A comparison of medetomidine-propofol and medetomidine-midazolam-propofol anesthesia in rabbits.

We evaluated and compared the effects of medetomidine-propofol and medetomidine-midazolam-propofol anesthesia in rabbits. Fourteen New Zealand White rabbits were randomly assigned to receive either medetomidine (0.25 mg/kg, i.m.)-atropine (0.5 mg/kg, i.m.)-propofol (4 mg/kg, i.v.) (n = 7) or medetomidine (0.25 mg/kg, i.m.)-atropine (0.5 mg/kg, i.m.)-midazolam (0.5 mg/kg, i.m.)-propofol (2 mg/kg, i.v.) (n = 7). Five minutes after medetomidine-atropine or medetomidine-atropine-midazolam i.m. injection, propofol was administered i.v. Both medetomidine and medetomidine-midazolam rapidly (within 5 minutes) immobilized all rabbits and greatly eased the i.v. administration of propofol. Endotracheal intubation was accomplished easily after propofol injection in both groups. There was no significant difference between medetomidine-propofol and medetomidine-midazolam-propofol-treated rabbits in heart rate, respiratory rate, mean arterial pressure, or end-tidal CO2. The addition of midazolam to the medetomidine-propofol regimen significantly (P < 0.05) prolonged the duration of ear-pinch analgesia (25.0 +/- 7.1 vs. 36.7 +/- 8.9 minutes), the time from extubation to sternal recumbency (0.0 vs. 26.7 +/- 8.1 minutes), and the time from extubation to standing (0.0 vs. 39.5 +/- 11.3 minutes) without inducing significant changes in arterial blood pressure and end-tidal alveolar CO2. We consider both medetomidine-propofol and medetomidine-midazolam-propofol combinations to be safe and effective regimens for induction and short-term anesthesia in rabbits.


Improved techniques for successful neonatal rat surgery.

Problems encountered in neonatal rat surgery include mortality due to anesthesia and postoperative mortality due to cannibalism or neglect by the dam. We required a method of anesthesia which would enable us to perform complicated, lengthy, recovery eye surgery on day-old rat pups. Because ethical concerns have been raised regarding hypothermia, the currently recommended procedure for anesthesia of newborn rats, we adapted two effective techniques for anesthetizing adult rats for use in neonates. In the first of these methods, halothane was administered via a gas anesthetic machine which allowed for precise regulation of anesthetic levels. The second method employed diluted Innovar-Vet, a neuroleptanalgesic drug combination that is easily administered by injection, with oxygen supplementation. Because each surgical procedure required 30 to 45 minutes and was technically demanding, it was important to minimize the loss of experimental animals due to cannibalism. To accomplish this, we developed an easy, noninvasive method to encourage acceptance of surgically manipulated pups by the dam, which included hand gentling and olfactory conditioning of pregnant females. All pups (63/63) survived eye surgery under halothane anesthesia and of those examined 7 days later, 55/57 (97%) were alive and appeared normal. Of the pups treated with Innovar-Vet, 16/16 (100%) survived anesthesia and all were normal in appearance when examined 7 days later. Our results suggest that using these anesthetic methods coupled with appropriate conditioning of the dam and handling of the pups contribute to successful neonatal rat surgery.


Mechanisms of cancer-induced hypercalcemia.

Cancer-associated hypercalcemia is due to the: (a) elaboration of systemically-acting humoral factors by neoplasms which alter calcium metabolism in bone, kidney, and intestine; or (b) stimulation of bone resorption at sites of tumor metastasis to bone. It is likely that both mechanisms occur in the same patient with certain neoplasms. There are many humoral factors that can be produced by tumors, secreted into the circulation, and have distant effects which induce hypercalcemia. The stimulation of increased osteoclastic bone resorption is a principal feature of humoral hypercalcemia of malignancy, but the kidney also plays an important role. In addition, intestinal absorption of calcium may be a factor in the pathogenesis of hypercalcemia in certain neoplasms. Parathyroid hormone-related protein plays a dominant role in the pathogenesis of HHM. PTHrP alone is able to induce nearly all of the clinical signs of HHM in experimental animals, but other humoral factors, such as cytokines, can interact with PTHrP to contribute to the development of hypercalcemia. Neoplasms which metastasize widely to bone and induce local osteoclastic bone resorption, such as multiple myeloma, also are capable of inducing hypercalcemia. Based upon existing data it is not clear what percentage of neoplasms which metastasize to bone and stimulate local bone resorption also are capable of stimulating hypercalcemia by systemic factors. Future research is needed to delineate the systemic and local factors associated with CAH; to define interactions of humoral factors in the pathogenesis of hypercalcemia; and to investigate the regulation of transcription, translation, modification, and secretion of hypercalcemia-inducing factors in normal and neoplastic tissues.


Effect of endothelin-1 on croton oil-induced granulation tissue in the rat. A pharmacologic and immunohistochemical study.

To date no attempts have been made to determine the role of the endothelial cell derived product, endothelin-1 (ET-1) in granulation tissue development. This study investigates the cellular immunolocalization of ET-1 and its pharmacologic effect on myofibroblast-mediated rat croton oil-induced granulation tissue contraction. The distribution, cellular localization and temporal production of ET-1 in the tissues was determined by immunohistochemistry at days 7, 14, 21, and 28. The contractile response of the granulation tissue to ET-1 was tested over the same time period, and it effects modified by use of calcium antagonists. The pharmacologic profile was correlated to the ultrastructural development of contractile fibroblast-like cells within the tissue. Endothelin-1 caused reversible concentration-dependent contraction of the granulation tissue. The 21-day granulation tissue was the most responsive, with a maximum increase in tension of 458.9 +/- 41.1 mg; this response could be inhibited by use of calcium antagonists. Of the calcium antagonists tested, verapamil (1 x 10(-4) M) was the most potent inhibitor, giving a 43% reduction in maximum amplitude of the response. It is suggested that entry of extracellular calcium via the L-type potential operated calcium channel, is involved in ET-1 induced responses in contractile fibroblast-like cells or myofibroblasts. Ultrastructural analysis showed a correlation between the pharmacologic sensitivity of the tissue and the development of contractile fibroblast-like cells. The number of cells expressing the phenotypic characteristics of a myofibroblast increased with time, and were first observed at day 7. Immunohistochemistry revealed the presence of increasing numbers of ET-1 labeled cells throughout the time course of study. The ET-1 positive cells were localized to the capillaries. Immunolabeling of serial sections with the rodent endothelial cell specific lectin, Bandeiraea simplicifolia isolectin B4 and factor VIII-related antigen, confirmed the specific localization of ET-1 to endothelial cells. We present evidence that ET-1 may be an endogenous modulator of myofibroblast-mediated granulation tissue contraction and that the use of calcium antagonists could afford a possible therapeutic control in the treatment of fibrocontractive diseases.


Heparin induces alpha-smooth muscle actin expression in cultured fibroblasts and in granulation tissue myofibroblasts.

Heparin increases alpha-smooth muscle actin expression in smooth muscle cells in vivo and in vitro. It has been recently suggested that alpha-smooth muscle actin expression in fibroblasts is a marker of myofibroblastic differentiation. We have examined the effect of heparin and of four nonanticoagulant heparin derivatives on alpha-smooth muscle actin expression by fibroblasts in vitro and in vivo. For in vitro experiments, heparin was added for 7 days to different fibroblastic cultures. We studied cell proliferation and alpha-smooth muscle actin protein and mRNA expression. For in vivo studies, osmotic minipumps filled with NaCl or tumor necrosis factor-alpha without or with nonanticoagulant heparin were implanted subcutaneously. After 14 days, newly accumulated connective tissues around the pumps were processed for immunofluorescence and electron microscopic and biochemical studies. In vitro, heparin inhibited proliferation and increased the expression of alpha-smooth muscle actin protein and mRNA. Analysis of [3H]thymidine incorporation in synchronized cells suggested that heparin produces a selection of alpha-smooth muscle actin expressing cells. In vivo, the local application of tumor necrosis factor-alpha resulted in formation of a typical granulation tissue: immunofluorescence showed that accumulated fibroblastic cells express alpha-smooth muscle actin only in the presence of heparin derivatives. In tumor necrosis factor-alpha treated animals, electron microscopic examination established the presence of myofibroblasts, but alpha-smooth muscle actin was expressed in microfilament bundles only in the presence of heparin derivatives. These results show that heparin and its nonanticoagulant derivatives influence the expression of alpha-smooth muscle actin in fibroblastic cells both in vitro and in vivo and that this effect is probably related to the selection of a particular cell subpopulation. They suggest a possible role for heparin during the formation and evolution of granulation tissue.


Intracellular actin as a marker for myofibroblasts in vitro.

Myofibroblasts are found in a wide variety of normal tissues and pathological conditions. It is suggested that myofibroblasts are derived from normal fibroblasts and share with smooth muscle cells the expression of actin microfilament bundles. The aim of this study was to establish if the myofibroblast phenotype from tissue expander capsules and Dupuytren's nodules could be distinguished from normal dermal fibroblasts by quantitation of intracellular actin and the ratio of polymerized (filamentous) actin to nonpolymerized (globular) actin. Cell lines were established from six patients from each group. In addition to quantitation of intracellular actin, the cells were characterized by criteria of light microscopy, ultrastructure, actin immunofluorescence, and growth rates. Dermal fibroblasts were the smallest and the most spindle-shaped but grew rapidly and had few actin microfilament bundles. By contrast, myofibroblasts from expander capsules were larger and more stellate, proliferated slowly, and had the most prominent microfilament arrays. Cells from Dupuytren's nodules were intermediate in phenotype. Substantial and significant differences in intracellular actin contents were found, ranging from 0.69 +/- 0.05 micrograms/10(4) cells in fibroblasts and 0.77 +/- 0.15 micrograms/10(4) cells for Dupuytren's nodule cells to 1.46 +/- 0.44 micrograms/10(4) cells in expander capsule myofibroblasts (p < 0.05). Similar findings were found with respect to ratios of fibroblast to globular actins, being 0.22 for fibroblasts and 0.38 for Dupuytren's nodule cells compared with 0.70 for expander capsule myofibroblasts (p < 0.01). Measurement of intracellular actin contents and fibroblast:globular actin ratios offers a rapid, sensitive, and reliable technique for establishment of the myofibroblast phenotype and has considerable advantages over traditional ultrastructural approaches for the study of myofibroblast differentiation/regression and in vitro responses to experimental manipulation.


