[Pneumothorax in multiple trauma. Radiologic and CT study]. This study was aimed at evaluating the necessity to perform chest Computerized Tomography (CT) in multiple traumatized patients to diagnose pleuropulmonary lesions and, particularly, pneumothorax: the correct identification of this condition, although minimal, is important especially in prevision of long anesthesias and/or positive end-expiratory pressure (PEEP) therapy. This assisted respiratory technique improves arterial oxygenation but causes a barotrauma which may cause some complications; particularly, a small undetected pneumothorax can suddenly increase so as to cause pulmonary collapse with sometimes dramatic symptoms. Chest X-ray films and CT scans, performed in rapid succession on patient's admission in Emergency Ward, were compared in 21 subjects. CT is indispensable in case of severe chest parietal lesions which can mask the radiological evidence of pulmonary or pleural conditions, as it occurred in 3 of our cases. Moreover, CT resulted more reliable than chest X-rays (18 versus 10 correct diagnoses) especially in the detection of small antero-inferior pneumothorax flaps, in which direct radiological signs cannot be identified, in default of radio-geometrical assumptions. Indirect radiological signs of pneumothorax must be recognized but critically considered in order to avoid over-staging.


[Radiologic characteristics of the thorax during therapy with interleukin-2]. Interleukin-2 is a glycoprotein physiologically produced by human lymphocytes which is capable of mediating some still unknown immunologic reactions. In vitro, interleukin-2 was seen to induce a lytic reaction against tumor cells through the activation of a cytolytic system of natural killer cells. If administered to man in heavy doses, it causes a clinical response in the treatment of metastases from melanoma and renal cell carcinoma in 20-40% of cases. However, the clinical use of the drug, in therapeutic doses, is prevented by the occurrence of several side-effects, the major one being increased permeability of alveolar vessels with capillary leak and interstitial pulmonary edema (Vascular Leak Syndrome in the English literature). Thus, this work was aimed at evaluating chest radiographs during interleukin-2 treatment to detect, in the pulmonary district, the early stages of the vascular leak syndrome--i.e., pulmonary edema, pleural and pericardial effusions. Forty-three patients had been treated for metastases from renal cell carcinoma and melanoma November 1989 through September 1991: standard chest radiographs demonstrated 26 cases (60%) of pulmonary edema, 14 cases (32%) of bilateral pleural effusions and 12 cases (27%) of pericardial effusions. Daily chest films of the patients undergoing interleukin-2 therapy allowed the early stage of the vascular leak syndrome to be depicted, thus enabling the physician to use the highest tolerated doses and eventually to stop infusion before marked respiratory distress develops.


[Bronchogenic carcinoma staging: comparison of magnetic resonance/computerized tomography]. The staging of bronchogenic carcinoma is an important factor to select the appropriate treatment. Indeed, the definition of locoregional spread and of hilar and mediastinal node involvement is essential for both correct preoperative assessment and prognostic evaluation of bronchogenic carcinoma. CT and MR imaging are the methods of choice in the evaluation of T and N, even though other techniques--e.g., US and nuclear medicine--can also provide valuable diagnostic information. The authors examined 50 patients with primary bronchogenic carcinoma by means of plain radiographs, CT and MR of the chest. MR and CT findings were compared with surgical results on the basis of TNM classification. In the evaluation of T, sensitivity and specificity were 66% and 88.6%, respectively, for CT and 76% and 92% for MR imaging. No statistically significant differences were found between the two imaging methods (p = 0.19). In the evaluation of N, sensitivity and specificity were 56% and 78%, respectively, for CT and 76% and 88% for MR imaging. A statistically significant difference was found between MR and CT accuracy rates (p = 0.934). CT and MR results were in disagreement especially in the evaluation of hilar lymph nodes. To date, MR imaging cannot be considered a substitute for or a routine adjunct to CT in the staging of bronchogenic carcinoma due to its poor spatial resolution, to the presence of artifacts (especially with high-intensity fields), its cost and limited availability. However, in the evaluation of specific anatomical regions--e.g., the pulmonary apex and the peridiaphragmatic region--MR can provide more diagnostic information than CT thanks to its multiplanarity and better contrast resolution.


[Echography in the diagnosis of patellar instability]. The authors examined with US the femoropatellar relationship on the lateral aspect of the knee in 20 patients (40 knees) with clinical symptoms of patellar instability; 20 healthy subjects (40 knees) were also studied as a control group. US examinations were performed with a 7.5 MHz probe, positioned perpendicular to the lateral aspect of the knee on a plane passing through femoral epicondyle and the middle third of patella. The results were compared with those obtained by means of conventional radiologic techniques and CT. US was useful to show lateral shift of patella, also in fully extended or in 30 degrees flexed knees-i.e., in the cases where conventional radiology meets with the greatest difficulties. CT is much more accurate but certainly more expensive and often not available. With progressive flexion of the knee, the gradual medialization of patella can be followed, which will be complete at a variable degree of flexion according to the initial lateral shift.


