regarded as a marker of even unknown liver disease, 96 incident OLP cases were screened through anamnestic, laboratory, instrumental investigations and gastroenterology consultation. The frequency of hepatopathies was 23/96 (24%): 7 had cirrhosis, 3 had chronic active hepatitis, 2 had chronic persistent hepatitis, 10 steatosis and 1 had undetermined liver disease. Eleven of these 23 patients (48%) had unknown hepatopathies, although five of them had severe liver disorders (cirrhosis, chronic hepatitis). Forty-four of 73 patients without definite liver disorders (60%) had at least one abnormal liver parameter. This results confirm frequent association of OLP with hepatic damage and moreover it shown that OLP may be an important clinical sign of symptomless hepatopathies.


[Oral lichen planus and liver pathology. II. The clinico-statistical correlations between oral manifestations and liver damage]. To characterize with more precision the association between oral lichen planus (OLP) and hepatopathies, 96 patients with OLP were separated in two groups ordered by presence or absence of liver diseases comparing some variables (age, sex, presence of pain, clinical variety, presence of skin lesions, alcohol consumption and exposure to drugs inducing hepatic injury) and evaluating the statistical significance. Factors associated with increased frequency of liver diseases were erosive variety of OLP (p = 0.024) and presence of pain (p = 0.026) (chi square test with Yates correction). It's confirmed that OLP patients with higher risk of liver disease are those that have erosive lesions with severe symptoms and often diffused in the entire oral cavity; furthermore, it's highlighted that the probability to find liver disease associated with reticular and plaque-like form of OLP is low, but not negligible.


[Lipoma of the tongue. A clinical case report]. Lipoma is a benign tumor of the adipose tissue. It is a common neoplasm but very rarely involves the tongue. Only 0.3% of all tumors involving the tongue are lipomas. A case of lipoma originating in the tongue is described. The tumor was removed and did not recur one year after excision.


[Cervicofacial actinomycosis. A case study]. A case of cervicofacial actinomycosis, sited in the central hyoid region, is reported. The Authors have emphasized the difficulties of the diagnosis. It's very important hat the clinical diagnosis of actinomycotic infection be confirmed by a positive culture test. Actinomycosis can be suspected if multiple recurrent pustular swellings are present, associated with any trauma or teeth extractions.


[Dermoid cysts of the mouth floor. A case report]. We report a large submandibular dermoid cyst located laterally at the floor of the mouth. Classification, etiopathogenesis, positive and differential diagnosis, treatment and prognosis are discussed. This anomaly is an infrequent congenital disorder that usually becomes apparent during the second or third decade of life. Prognosis is excellent after correct surgical treatment.


[Oral candidiasis as the first manifestation of HIV (human immunodeficiency virus) infection. An analysis of 2 cases]. The authors report two cases in which unexplained oral candidiasis led to the diagnosis of HIV infection with clinical form of AIDS-related complex (ARC). It is highlighted that the dentist showed investigate the causes of every unexplained oral candidiasis in adult because this opportunist infection may be the first sign of immunosuppression associated with AIDS and AIDS-related syndromes.


[The use of kinesiography and electromyography in assessing the outcome of a fracture of the mandibular condyles]. The purpose of this work is to consider the sensibility, reliability, and utility of the computerized electromyography and kinesiography in the diagnosis and study of the functional results in patients affected of single or bilateral previous fractures of the condyles. The Authors analyse three clinical parameters and compare them with thirteen parameters gathered from the computerized data and the kinesiogram and electromyogram analysis of a selected sample of thirteen patients with previous fractures of the condyles. This comparison has shown the greatest reliability and sensibility (a larger quantity of instrumental data as regards the clinical checkup and absence of false negative diagnosis) of these techniques with regard to ordinary clinical checkup. Furthermore the features of objectivity, non invasion and easy repetition, indicate that computerized electromyography and kinesiography play an important role in the diagnosis and study of the functional results of fractures of the condyles and in the follow-up examination.


Unintended childbearing: pregnancy risk assessment monitoring system--Oklahoma, 1988-1991. Unintended pregnancies may be associated with delays in the initiation of prenatal care and behaviors during pregnancy that increase the risk for adverse birth outcomes (1,2). Based on estimates from the 1988 National Survey of Family Growth, 28% of births were mistimed during the 3-4 years before the survey, and 12% were unwanted (3). In Oklahoma, family-planning services are provided as an element of the state's maternal and child health program efforts, and the state has made a priority of identifying mothers at high risk for unintended pregnancy. This report summarizes an analysis of data from the Oklahoma Pregnancy Risk Assessment Monitoring System (PRAMS) to assess the risk for unintended childbearing in Oklahoma during 1988-1991.


Abortion surveillance: preliminary data--United States, 1990. For 1990, CDC received data on legal induced abortions from 52 reporting areas: 50 states, New York City, and the District of Columbia. This report presents preliminary data for 1990.


Update: influenza activity--United States and worldwide, 1992-93 season. Influenza activity in the United States is monitored by CDC through surveillance systems maintained cooperatively with state and local health departments (1); in addition, CDC receives reports of worldwide influenza activity from international World Health Organization (WHO) collaborating laboratories and from WHO, Geneva. This report summarizes surveillance for influenza in the United States and worldwide during the 1992-93 season through December 5, 1992.


Selected behaviors that increase risk for HIV infection, other sexually transmitted diseases, and unintended pregnancy among high school students--United States, 1991. Since the 1970s, sexual activity has increased among adolescents in the United States (1); at the same time, rates of sexually transmitted diseases (STDs) (1), unintended pregnancy (2), and--beginning in the 1980s--human immunodeficiency virus (HIV) infection (3,4) also have increased among adolescents. This report presents 1991 self-reported data from students in grades 9-12 about behaviors that can result in HIV infection, other STDs, or unintended pregnancy.


Imported human rabies--France, 1992.

Imported human rabies--France, 1992. Wildlife rabies has been enzootic in France since 1968; however, 13 of the 14 human cases in France were imported, and one was in a person infected through a corneal transplant (1). On May 9, 1992, a 3-year-old boy who resided in Algeria died from rabies encephalitis in Paris. This report summarizes the investigation of this case by the Pasteur Institute.