A morphometric study of the blood-brain barrier in Alzheimer's disease.

Abnormalities in the human blood-brain barrier may contribute to the pathogenesis of Alzheimer disease (AD). Morphometric parameters relevant to integrity of the blood-brain barrier (cerebral capillary endothelium) were assessed in brain biopsies from patients with AD and compared with values from age-matched nondemented controls. Alzheimer patients showed diminished mitochondrial density and area within cerebral capillary endothelium, an increased number of capillary profiles containing pericytes (a possible second line of defense when the capillary endothelium fails), and features of inter-endothelial junctions that suggest 'leakiness' of the blood-brain barrier. The data indicate subtle but definite abnormalities suggesting compromise of the blood-brain barrier in AD that may contribute to its pathogenesis, and support neuropharmacologic and morphologic studies that suggest that a form of denervation microangiopathy may occur in AD brain, possibly secondary to loss of neurons from the pontine locus ceruleus. The changes may also play a role in the deposition of A4 Alzheimer amyloid within cerebral microvessel walls.


Involvement of activated periglomerular leukocytes in the rupture of Bowman's capsule and glomerular crescent progression in experimental glomerulonephritis.

In an experimental model of crescentic glomerulonephritis, we have investigated whether periglomerular leukocytes are involved in (a), the disruption of Bowman's capsule (BC), and (b) the progression of cellular crescents. Experimental crescentic glomerulonephritis was induced in inbred Sprague-Dawley rats using passive accelerated anti-glomerular basement membrane disease. Groups of 4 animals were sacrificed at 3, 7, 14, 21, and 28 days after administration of nephrotoxic serum. Periglomerular infiltration of macrophages and T cells was evident at day 3, although focal accumulation of activated mononuclear cells (IL-2R+) was not apparent in this area until day 14. BC rupture in some glomeruli was first evident at day 14, and this was seen in all 12 animals from days 14 to 28. Similarly, glomerular crescent formation was first apparent at day 14, and from days 14 to 28, 11 of 12 animals displayed crescent formation (25 to 74% crescentic glomeruli). Examination of glomeruli (> or = 200/animal) within periodic acid-Shiff stained sections found that BC disruption invariably occurred at sites of prominent focal periglomerular mononuclear cell infiltration. Monoclonal antibody labeling revealed that T cells and IL-2R+ cells were restricted to focal infiltrates at sites of BC rupture, whereas macrophages were more widely distributed throughout the periglomerular area. A key finding was that while BC disruption occurred in both the presence and the absence of crescent formation, it was always associated with prominent periglomerular leukocytic infiltration. In this model, most cellular crescents contained leukocytes (88.8 +/- 2.1%). In the presence of an intact BC, macrophages constituted the predominant leukocyte cell type within these crescents. However, when BC was ruptured, although the number of macrophages remained unchanged, a marked accumulation of both T cells and IL-2R+ cells occurred within crescents. Progressive fibrous organization of cellular crescents was observed only in those glomeruli in which BC was disrupted. The results suggest that: (a) activated periglomerular mononuclear cells may cause disruption of BC via a delayed-type hypersensitivity mechanism, (b) rupture of BC facilitates entry of activated periglomerular T cells and fibroblasts into Bowman's space leading to progressive fibrous organization of cellular crescents, and (c) disruption of BC may be a general mechanism of progressive glomerular damage mediated by periglomerular leukocytes irrespective of crescent formation.


Nephritogenicity of anti-proteoglycan antibodies in experimental murine lupus nephritis.

Cross-reactivity between anti-DNA antibodies and heparan sulfate (HS)/heparan sulfate-proteoglycan (HS-PG) of glomerular basement membrane has been previously reported. Conceivably, this determines the final outcome of glomerular injury in lupus nephritis. We investigated the status of glomerular injury in NZB/NZW F1 mice after the administration of rabbit anti-HS-PG antibody (experiment group). The controls received normal rabbit IgG only. All experimental animals became proteinuric 2 weeks after the administration of anti-HS-PG. The animals of the older age group (16 weeks) had significant hematuria as well. Their glomeruli exhibited hypercellularity with a heavy influx of polymorphonuclear leukocytes and monocytes into their capillaries, and some of them exhibited crescentic changes. Electron-dense deposits were present in subepithelial, subendothelial, and mesangial regions of the glomeruli. The control group had normocellular glomeruli with a few mesangial deposits. Mouse IgG and C3 displayed a granular pattern of immunofluorescence in the experimental group. Anti-rabbit IgG titers in the serum were higher in the control group, which lower in the renal glomerular eluates. No significant differences were observed in the concentrations of anti-dsDNA and -ssDNA either in the sera or in the eluates. There was also no difference between the control and experimental group in terms of antibody synthesis by the splenic lymphocytes and their proliferation subsequent to antigenic challenge. Data suggest that administration of anti-HS-PG accentuates the glomerular injury during the natural course of lupus nephritis in (NZB/NZW F1 mice; seemingly these two antibodies (anti-HS-PG and -DNA) do not competitively inhibit the binding of the other to the same anionic sites of glomerular basement membrane enriched with heparan sulfate in vivo.


Tubule-tubule and tubule-arteriole contacts in rat kidney distal nephrons. A morphologic study based on computer-assisted three-dimensional reconstructions.

Functional investigations of the tubulo-glomerular feedback mechanism have indicated the existence of a contact between the distal nephron and the macula densa region. The structural justification of such a contact is investigated. Tubule-tubule and tubule-arteriole contacts were investigated in distal nephrons from normal rat kidneys. Computer-assisted three-dimensional reconstructions of distal nephrons were made from serial sections of renal cortical tissue and selected sections were examined by electron microscopy. In 14 of 15 reconstructed nephrons, the distal convoluted tubule or the connecting tubule approached the macula densa region. A wall-to-wall contact between two tubules corresponding to a three-dimensional distance below 28 microns between the axes of the two tubules was found in only five of the reconstructed tubules. The distal nephron contacts to afferent and efferent arterioles of the same nephron were also examined. The efferent arteriole revealed no consistent contacts but the afferent arteriole contacted the distal convoluted tubule/connecting tubules consistently in all 10 of the superficial nephrons and in 3 of 5 midcortical nephrons. Electron microscopy confirmed a close contact between the distal tubule and the afferent arteriole in superficial nephrons and small nerves were often found at or near the site of contact, but the morphology at the site of contact was not unique. The arteriole contacts were made with late distal convoluted tubules, connecting tubules, or cortical collecting ducts. In conclusion, the present study shows that tubule-tubule contacts are inconsistent between the macula densa region and the distal nephron but that the tubule-afferent arteriole contact is consistent and close in superficial nephrons. This morphology is compatible with the existence of a feedback mechanism between the superficial distal nephron and the afferent arteriole, apart from the one located at the juxtaglomerular apparatus.


Identification of beta-subunit of GTP-binding regulatory protein in mitotic spindle.

The heterotrimeric GTP-binding regulatory protein (G protein) is important in membrane signal transduction. Since the function of the beta-subunit of G protein (G beta) in tumor cells is not well-documented, identification of G beta in tumor cells was performed. Immunolocalization, Western blotting, and immunoprecipitation of G beta in mammalian tumor and normal cells were investigated using rabbit antisera against amino and carboxyl terminal peptide fragments of G beta. A human nasopharyngeal carcinoma cell line (NPC-TW039) was used as the cell model because of its short doubling time. Anti-G beta immunoreactivity was found to be associated with the plasma membrane and the mitotic spindle throughout the mitotic phase of cell replication. Colcemid pretreatment resulted in random distribution of the anti-G beta reaction product in the mitotic cells. The same phenomenon was also seen in various other tumor and normal cell lines. When solubilized membranous, cytosolic, and mitotic spindle fractions were analyzed by Western blotting, G beta (35 +/- 1 kDa) was found to be associated with the plasma membrane and mitotic spindle fractions. Immunoprecipitation of isolated mitotic spindles with anti-G beta further confirmed these results. These findings indicate that G beta is closely associated with the mitotic spindle as well as the plasma membrane and may be important in regulation of cell mitosis in addition to transmembrane signal transduction.


Immunohistochemical and in situ hybridization studies of androgen receptor expression in a transplantable androgen-independent prostatic carcinoma line (AIT) of Noble rats.

In a previous study, we had shown that testosterone (T) administration to castrated Noble (NBL) rats, bearing an androgen-independent prostatic carcinoma line (AIT), caused a dramatic increase in high-affinity nuclear-androgen binding sites in the neoplasms. This increase in nuclear androgen receptors (AR) was accompanied by a transient doubling of the mitotic index in the tumors. In our current study we used immunohistochemistry and in situ hybridization to investigate the effects of androgen withdrawal and replacement on AR expression at the molecular/cellular level in the AIT. Results from immunohistochemical studies of AR expression in the AIT were compared with those from the prostates of intact, castrated, and castrated T-treated rats. Immunopositive staining for AR was found only in the nuclei of prostatic cells from the glands of intact, castrated or castrated T-treated animals. A few immunopositive tumor cells were present in AITs carried in untreated castrated hosts. In all instances, the reaction product was found in the cytoplasm, but it was also present in the nuclei of some tumor cells. Five days of T administration to castrated AIT-bearing rats caused a dramatic increase in immunopositive tumor cells. Nuclear staining was observed in all positive cells, but the reaction product was also present as well in the cytoplasm of some tumor cells. No differences in AR mRNA expression was detected by in situ hybridization studies of the AITs from castrated and castrated T-treated rats. The differences in localization of AR between normal prostate and carcinoma cells may reflect alterations in DNA binding domains of the AR protein that occurred with neoplastic transformation. Our in situ findings suggest that unlike the normal prostate, where AR mRNA levels are autoregulated by androgen, AIT cells constitutively express these transcripts. Taken together, our findings suggest that the T-mediated increases in nuclear AR in the AIT, detected previously by binding assay and now by immunohistochemistry, are likely the result of post-transcriptional modifications in the receptor protein.


Changes in antioxidant enzymes in isolated cardiac myocytes subjected to hypoxia-reoxygenation.