[Role of computerized tomography in the densitometric assessment of lithiasis of the gallbladder]. Radiolucent gallstones frequently contain significant calcium deposits. Their detection is important to select the patients to submit to medical gallstone dissolution. Since CT facilitates the identification of calcifications undetected at conventional radiologic procedures, 60 patients were studied with CT. All of them had US confirmation of cholelithiasis and in the whole of cases an X-ray examination of the right upper abdominal quadrant was performed (for the identification of radiopaque stones), together with oral cholecystography (to evaluate gallbladder function). CT attenuation values of the stones were measured and the patients subsequently divided into 2 groups; the threshold value was 50 HU: below it, the stones were considered hypo- or isodense (group I); above it, they were considered hyperdense (group II). Later on, 28 patients (14 from group I and 14 from group II) were selected for chemical dissolution with ursodeoxycholic acid over a 1-year period. US examinations were performed at 6 and 12 months. Seventy per cent of the patients in group I responded to treatment (50% with complete stone dissolution and 20% with partial dissolution), whereas no patient in group II had complete dissolution and only 30% had partial response.


[Liver transplantation: diagnostic imaging in the preoperative assessment]. The correct selection of patients for liver transplantation, which is essential for surgical success, requires thorough radiological evaluation. The authors present their experience on 94 pretransplant adult patients that underwent a total of 251 diagnostic exams (Doppler US, CT, angiography and cholangiography) and interventional radiology maneuvers (biopsy, chemoembolization, biliary drainage). Three sclerosing cholangitis, 3 Budd-Chiari syndromes and 20 hepatocellular carcinomas in cirrhotic patients were identified; venous collaterals were present in 62.7% of the cases, 12.8%, of which had important spontaneous porto-systemic shunts; 6 patients had portal thrombosis; 20 arterial variations were found. Interventional maneuvers were useful and free of complications. US, CT and angiographic findings of each patient were compared. Integrating informations from different exams allowed a significant increase in the accuracy of diagnostic conclusions. Thanks to interventional maneuvers 5 patients could be selected for transplantation (hepatic arterial lipiodolization stopped the growth of 4 hepatic neoplasms; 2 infected fluid collections were sterilized by percutaneous US-guided drainage and topic therapy.


[Liver transplantation: role of the radiologic methods in the postoperative period]. Some complications of liver transplantation appear as aspecific clinical and blood test abnormalities; others--e.g., hepatic artery thrombosis in the immediate postoperative period and stenosis of the biliary anastomosis before T-tube removal--require early diagnosis. These considerations justify the need of frequent radiologic examination in both the complicated course and the follow-up. The authors report their experience in 59 adult patients submitted to liver transplantation for irreversible liver disease in advanced stage (49 with cirrhosis, 10 with HCC; 5 with cholestatic hepatopathy; 3 with fulminant hepatitis; 1 with Budd-Chiari syndrome; 1 with metastatic APUDoma). Two hundred and sixty-three radiological examinations were performed (Doppler US, CT, angiography and cholangiography) which showed numerous early and delayed complications: 13 of them were treated with interventional radiology maneuvers (US-or CT-guided percutaneous drainage of fluid collections, biliary drainage, bilioplasty, arterial transcatheter embolization). Our results demonstrate that diagnostic and operative radiology are essential for the success of liver transplantation; integrated imaging is particularly important in the diagnosis of complications, while interventional radiology techniques can be usefully employed in their treatment.


[Ultrasound-guided biopsy of small abdominal lesions. Methodology implications]. In the present study the diagnostic accuracy of US-guided fine-needle biopsy was evaluated in a series of 219 abdominal lesions < or = 3 cm in diameter (21 between 0.6 and 1 cm; 83 between 1.1 and 2 cm; 115 between 2.1 and 3 cm). One-hundred-eighty-three of them were located in the liver and 36 in other abdominal organs (pancreas, 10, adrenals 9, lymphnodes 9, kidney 5, spleen 3). Biopsies were performed with "free-hand" technique using up-to-date ultrasound equipment. The demonstration of the correct location of the needle tip at the time of sampling was looked for with great care. The sensitivity rate was 93%, with a progressive improvement with the increase of the lesion size (83.3% between 0.6 and 1 cm; 91.1% between 1.1 and 2 cm; 95.4% between 2.1 and 3 cm). The specificity rate was 100%. In 207 cases in which the location of the needle tip was clearly demonstrated, the sensitivity reached 97.3% and the negative predictive value 93%. No noteworthy complications were observed. Ultrasonography is a highly reliable guidance modality also in biopsies performed on small abdominal lesions; if the correct location of the needle tip is clearly shown, even a diagnosis of benignity can be confidently made.