Regulation of Ca2+ release from sarcoplasmic reticulum in skeletal muscles. Ca2+ release from skeletal sarcoplasmic reticulum (SR) could be regulated by at least three mechanisms: 1) Ca2+, 2) calmodulin, and 3) Ca2+/calmodulin-dependent phosphorylation. Bell-shaped Ca(2+)-dependence of Ca2+ release from both actively- and passively-loaded SR vesicles suggest that opening and closing of the Ca2+ release channel could be regulated by [Ca2+o]. The time- and concentration-dependent inhibition of Ca2+ release from skeletal SR by calmodulin was also studied using passively-Ca2+ loaded SR vesicles. Up to 50% of Ca2+ release was inhibited by calmodulin (0.01-0.5 microM); this inhibition required 5-15 min preincubation time. The hypothesis that Ca2+/calmodulin-dependent phosphorylation of a 60 kDa protein regulates Ca2+ release from skeletal SR was tested by stopped-flow fluorometry using passively-Ca2+-loaded SR vesicles. Approximately 80% of the initial rates of Ca(2+)-induced Ca2+ release was inhibited by the phosphorylation within 2 min of incubation of the SR with Mg-ATP and calmodulin. We identified two types of 60 kDa phosphoproteins in the rabbit skeletal SR, which was distinguished by solubility of the protein in CHAPS. The CHAPS-soluble 60 kDa phosphoprotein was purified by column chromatography on DEAE-Sephacel, heparin-agarose, and hydroxylapatite. Analyses of the purified protein indicate that the CHAPS-soluble 60 kDa protein is an isoform of phosphoglucomutase (PGM). cDNAs encoding isoforms of PGM were cloned and sequenced using synthetic oligonucleotides. Two types of PGM isoforms (Type I and Type II) were identified. The translated amino acid sequences show that Type II isoform is SR-form.(ABSTRACT TRUNCATED AT 250 WORDS)


Incorporation of 3H-N-ethylmaleimide into sheep red cell membrane thiol groups following protection by diamide-induced oxidation. The thiol oxidant diazene dicarboxylic acid bis [N,N-dimethylamide] (diamide) is known to reversibly activate K-Cl cotransport in sheep red blood cells. Although the detailed mechanism of activation is unknown, functional thiols at the membrane or at the cytoplasmic level are recognized as important. To search for membrane bound thiols involved in the regulation of K-Cl cotransport, sheep red cells were first exposed to diamide at concentrations activating K-Cl cotransport, and then to the alkylating agent N-ethylmaleimide (NEM) in order to block non-oxidized thiols. White ghosts, prepared by osmotic lysis from these cells, were again treated with NEM followed by reduction of the diamide-induced dithiols with dithiothreitol (DTT) concentrations known to reverse the diamide-induced K-Cl flux. Maximum 3H-NEM incorporation into the DTT-reduced thiols occurred at 50 microM DTT. Saturation labelling by 3H-NEM of about 2 x 10(4) diamide-protected thiols/cell occurred at 25 microM NEM. Diamide protected about 0.1% of all membrane thiols chemically determined earlier. Membranes from high K (HK) and low K (LK) sheep red cells did not differ significantly in the number of diamide-protected thiols, and polyacrylamide gels revealed a similar protein distribution of 3H-NEM-labelled thiols. Since diamide is known to stimulate K-Cl flux in LK cells ten times more than in HK cells this finding is consistent with the hypothesis of a cytoplasmic control effecting different K-Cl flux activities in the membranes of the two cation genotypic red blood cells.


Influence of tight junctions on the interaction of salts with lingual epithelia: responses of chorda tympani and lingual nerves. The role of tight junctions in modulating responses from chorda tympani (taste) and lingual (general sensory) nerves are clarified in regard to their responses to salts. Chorda tympani (CT) responses elicited by organic sodium salts require greater Na+ concentrations to elicit the same magnitude of response as NaCl. These data can be understood in terms of the organic anions (compared with Cl-) producing larger liquid-junction potentials across tight junctions between taste cells which, in turn, reduces Na+ influx into taste cells via amiloride-inhibitable channels. The anion contribution to the CT response to different Na+ salts can be eliminated (or enhanced) by voltage clamping the tongue with negative (with respect to the serosal solution) potentials. Whole nerve recordings from the lingual branch of the trigeminal nerve elicited by NaCl (and other salts) were reversibly inhibited by the tight junction blocker, LaCl3. These data suggest that small hydrophilic molecules elicit responses from trigeminal fibers by diffusing across tight junctions between epithelial cells and altering the composition of the extracellular space.


Probing the structure of the Neurospora crassa plasma membrane H(+)-ATPase. The structure of the Neurospora crassa plasma membrane H(+)-ATPase has been investigated using a variety of chemical and physiochemical techniques. The transmembrane topography of the H(+)-ATPase has been elucidated by a direct, protein chemical approach. Reconstituted proteoliposomes containing purified H(+)-ATPase molecules oriented predominantly with their cytoplasmic surface facing outward were treated with trypsin, and the numerous peptides released were purified by HPLC and subjected to amino acid sequence analysis. In this way, seventeen released peptides were unequivocally identified as located on the cytoplasmic side of the membrane, and numerous intervening segments could be inferred to be cytoplasmically located by virtue of the fact that they are too short to cross the membrane and return between sequences established to be cytoplasmically located. Additionally, three large membrane-embedded segments of the H(+)-ATPase were isolated using our recently developed methods for purifying hydrophobic peptides, and identified by amino acid sequence analysis. This information established the topographical location of virtually all of the 919 residues in the H(+)-ATPase molecule, allowing the formulation of a reasonably detailed model for the transmembrane topography of the H(+)-ATPase polypeptide chain. Separate studies of the cysteine chemistry of the H(+)-ATPase have demonstrated the existence of a single disulfide bridge in the molecule, linking the NH2- and COOH-terminal membrane-embedded domains. And, analyses of the circular dichroism and infrared spectra of the purified H(+)-ATPase have elucidated the secondary structure composition of the molecule. A first-generation model for the tertiary structure of the H(+)-ATPase based on this information and other considerations is presented.


Regulation of the skeletal sarcoplasmic reticulum Ca(2+)-ATPase by phospholamban and negatively charged phospholipids in reconstituted phospholipid vesicles. The Ca(2+)-ATPase of skeletal sarcoplasmic reticulum was purified and reconstituted in proteoliposomes containing phosphatidylcholine (PC). When reconstitution occurred in the presence of PC and the acidic phospholipids, phosphatidylserine (PS) or phosphatidylinositol phosphate (PIP), the Ca(2+)-uptake and Ca(2+)-ATPase activities were significantly increased (2-3 fold). The highest activation was obtained at a 50:50 molar ratio of PS:PC and at a 10:90 molar ratio of PIP:PC. The skeletal SR Ca(2+)-ATPase, reconstituted into either PC or PC:PS proteoliposomes, was also found to be regulated by exogenous phospholamban (PLB), which is a regulatory protein specific for cardiac, slow-twitch skeletal, and smooth muscles. Inclusion of PLB into the proteoliposomes was associated with significant inhibition of the initial rates of Ca(2+)-uptake, while phosphorylation of PLB by the catalytic subunit of cAMP-dependent protein kinase reversed the inhibitory effects. The effects of PLB on the reconstituted Ca(2+)-ATPase were similar in either PC or PC:PS proteoliposomes, indicating that inclusion of negatively charged phospholipid may not affect the interaction of PLB with the skeletal SR Ca(2+)-ATPase. Regulation of the Ca(2+)-ATPase appeared to involve binding with the hydrophilic portion of phospholamban, as evidenced by crosslinking experiments, using a synthetic peptide which corresponded to amino acids 1-25 of phospholamban. These findings suggest that the fast-twitch isoform of the SR Ca(2+)-ATPase may be also regulated by phospholamban although this regulator is not expressed in fast-twitch skeletal muscles.