Intracellular antioxidants have been shown to be depressed during hypoxia, and recovery upon reoxygenation has been correlated with the available antioxidant reserve. To test whether these antioxidant changes are also occurring at the cardiac myocytes level, we studied changes in antioxidant enzyme activities as well as cell injury in isolated cardiac myocytes exposed to hypoxia and reoxygenation. Isolated Ca(2+)-tolerant myocytes from adult male rats were subjected to 30 minutes hypoxia and 15 minutes reoxygenation. Antioxidant enzymes superoxide dismutase, glutathione peroxidase, catalase; lipid peroxide content; electrolytes (Na+, Ca2+); morphology; and high energy phosphates (ATP, ADP, AMP, creatinine phosphate) were studied in these myocytes. The effects of exogenous catalase (40 units/ml) on hypoxia-reoxygenation induced changes in myocytes were also studied. Hypoxia resulted in a reduction in Mn superoxide dismutase and glutathione peroxidase activities with no change in CAT activity and malondialdehyde content. Reoxygenation of hypoxic cells resulted in recovery of Mn superoxide dismutase but not in glutathione peroxidase activity. Reoxygenation was without any effect on catalase activity, but a significant increase in the malondialdehyde content was seen. Hypoxia as well as reoxygenation caused a reduction in the number of rod-shaped cells with a parallel increase in hypercontracted as well as round cells. There was a significant increase in the myocyte Na+ and Ca2+ content during both hypoxia and reoxygenation, and this was accompanied by leakage of lactate dehydrogenase into the perfusion medium. These changes due to hypoxia and reoxygenation were significantly attenuated by addition of catalase (40 units/ml). High energy phosphates ATP, ADP, and AMP declined during hypoxia, and creatine phosphate was significantly reduced during reoxygenation. Hypoxia induces specific antioxidant changes in the isolated cardiac myocytes. Reduced ability to remove hydrogen peroxide appears to be an important determinant of myocyte injury during reoxygenation.


Modelling coccidial infection in chickens: emphasis on vaccination by in-feed delivery of oocysts.

Trickle immunization of poultry by incorporating wildtype strains of coccidia in the feed has been shown to be an effective and practical means of controlling coccidiosis. Here we develop a mathematical model of the life cycle of Eimeria tenella and estimate the model parameters from extant experimental studies. Numerical solutions of the model compare well with experiment. The model provides quantitative estimates of the required trickle immunization hitherto only available after extensive time-consuming trials.


A model of postnatal formation of alveoli in rat lung.

In rats, and many other species, most lung alveoli are formed after birth. Septation of the large air saccules existing at birth has been considered as the main mechanism for alveoli formation. However, other undefined means of alveolarization have also been postulated to account for the large increase in gas-exchange surface area that takes place in the lung as the rat grows larger. Moreover, recent results show that the majority of alveoli in rat lung are formed by means other than septation of saccules existing at birth, but these mechanisms have not been identified up to the present. In this study, a mathematical model of alveolarization in rat lung is presented. The model is based on three postulates: (a) new saccules continue to be formed up to adulthood according to certain rules; (b) all these saccules subsequently septate generating a certain number of alveoli; (c) once formed, the saccules (and alveoli) do not change in volume, but newly-formed saccules are larger than the preceding ones according to a given law. The model accurately predicts the experimentally-known values at different ages of total alveolar volume, alveolar number, volume of the average alveolus, gas-exchange surface area, and alveolar volume distribution for normal rats and for rats in which septation is inhibited by treatment with dexamethasone or hypoxia during the early postnatal weeks of life.


Kin selection in density regulated populations.

The process of kin selection has both intra- and inter-group components (Hamilton, 1975, in: Biosocial Anthropology Wade, 1980). Group advantageous characteristics can evolve when inter-group differences in fertility are sufficiently great to overcome any within-group disadvantage of the trait. The potential magnitude of inter-group differences in fertility is determined largely by the way a population is regulated. Inter-group differences decrease as the spatial scale over which a population is regulated becomes increasingly localized. The present paper extends previous work by Boyd (1982, Anim. Behav. 30, 972-982) on the quantitative relation between kin selection and density regulation. A simple genetic model is employed to examine the conditions under which the interaction of local density regulation and kin selection can maintain a stable polymorphism. The ecological factors determining the spatial and temporal scale of density regulation are discussed. Finally, the results are applied to two biological cases in which local density regulation may be influencing the direction of phenotypic plasticity in group advantageous characters.


Neurite branching pattern formation: modeling and computer simulation.

A model for nerve cell pattern formation is proposed in this paper. The model is based on some experimental results and an assumption that there is a kind of inhibitive interaction between growing neurites on the same nerve cell. In this paper, this interaction is termed lateral inhibition. A group of ordinary differential equations are used to describe the elongation of the terminal neurite segments of individual nerve cells. Computer simulation and comparison of it with in vitro studies are also made in this paper.


[Thoracic radiography in Pneumocystis carinii pneumonia in AIDS patients. Presentation forms and clinical course].

We intend to determine the frequency of the different radiographic findings of Pneumocystis carinii pneumonia in patients with AIDS. We retrospectively review the chest roentgenograms of 30 patients at admission to the hospital (group I [n = 30]), at follow-up (group II [n = 30]) and after clinical recovery (group III [n = 15]). Diffuse bilateral interstitial disease was the most frequent radiographic finding at admission (76.6%) and at follow-up (60%). Atypical radiographic findings were: normal chest radiograph (group I [n = 3]), nodules (group I [n = 2], group II [n = 2], group III [n = 1]), thin wall cysts (group II [n = 1], group III [n = 1]), cavitated lesion (group II [n = 1], group III [n = 1]), pneumothorax (group II [n = 2], group III [n = 1]), pleural effusion (group III [n = 2]), asymmetrical distribution of the pulmonary lesion (group I [n = 2], group II [n = 3]) and predominant upper lobe involvement (group II [n = 1], group III [n = 1]). The atypical findings were greater during follow-up (group II [n = 33.3%], group III (46.6%) than at admission (group I [n = 23.4%]). It is important to know the frequency and multiplicity of the radiographic findings of Pneumocystis carinii pneumonia in order to establish the diagnosis and differentiation from other infectious diseases or other causes of pulmonary disease in patients with AIDS.


[Treatment of gram negative bacilli bacteremia with intramuscular ceftriaxone in home care].

Bacteremias by gram negative bacilli (BGNB) are serious diseases which normally require hospital admission. In accordance with the pharmacokinetic characteristics of ceftriaxone, the possibility of treating such processes with home care (HC) and the existence of advantages for both the patient and the hospital were evaluated. Twenty patients were prospectively studied. Upon obtaining clinical stability in the hospital the possibility of following home care (HC) treatment was evaluated. Ceftriaxone was administrated at intramuscular doses of 1g/24 h. The clinical and bacteriologic response, patient satisfaction and treatment time were estimated. The origin of the bacteremia was varied as was the type of gram negative bacilli responsible. All the patients evolved favorably with no relevant secondary effects. The mean length of treatment was 12.75 days per patient. The antibiotic was mainly administered at home (83%), permitting a mean reduction of 10.5 hospital stays per patient. The social and psychologic advantages for the patients were evident. This study confirms the possibility of treating stable phase gram negative bacilli bacteremias at home efficiently with the supervision of home care teams leading to a substantial reduction in hospital expenses and patient satisfaction.


[Epidemiology, clinical course++, prognosis and treatment of thrombocytopenia associated with human immunodeficiency virus type 1 infection: analysis of 41 cases].

Thrombocytopenia is one of the manifestations of infection by the human immunodeficiency virus-1 (HIV-1). A series of 41 patients were studied over a period of 2 years. The study was prospectively carried out with a control group of 80 patients with the epidemiology, clinical manifestations, prognosis and treatment of this process being evaluated. The risk groups were: intravenous drug users (IVDU) (78%), homosexuals (12%) and heterosexuals (7%), patients with thrombocytopenia as the only manifestation (group IV-E) constituted the largest group with 30 cases. In 50% of the patients both diseases (thrombocytopenia and HIV infection) were simultaneously diagnosed. Nine patients (22%) vs 35% in the control group evolved to more advanced stages of the infection. Only 39% of the cases had hemorrhagic manifestations being more frequent in the IV-E group (47%) than in the remaining patients (18%). With regards to treatment, only 1 case responded completely with danazol. Steroids had variable, although evaluable, results with minimum secondary effects. The infusion of gammaglobulins achieved 80% of complete, although transitory, responses. Zidovudine obtained a positive response in 17/25 cases. Finally, splenectomy was performed in three patients definitively resolving the thrombocytopenia. In thrombocytopenia associated with human immunodeficiency virus-1 (HIV-1) infection the distribution by groups of risk is equal to that of the rest of infected patients. Appearing early in the natural history of HIV infection, thrombocytopenia presents few clinical manifestations and does not constitute a factor of bad prognosis. The treatment of choice is zidovudine at doses of 500 mg/day.


[Still's disease in adults and polymyositis. An infrequent association].

A case of coexistence of adult onset Still's disease and idiopathic inflammatory myopathy is reported in a patient with antecedent of Graves-Basedow disease. Although myalgias are common during the flares of adult onset Still's disease, a review of literature only disclosed two previous cases of polymyositis associated to adult onset Still's disease. A high index of suspicion is needed in order to diagnose such a rare association which has relevant prognostic and therapeutic implications. Treatment with methotrexate was started in order to control myopathy, resulting in improvement of both polymyositis and adult onset Still disease. A possible role of methotrexate in the management of adult onset Still's disease is suggested.


[Predictive factors of mortality in severe craniocerebral trauma].

The prediction of mortality in severe head injury is of interest for the evaluation of patient prognosis and to also permit therapeutic measures to be considered and improve knowledge of this problem. A multiple logistic regression model was developed and validated from the data obtained from a series of 231 patients hospitalized for the above mentioned condition. Seventy-five percent of the patients were used to define the model with the remaining 25% validating the same. The variables included in the model were: intraventricular hemorrhage, odds ratio = 20.4 (confidence interval 95%: 3.56-116); compression of basal cistern and/or of the III ventricle, odds ratio = 11.5 (4.43-29.8); mydriatic pupils in both eyes, odds ratio = 5.71 (1.32-24.6); age, odds ratio = 1.03 (1.01-1.05) and Glasgow scale upon admission, odds ratio = 0.57 (0.43-0.75). The maximum global value of the model (84.9%) corresponded to a sensitivity of 84.5% and specificity of 85.2%. The cut-off point of probability of death was found to be 0.475. In the validation of the model the highest global value (84.2%) was also observed at the cut-off point of 0.475 with a sensitivity of 84.2% and specificity of 84.4%. The predictive factors of mortality in severe head injury are the evidence of hemorrhage in the cerebral ventricles, mydriasis and a low score on the Glasgow scale. The model presented is useful and valid for carrying out the prediction of mortality at the time of admission and is also easy to apply since the variables used are obtained in the initial examination of the patients with severe head injury.