[Role of endovesical echography in the assessment of bladder neoplasms]. The correct assessment of T (depth of infiltration of bladder wall by cancer) is relevant to plan therapy. In fact, besides staging the local lesion, this can predict pelvic and lumboaortic lymphnode involvement (N parameter) statistically. At the INRCA Hospital in Florence, from January 1987 to December 1989, transurethral US was performed on 66 patients affected with bladder carcinomas, in order to assess the value of this diagnostic method; in all patients pathologic staging on surgical specimens from TUR (63 cases) and cystectomy (3 cases) was performed. Follow-up lasted 24 months at least. When comparing US staging (according to Holm classification) to postoperative histopathologic findings, our results showed that US tends to overstage the lesions, while no understaged tumors were seen in our series. Diagnostic accuracy was 70%. It must be pointed out that TRUS demonstrated hidden submucosal tumors in two patients previously treated with intravesical chemotherapy. Retrospectively, we were able to detect causes of error in cancer staging in some cases--i.e., large carcinomas, calcifications on tumors, radiotherapy scars, bladder wall inflammation due to intravesical BCG therapy. Moreover, some lesions which appeared to have been overstaged with TRUS and which had been treated according to histopathologic findings from TUR exhibited recurrence or disease progression. This was probably due to incomplete TUR and to the presence of residual tumor in the bladder wall.


[Radiodiagnosis of ureteral and bladder hernia. A further case contribution]. The radiologic features of ureteral and bladder hernias are poorly known. These hernias can be located in 5 compartments, being extremely rare in 2 of them--the chest and lumbar sectors, where only 2 cases are reported in literature. In the other 3 compartments--i.e., ischiatic, crural and inguinal sectors--bladder and ureteral hernias are less uncommon findings. Over a relatively short period of time, 5 bladder hernias were observed--3 ischiatic, 1 inguino-scrotal and 1 crural cases--and 1 double ureteral hernia, which was inguinal on the right-hand side and ischiatic on the left-hand side. Thus, we reviewed the main urographic and cystographic signs on the basis of a previous report by one of us. In discussing the new cases, we emphasize the importance of a few typical diagnostic signs, which follow: asymmetry and anomalous location of herniated organs, ureter protrusion beyond the pelvic bones outline, the presence of ureteral spiral ("curlicue sign"), and bladder walls indentation.


[Seminal vesicles: echographic findings in 244 subjects. Evaluation of anatomic data and correlations with pathologic prostatic-vesicular parameters]. Over a 2-year period (1989-90), about 400 cases were examined (out of nearly 2,500 US examinations of the prostate), 244 of which had subsequent bioptic, surgical or autoptic confirmation. This paper reports the anatomic, clinical and pathologic data relative to the seminal vesicles of 244 subjects who underwent transrectal US of the prostate for different clinical indications. Our biometric values were slightly different from those reported in literature, the latter being based on autoptic findings. Agenesis and monolateral ectopia were confirmed to be extremely rare: 4 cases only (1.6%) in our series. A typical finding was the nearly perfect symmetry; in size and structure, of the two seminal vesicles in the same subject; as a matter of fact, a loco-regional pathologic condition was detected in all the patients (14) with asymmetry. A hundred per cent agreement was observed between the US patterns of the seminal vesicles and the prostatic patterns in case of acute/subacute prostatic inflammation involving also the 2 glands: this parameter can be used to follow the clinical course of the inflammatory process.


[Computerized tomography follow-up after percutaneous renal lithotripsy]. Even though extracorporeal shock wave lithotripsy (ESWL) is nowadays considered the treatment of choice for the majority of upper urinary tract calculi, percutaneous stone removal will continue to be an alternative treatment method in selected cases. Therefore, percutaneous techniques must not be forgotten by the interventional radiologist. In order to assess the effects and the potential damage caused by this interventional procedure to kidney and perirenal tissues, CT was performed on 20 patients before and after percutaneous nephrolithotripsy. In the cases where no complications occurred during the maneuver, post-nephrolithotripsy scans demonstrated low incidence of significant renal abnormalities. Thickening of pararenal fascia (8 patients) and irregular renal outline (10 patients) were our most frequent findings. In 5 patients we found edema of the pyelo-ureteral junction, in 3 thickening of the bridging perinephric septa and retained stone fragments, in 2 perirenal hematomas, in one a subcapsular fluid collection. Urinoma with pelvic laceration was demonstrated in the only patient in whom the maneuver presented marked technical problems. On the basis of this series of pre- and post-nephrolithotripsy CT scans of treated kidneys, the authors conclude that this percutaneous technique is quite atraumatic.