Changes in adrenergic receptors during the development of heart failure. Moderate and severe stages of congestive heart failure due to the loss of myocardium upon coronary occlusion in rats was associated with an increase in alpha-adrenergic receptors and a decrease in beta-adrenergic receptors in the viable left ventricle. However, at early stages of heart failure the number of beta-adrenergic receptors was decreased without any changes in the number of alpha-adrenergic receptors. The affinities of these receptors to alpha receptor antagonist (3H-prazosin) and beta receptor antagonist (3H-dihydroalprenolol) were not altered in the failing hearts. On the other hand, the pattern of changes in both alpha- and beta-adrenergic receptors in heart membranes treated with oxygen free radical generating system was different from that seen in the failing hearts. In particular, the affinities for these receptors were decreased whereas the number of beta-receptors was increased and the number of alpha-receptors was decreased or unchanged. These results indicate that alterations in the adrenergic receptors in heart failure are not due to the formation of oxygen free radicals.


Magnesium homeostasis in cardiac cells.

Magnesium homeostasis in cardiac cells. Several aspects of Mg2+ homeostasis were investigated in cultured chicken heart cells using the fluorescent Mg2+ indicator, FURAPTRA. The concentration of cytosolic Mg2+ ([Mg2+]i) is 0.48 +/- 0.03 mM (n = 31). To test whether a putative Na/Mg exchange mechanism controls [Mg2+]i below electrochemical equilibrium, we manipulated the Na+ gradient and assessed the effects on [Mg2+]i. When extracellular Na+ was removed, [Mg2+]i increased; this increase was not altered in Mg-free solutions, but was attenuated in Ca-free solutions. A similar increase in [Mg2+]i, which was dependent upon extracellular Ca2+, was observed when intracellular Na+ was raised by inhibiting the Na/K pump with ouabain. These results do not provide evidence for Na/Mg exchange in heart cells, but they suggest that Ca2+ can modulate [Mg2+]i. In addition, removing extracellular Na+ caused a decrease in intracellular pH (pHi), as measured by pH-sensitive microelectrodes, and this acidification was attenuated when Ca2+ was also removed from the solution. These results suggest that Ca2+ and H+ interact intracellularly. Since changes in the Na+ gradient can also alter pHi, we questioned whether pH can modulate [Mg2+]i. pHi was manipulated by the NH4Cl prepulse method. NH4(+)-evoked changes in pHi, as measured by the fluorescent indicator BCECF, were accompanied by opposite changes in [Mg2+]i; [Mg2+]i changed by -0.16 mM/unit pH. These NH4(+)-evoked changes in [Mg2+]i were not caused by movements of Mg2+ or Ca2+ across the sarcolemma or by changes in cytosolic Ca2+. Additionally, pHi was manipulated by changing extracellular pH (pHo).(ABSTRACT TRUNCATED AT 250 WORDS)


War against famine, for nutrition.

War against famine, for nutrition. In Somalia, the world is fighting an unprecedented war in the name of basic nutrition. In the United States, the government has gone overboard on the matter of nutrition and health.


Communal nesting patterns in mice implicate MHC genes in kin recognition. House mice (Mus musculus domesticus) form communal nests and appear to nurse each other's pups indiscriminately. Communal nesting probably functions to reduce infanticide, but it also makes females vulnerable to exploitation if nursing partners fail to provide their fair share of care. Kinship theory predicts that females will preferentially form communal nests with relatives to minimize exploitation and further increase inclusive fitness. Here we provide evidence from seminatural populations that females prefer communal nesting partners that share allelic forms of major histocompatibility complex genes. Such behaviour would lead to the selection of close relatives as communal nesting partners. Although criteria for the demonstration of kin recognition are currently embroiled in controversy, this is the first vertebrate study to meet Grafen's restrictive requirements: discrimination is based on genetic similarity at highly polymorphic loci, incidental correlations due to relatedness are experimentally controlled, and strong reasons exist for expecting the assayed behaviour to be kin-selected.


The perception of heading during eye movements. When a person walks through a rigid environment while holding eyes and head fixed, the pattern of retinal motion flows radially away from a point, the focus of expansion (Fig. 1a). Under such conditions of translation, heading corresponds to the focus of expansion and people identify it readily. But when making an eye/head movement to track an object off to the side, retinal motion is no longer radial (Fig. 1b). Heading perception in such situations has been modelled in two ways. Extra-retinal models monitor the velocity of rotational movements through proprioceptive or efference information from the extraocular and neck muscles and use that information to discount rotation effects. Retinal-image models determine (and eliminate) rotational components from the retinal image alone. These models have been tested by measuring heading perception under two conditions. First, observers judged heading while tracking a point on a simulated ground plane. Second, they fixated a stationary point and the flow field simulated the effects of a tracking eye movement. Extra-retinal models predict poorer performance in the simulated condition because the eyes do not move. Retinal-image models predict no difference in performance because the two conditions produce identical patterns of retinal motion. Warren and Hannon observed similar performance and concluded that people do not require extra-retinal information to judge heading with eye/head movements present, but they used extremely slow tracking eye movements of 0.2-1.2 deg s-1; a moving observer frequently tracks objects at much higher rates (L. Stark, personal communication). Here we examine heading judgements at higher, more typical eye movement velocities and find that people require extra-retinal information about eye position to perceive heading accurately under many viewing conditions.


Three-dimensional illusory contours and surfaces. Under general viewing conditions, objects are often partially camouflaged, obscured or occluded, thereby limiting information about their three-dimensional position, orientation and shape to incomplete and variable image cues. When presented with such partial cues, observers report perceiving 'illusory' contours and surfaces (forms) in regions having no physical image contrast. Here we report that three-dimensional illusory forms share three fundamental properties with 'real' forms: (1) the same forms are perceived using either stereo or motion parallax cues (cue invariance); (2) they retain their shape over changes in position and orientation relative to an observer (view stability); and (3) they can take the shape of general contours and surfaces in three dimensions (morphic generality). We hypothesize that illusory contours and surfaces are manifestations of a previously unnoticed visual process which constructs a representation of three-dimensional position, orientation and shape of objects from available image cues.