[Experience with 150 subcutaneous venous reservoirs for venous access and infusion for the treatment of adult patients with oncologic and hematologic disorders and acquired immunodeficiency syndrome].

In the present study the year experience of a multidisciplinary team (oncologic, unit for the acquired immunodeficiency syndrome, and surgery) with the use of a new method of central intravenous administration of medication such as that of subcutaneous venous reservoirs (SVR) is reviewed. The subcutaneous injection capsules were implanted as a venous access in 150 surgical procedures in 146 patients from October 1985 to April 1991 with a total follow up of 29.190 days and a mean length of 251 days for SVR. Sixty-two percent (94 implantations) of the SVR were implanted in the out patient clinic, 20% (30 patients) were admitted for placement of the reservoir although this was only indicated in the first two years of the series, 13% (20 patients) during hospitalization for the base disease and only 4% (6 patients) were specifically admitted for surgical preparation (plasma, platelets, and others). SVR were used for chemotherapy (124 cases, 82%), repeated transfusions (6 cases, 4%) and chronic medication (acquired immunodeficiency syndrome, infections) (30 patients, 20%). Forty-two percent permitted chemotherapy administration by continual transfusion on an out patient regime. A series of mechanical complications (3 cases, 2%), septic (9 episodes in 7 patients, 5%) and thrombotic (8 of the catheter) (5%) and 4 of the central veins (2%) were observed. In the present series the rate of infections (5%) (0.072 episodes of bacteremia per 100 days/patient) and thrombosis (3%) was very low due to a strict protocol of maintenance and control by the medical team and hospital staff. The need for radiologic control during surgery is emphasized although, as demonstrated in the present review, the technique of localization by a cath-finder (external detector) permits greater speed with the same security. The degree of patient satisfaction and the minimum incidence of serious complications in determined risk groups (neutropenia, acquired immunodeficiency syndrome) demonstrates that subcutaneous venous reservoirs (SVR) constitute an excellent method as a chronic venous access. The SVR present a lower rate of complications if compared with any historic series of external vascular catheterization.


[Factors associated with hypoalphalipoproteinemia].

Hypoalphalipoproteinemia (HALP) is the most frequent lipid alteration found in patients with myocardial infarction at an early age. It is defined by amounts of lipid cholesterol at high density lipoproteins (cHDL) lower than 10% according to age and sex. The aim of this study was to know the frequency of main factors which reduce the levels of cHDL in a group of subjects with and without HALP. Pathological antecedents, consumption of drugs, alcohol and cigarettes, the presence of obesity and levels of cholesterol, triglycerides, cHDL, glucose and urea were studied in a group of 1825 males. The study was performed in the course of medical examinations for workers. The consumption of cigarettes, the index of body mass (IBM) and the prevalence of diabetes mellitus were higher in the group of subjects with HALP. Hypertriglyceridemia (triglycerides > or = 200 mg/dl) was found in 31% of the subjects with HALP vs 10% in the control group (p < 0.001); hypocholesterolemia (cholesterol < or = 150 mg/dl) was also significantly greater (9.8% vs 4.3%, p < 0.01). Altogether, in 64% of the subjects with HALP, factors which may decrease cHDL were associated. Of the factors studied, the number of triglycerides, IBM and the number of cigarettes consumed per day were the independent factors which most significantly contributed to the decrease of cHDL in the regression analysis. Most of the subjects with hypoalphalipoproteinemia present other modifiable factors such as an elevated index of body mass, cigarette consumption and high amounts of triglicerydes, the correction of which constitutes the base for treatment of this disorder.


[Influence of arterial pressure and plasma renin activity on tubular reabsorption of sodium].

With the aim of confirming the possible existence of an increase in the fractional proximal reabsorption of sodium in the development of essential hypertension, the tubular dynamics of sodium were compared by the lithium clearance technique in a group of hypertensive patients and controls. Following a week of drug suspension 186 patients with slight or moderate essential hypertension and 37 normal subjects with homogeneous sodium ingestion were studied. A clearing period of 90 minutes prior to the administration of a tracing doses of lithium was considered to calculate the fractional proximal and distal reabsorption of sodium in terms of glomerular filtration. In addition to global comparison of the measurements, the hypertensives were classified and compared according to mean arterial pressure (MAP) and percentages of plasma renin activity (PRA). No differences were found in tubular dynamics of sodium between hypertensive and normotensive patients. Neither did the degree of hypertension induce differences. However, upon classifying the patients according to PRA, it was found that those with PRA higher than 0.5 ng/ml-1/h-1 had less secondary natriuresis to a greater fractional distal reabsorption of sodium (p < 0.05). The findings of the this study do not support the possible existence of a primary defect of the transport of sodium in the proximal tubule in the origin and/or maintenance of essential arterial hypertension.


[Cervicobrachial fibromatosis presenting in the mother and the child simultaneously].

Fibromatosis is the proliferation of connective tissue with local infiltrative growth and a tendency to relapse in contrast with fibrosarcoma which never produces metastases. Two patients, a mother and son diagnosed with fibromatosis of initial cervical location in whom surgical extirpation and complementary radiotherapy were performed. The mother underwent polychemotherapy (adriamicine plus dacarbazine) because of extensive relapse. Definitive resolution was achieved in both cases.


[Renal transplantation in children: punction-aspiration biopsy and renogram with 99mTc-DTPA].

Renal transplantation in children raises numerous diagnostic problems. The renography obtained with diethyltriaminopentaacetic acid marked with (99mTc metastable technetium (99mTc-DTPA) was compared with fine needle aspiration biopsy (FNAB) in search of a better interpretation of post-transplant crisis: rejection, acute tubular necrosis, toxicity by cyclosporin A and infection. Sixteen acute post-transplant episodes were studied in 13 children submitted to renal transplantation. The post-transplant time was 6 days to 2.5 years. The basal renography and FNAB were carried out following the initial clinical manifestations and over a period of less than one week. The vascular and renographic phases were evaluated by interpreting the renography and were compared to previous renographies. The diagnosis of the aspiration biopsy was expressed as: normal, acute tubular necrosis, total necrosis, toxicity by cyclosporin A, viral infection and rejection. Results agreed in 14 out of 16 cases: 1 normal, 3 acute tubular necrosis by renography and cellular necrosis by cytology, 9 rejections and 1 infection (increase in renal transit time). In the 2 cases with total necrosis of 100% followed by loss of renal allograft, the renographic diagnosis was severe vascular rejection with a negative prognosis. In this series FNAB confirmed the renography as useful in the early diagnosis of complications which may appear in children undergoing renal transplantation.


[Psoas abscess: diagnostic and therapeutic usefulness of echography and computerized tomography].

Psoas abscess (PA) is a clinically infrequent entity. The abscess may form spontaneously (primary PA) or as a complication of contiguous infection (secondary PA). The use of ultrasonography (US) and computerized tomography (CT) facilitates diagnosis and treatment of a disorder which previously required surgery. Nineteen cases of PA diagnosed over the last 7 years were retrospectively studied. Confirmation of diagnosis was established by exteriorization of pus with US, CT or during surgery. Three primary PA (16%) and 16 secondary PA (84%) were diagnosed. The foci of origin of the secondary PA were: urologic (50%), rachydeal (25%), gastrointestinal (12.5%) and iatrogenic lumbar infection (12.5%). The most frequent germs in the primary PA were: Staphylococcus aureus (67%) and in the secondary PA, enterobacteriae (50%). The diagnostic profitability of US was 41% (7/17) and for CT was 100% (15/15). Percutaneous drainage was performed in 9 patients which failed in 2 cases due to compactness of pus (22%) and in another 2 because of undiagnosed osteomyelitis (22%). Two patients (10%) with underlying disease died despite adequate medical-surgical treatment. Psoas abscess were secondary in 84% of the patients studied with most being due to enterobacteriae. The diagnostic profitability of computerized tomography was greater than that of ultrasonography (100% vs 41%). Percutaneous drainage is a valid therapeutic alternative. Relapse observed in this study was due to previously undiagnosed osteomyelitis.


[Systemic chronic candidiasis following typhlitis caused by Candida albicans].

Typhlitis is an infrequent infectious complication which may appear during a period of intense granulocytopenia, generally in patients with acute leukemia. The most common causal germs are Gram negative bacilli although the importance of Candida sp. as an etiologic agent of this disease is ever more frequent. The case of a 14 years old patient with acute lymphoblastic leukemia who, after chemotherapy treatment, presented typhlitis by Candida albicans followed by chronic systemic candidiasis (CSC) is described. The role that Candida albicans may play in some cases of typhlitis is discussed as is the relation between the appearance of typhlitis and the posterior development of CSC.


[Rapid method for identifying Escherichia coli and species of the Proteeae tribe in urine].

To evaluate the possibility of using the determination of beta-glucuronidase and phenylalanine deaminase activity directly from urine samples for rapid detection (2 hours) of the presence of Escherichia coli and species of the Proteeae tribe. To detect beta-glucuronidase activity methyl-umbelipheryl-beta-D-glucuronic was used as a substrate. The presence of fluorescence after incubation at 37 degrees C for 2 hours indicated a positive reaction. While phenylalanine was used as a substrate for detecting phenylalanine deaminase activity, FeCl3 was added after incubation at 37 degrees C for 2 hours with a greenish color being observed indicating phenylalanine deaminase activity. The detection of Escherichia coli by beta-glucuronidase activity presented sensitivity and specificity of 0.91 and 0.99, respectively. The positive predictive value was 0.96 and the negative predictive value was 0.98, whereas the determination of the phenylalanine deaminase activity with the aim of detecting species of the Proteeae tribe presented the following results; sensitivity 0.92, specificity 0.99, positive predictive value 0.94 and negative predictive value 0.99. The determination of beta-glucuronidase and phenylalanine deaminase activities directly from urine sediment has been demonstrated as a rapid and specific test for detecting the presence of Escherichia coli and species of the Proteeae tribe, therefore it must be considered as a useful test in early diagnosis of urinary infection thereby facilitating the administration of appropriate antibiotic treatment.


[Anti-endothelial cell antibodies in systemic lupus erythematosus: association with vascular and renal lesions].