[Results of conservative treatment of stage I-II carcinoma of the breast. Analysis of 311 patients]. From January 1984 through December 1990, 311 patients affected with breast cancer were treated with quadrantectomy plus lymphadenectomy and radiation therapy (QUART) at the Umberto I Hospital in Mestre, Italy. The patients with positive nodes (N+) were treated with adjuvant chemotherapy (CMF) or hormonotherapy (Tamoxifen) according to pausal status. Most patients were in the 5th, 6th and 7th decades of life; 60.5% of them were over 50. Staging was always performed according to TNM classification (UICC criteria) and demonstrated mostly stage-I lesions (66.9%). Overall and disease-free (NED) survival rates were 95%; mean survival rates were 7.47 (+/- 0.138) and 7.22 (+/- 0.164) years, respectively. Ten patients died (5 from breast cancer); 6 local relapses were observed and 8 metastases. Metastases were seen mostly in patients with breast cancer in the internal quadrants (QI) N0, with no statistically significant differences relative to the other groups. This is probably due to the existence of an axillary pN0 and parasternal N+ group of patients, who receive insufficient treatment.


[Radon levels in interiors in Valtellina, on the Angera hills and in the high valley of the Cervo river]. The results are reported of an investigation carried out from 1988 to 1990 in many houses in various sites in Lombardy and Piedmont. Measurements were actually carried out in Valtellina, in Angera--on the Lombard side of lake Maggiore--and in the high valley of the river Cervo, north of Biella. The patterns of radon immission in houses due to buildings materials and also to soil emissions are described. Average values of radon levels were obtained using track-etch detectors, whereas fluctuations were recorded daily with a unit capable of detecting alpha particles in real time. Some of the values obtained in 28 Valtellina towns were quite high--e.g., about 1,000 Bq/m3 in towns along the Insubrica fault. The area around Bormio and the Masino valley did not exhibit high radioactivity levels. A total number of nearly 100 houses were investigated in Angera; the highest radon concentrations were observed in cellars and especially in the areas where fractures are bigger and more diffuse. One particular house was accurately examined with real-time analysis of radon fluctuations. Four small towns in the pluton area were investigated in the valley of the river Cervo. In this instance, values were generally high (mean concentration: 842 Bq/m3); the highest concentrations were found in cellars and in ground-floor rooms.


[Teleradiography for diagnosis in emergency care. A clinical experience]. This work was aimed at evaluating the role of teleradiology in a diagnostic emergency room. Over a 6-month period (September 1991-February 1992), 2,000 films made in the emergency room were transmitted to a resident radiologist 1 kilometer away: each examination included patient's data (sex, age, site of trauma, etc.) which were sent by the admitting physician. A teleradiology system (Lumiscan 100 AT&T and Philips) was used. Films were digitized on a 1024 x 1024 x 8-bit image matrix and then transmitted over a dedicated standard phone line to the Department of Radiology. The autograph report was sent by fax to the emergency room. Four radiologists, of varying experience, independently reviewed a sample of 179 digitized radiographs and, 30 days later, the original films on a conventional light-box. The results appear to be encouraging because no significant differences were observed in the performance of any of the radiologists. Good video/films agreement was obtained, together with high sensitivity and specificity. A good result was the relatively small number (0.4% of all examined cases) of false negatives diagnosed on faxed films relative to the actual clinical diagnosis.


[Conventional radiology, digital radiology with photostimulable phosphor, laser digitalization of thoracic radiographic films at the bedside. A comparative study]. The bedside chest images obtained with conventional radiology and with "on line" and "off line" digital modalities were compared to evaluate the respective capabilities in visualizing chest anatomical structures. Seventy patients were submitted to bedside chest examinations with a portable unit; both a conventional film and a digital system (PCR Graphics 1, Philips) with photostimulable phosphor imaging plate were fitted in the radiographic cassette. The former was digitized using an "off line" laser beam unit (FD 2000, Dupont); the latter was subsequently postprocessed by modifying contrast, optical density and spatial frequencies. Thus, 4 different viewing modalities were obtained for each examination: a) conventional radiography; b) standard digital radiography; c) postprocessed digital radiography; d) digitized conventional radiography. Detectability rates of chest anatomical structures were analyzed by 4 independent radiologists on the different images and expressed by a score 1-4. The values were always higher with digital modalities than with the conventional one and the differences were statistically significant (Student's t-test modified by Bonferroni). In particular, the greatest difference was found between c) and a) in retrocardiac lung parenchyma and in skeletal structures, in favour of c). Concerning the comparative adequacy of the various digital modalities, higher detectability rates of chest anatomical structures were obtained with c), but also with b), than with d).