Association of dystrophin-related protein with dystrophin-associated proteins in mdx mouse muscle. Dystrophin is associated with a complex of muscle membrane (sarcolemmal) glycoproteins that provide a linkage to the extracellular matrix protein, laminin. The absence of dystrophin leads to a dramatic reduction of the dystrophin-associated proteins (156DAG, 59DAP, 50DAG, 43DAG and 35DAG) in the sarcolemma of patients with Duchenne muscular dystrophy and mdx mice. Here we demonstrate that dystrophin-related protein (DRP, utrophin), an autosomal homologue of dystrophin, is associated with an identical or antigenically similar complex of sarcolemmal proteins and that DRP and the dystrophin/DRP-associated proteins colocalize to the neuromuscular junction in Duchenne muscular dystrophy and mdx muscle. The DRP and dystrophin/DRP-associated proteins are found throughout the sarcolemma in small-calibre skeletal muscles and cardiac muscle of adult mdx mice. Because these muscles show minimal pathological changes, our results could provide a basis for the upregulation of DRP as a potential therapeutic approach.


Primary structure of dystrophin-related protein. Dystrophin-related protein (DRP or 'utrophin') is localized in normal adult muscle primarily at the neuromuscular junction. In the absence of dystrophin in Duchenne muscular dystrophy (DMD) patients, DRP is also present in the sarcolemma. DRP is expressed in fetal and regenerating muscle and may play a similar role to dystrophin in early development, although it remains to be determined whether DRP can functionally replace dystrophin in adult tissue. Previously we described a 3.5-kilobase complementary DNA clone that exhibits 80 per cent homology to the C-terminal domain of dystrophin. This sequence identifies a 13-kilobase transcript that maps to human chromosome 6 (refs 2, 11). Antibodies raised against the gene product identify a polypeptide with a relative molecular mass of about 400K in all tissues examined. To investigate the relationship between DRP and dystrophin in more detail, we have cloned and sequenced the whole DRP cDNA. Homology between DRP and dystrophin extends over their entire length, suggesting that they derive from a common ancestral gene. Comparative analysis of primary sequences highlights regions of functional importance, including those that may mediate the localization of DRP and dystrophin in the muscle cell.


Raf functions downstream of Ras1 in the Sevenless signal transduction pathway. Specification of the R7 cell fate in the developing Drosophila eye requires activation of the Sevenless (Sev) receptor tyrosine kinase, located on the surface of the R7 precursor cell, by its interaction with the Boss protein, expressed on the surface of the neighbouring R8 cell. Four genes that participate in the intracellular transmission of this signal have so far been identified and molecularly characterized: Ras1, Sos, Gap1 and sina (refs 4-8). The Drosophila homologue of the mammalian Raf-1 serine/threonine kinase, which has been implicated in signal transduction pathways activated by many receptor tyrosine kinases (reviewed in refs 9 and 10), is encoded by the raf locus (also known as l(1)polehole, Draf-1 or Draf). Here we show that the Drosophila Raf serine/threonine kinase also plays a crucial role in the R7 pathway: the response to Sev activity is dependent on raf function, and a constitutively activated Raf protein can induce R7 cell development in the absence of sev function. We also present genetic evidence suggesting that Raf acts downstream of Ras1 and upstream of Sina in this signal transduction cascade.


SEC21 is a gene required for ER to Golgi protein transport that encodes a subunit of a yeast coatomer. Non-clathrin coated vesicles have been implicated in early steps of intercompartmental transport. A distinct set of coat proteins are peripherally associated with the exterior of purified mammalian intra-Golgi transport vesicles. The 'coatomer', a cytosolic complex containing a similar subunit composition to and sharing at least one subunit (beta-COP) with the coat found on vesicles, has been postulated to be the precursor of this non-clathrin coat. Here we describe the characterization of SEC21, an essential gene required for protein transport from the endoplasmic reticulum to the Golgi in the yeast Saccharomyces cerevisiae. The 105K product of this gene, Sec21p, participates in a cytosolic complex that we show to be a yeast homologue of the mammalian coatomer. These observations demonstrate that a non-clathrin coat protein plays an essential role in intercompartmental transport.


[How much information is retained by participants in clinical trials?]. To assess which information participants of the Dutch TIA trial could remember from the informed consent procedure. Descriptive investigation. The University Hospital Utrecht and the University Medical Centre Amsterdam. One hundred of the 308 patients from 2 of the 63 participating clinical centres (the University Hospital Utrecht and the University Medical Centre Amsterdam), were selected at random for telephone interviews. Nineteen were not interviewed, most of them because they did not have access to a telephone. By a weighted score based on the replies the influence of some baseline variables was explored. The information sheet that patients had received was analysed with the readability tests of Flesh and Fry. Eighty-six percent of all patients were aware of the correct diagnosis. The name and action of the trial drug Ascal (a brand of acetylsalicylic acid) were retained better than those of atenolol. The nature of the disease and therapy were better known than the design of the trial. Of the baseline variables explored only the level of education was significantly related to what patients remembered about the trial. The readability of the information sheet required more education than was intended. Although we did not study a random sample the conclusion seems warranted that the level of information was not optimal in this trial.


[Intellectual development of patients with phenylketonuria; 15-year national screening in The Netherlands]. To evaluate the intellectual development of patients with phenylketonuria (PKU) or hyperphenylalaninaemia (HPA). Longitudinal follow-up study. University Children's Hospitals of Amsterdam, Groningen, Nijmegen, and Rotterdam. In September 1974 a nationwide neonatal screening for PKU started in the Netherlands. We obtained data on the intellectual development of 116 patients (101 classical PKU, 15 HPA), all detected and treated in the first 15 years of this screening. The children were tested at 6 ages with different instruments for the assessment of intellectual functions, and the scores were compared with the test norms. Performance and verbal capacities were determined as well as possible sex-related differences. Our data show that the levels of intellectual functioning of PKU and HPA patients do not differ from test norms until the age of 8 yr 6 months. In the older PKU patients there appears to be a trend towards lower IQ scores. We found no sex differences in the mental functioning of PKU patients. Continuation of this study is necessary in order to investigate possible negative effects of PKU on cognitive functioning, especially in the older age groups.


[Fever caused by neuroleptics].

[Fever caused by neuroleptics]. If fever arises in patients using neuroleptic drugs, it is possible that the fever is an adverse reaction to the drug. Two cases are reported of patients who developed fever to neuroleptic agents. In one patient it probably concerned a reaction to the solvent of the sustained-action preparation of the drug. The other patient developed fever probably as part of the neuroleptic malignant syndrome.


[14 years of screening for cervix carcinoma in a family practice]. Since 1975 the general practitioners of 'Ons Medies Centrum' in Oss have been inviting women systematically for cervical screening and cervical smears. The attendance and protection rate were evaluated for the period 1975-1989. 85% of the women 35-54 years of age had had a cervical smear within 5 years after they entered the general practice or had not been invited because of a total hysterectomy. After a starting period of a few years the protection rate stabilised at 75%. There was no relation between residential quarter, health insurance, ethnic origin and attendance for the screening. Age was the only factor related to attendance: the attendance rate among older women was lower.