The aim of this study was to know the prevalence and characteristics of endothelial anticellular antibodies (EAA) in systemic lupus erythematosus and its relation with the clinical and immunologic manifestations of this entity. A prospective study of 50 patients (44 females and 6 males) diagnosed with SLE was carried out. EAA and anticardiolipin antibodies (ACA) were determined by the ELISA technique, lupic anticoagulant by coagulometric techniques, antinuclear antibodies by indirect immunofluorescence, anti-DNA antibodies by the Farr technique, anti-ENA by contra-immunoelectrophoresis and the complement values by radial immunodiffusion. The statistical study was carried out by chi-square test and Fisher test. Positive titers of EAA were observed in 29 (58%) of the patients with SLE. The patients with EAA presented greater prevalence of both, vascular lesions (31% vs 5%, P < 0.05) and kidney involvement (62% vs 29%, p < 0.05) than those without EAA. Patients with EAA also presented a higher prevalence of antiphospholipid antibodies than patients without EAA (59% vs 10%, p < 0.001). No association was found between EAA and the titers of antinuclear antibodies, anti-DNA, anti-ENA or complement levels. Endothelial anticellular antibodies appear with greater frequency in patients with systemic lupus erythematosus and are more often associated with vascular and kidney involvement and with the detection of antiphospholipid antibodies suggesting that they may play an etiopathogenic role in the production of these lesions.


[Low risk of acquiring the hepatitis C virus for the health personnel].

The hepatitis C virus (HCV) is transmitted by the same routes as that of hepatitis B (HBV) and that of the human immunodeficiency virus (HIV). Health care workers have been considered at risk although of different intensity for acquiring the HBV and HIV with the risk of acquiring the HCV being ignored. The presence of anti-HCV was investigated in 338 hospital workers, 110 proceeding from risk areas without direct contact with patients (laboratories and cleaning staff), 141 in direct contact and 87 with accidental risk (needle pricks or splashing of blood products) whom, at the time of the accident were anti-HCV negative. In the latter a minimum period of 6 months, which reached one year in 50% of the cases, elapsed to permit seroconversion. Three hundred seventy-seven healthy women were used as controls. The presence of anti-HCV was investigated with a second generation enzymoimmunoanalysis system confirming the results obtained with RIBA. The workers in zones of risk without direct patient contact presented global seroprevalence of anti-HCV of 1.8% with no statistical difference obtained between those who attended patients directly (1.4%) or the control group (2.1%). HCV transmission was not detected in any of the workers who experienced a high risk accident. The results concerning the study of the risk of health care workers to obtain hepatitis C suggest that the risk of transmission of the hepatitis C virus in these personnel is low.


[Retrospective evaluation of the effectiveness of the BCG vaccine campaign in newborns of Barcelona].

The aim of this study was to know the efficacy of the BCG vaccination campaign of the newborns of Barcelona carried out during the period from 1966-1974. To achieve this aim an epidemiologic investigation was undertaken by an observational analytical study of paired cases and controls. Two hundred and fifty randomly selected cases were studied between 1978-1988 from between 4-21 years of age during the study period. The cases were paired with 750 controls (1:3) with identical conditions and age, sex and place of residence. Statistical analysis of data was performed by the specific methods for this type of study. The estimated gross odds ratio was 0.68; the interval of confidence 95% and 0.51-0.91 (p < 0.025). The efficacy of this vaccination campaign was estimated as weak at 32%, in the age group and investigation time being greater in males and diminished with time. The percentage of new cases of tuberculosis potentially prevented by this campaign was calculated at 13%. The weak efficacy of the BCG vaccination campaign may be attributed not only to the unforeseen effects of this vaccine but also to the deficient operative aspects of the campaign itself.


[The evolution of mortality from ischemic heart disease in Basque Country 1975-1990].

Given the importance of ischemic cardiopathy (IC) as a cause of death in industrialized countries, the trend of mortality by IC in people from 30 to 69 years of age residing in the Basque Country between 1975-1990 were studied. Furthermore, the evolution of the mortality by cardiac diseases and by other causes which may compete with IC in the certification or coding of the cause of death was studied. The rate of mortality standardized by age by the direct methods were estimated from data from the Natural Movement of Population. The trend was graphically studied and quantified by means of the percentage difference between the rates. Mortality by IC decreased between 1975-1990 by 37% in men and 46% in women with a mean annual percentage decrease of 2.8% and 2.9%, respectively. Mortality by cardiac disease decreased 34% in men and 52% in women. Mortality by ischemic cardiopathy in the Basque Country has significantly decreased in both sexes. This decrease is not explicable by possible changes over the years in the practises of certification or coding of the cause of death.


[Evolution of mortality from principal chronic diseases in Spain 1975-1988].

Most mortality in developed countries is attributable to chronic non transmittable diseases, many of which are theoretically susceptible to prevention. The tendency of mortality by the principal chronic diseases in Spain is reviewed with different prevention strategies of the same being discussed. The 9 chronic diseases which presented the highest mortality rate in Spain in 1988 are included. The rates of mortality, adjusted by age/year in males and females was calculated from the data of deaths by age, sex and cause of death from death statistics. Moreover, the percentage of the mean annual change of these during the periods 1975-1981 and 1982-1988 have also been calculated. Except for mortality by malignant tumor of the colon and rectum, malignant lung tumor in males and malignant breast tumors in women, which had an increase, the remaining diseases in the adjusted mortality rate by age decreased between 1975-1988. Among the diseases in which the rate of mortality has increased there is only that of malignant lung tumors for which one factor has consistently been identified as responsible for this increase, that being smoking. The possible influence of the control of arterial hypertension in the decrease in mortality of cerebrovascular disease must be emphasized. Moreover, the impact which the ninth review of the International Disease Classification had in the reduction in mortality by chronic bronchitis, emphysema and asthma must also be pointed out.


[Incidence of hip fractures in Cantabria].

Fracture of the hip constitutes a serious social/health care problem with very little information concerning incidence in Spain being available. The diagnosis of hospital admissions and the diagnosis of release from the traumatology units of health care centers for acute patients in Cantabria were reviewed. The study was carried out from the 1st of January to the 31st of December 1988 and only included patients over 49 years of age. Patients who did not habitually reside in the region were excluded. The following data were collected in each case: age, sex, place of residence (urban or rural), time of the year, side fractured, type of injury, previous contralateral fracture and perioperative mortality. The rate of fracture referred to the population of more than 49 years of age was 277/100,000 in the case of females and 100/100,000 for males. The mean age of women was 80.4 +/- 8.5 years and of men was 76.9 +/- 10.9 years (p > 0.02), respectively. No differences were observed with regard to the place of residence or the time of year. The fracture was left sided in 61% of the females and 58% of the males. The injury was almost always due to a fall. Six percent of the patients had a previous contralateral fracture. Perioperative mortality was 6%. The incidence of hip fracture in Cantabria is similar to that of other regions in Spain and lower to that of parts of central and northern Europe and the United States.


[Serologic diagnosis of Lyme disease in patients with undifferentiated arthritis. Diagnostic problems].

Arthritis is a frequent manifestation of Lyme disease. The diagnosis of this disease is especially supported by serological techniques which however have false positives or negatives. The aim of this study was to establish the frequency of serologies positive to Borrelia burgdorferi in patients with non-filiated arthritis and in other well defined rheumatic diseases. A prospective study was performed to detect antibodies (AB) versus Borrelia burgdorferi in 43 patients with undifferentiated arthritis and in 100 patients with articular disease of precise diagnosis (rheumatoid arthritis, systemic lupus erythematosus, psoriasis arthropathy, and reactive arthritis/Reiter's syndrome). The technique was performed by indirect immunofluorescence and was repeated by enzymoimmunoassay in doubtful or positive results. Titers greater than 1/256 were considered as positive. Positive serology was found in two patients with undifferentiated arthritis and in one patient with Reiter's syndrome. None of the three patients referred the antecedent of erythema chronicum migrans. Positive serology was not observed in any of the patients with rheumatoid arthritis, systemic lupus erythematosus or psoriatic arthritis. A small proportion of patients with undifferentiated arthritis or Reiter's syndrome presented positive serology at low titers versus Borrelia burgdorferi with the interpretation of these results being difficult. The frequency of seropositivity in rheumatoid arthritis and systemic lupus erythematosus is very low.


[Poisoning by delayed-release verapamil in an uremic patient].

The appearance of toxic effects upon consumption of delayed release verapamil at therapeutic doses (120 mg/12 h) in a 64 year old patient with renal failure is described. The patient presented hypotension, bradycardia due to auriculoventricular block, hepatotoxicity, slight hyperglycemia, hyperpotassemia and metabolic acidosis with increased anionic gap. The picture remitted spontaneously with support treatment following discontinuation of the medication. The pathogenesis of the syndrome and the possibility that the hepatotoxicity was the triggering factor are discussed. Extreme precaution is recommended when this type of drugs is used in severe uremic or diabetic patients.


[Inadequate demand in a pediatric hospital emergency department: factors involved].

The massification of pediatric hospital emergency departments (PED) is due to bad use of the same by a large number of users. The causes related with this inadequate use have not been properly evaluated. A sample representative of the population demanding medical care in a PED of a regional hospital was studied with the motives and sociodemographic and cultural factors presumably related with this inadequate demand being analyzed. 52% of the cases had had no previous contact with the primary level of health care and 79% had gone to the PED on their own initiative. With regard to consultations, 65.0 +/- 4.8% were catalogued as inadequate and a statistical relation was found with the age of the patient (less than one year), place of residence (urban) and the arrival by initiative of the patients themselves. Pediatric hospital emergency departments receive a high number of inadequate consultations at the second level of health care. The importance of the age of the patient, accessibility of pediatric hospital emergency departments and who takes the initiative to come must be emphasized as predictive variables of the bad use of these pediatric departments.


[A new genetic technology makes the production of human monoclonal antibodies simpler].