[The use of digital techniques with storage phosphors for orthopantomography. Preliminary note]. Digital panoramic tomographies with light-emitting phosphors were obtained in 39 patients, during a study on the clinical applications of digital imaging. Performing digital panoramic radiographies required the preliminary adaptation of the imaging plates to the cassette holder of the radiographic equipment. The digital images were post-processed according to two different protocols, both of which were recorded for each patient. The former image was quite similar to standard X-ray films and was called "analogic-like". The latter, called "xeroradiographic-like", featured a flattening of the overall contrast together with detail contrast enhancement due to the presence of an edge effect, as it occurs in xeroradiography. Digital panoramic tomography allows a marked reduction in patient's exposure to X-rays. In addition, this technique offers constant high-quality results, due to the possibility of recovering over- or under-exposed images during post-processing. Xeroradiographic-like digital films may reduce the sharp contrast that is often present between the anterior and the lateral portions of the maxillary and mandibular arches, thus improving the diagnostic reliability of the examination. Other modalities of digital post-processing may be helpful to depict gingival soft tissues, with obvious advantages for the study of periodontal diseases.


Disease markers and new therapeutics. Dual objectives of genetics in rheumatology. Genetic studies in rheumatology have led us down a path with two practical endpoints. On the one hand, sophisticated molecular genetics provides specific markers with which to predict disease risk. On the other hand, these same studies have identified likely genetic and molecular intermediates in the pathway of disease, offering new possibilities for targeted intervention and immunotherapy.


Prediction of susceptibility to rheumatoid arthritis by human leukocyte antigen genotyping. Recent methodologic advances now allow the precise identification of HLA genes in individuals. Population studies using these methods have pinpointed the HLA alleles strongly associated with rheumatoid arthritis (RA). This article summarizes the current status of these RA-associated HLA genes in disease susceptibility and uses that information to derive estimates of risk ratios for prediction of disease in an individual.


Immunoglobulin V genes in rheumatoid arthritis. Recent studies have revealed that a broad spectrum of Ig V genes (VH, V kappa, V lambda) contribute to the rheumatoid factor (RF) and non-RF produced by B cells in patients with rheumatoid arthritis (RA). This result contrasts with the restricted V gene use of paraprotein IgM RF. Certain VH and VL genes, however, appear more often in RA than expected from random expression, including some of the paraprotein-associated V genes. Many V genes expressed in RA are the same as those found in the fetal/CD5+ repertoire, suggesting an important role for CD5+ B cells in RA. Somatic mutations suggest that the B-cell response in RA is at least in part antigen-driven, although many Ig in RA have little or no mutation. Improved detection of V-gene polymorphisms now enable study of Ig V gene RFLP in RA.


Immunogenetics of spondyloarthropathies. The association of HLA-B27 with ankylosing spondylitis and related spondyloarthropathies has been known for two decades and has provided a great impetus to the epidemiologic studies and also helped broaden the clinical spectrum of these diseases. The etiology of these diseases is likely to be multifactorial and include genetic, immunologic, and environmental mechanisms. The detailed three-dimensional x-ray crystallographic structure of B27 has now been reported. It has revealed electron density compatible with oligopeptides that are nine amino acid-long (nonamers) bound in the antigen-binding cleft of the molecule. Microsequence analysis of 11 peptides eluted from the antigen-binding cleft has confirmed that all are nonamers. The most restricted position in the bound peptide is the second position, where all the 11 peptides contain arginine. The side chain of arginine extends into the B pocket ("45 pocket"), which seems to act as a specificity side pocket in the antigen-binding cleft of the B27 molecule. It is very likely that an understanding of the detailed structure of B27, including the peptide-binding motif and the structural domains recognized by cytotoxic T cells, along with the recent development of the B27 transgenic rat model for spondyloarthropathies, will further enhance our understanding of the immunogenetics of these diseases. It is hoped that this will lead to the source of the arthritogenic triggers and possibly disease prevention by antigen-specific immunomodulation. Because T-cell activation is initiated by the formation of antigen-MHC complexes that are the ligands that are recognized by the antigen-specific T-cell receptor (TCR), it might be possible to inhibit this activation by blocking the antigen-binding cleft of MHC molecules by using high-affinity MHC-binding peptides (MHC blockade) or by a novel, new, and more efficient method of TCR antagonism.


Genetics of systemic lupus erythematosus. Systemic lupus erythematosus (SLE) is a complex autoimmune disease in which multiple genes appear to play important roles in pathogenesis. Hereditary deficiencies, both complete and partial, of several components of the complement system clearly predispose to lupus. HLA class II alleles appear to mediate specific autoantibodies, many of which are pathogenic. Modern molecular techniques are now providing insight into the specific major histocompatibility complex class II polymorphisms that are associated with different autoantibodies in SLE. Other genetic systems also may be important.


Genetics of the complement system and rheumatic diseases. The complement system, especially the early components of the classic pathway, are critically involved in immune complex processing. The deposition of clusters of complement component C3b on a target marks it for elimination, primarily through an interaction with complement receptors. Not surprisingly, total and partial deficiencies of certain complement components and C3b receptors are associated with rheumatic diseases, particularly systemic lupus erythematosus. This predisposition is explicable, based on the critical role complement plays in immune complex handling.