[Evaluation of the organization of the mass screening program for cervix cancer in northern Limburg]. The 1990 programme for screening of cervical cancer in North Limburg in the Netherlands was evaluated with a view improving the programme. Information was gathered from women in the screening programme, general practitioners, the health insurance company, the laboratory, and the city councils. With data from literature estimates were made of the effects of the screening in the region. All participants in the screening programme were satisfied with the set-up of the programme. 52% of all women did respond to the invitation for a smear, (in the first 7 months 3620 smears were made). 31% of the women did not need a smear because the uterus had been completely removed or because a smear had been made shortly before. 5% of the women did not receive an invitation. Only 11% of the women who needed a smear did not respond to the invitation, because of lack of time or objections. A so-called 'protection degree' for cervical cancer of 83% was achieved. The degree of protection was the same for different villages, age groups and income levels. The invitation of 12,000 women each year for a smear, leads to an estimate of 185 follow-up tests, detection of 20 women with abnormal results, unnecessary (minor) treatment of 12 women, prevention of two to three major treatments and of one to two deaths per year. Because of the limited positive effects and the relatively large negative effects the authors think that the cervical screening programme is questionable.(ABSTRACT TRUNCATED AT 250 WORDS)


[Placement in a nursing home does not automatically lead to increased use of drugs]. To determine whether the use of drugs increases during a stay in a nursing home. Fifteen nursing homes in Groningen and Haren. Prospective study. In 250 persons admitted to a nursing home in the period December 1986-December 1987 the following data were determined: the mean number of different drugs, the total quantity of drugs used expressed in DDDs (Defined Daily Dose), the number of diagnosis and the functioning. The mean number of different drugs used per person per quarter increased significantly (4.5 in the first quarter as against 5.7 in the fourth quarter). The total quantity of drugs expressed in DDDs used per person per quarter, and the mean duration of their being prescribed did not change significantly. An exception were dermatological preparations (0.13 DDDs in the first quarter as against 0.42 DDDs in the fourth quarter), probably in connection with decubitus. A stay in a residential home does not necessarily lead to use of larger quantities of drugs (DDDs). However, there are indications that placement may lead to a greater diversity of the drugs used.


[Henoch-Schönlein purpura following treatment with streptokinase]. This article presents the clinical history of a man aged 64 who developed Henoch-Schönlein purpura after administration of streptokinase for acute myocardial infarction. Because of the increasing use of streptokinase it is assumed that type III hypersensitivity reactions to streptokinase will be seen more frequently. The first symptoms may arise after discharge from the hospital, as symptom-free periods of 3 to 21 days have been reported.


[The value of skull and cervical spine radiography in patients following blunt head injury]. In a consecutive series of 100 patients with blunt head trauma the efficacy of routine skull and cervical radiography was studied. Neurocranial and facial skeletal lesions were present in 8 patients, only 1 skull fracture being completely unsuspected clinically. In all 79 patients without cervical signs or symptoms the cervical spine films were within normal limits. Only two of the 21 patients with some form of local cervical spine symptomatology presented with traumatic changes. In 19 patients the cervical spine films did not demonstrate the cervicothoracic junction to satisfaction. Although this study confirms the low yield of routine conventional radiography in patients with blunt head trauma, the authors state that optimal conventional examination of the cervical spine is mandatory in all patients with blunt head trauma and the slightest suspicion of cervical symptoms or complaints and in those patients in whom either clinical examination or the clinical history is not completely satisfactory. The cervicothoracic junction should be adequately visualised. A CT or MRI scan of the brain should be preferred over conventional skull films in those patients in whom examination of the skull is considered indicated.


[Is skull radiography indicated in patients with head injuries?]. The value of the radiographic finding of a skull fracture in predicting intracranial haematoma is assessed in this study. Patients with a skull injury can be divided into three risk groups, based on the history and examination findings. The low-risk group includes patients who are asymptomatic or have scalp haematoma, lacerations, headache or dizziness. The moderate-risk group includes patients who have posttraumatic amnesia and/or alcohol intoxication and those who are suspected of having a skull fracture. The patients in the high-risk group have clear symptoms and signs such as depressed level of consciousness or focal neurological signs. The records of 1218 patients were studied. The risk group, the existence of a skull fracture and development of intracranial haematoma were determined. Not a single haematoma was found in the low-risk group. Therefore skull radiography had no significance in this group. In the moderate-risk group two patients had an intracranial haematoma, of whom one patient had a skull fracture. Negative skull radiography therefore did not fully exclude intracranial complications. There were many patients with an intracranial haematoma in the high-risk group, both in the presence and the absence of a skull fracture. CT scanning is the best method of detecting an intracranial haematoma in this group.


[Meeting reports in the Nederlands Tijdschrift voor Geneeskunde; value for readers and associations]. To determine the objective of scientific association proceedings in the Nederlands Tijdschrift voor Geneeskunde (NTvG) and whether the objective is met by publication. Interview. The editorial office of NTvG MATERIAL AND METHODS: The clinical relevancy of the proceedings published in 1990 and 1991 was determined using selection criteria. 53 (former) secretaries of scientific associations which publish their proceedings in NTvG were interviewed by written questionnaire, and 101 physicians were interviewed by telephone, asking for their opinion on the objective and the use of publishing the proceedings. Of the proceedings (1610 abstracts) published in 1990 and 1991 20% were considered clinically relevant. The opinion of the secretaries of the associations was that the objective of the proceedings is to record medical information and to provide a medical newspaper for the latest reports of the associations, mostly intended for all readers of the NTvG. The secretaries usually correct the abstracts with respect to form and to a lesser extent to informative value. Editorial office selection of the abstracts was not considered desirable, guidelines with regard to writing an abstract of the proceedings were appreciated. More than half of the family physicians read the proceedings, but often considered them too specialised. Half of these thought editorial office selection of the abstracts advisable. About 80% of the specialists read the proceedings, of which the informative value was considered variable. They disapproved of editorial selection. In general physicians read the proceedings very selectively. The clinical relevancy of the abstracts of the proceedings leaves much to be desired. The objective is to provide a medical record and a newspaper for all readers, but these read the proceedings very selectively. The informative value could be improved. Abstract selection should be in the hands of the associations' secretaries only, but guidelines from the editorial office on writing abstracts are welcomed.


Transtracheal oxygen: a step beyond the nasal cannula for long-term oxygen therapy. Transtracheal oxygen represents an important advance in the technology of long-term oxygen therapy. As an oxygen conserving technique, it allows increased physical activity with smaller ambulatory and portable units and facilitates the management of patients with refractory hypoxemia outside of the hospital. There is increasing evidence that transtracheal oxygen therapy provides significant physiologic benefits beyond those achieved with the nasal cannula because of tighter control of oxygen therapy and fewer episodes of hypoxemia as a result of uninterrupted 24-hour oxygen therapy. Transtracheal oxygen therapy should be viewed as a program for long-term oxygen administration and not simply as a procedure that involves the insertion of a catheter into the tracheal. Careful patient screening and patient education is important to avoid complications. The program is best administered through regional centers with a team approach to patient care.