New advances in DNA technology have enabled repertoires of antibodies to be cloned and expressed in bacteria (E coli), thus creating libraries of antibody DNA. In principle, heavy and light chain DNA is amplified from lymphocyte RNA and combined into vectors that enable antibody molecules to be expressed on the surface of phage particles which carry the DNA for the corresponding antibody in their genomes. The system constitutes an ideal tool for use in selecting even rare antibodies from libraries of millions. The new advances have greatly facilitated the generation of monoclonal antibodies against various substances. In particular, human monoclonal antibodies are now more easily obtained with DNA technology than with the methods previously used. Many of the antibodies generated with the new techniques were derived from lymphocyte RNA from immune donors, though the isolation of specific antibodies from libraries originating from donors who have never been in contact with the particular antigens has recently been reported. Moreover, the binding characteristics of the immunoglobulins isolated have subsequently been enhanced in vitro. Thus, modern antibody cloning techniques give promise of allowing the generation of a wide range of specific antibodies from a single, diverse library of antibodies kept 'on the shelf' in the laboratory, without needing to immunise humans or animals. The impact on biomedical science is likely to be profound, as specific reagents for use in research or therapy will be easily obtained, irrespective of whether human or other mammalian antibodies are required.


[Alzheimer's disease--an amyloid disease of the brain].

During recent years, Alzheimer's disease (AD) has attracted increasing interest among clinicians and neuropathologists throughout the world. The amyloid core of the neuritic plaques found in the brains of individuals with the disease has been shown to be composed of a distinct peptide formed through proteolytic degradation of a large precursor protein, the Alzheimer amyloid precursor protein (APP), which exists in at least three isoforms differing from each other in the splicing of the primary transcript from which they derive. Although the physiological function of APP remains unknown, it has been suggested to function as a protease inhibitor and to be important to the blood coagulation system. The gene encoding APP is located on the long arm of chromosome 21. Individuals with Down's syndrome (trisomy 21) often develop AD in early middle age, suggesting that the 50 percent increase in APP, gene expression may promote the development of the disease. Mutations in the APP gene have also been shown to be associated, probably pathogenetically with familial forms of AD. The conclusions drawn from these studies include (i) that the amyloidosis associated with AD is probably a central pathogenetic factor and (ii) that the development of drugs capable of inhibiting amyloidosis might be an appropriate strategy for the treatment of AD.


Magnetic resonance imaging: a new window into industrial processing.

Although the most important use of nuclear magnetic resonance imaging (MRI) continues to be for diagnostic medicine, recognition is being gained for many nonmedical applications. Examples include the following areas: petrogeology, food, agriculture, polymers and polymer-composites, and pharmaceuticals. These areas all involve studies of species that have short spin-spin relaxation times, and consequently need far fast gradient switching. These technical details are discussed and typical applications given.


In vivo NMR in pharmaceutical research.

In vivo NMR techniques are currently well established in pharmaceutical research and will likely become increasingly important in the future, as they procure noninvasively morphological, physiological, and biochemical information. The status of magnetic resonance imaging (MRI) and spectroscopy (MRS) in drug development is discussed on the basis of the characterization and evaluation of a rat model of ischemic stroke and the development and profiling of drugs for cerebral ischemia in this model. It can be concluded that MRI is well suited for drug screening (quantitative determination of lesion size), while dynamic MRI and MRS techniques provide relevant information on the mechanism of drug actions. The possibility to follow changes, pathological and therapeutic, in the same individual is important from two points of view. First, variations due to interindividual differences may be eliminated, increasing the statistical power of the results. Second, dose and/or time dependence of a drug can be explored in the same individual. As a result, the number of animals required for a study will be reduced, which from both ethical and economic aspects is highly desirable.


Spatially resolved NQR.

Pure nuclear quadrupole resonance (NQR) was combined with a rotating-frame imaging technique (rho NQRI). The method is suitable for powdery or crystalline materials containing quadrupole nuclei. The spatial information is encoded in the amplitudes of the free-induction decays (FIDs) by gradients of the radio frequency amplitude of the excitation pulse. The pulse length is incremented in a series of experiments so that a pseudo-FID can be formed from the intensities of a selected NQR line. A deconvolution procedure is used for the analysis of the pseudo-FIDs. The result is a sample profile along the gradient direction. The technique is particularly suitable for the detection of the spatial distribution of physical parameters producing NQR line shifts. Examples are stress or temperature. Two-dimensional images can be produced by rotating the sample step by step. For each orientation a profile across the sample is evaluated. A backprojection reconstruction formalism then permits the rendering of two-dimensional NQR images.


Magnetic resonance imaging: applications of novel methods in studies of porous media.

NMR imaging is finding broad applications in nonbiological areas including the study of fluid flow and fluid ingress in porous media. The porous media include at the one end mineral rocks and various building materials through various solid plastic materials to foodstuffs at the other end of the spectrum. The fluids within these various media range from crude oil and water mixtures, and water itself, to a range of organic solvents in plastic materials. This paper is concerned with the flow and ingress of water through Bentheimer sandstone and Ninian reservoir specimens, and also in solid nylon blocks.


Rapid line scan technique for artifact-free images of moving objects.

Moving objects (e.g., heart, lung, chest wall, etc.) typically cause artifacts to appear in two-dimensional Fourier transform ("spin warp") images. The rapid line scan (RLS) technique is a simple inexpensive technique that can rapidly produce artifact-free images of moving objects, without requiring enormous magnetic field gradients or periodic motions. The basic concepts and potential industrial applications of the RLS technique are described.


NMR imaging of solids with magic angle spinning.

Different aspects of solid state NMR imaging are reviewed, with emphasis on imaging in combination with line narrowing, especially in combination with magic angle spinning. Experimental results obtained with the latter technique are discussed, along with the implications of magic angle spinning on slice selection.


Lee-Goldburg solid-state imaging.

A new approach to solid-state imaging (SSI) is presented. The method relies on narrowing the resonance line using the Lee-Goldburg sequence. The technique is easy to implement in practice and may find widespread applications in materials science.


Partial cerebral ischemia assessed by "in vivo" 31P NMR spectroscopy in rats.

31P NMR spectroscopy was used to assess the cerebral ischemia status in rats by measuring the relative levels of phosphate metabolites. Partial cerebral ischemia was induced in 49 rats by reversible occlusion of the carotid arteries. Rats were intubated and mechanically ventilated on a hypoxic gas mixture. Physiological parameters such as temperature and arterial pressure were strictly controlled during the experiments. 31P spectra were acquired at 7 T during basal observation, for 15-20 min after the induction of ischemia, and for 1 hr after reperfusion. Depletion and increase in PCr and Pi levels, respectively, were already observable in the collected spectra within few minutes after the onset of ischemia. No appreciable changes were found in the ATP levels.


Magnetization filters: applications to NMR imaging of elastomers.

The general Fourier scheme for parameter selective imaging is subdivided into three periods: A preparation period for application of magnetization filters, an evolution period for space encoding, and a detection period for acquisition of the spectroscopic dimension. Depending on sample requirements and available time, the first and the last period can be omitted. Preparation of the initial magnetization for space encoding by appropriate filters is a powerful and time-saving way to introduce parameter-selective image contrast. This is illustrated by filters of molecular dynamics, which are sensitive to segmental motion in different time windows for contrast enhancement in composite and aged elastomers. Further contrast amplification is achieved by computing the difference of images acquired with different filter settings.


Multiple pulse NMR imaging of polymers and chemistry.

Multiple pulse line narrowing techniques can be used to improve resolution and sensitivity in solid state NMR imaging. For example, pulse sequences which remove homonuclear dipolar broadening have been used to image proton-containing materials. Further enhancements in resolution and sensitivity are obtained by removing inhomogeneous interactions such as chemical shift, susceptibility, and heteronuclear dipolar broadening. Pulse sequences have been designed which provide efficient line narrowing over large spectral widths by taking into account the experimenter's control over the amplitude and time dependence of the gradient-induced resonance offset. These methods have been applied to centimeter sized samples to obtain images of polymers, composite materials, and gas-solid chemical reactions. T1 and T2 contrast allows differentiation between materials.


Proton spin lattice relaxation in aromatic polymers.

The most striking requirement for the NMR imaging of an object is that this object should be made with components having different NMR parameters. In most cases these parameters are due to the presence of a fluid and to its mobility, thus measurable parameters are proton signal intensity contrasted in T1 or T2. From the glass transition temperature Tg, by decreasing the temperature, all nonaromatic polymers as well as any well degassed polymers, show a continuous increase of their proton spin-lattice relaxation, which at low temperature is usually larger than 10-20 sec. However, due to O2 molecules selectively adsorbed on aromatic rings, non-degassed aromatic polymers show a marked shortening of the proton spin-lattice relaxation. This effect is maximal at rather low temperature, where T1 can be shorter than 1 msec, and in many known cases shorter than 500 msec. Since the amount of sorbed-O2 is a function of the chemical nature of the polymer, the type of crystallinity (polymorphism of semicrystalline polymers), the crystalline-amorphous ratio, and so on, a careful study of T1 relaxation as a function of the temperature can define optimal conditions for T1 contrast. Examples regarding polymorphism in syndiotactic polystyrene, butadiene-styrene block copolymers and blends, and poly(phenylene) oxide, will be discussed.


Potential industrial applications of inhomogeneous broadening imaging.

Variations in magnetic susceptibility at air-water interfaces can result in inhomogeneous broadening of the NMR line. By special asymmetrical imaging techniques, originally developed for lung imaging, images can be formed of only those molecules that experience this inhomogeneous broadening. The basic concepts and latest developments in inhomogeneous-broadening-imaging techniques are described. Potential industrial applications are also discussed.


Special-purpose MRI equipment for medical and industrial applications.

A brief survey of the permanent magnet design techniques that are made possible by the availability of modern magnetic materials is followed by experimental results and some consideration of their practical applicability to the realization of MRI magnets.


Quantitative NMR imaging of multiphase flow in porous media.

Quantitative description of multiphase flow in porous media and local saturation distributions at steady states are of fundamental importance for petroleum recovery. The use of MRI provides an unprecedented means for obtaining such information. In this paper, profile imaging techniques for quantitative evaluation of fluid saturations during flow experiments in porous media are developed. The procedures for overcoming problems arising from very short, fluid saturation-dependent and spatial variation of T2, which are common in porous media, were addressed. The general methods developed should also be applicable to similar inhomogeneous biological systems. Experimental NMR imaging measurements of two-phase displacement were conducted in several limestones and sandstones representing various different types of pore structures, including a macroscopically homogeneous structure, a laminated structure, and a sample that exhibits porosity at different scales. The advantages of using each different type of profile imaging sequence to investigate flow in different types of porous structures are demonstrated. Images showing many features of multiphase flow, including nonuniform flow through different bedding structures, are obtained during the flow experiments. The use of profile images for obtaining many important petrophysical properties, such as permeability, porosity, saturation, and pore structural information, is discussed.