Nerve lesions induced by macrophage activation. The neuropathies associated with infectious processes, including leprosy, retroviral infections and Chagas' disease, represent the largest group of neuropathies in the world. Segmental demyelination and axonal degeneration of nerve fibres are associated with inflammatory infiltrates which contain a large number of mononuclear phagocytes. In order to learn more about the role played by macrophage activation in the nerve lesions observed in inflammatory neuropathies, we have performed a morphological study of nerves injected with products of activation of macrophages including proteolytic enzymes and cytokines (tumour necrosis factor and alpha beta-interferon). We have also studied the effects on nerve fibres of macrophages activated by ingestion of proteose-peptone, a foreign protein, and in the course of a delayed-type hypersensitivity (DTH) reaction. We have found that proteases and urokinase were potent demyelinating agents and that activated macrophages were also able to induce significant demyelination of neighbouring fibres. In contrast, injection of TNF alpha induced more severe nerve lesions consisting of axonal degeneration of the majority of nerve fibres. We thus conclude that infected macrophages which penetrate the endoneurium and macrophages activated in a DTH reaction can both cause neuropathy.


The role of the acute-phase protein alpha 1-antichymotrypsin in brain dysfunction and injury. The crystal structure of proteolytically modified human ACT has been solved at 2.7-A resolution (Baumann et al., 1991). The final model consists of 374 amino acids, 126 solvent molecules and 5 sugar residues. Asn70 is glycosylated and Asn104 is probably glycosylated. The role of carbohydrates in serpin function may be 3-fold: secretion, removal from circulation and recognition by receptors for complex uptake (Travis et al., 1990). Experiments with recombinant, non-glycosylated ACT have shown that glycosylation has no effect on the association rates of ACT with its target proteases (Rubin et al., 1990). The X-ray diffraction studies also revealed that a certain ACT region is involved in DNA binding, although the physiologic relevance of this binding is still unknown. Using a plethora of techniques, scientists are starting to understand the role of ACT in health and disease. It is 14 years since ACT was first purified (Travis et al., 1978) and 9 years since its gene was cloned (Chandra et al., 1983). We have learned considerably about this protease inhibitor in humans and rodents; in inflammation, cancer and AD; as binding to proteases (irreversibly), to the A beta (irreversibly) and to DNA. However, there are still open avenues for research. These include: finding the proteases that ACT inhibits in brain, identifying the cellular receptors which bind ACT-protease complexes and elucidating the DNA-binding phenomenon. Recently, 4 mutations have been found in APP. The first mutation at position 22 of A beta was detected in HCHWA-D by Levy et al. (1991).(ABSTRACT TRUNCATED AT 250 WORDS)


Macrophages, mycobacteria and HIV: the role of cytokines in determining mycobacterial virulence and regulating viral replication. The marriage of two scourges, one old (mycobacterial disease) and one new (HIV), has presented an enormous challenge to the medical and public health communities, and has stirred renewed interest in mechanisms for immune control of mycobacterial infection. Virulence of both M. avium and M. tuberculosis appears to be inversely related to the capacity of the microorganisms to induce production of protective cytokines in infected hosts. TNF alpha and IFN gamma are central to this process, and mycobacterial polysaccharides may be their main determinant. Despite these similarities, M. tuberculosis and M. avium cause illnesses at the polar extremes of HIV disease. Tuberculosis, occurring early in the course of HIV disease, may promote HIV replication in otherwise latently infected cells via induction of cytokines. As such, the potential exists for accelerated progression to AIDS due to the mutual synergy of these pathogens.


Diminished mephobarbital anticonvulsant action following diphenhydramine pretreatment. Diphenhydramine and other antihistamines produce biphasic effects on drug disposition and lower seizure threshold, thereby potentially diminishing the efficacy of anticonvulsants such as mephobarbital. Accordingly, the influence of diphenhydramine (50 mg/kg, IP) pretreatment on the anticonvulsant activity of mephobarbital (50 mg/kg, IP) was determined in adult female Swiss-Webster mice given pentylenetetrazol (SC). Diphenhydramine lowered the pentylenetetrazol convulsive dose (CD50) by 60%. Administration of diphenhydramine in combination with mephobarbital produced a 65% decrease in the CD50 of pentylenetetrazol in comparison with that of animals given mephobarbital plus pentylenetetrazol. Pharmacokinetic evaluation of mephobarbital blood level data indicates that the mechanism responsible for the observed interaction between diphenhydramine and mephobarbital involves a decrease in mephobarbital uptake from the administration site.