Need for primary care.

Need for primary care. This paper is a renewed call for medical schools to address the societal need for more primary care physicians. Numerous studies from the literature are cited as background for this paper. The Author retraces the historical beginnings of the specialty of Family Practice and some of the more recent events which highlight the need for more primary care physicians. The author concludes that there is a societal need for more primary care physicians and that medical schools should respond to this need.


Multidrug regimens in moderate & severe hypertension. We have briefly discussed the antihypertensive drug interactions which result in additive or synergistic actions on lowering of blood pressure when they are administered concomitantly. The choice of antihypertensive agents should be individualized based on the patient's age, race, sex, weight prior therapy, coexisting diseases, underlying diseases, and the pathophysiology of the disease. The goal of antihypertensive treatment extends not only to the control of hypertension per se but also to the reduction of side effect profiles, the treatment of co-existing diseases and optimizing quality of life.


Natural history of at-risk Lynch syndrome family members with respect to adenomas. Our goal is to determine colon cancer surveillance strategy in patients at risk for Lynch's syndrome. Asymptomatic persons at 50% risk of having Lynch syndrome (age 25-70 years) were enrolled in colonoscopic screening. Those without adenomas were asked to return in one year. Those with adenomas were asked to return in six months because of concern for rapid malignant degeneration. Twenty-five males and thirty females participated. On initial exam, eight of fifty-five patients (14.5%) had adenomas. Logistic regression showed a significant effect of age on the probability of finding adenomas at initial examination (p < 0.02). Followup was available in 27 patients (mean 35.5 months). Kaplan-Meier estimation of time to finding new or previously missed adenomas was 58 months for patients clear on first colonoscopy and 16 months for patients who had adenomas on first exam (p < 0.01). One adenocarcinoma has been found arising in a tubulovillous adenoma. The short-term risk of colorectal cancer in Lynch syndrome relatives without adenomas is low, as is the risk in those who have had all visualized adenomas removed.


Merging the departments of psychiatry of a private and state university: the Nebraska experience. Medical colleges throughout the nation are being pressured to decrease the costs of medical education. In some of our smaller cities, the duplication of faculty expertise and costly technological resources at distinct but neighboring campuses has led to training costs far beyond what can be comfortably supported by either the institutions or their students. While the trend toward collaboration or mergers between identical medical departments on adjacent campuses is gaining ground, the methods required to achieve success in these ventures remain relatively uncharted. This paper provides an overview of the creation of successful merger between the departments of Psychiatry of Creighton University School of Medicine and the University of Nebraska College of Medicine. The development of the merger from conception to completion, along with the lessons learned along the way, are offered in the hope that other medical departments may benefit.


[Cerebral vasospasm. Experimental study]. We have studied chronic vasospasm (V.S.) on a primate model (Cynomolgus monkey). The conclusion of several studies are: V.S. is related to the presence of adherent clots along cerebral arteries and when severe may lead to cerebral infarction. Clots removal within 48 h. following subarachnoid hemorrhage reduces V.S. intensity. Free radicals and iron dependent lipidic peroxidation have been involved in cerebral ischemia development. A new aminosteroid (U 74006 F) can act as a free radical phagocyte and antagonize iron dependent lipid oxidation. Histological V.S. changes are less important after S.A.H. with 74006F treatment. Oxyhemoglobin high concentration from red blood cells (R.B.C.) hemolysis has been reported to be responsible for V.S. Therefore induction of R.B.C. release from the clots before hemolysis occurs could prevent from high concentration of oxyhemoglobin. Plasminogen activator can prevent V.S. when used during 72 h. following subarachnoid hemorrhage.


[Effect of nimodipine on vasospasm of cortical arteries. Experimental study]. The efficacy of the calcium channel blocker Nimodipine (N) in prevention and treatment of chronic cerebral vasospasm (V.S.) after subarachnoid haemorrhage (S.A.H.) was tested in a blind randomized experimental study. Twenty seven dogs (French Grande Venerie) weighing between 40 to 50 kg, were randomly assigned in three groups. Under general anesthesia, each animal underwent baseline angiography, followed by right frontotemporal craniectomy. A retractor was placed under the temporal lobe and the arachnoid membrane over the internal carotid artery was dissected. 10 ml of autologous arterial blood was placed around the internal carotid artery, and 5 ml of arterial blood was injected into the cisterna magna. Group I was placebo group: ten randomly pre selected animals received a placebo. Group II was preventive group: seven animals received N (5 mg/kg) per os each day, from D0. Group III was curative group: ten animals received N (5 mg/kg) per os each day, from D2. At Day 2 and Day 5, all animals underwent a control angiography. The basilar artery, the internal carotid artery were measured. The craniectomy was reopened and the cortical arteries were measured with a calibrated optical micrometer. Intergroup comparisons at Day 0, Day 2 and Day 5, were made by analysis of variance. The level of significance was n < 0.05. V.S. was defined as a reduction in vessel caliber of 10% or greater, compared to baseline value. In the placebo group (Group 1), V.S. of the basilar and cortical arteries was present in all cases, from D2 to D5.(ABSTRACT TRUNCATED AT 250 WORDS)


[Diagnosis of vasospasm: comparison between arteriography and transcranial Doppler. A series of 112 comparative tests]. 56 consecutive patients with ruptured aneurysm (An) were studied. The An localisation were: anterior communicating artery (ACoA) 26 cases, internal carotid artery (I.C.A.) 13 cases, Middle cerebral artery (M.C.A.) 11 cases, Pericallosal artery (P.C.A.) 4 cases, anterior cerebral artery (A.C.A.) 2 cases. Nimodipine infusion was started as soon as the diagnostic was established. Transcranial Doppler (T.C.D.) and angiography (A degrees) were performed at the arrival and 10 to 12 days after surgery. Surgery was performed in the 72 first hours after S.A.H. in 79% of the cases. 112 comparisons A degrees-T.C.D. were available. An A degrees vasospasm (V.S.) was assessed if the reduction of calibre was 25% or more, on T.C.D. V.S. was assessed if mean cerebral flow (M.C.F.) was equal to or more than 130 cm/sec. There were 15 cases of A degrees V.S. in 14 patients: 2 cases before surgery, 1 case before and after surgery in the same patient and 11 cases after surgery. D.T.C. exhibited 11 cases of V.S. at the level of M.C.A.; there were 11 true positive, 0 false positive, 97 true negative and 4 false negative. The diagnosis of V.S. was always correct with T.C.D. when A degrees V.S. was present at the level of M.C.A., it was not made when A degrees V.S. was restricted to the initial part of A.C.A. (A1) uni or bilaterally: 3/6 cases of ACoA. An rupture or to I.C.A.: 1/4 case of I.C.A. An. rupture.(ABSTRACT TRUNCATED AT 250 WORDS)


[Cerebral blood flow in the determination of vasospasm and surgical decision]. The interest of C.B.F. studies performed on patients with subarachnoid haemorrhage is discussed on the basis of the literature and of our experience of 142 cases. C.B.F. results in basic condition are influenced by many factors which make its use very limited and especially during the first days after haemorrhage (J0-J3). However, the analysis of the evolution of C.B.F. values in the same patient and moreover the C.B.F. reactivity to acetazolamide are good indicators of the occurrence of a vasospasm; progressive drop of the C.B.F. or poor reactivity are generally observed before clinical signs of vasospasm. Our policy is therefore to decide the date of surgery according to C.B.F. values but only for patients planned for delayed surgery (after the 3rd day).