Quantitative measurement and imaging of transport processes in plants and porous media by 1H NMR.

NMR and MRI have been applied to transport processes, that is, net flow and diffusion/perfusion, of water in whole plants, cells, and porous materials. By choosing proper time windows and pulse sequences, magnetic resonance imaging can be made selective for each of the two transport processes. For porous media and plant cells the evolution of the spatial distribution of excited spins has been determined by q-space imaging, using a 20 MHz pulsed 1H NMR imager. The results of these experiments are explained by including spin-relaxation and exchange at boundaries. A 10 MHz portable 1H NMR spectrometer is described, particularly suitable to study the response of net flow in plants and canopies to changing external conditions.


Immiscible fluids permeability by T1 imaging.

Soil pollution by hydrocarbon compounds is an important part of the more general pollution problem. Some analogies with research problems encountered in studies of oil reservoirs in rocks suggested to us the opportunity to study the pollution dynamics by imaging the spatial distribution of the pollutant in a wet soil model by an NMR imaging technique. Some preliminary results using T1-weighted imaging are reported here.


Diffusion and spatially resolved NMR in Berea and Venezuelan oil reservoir rocks.

Conventional and spatially resolved proton NMR and relaxation measurements are used in order to study the molecular motions and the equilibrium and nonequilibrium diffusion of oils in Berea sandstone and Venezuelan reservoir rocks. In the water-saturated Berea a single line with T*2 congruent to 150 microseconds is observed, while the relaxation recovery is multiexponential. In an oil reservoir rock (Ful 13) a single narrow line is present while a distribution of relaxation rates is evidenced from the recovery plots. On the contrary, in the Ful 7 sample (extracted at a deeper depth in a different zone) two NMR components are present, with 3.5 and 30 KHz linewidths, and the recovery plot exhibits biexponential law. No echo signal could be reconstructed in the oil reservoir rocks. These findings can be related to the effects in the micropores, where motions at very low frequency can occur in a thin layer. From a comparison of the diffusion constant in water-saturated Berea, D congruent to 5*10(-6) cm2/sec, with the ones in model systems, the average size of the pores is estimated around 40 A. The density profiles at the equilibrium show uniform distribution of oils or of water, and the relaxation rates appear independent from the selected slice. The nonequilibrium diffusion was studied as a function of time in a Berea cylinder with z axis along H0, starting from a thin layer of oil at the base, and detecting the spin density profiles d(z,t) with slice-selection techniques. Simultaneously, the values of T1's were measured locally, and the distribution of the relaxation rates was observed to be present in any slice.(ABSTRACT TRUNCATED AT 250 WORDS)


Paramagnetic water proton relaxation enhancement: from contrast agents in MRI to reagents for quantitative "in vitro" assays.

The use of stable complexes of paramagnetic metal ions as probes in analytical applications of the NMR technique is discussed. Two examples are given that involve the determination of the total Fe3+ content of human serum transferrin (Tf) and the extent of glycation of human serum albumin (HSA). The method is based on the measurement of the longitudinal water proton relaxation times, conveniently altered following a selective chemical interaction between the substrate and the paramagnetic probe.


Copper-D-penicillamine complex as potential contrast agent for MRI.

In vitro and in vivo proton T1 data are reported that demonstrate that the paramagnetic copper-D-penicillamine complex can be applied as a potential contrast agent to magnetic resonance imaging.


Quantitative estimation of brain white matter abnormalities in elderly subjects using magnetic resonance imaging.

Twenty-five elderly subjects were examined with brain magnetic resonance imaging (MRI). The subjects were divided into two groups: those with Mini-Mental State Examination (MMSE) scores above 25, and those subjects with MMSE scores between 18 and 24. The degree of white matter abnormalities (WMA) (expressed as relative volumes) as well as the presence of cerebrovascular risk factors were evaluated in the two groups. We found that a) subjects with low MMSE scores had significantly larger relative volumes of WMA than the subjects with higher scores, b) a significant correlation (rs = 0.53, p < 0.009) between MMSE scores and the relative volume of WMA was also established, and c) a weak significant correlation (rs = -0.51, p < 0.05) between arterial blood pressure and WMA was found in the subjects with high MMSE scores. Besides these findings no other correlations between the presence of cerebrovascular risk factors and WMA were found in any of the groups.


Identification of patients with hereditary haemochromatosis by magnetic resonance imaging and spectroscopic relaxation time measurements.

A total of 4302 healthy blood donors were screened for elevated serum ferritin and transferrin saturation. Fifteen had increased serum ferritin at a follow-up examination. Five relatives of these donors also entered the study. Eleven patients had elevated liver iron concentrations, while five had normal liver iron concentrations. The R2 relaxation rate in the liver was first measured with a conventional multi-spin-echo imaging sequence, and then by a volume-selective spectroscopic multi-spin-echo sequence, in order to achieve a minimum echo time of 4 msec. No correlation was found between the relaxation rate R2 and the liver iron concentration, when R2 was calculated from the imaging data. Multi-exponential transverse relaxation could be resolved when the spectroscopic sequence was used. A strong correlation between the initial slope of the relaxation curve and the liver iron concentration was found (r = 0.90, p < 0.001). Signal intensity ratios between liver and muscle were calculated from the first three echoes in the multi-echo imaging sequence, and from a gradient echo sequence. A strong correlation between the logarithm of the signal intensity ratios and the liver iron concentration was found. Although both spectroscopic T2 relaxation time measurements and signal intensity ratios could be used to quantify liver iron concentration, the gradient echo imaging seemed to be the best choice. Gradient echo imaging could be performed during a single breath hold, so motion artifacts could be avoided. The accuracy of liver iron concentration estimates from signal intensity ratios in the gradient echo images was about 35%.


Cine MR voiding cystourethrogram in adult normal males.

Cine voiding cystourethrogram was performed in 15 normal subjects using T1-weighted Turbo FLASH sequence. It showed the sequence of emptying of bladder, detrusor muscle contraction, opening of the sphincters, and various parts of urethra. It was found to be a good noninvasive test to study the dynamics of lower urinary tract without disturbing the state of the physiology.


Outflow refreshment angiography: a bright blood, bright static tissue technique.

A new "bright blood" strategy, outflow refreshment imaging, is introduced in which a number of overlapping slices are excited in rapid succession. Flowing spins that refresh each overlapped slice portion contribute a bright signal. Additionally, static tissue in each non-overlapped slice portion also yields a bright signal. However, the flow/static contrast is comparable to that produced in inflow refreshment images, and angiograms can be generated by conventional maximum intensity projection processing. The dual ability to visualize angiograms and static tissue images is a major benefit of the strategy. Computer simulations of flow sensitivities and in vivo results are presented which compare the outflow and inflow refreshment imaging strategies.


Magnetic resonance imaging and pulsed Doppler sonography of poststenotic jets: correlation between signal void and flow velocity distribution.

To correlate the appearance of poststenotic jets on gradient echo images with features of localized Doppler spectra of the jets, we studied an in vitro model of steady flow-through stenoses of 86, 96, and 99% area reduction. As fluids, water and a 40% glycerol solution in water were used. MRI was performed with a 1.5 T whole body imager and gradient echo images were obtained in planes parallel to the direction of flow. Doppler spectra were acquired separately from the MR measurements at 1 cm intervals for a distance of 10 cm downstream from the stenosis. Poststenotic signal void was observed for water and for the 40% glycerol solution only if the mean velocity within the stenosis exceeded a limit of 50-60 cm/sec. On the MR images, the jets could be divided into two segments: A proximal jet segment of uniform width equal to the diameter of the stenosis, followed by a distal jet segment which was characterized by broadening and then dissipating signal void. Except for the 99% stenosis, a high signal intensity core was present within the proximal jet segment. In the proximal jet segment, the Doppler measurements showed a low temporal fluctuation of the maximal flow velocity and only little flow opposite to the main flow direction. In the distal jet segment, the velocity fluctuation and the intensity of reverse flow increased sharply. The high signal intensity core of the jet was associated with a poststenotic zone of constant maximal flow velocity. The results demonstrate a close relationship between characteristic features of poststenotic jets in MRI and pulsed Doppler sonography.


Evaluation of two new gadolinium chelates as contrast agents for MRI.

Two new gadolinium chelates were investigated for potential use as tissue-specific contrast agents for magnetic resonance imaging. In vitro measurements of stability constants, octanol/water partition coefficients and relaxation times in solutions of water and human serum albumin (HSA) were performed with each new chelate and compared with gadolinium-diethylenetriamine pentaacetic acid, Gd(DTPA). Biodistribution studies and magnetic resonance imaging in rats were used to evaluate the new chelates in vivo. The stability constants (log K) of gadolinium-N,N''-bis(3-hydroxy-6-methyl-2- pyridylmethyl)diethylenetriamine-N,N',N''-triacetic acid, Gd(DTTA-HP), and gadolinium-1,7,13-triaza-4,10,16-trioxacyclooctadecane-N,N', N''-triacetic acid, Gd(TTCT), were determined to be 23.65 and 18.07, respectively. These can be compared to a literature value of 22.46 for Gd(DTPA). Octanol/water partition coefficients for both complexes showed they were more lipophilic than Gd(DTPA). Gd(DTTA-HP) exhibited a smaller relaxivity in water but a larger relaxivity in 4% HSA than Gd(DTPA). Gd(TTCT) exhibited a lower relaxivity than Gd(DTPA) in both water and 4% HSA. Both complexes showed similar biodistributions to Gd(DTPA) no carrier-added concentrations. Gd(DTTA-HP) had a greater percent change in signal intensity than Gd(DTPA) on T1-weighted spin-echo images in the heart, liver, and kidney. Percent change in signal intensity for Gd(TTCT) was lower than Gd(DTPA) in heart, liver, and kidney.


MRI contrast-dose relationship of manganese(III)tetra(4-sulfonatophenyl) porphyrin with human xenograft tumors in nude mice at 2.0 T.