Therapeutic parameters of methylprednisolone treatment for retinal photic injury in a rat model. Methylprednisolone (MP) has been prescribed for the treatment of solar retinopathy presumably because of its anti-inflammatory effect. Recently, high doses of MP have been shown to ameliorate light-induced photoreceptor degeneration, and the mechanism of action was suggested to be the inhibition of lipid peroxidation. In this study we examined the dose-response effect and the effect of delayed treatment with MP in an established rat model of retinal photic injury. Animals received intraperitoneal injections of either MP (8, 160, or 320 mg/kg/day) or saline solution (as a control) for 2 days. Injections were started simultaneously with the commencement of light exposure or delayed for 6 or 24 h. The animals were sacrificed 6 days after light exposure, and the retinal damage was assessed by light microscopy and morphometric measurement of the outer nuclear layer (ONL) thickness. Morphologically and morphometrically, treatment with 8 mg/kg/day of MP was not effective, while treatment with 160 mg/kg/day caused better preserved photoreceptors and a thicker ONL compared with the controls (P less than 0.001). Animals administered with a dose of 320 mg/kg/day showed more severe damage to photoreceptors, resulting in a thinner ONL (P less than 0.05). When treatment with 160 mg/kg/day was delayed for 6 h, a similar efficacy as in the no-delay group was noted, but when treatment was delayed for 24 h, no beneficial effect was observed (P = 0.19). Our results demonstrated that early treatment with high doses of MP ameliorated retinal photic injury in rats.


The effect of maternal administration of enalapril on fetal development in the rat. Enalapril (MK, 421), an angiotensin converting enzyme inhibitor, was tested for teratogenicity using Wistar rats. The drug was given by oral intubation, from 6-15 days of gestation, at the doses of 0, 3, 10 and 30 mg/kg/day. Reduction in body weight and food consumption were observed in the treated dams. However, food efficiency index, assessed at different periods of gestation was found to be unaffected. On day 20 of gestation, all the dams were sacrificed by cervical dislocation and sign of maternal toxicity, reproduction indices and fetal measures were recorded. The dams treated with enalapril at only the doses of 10 and 30 mg/kg, produced significant decrease in numbers of implants, litter size and incidence of reabsorbed fetuses, and also reduced neonatal growth. No such effects were observed at the lowest dose level (3 mg/kg) used. External, visceral and skeletal examinations of the fetuses of enalapril-treated dams showed several types of variations in all groups, but no consistent pattern were observed. However, a slight increase in skeletal variations was seen with the highest dose (30 mg/kg) group. The data of the present study under the conditions described herein and at the doses employed, revealed no evidence of teratogenesis, but numerous deleterious effects on the fetus were evident.


Suppression of intestinal smooth muscle contraction by phenolic compounds. Wood creosote, a mixture of guaiacol, creosol, and other related phenolic compounds, suppresses the spontaneous longitudinal phasic contractions of an isolated rat ileal segment. Thirty-two phenolic compounds were screened for this activity to identify the active substances in wood creosote. Of the 32 compounds tested, 2,3,6-trimethylphenol, 2,4,6-trimethylphenol, and 4-ethylguaiacol were most effective and their respective IC50 values were 0.035, 0.037, and 0.043 mM. Guaiacol and creosol, the chief constituents of wood creosote, were moderately effective and their respective IC50 values were 0.18 and 0.13 mM. Other phenolic compounds in wood creosote also suppressed the ileal contraction although their IC50 values differed markedly from each other. These results suggest that practically all of its constituent phenolic compounds contribute to wood creosote's capacity to suppress ileal contraction.


The effect of calcium on disodium monofluorophosphate absorption from the gastrointestinal tract of rats. The absorption of fluoride from disodium monofluorophosphate with or without added calcium has been studied in ligated stomachs and duodena of rats, in vivo. Measurements of fluoride absorption from sodium fluoride were also carried out for comparative purposes. The formation constant of the soluble, neutral calcium monofluorophosphate complex has been determined at 20 degrees, 25 degrees and 37 degrees C. Its value at 37 degrees C being 315 +/- 10 (molar units). The influence of increasing concentrations of calcium on alkaline phosphatase (E.C.3.1.3.1) activity with disodium monofluorophosphate as substrate has been also studied. Gastric absorption of 2 mM disodium monofluorophosphate in the presence of 50 mM calcium was much slower than that of 2 mM disodium monofluorophosphate alone. The latter was slower than that of 2 mM sodium fluoride. The opposite situation has been found for the duodenal fluoride absorption. Results obtained are interpreted in terms of the occurrence of an intestinal monofluorophosphate hydrolysis prior to its absorption as fluoride. In addition, data presented suggest an independent and parallel pathway of fluoride absorption in the form of the liposoluble calcium monofluorophosphate complex.