[Contribution of 99m Tc-HMPAO single-photon emission-computed tomography to the perioperative evaluation of subarachnoid hemorrhage caused by ruptured aneurysms]. Twenty one cases of proven subarachnoid hemorrhage (S.A.H.) have been analysed in a protocol especially including transcranial doppler (T.C.D.) and 88mTc-H.M.P.A.O. single photon emission tomography (H.M.P.A.O.-S.P.E.C.T.). Seventeen patients were intraoperatively studied. All data were compared with clinical grading, computerized tomography (C.T.) and angiography. S.P.E.C.T. is a quite recent method of measuring and three-dimensional imaging of brain perfusion. It provides important information for the diagnosis of ischemic syndromes in S.A.H. Sixty-two S.P.E.C.T.-scans were performed in twenty one patients. Fifty-eight were abnormal and showed significant abnormalities of brain perfusion varying in extent and severity. In this preliminary study, we set out to validate the clinical use of H.M.P.A.O.-S.P.E.C.T. for the diagnosis of "vapospasm" comparing S.P.E.C.T. data with classical criteria. We propose a classification which allowed us to quantify the ischemic risk in an attempt to adapt the global therapeutic management to hemodynamic data. This method appears to be very sensitive and reliable in this field. It will introduce, if these first results are confirmed, important criteria for the evaluation of patients presenting with S.A.H. as far as prognosis and treatment are concerned, especially in regard to timing of surgery and institution of medical hemodynamic therapy.


[Vasospasm, early surgery and nimodipine. A series of 120 consecutive cases of surgically treated ruptured aneurysm]. A total of 120 consecutive ruptured aneurysms (An) were managed according to a radio clinical investigation protocol. Preoperative evaluation included clinical grading (Hunt & Hess classification) (3 patients were Gr. I, 62 Gr. II, 27 Gr. III, 13 Gr. IV, 15 Gr. V) angiography (A degree) and C.T.Scan grading. Nimodipine infusion was started before surgery (1 mg/Kg/h). Surgery was performed from Day 0 to Day 3--Control A degrees and C.T.Scan were performed 10 to 12 days after surgery. Post operative C.T.Scan hypodensities were evaluated according to preoperative C.T.scan anc control A degrees. The outcome was evaluated according to the Glasgow Outcome Score (G.O.S.) and the causes of sequelae and decreases were listed according to vasospasm (V.S.), initial hemorrhage and post operative thrombosis (T.H.R.). The outcome was good or excellent in 95.4% of 65 Gr. I.II cases, in 85.9% of 92 Gr. I.II.III cases. Among the causes of disability or death only one case of diffuse severe V.S. was noted; besides that and according to our experience V.S. incidence was lower in this series (25%) than in our previous experience. It is stated that nowadays with Nimodipine treatment and early surgery V.S. is no more a problem.


[Transluminal angioplasty in the treatment of vasospasm. Value of transcranial Doppler in the diagnosis and follow-up]. Vasospasm (V.S.) transluminal angiographic treatment (T.L.A.) is recommended in case of symptomatic V.S. before or after surgery. V.S. diagnosis and follow up after T.L.A. rely on clinical and transcranial doppler (T.C.D.) data. Before T.L.A. angiography (A degrees) demonstrates V.S. degree and location. T.L.A. technic is described. The authors report 14 cases of T.L.A. (7 before and 7 after surgery). Before surgery in 4 cases patients exhibited ischemic symptoms from V.S.: 2 died (one from reanimation problems the other from a new hemorrhage). After surgery of 7 patients one died from artery rupture, one from extra-neurologic complication. T.C.D. capacity to follow up V.S. is emphasized. As soon as T.L.A. is performed the mean cerebral blood flow (C.B.F.) decreases (< 100 cm/s) and does not increase anymore. At the level of non dilated arterial segments V.S. may increase after T.L.A.: it is then recommended to dilate all the spastic arteries, as far as it is possible. After T.L.A. C.B.F. may decrease in arteries far from the dilated ones probably because arterial supplies are no more necessary.


[Juxtabulbar neurinoma of the spinal accessory nerve]. A 27-year-old woman presented with right spinal accessory juxtabulbar schwannoma, associated with hydrocephalus. The only specific clinical symptom was long-standing weakness of the right trapezius. C.T. scan evoked a cerebellar tumor, whilst the jugular foramen appeared normal. Vertebral angiography was not decisive. M.R.I. suggested an extra-axial tumor. Post-operative evolution was entirely favourable. Schwannomas of the 9th, 10th and 11th cranial nerves are generally located at the level of the jugular foramen but can also be observed along the extracranial path of these nerves. An intracranial paramedial, or so-called "intracisternal" localization is rare and is best diagnosed by magnetic resonance imaging.


[Deep sylvian meningioma. Apropos of a case. Review of the literature]. One case of deep sylvian meningioma without dural attachment is reported. Ten cases have been described in the literature leading to discussion of histological origin, clinical characteristics, neuroradiological data and surgical results.


[Neurinoma of the oculomotor nerves. Apropos of 2 cases]. The authors report two cases of neurinomas of the oculomotor nerves: one neurinoma of the oculomotor nerve and one of the abducens nerve. The study of 30 cases in the previous literature points out the major striking features of these tumors. Both headaches and oculo-motor palsies are the most regular clinical features. They are not typically suggestive. Therefore the diagnosis is difficult among all the tumors of cavernous sinus and surrounding structures. C.T. scan and M.R.I. with the clinical history should readily allow pre-operative diagnosis. These data are insufficient to distinguish the affected nerve. The surgical treatment is not always complete due to the tumor infiltration into the cavernous sinus.