Previously we reported that Mn(III)tetra(4-sulfonatophenyl) porphyrin, MnTPPS4, is a contrast agent which can effectively enhance tumor detection by MRI. By imaging 30 additional athymic nude mice bearing subcutaneous MCF-7 WT human breast carcinoma xenografts, we have extended dose-contrast relationships over a wide range of intraperitoneal (IP) doses ranging from 0.025 to 0.50 mmol/kg. The benefits of IP injection are higher possible doses on a volume basis and a reduction in toxicity versus IV administration. Full coronal cross-section images have been obtained on a 2-T spectrometer. Although individual tumor masses displayed different distribution patterns, reflective of their internal morphology, single doses of 0.10 mmol/kg or greater were necessary to produce a detectable effect. At a dose of 0.50 mmol/kg, marked enhancement was produced. Multiple small dosages administered over the course of several days before imaging did not produce increased enhancement. Preliminary results on the new porphyrin derivative, MnTPPS3, indicate that the ratio of the toxic dose to the effective dose may be adjustable to render this class of agents clinically useful.


Surface coil imaging of rat spine at 7.0 T.

An inductively coupled surface coil for imaging the rat spine at 7 T is described. This planar circular probe was made from microwave substrate to limit the size of the coil and to minimize the magnetic susceptibility. The surface coil was used as a single transmit/receive coil and as a receive-only coil with a birdcage body coil for excitation. The signal-to-noise ratio (SNR) of the probe was compared to a 5-cm birdcage coil and exceeded the birdcage coil's SNR by three to six times at superficial structures. The main advantages of the probe are an improved SNR for superficial structures and a simple design and use. Images with 50 x 50 x 500 micron voxels were obtained of the rat spine with excellent anatomical detail.


In vivo NMR T2 relaxation of experimental brain tumors in the cat: a multiparameter tissue characterization.

Experimental gliomas (F98) were inoculated in cat brain for the systematic study of their in vivo T2 relaxation time behavior. With a CPMG multi-echo imaging sequence, a train of 16 echoes was evaluated to obtain the transverse relaxation time and the magnetization M(0) at time t = 0. The magnetization decay curves were analyzed for biexponentiality. All tissues showed monoexponential T2, only that of the ventricular fluid and part of the vital tumor tissue were biexponential. Based on these NMR relaxation parameters the tissues were characterized, their correct assignment being assured by comparison with histological slices. T2 of normal grey and white matter was 74 +/- 6 and 72 +/- 6 msec, respectively. These two tissue types were distinguished through M(0) which for white matter was only 0.88 of the intensity of grey matter in full agreement with water content, determined from tissue specimens. At the time of maximal tumor growth and edema spread a tissue differentiation was possible in NMR relaxation parameter images. Separation of the three tissue groups of normal tissue, tumor and edema was based on T2 with T2(normal) < T2(tumor) < T2(edema). Using M(0) as a second parameter the differentiation was supported, in particular between white matter and tumor or edema. Animals were studied at 1-4 wk after tumor implantation to study tumor development. The magnetization M(0) of both tumor and peritumoral edema went through a maximum between the second and third week of tumor growth. T2 of edema was maximal at the same time with 133 +/- 4 msec, while the relaxation time of tumor continued to increase during the whole growth period, reaching values of 114 +/- 12 msec at the fourth week. Thus, a complete characterization of pathological tissues with NMR relaxometry must include a detailed study of the developmental changes of these tissues to assure correct experimental conditions for the goal of optimal contrast between normal and pathological regions in the NMR images.


A study of T1-weighted 31phosphorus MR-spectroscopy from patients with focal and diffuse liver disease.

31P-MR-Spectroscopy was performed in 28 patients with focal (n = 23) and diffuse (n = 5) liver disease and in 18 healthy volunteers. The spectra were obtained with a whole body scanner operating at 1.5 T by using a surface coil. To get T1-weighted 31P-spectra a short TR of 600 msec was taken, because T1-weighted spectra of focal liver disease were more significantly different from spectra from healthy volunteers than density weighted ones. The VOI from patients with focal superficial alterations showed a mean volume of 172 ml, with diffuse liver disease 196 ml, and from volunteers 158 ml. Focal tumors filled up the VOI on an average of 70%. This investigation demonstrated that PME/beta-ATP- and PDE/beta-ATP-ratios were sensitive indicators for focal liver disease. As a result of this study we could establish a significant increase of PME/beta-ATP- (0.75 +/- 0.30) and PDE/beta-ATP-ratios (1.68 +/- 0.62) in patients with superficial focal liver metastases (n = 19) compared to the control group (PME/beta-ATP: 0.49 +/- 0.17, PDE/beta-ATP: 1.24 +/- 0.24; t-test: p < 0.02). Patients with a hemangioma (n = 1), liver infarction (n = 1), empyema of gallbladder (n = 1) and a hepatic involvement by a malignant lymphoma (n = 1) showed a similar increase of PME/beta-ATP and/or PDE/beta-ATP. Up to now spectral changes seemed to be non-specific. The ratios of 31P metabolites of the cirrhoses (n = 4) and the fatty liver (n = 1) did not show any characteristic changes versus the volunteers.


Localized in vivo 1H spectroscopy of human skeletal muscle: normal and pathologic findings.

To obtain high signal to noise ratio in small volume elements (8 cm3), in vivo 1H NMR spectroscopy of normal and diseased human skeletal muscle was performed using a double spin-echo localization method on a 1.5-T whole body system. High resolved spectra of normal calf muscle show the well known resonances of lipids (methyl, methylene, olefinic, and other fatty acid resonances), creatine/phosphocreatine, choline/carnitine, taurine, and histidine with good intraindividual reproducibility. Pronounced intraindividual differences in the lipid range were found between different upper thigh muscle groups. On pathologic conditions like myopathy, myositis or irradiation damage the spectral lipid content was increased. Three months after local irradiation of the medial vastus muscle (50 Gy), the localized 1H NMR spectrum showed a complete loss of the choline and creatine signals. In a case of M. Behçet with muscular involvement the relative reduction of the choline signal may provide an insight in the pathobiochemistry. The results of our investigations in nine healthy volunteers and three patients are presented in detail including relaxation times of the metabolites.


Three-dimensional 1H spectroscopic imaging of cerebral metabolites in the rat using surface coils.

Three dimensional metabolite maps of protonated metabolites were obtained using 1H magnetic resonance spectroscopic imaging at 7 T. Surface coils were used to increase sensitivity and spatial resolution significantly over a volume coil two-dimensional acquisition. Adiabatic pulses were employed to provide homogeneous B1 excitation and frequency selective refocusing over the volume of the rat brain. These techniques were employed to obtain three-dimensional spectroscopic imaging spectra from nominal voxel volumes of 9-30 microliters from rat brain. The improved spatial resolution and sensitivity are also demonstrated with studies of focal ischemia in the rat.


Noninvasive in vivo 13C-NMR spectroscopy of a 13C-labeled xenobiotic in the rat.

This study demonstrates that the xenobiotic product, 1-(o-chlorophenyl)-1-(p-chlorophenyl)-2,2-dichloro-3-13C-propane can be monitored in the liver of an intact animal by in vivo 13C surface coil NMR spectroscopy after intraperitoneal administration. The carbon-13 label could be detected after a single dose of only 200 mg/kg of the product. The intrahepatic changes of the signal intensity of the labeled product were monitored as a function of time. No signals corresponding to metabolites could be detected.


In vivo relaxation of N-acetyl-aspartate, creatine plus phosphocreatine, and choline containing compounds during the course of brain infarction: a proton MRS study.

Localized water suppressed proton spectroscopy has opened up a new field of pathophysiological studies of severe brain ischemia. The signals obtained with the pulse sequences used so far are both T1 and T2 weighted. In order to evaluate the extent to which changes in metabolite signals during the course of infarction can be explained by changes in T1 and T2 relaxation times, eight patients with acute stroke were studied. STEAM sequences with varying echo delay times and repetition times were used to measure T1 and T2 of N-acetyl-aspartate (NAA), creatine plus phosphocreatine (Cr+PCr) and choline containing compounds (CHO) in a 27-ml voxel located in the affected area of the brain. Ten healthy volunteers served as controls. We found no difference in T1 or T2 of the metabolites between the patients and the normal controls. The T2 of CHO was longer than that of NAA and Cr+PCr. Our results indicate that spectra obtained in brain infarcts and normal tissue with the same acquisition parameters are directly comparable with respect to relative signal intensities as well as signals scaled with internal and external standards.


Tissue characterization by image processing subtraction: windowing of specific T1 values.

A method for windowing specific T1 values is presented. A 1.0 T imager with two routine pulse sequences was employed: A T1-weighted spin echo (SE) sequence and a short tau inversion recovery STIR sequence (fat-suppressed IR). A T1 window for fat was obtained by subtracting the STIR image from the SE image. Negative values were coded black. The method was tested on a normal human thigh, on a human liver with confirmed fatty infiltration, and on the livers of four live burbots. The fat-containing tissues of the two human volunteers were well depicted. The differences in fat concentration among the burbot livers were also clearly shown. The fat intensity seen in the images correlated well with the chemically measured fat concentration. This subtraction method for windowing T1 values proved feasible for fat. The method could be used for tissues with other short T1 values as well.


MR of an adrenal pseudocyst.

We describe the appearance of an adrenal pseudocyst on MRI and CT. The MR characteristics of the lesion were noteworthy in that the lesion had two components with different imaging characteristics. The larger component was of low signal intensity on both T1- and T2-weighted images and might have been confused with an adrenal adenoma.


Physician estimates of substance abuse in Baltimore and Cumberland: 1991.

By identifying and counseling substance abusers within their own practices, primary care physicians can play a major role in reducing levels of substance abuse. How proficient area physicians are in identifying substance abuse is examined by comparing physician estimates of substance abuse in their patient populations with local and national statistics.


Functional improvement in geriatric trauma patients admitted to a dedicated rehabilitation hospital.

A retrospective study was undertaken of trauma patients over 55 years of age who were admitted to a rehabilitation hospital during an 18-month period. Significant risk factors for poorer in-hospital improvement in functional independent measures were male sex, having an offspring listed as next of kin, pre-injury diabetes mellitus and/or dementia, and number of co-morbidities. Being married was found to be protective.


Ophthalmomyiasis externa: a case report.

A three-year-old white male presented with an extremely painful abscess of the nasal portion of the right upper eyelid. A larva identified as family Cuterebridae, genus Cuterebra sp, was removed from the abscess, permitting its rapid resolution. This represents an unusual patient with external ophthalmomyiasis who enjoys excellent nutritional and environmental surroundings.


Two centuries of medical organization and licensure in Maryland.

In 1766, the first American medical society was established in New Jersey. It was not until 1968, more than 200 years later, that the state medical societies would finally mold a satisfactory means of medical qualification and licensure.