[Postoperative dural tightness. Value of suturing of the pericranium in surgery of the posterior cranial fossa]. It is difficult to have the dura-mater of the posterior fossa tightly closed, with no excessive traction especially when it was necessary to coagulate some vessels. The use of a pericranial graft taken in the interparietal area on up of the occipital craniotomy permits a tight closure, preventing pseudomeningocele via diffusion of CSF, and without tension gaining space which permits a better tolerance of the post-operative cerebellar oedema.


In vivo neurotoxicity of beta-amyloid [beta(1-40)] and the beta(25-35) fragment. We examined the histological changes produced by injections of beta-amyloid [beta(1-40)], and control peptides in rat and monkey cerebral cortex. beta(25-35) injections were also studied in rat cortex. Standard immunoperoxidase procedures were used to detect the distribution of tau, MAP2, beta(1-40) and ALZ 50 immunoreactivity. All injections produced localized necrosis at the injection site surrounded by a zone of neuronal loss and gliosis. In rat cortex, lesions produced by solubilized beta(1-40) and beta(25-35) in water were generally larger than those produced by control peptides. Tau and ALZ 50 antibodies labeled neurites and diffusely positive perikarya around beta(1-40) injections, whereas MAP2 staining was reduced, paralleling the distribution of neuronal loss and gliosis. In aged primate cortex, beta(1-40) lesion size was dose dependent. Hyalinized, ALZ 50 positive neurons, and abnormal neurites were prominent around the injection site. Although beta-amyloid is acutely neurotoxic in both rat and monkey cerebral cortex, neuronal degeneration in the primate more closely resembles that found in AD.


Effect of beta amyloid peptides on neurons in hippocampal slice cultures. Several investigators have described the neurotrophic and neurotoxic effects of beta amyloid peptide fragments on dissociated hippocampal neurons in culture. In these prior studies, the peptides were added to dissociated cultures between day 0 and day 4 in vitro, before hippocampal neurons are fully mature. We have analyzed the neurotrophic and neurotoxic effects of beta amyloid fragments beta 1-28, beta 25-35 and beta 1-40 on hippocampal slice cultures, whose physiology and morphology resembles the intact hippocampus. Addition of beta 1-28 or beta 25-35 to the growth medium did not produce significant changes in dendritic length or number of branches. Nerve growth factor, previously reported to enhance the neurotoxic effects of beta 1-40 on dissociated hippocampal neurons in culture, did not significantly enhance the neurotrophic effects of beta 1-28. To achieve high local concentrations of peptides and to avoid potential access problems in the cultures, we injected beta 1-28, beta 25-35, and beta 1-40 directly into the cultures. Amyloid-mediated neurotoxicity was not observed for beta 1-28 or beta 25-35, but beta 1-40 appeared to produce neurodegeneration around the site of injection.


The acute neurotoxicity and effects upon cholinergic axons of intracerebrally injected beta-amyloid in the rat brain. The acute neurotoxicity and effects upon cholinergic axons of an intracerebrally injected synthetic peptide corresponding to the first 1-40 amino acids of beta-amyloid protein (beta AP1-40) was studied in rats. A synthetic peptide with the reverse sequence (beta AP40-1) or the vehicle alone were injected in the contralateral hemisphere as control. The size of the resulting lesions was quantified in serial sections using an image analyzer. Counts of cholinergic and noradrenergic fibers were also obtained around the lesion area. The results revealed that beta AP1-40 was significantly more toxic than both reverse peptide and the vehicle. The latter two, however, also caused considerable neurotoxicity. beta AP1-40 was toxic to both cholinergic and noradrenergic fibers to the same extent, and this toxicity was limited to the immediate vicinity of the lesion. This study confirms and extends the results of previous studies reporting neurotoxic effects of intracerebrally injected beta-amyloid in the rat. Our results also show that beta AP1-40 itself is not the source of the altered acetylcholinesterase enzyme activity that has been described in the plaques and tangles of Alzheimer's disease.


Lack of Alzheimer pathology after beta-amyloid protein injections in rat brain. In order to establish a direct relationship between beta-amyloid protein (beta AP) and in vivo neurotoxicity, we made intraparenchymal injections and Alzet pump infusions of beta AP into the hippocampus and cortex of adult rats. We tested a number of synthetic beta AP peptides (beta AP 1-40, 1-38, and 25-35) and peptide controls (scrambled and reversed 1-40, and scrambled and reversed 25-35) over a wide range of concentrations and in a variety of vehicles. The rats were sacrificed from 2-35 days following the implant, and the brains examined by standard immunohistochemical and histological methods used to evaluate the pathologies associated with Alzheimer's disease. We report the lack of Alzheimer related pathology and no significant morphological differences between the beta AP peptide and the peptide and vehicle control injections. These observations indicate that the simple intraparenchymal injection of beta AP in the rat brain is not an appropriate model of Alzheimer-related neurotoxicity.


Implants containing beta-amyloid protein are not neurotoxic to young and old rat brain. Because the cellular effects of beta-amyloid protein (beta-AP) are currently unclear, we evaluated the in vivo effects of beta-AP implants in a lipid matrix to prolong tissue exposure in the brains of rats. Young 3-month-old rats and aged 18-month-old rats received implants of beta-AP prepared in a cocoa butter matrix in the dorsal hippocampus and corpus striatum on one side of the brain and implants of either prolactin or scrambled beta-AP peptide in cocoa butter on the contralateral side. The old rats also received implants of beta-AP embedded in a cholesterol matrix or cholesterol alone in the frontal cortex. The young rats were sacrificed 3-4 days after implantation, while the old rats were sacrificed 6-8 weeks after implantation. Lesion size on the beta-AP implanted side did not differ significantly from lesion size observed with control peptides. Bielschowsky silver staining revealed few argyrophilic neurites and axonal spheroids associated with either beta-AP or control implants. Alz 50 and ubiquitin immunoreactivity were not observed. None of the implant sites demonstrated cytopathology characteristic of Alzheimer's disease. The results of this study indicate that beta-AP implantation into the brains of rats produced no consistent effect beyond that seen with control peptide implants.


beta-Amyloid neurotoxicity: a discussion of in vitro findings. Significant advances in Alzheimer's disease (AD) research require definitive, reproducible findings from all employed paradigms. Recently, the existing in vitro data addressing the possible contribution of beta-amyloid protein to AD neuropathology have been the subject of controversy. We summarize and interpret existing data and discuss relevant methodological issues. We suggest that in vitro data support the conclusion that beta-amyloid peptides decrease the viability of cultured neurons and that this effect can be enhanced by subsequent insults.


Failure of beta-amyloid protein fragment 25-35 to cause hippocampal damage in the rat. Considerable excitement has been generated as of late over reports that fragments of the amyloid precursor protein can be neurotoxic both in vivo and in vitro. In this brief report we study the neurotoxicity of the fragment corresponding to amino acids 25-35 of the beta-amyloid protein in the hippocampus in vivo. Under the conditions studied, we do not observe any evidence of consistent, dose-related damage above that seen with vehicle alone.