Problems and timing in the removal of silicone oil. The risk associated with silicone oil removal after complex vitreoretinal surgery is unclear. Therefore, a cohort of 87 consecutive cases of silicone oil removal were analyzed. Eyes with attached retina before silicone oil removal with a follow-up of at least 5 months were included into the study. Forty-eight eyes had severe proliferative diabetic retinopathy; 39 eyes had complex proliferative vitreoretinopathy or giant retinal tears after trauma. Additional clinical features included the presence of a secondary cataract or secondary glaucoma in some eyes. The rate of postoperative complications was different in the two groups: 75% of proliferative diabetic retinopathy patients remained attached; of proliferative vitreoretinopathy patients, only 48.5% remained stable. Whereas success was independent of the duration of intraocular silicone oil tamponade in proliferative diabetic retinopathy, removal of silicone oil was more successful in cases of proliferative vitreoretinopathy in which there was a longer period of silicone oil tamponade. Complications occurring usually were severe and led to a loss of visual acuity. The removal of silicone oil from eyes with secondary glaucoma resulted in an improvement in 68% of patients. The rate of vitreoretinal complications after silicone oil removal, even in cases with a clinically stable-appearing retina, is rather high. Silicone oil removal therefore has to be considered a procedure posing new and ill-defined risks, especially if the indications for the use of silicone oil as an internal tamponade are rather strict. Exact criteria for the timing and safe removal of silicone oil in these complex vitreoretinal disorders still need to be defined.


Identification of silicone oil in the retina after intravitreal injection. Retinal tissue obtained from 2 eyes that had been injected with silicone oil for 2 years was stained with monoclonal antibodies against macrophages and studied by light and electron microscopy and energy-dispersive x-ray analysis. Both specimens showed areas with a relatively intact architecture as well as parts with loss of normal structure. In both areas, immunostaining showed single intraretinal macrophages. Energy-dispersive x-ray results clearly demonstrated that some of the intracellular and extracellular vacuoles within the retina represented the storage sites of silicone.


A quantitative in vitro model for silicone oil emulsification. Role of blood constituents. To understand why some patients seem to be protected from emulsification and others are not, the authors developed an in vitro model for quantitative analysis of silicone oil emulsification. The pro-emulsifying potential of substances and blood components that may have access to the vitreous cavity in a patient's eye was analyzed. In this model, red blood cell ghosts had the highest emulsifying effect; plasma and lymphocytes also had a significant emulsifying effect. Phospholipids in membranes and other soluble blood components may play important roles in this process. These results suggest the importance of avoiding and removing hemorrhage and avoiding inflammation when silicone oil is used in vitreoretinal surgery.


Experimental evaluation of in vitro stability of purified polydimethylsiloxanes (silicone oil) in viscosity ranges from 1000 to 5000 centistokes. One of the main problems in the clinical use of silicone oil in vitreoretinal surgery is the instability of the material in terms of emulsification. Fine silicone oil droplets can cause a secondary glaucoma by blocking aqueous outflow. Intravitreally applicable silicone oils comprise an inhomogeneous group of materials, and the rate of emulsification depends on the physicochemical properties of the silicone oils. Clinically most frequently used silicone oils are highly purified polydimethylsiloxanes with a viscosity of 1000 centistokes (cs) to 5000 cs. Low-viscosity silicone oils are preferred by some surgeons because of easier surgical handling and easier removal out of the vitreous. The authors investigated highly purified polydimethylsiloxanes in viscosity ranges of 1000 cs, 2000 cs, 3000 cs, 4000 cs, and 5000 cs with regard to their in vitro stability to evaluate the optimal range of viscosity with acceptable material stability. The comparative stability tests were performed with 0.1% salt solutions of albumin, acidic alpha-1-glycoprotein, fibrin, fibrinogen, gamma globulins, and very-low-density lipoprotein as emulsifiers. Silicone oil at 5000 cs was in all cases distinctly more stable than the silicone oils with a viscosity up to 4000 cs. A positive correlation between the degree of viscosity and an increase of material stability was not found with all emulsifiers. When very-low-density lipoprotein, albumin, and fibrin served as detergents, a remarkable stability gain was achieved only at 5000 cs.(ABSTRACT TRUNCATED AT 250 WORDS)


Systemic antibiotic prophylaxis in penetrating ocular injuries. An experimental study. Intraocular concentrations of systemically administered gentamicin and cefazolin in eyes after a standard penetrating ocular injury were measured to determine the effect of eye injury on ocular pharmacokinetics. Twenty pigmented rabbits were divided into two groups. A standard, 8-mm wound was made at the pars plana of one eye in each animal. Group 1 consisted of 10 rabbits that were treated with cefazolin (75 mg/kg), and Group 2 consisted of 10 rabbits that were given gentamicin (2 mg/kg). Fellow eyes, which sustained no trauma, served as control eyes. All groups received intravenous injections every 8 hours for 72 hours, beginning immediately after repair of the wound. After 72 hours, samples were obtained from the anterior chamber, vitreous cavity, and serum. Standardized bioassays for detection of gentamicin or cefazolin were performed. Significant concentrations of intravitreal cefazolin (9.6 micrograms/ml) and gentamicin (0.60 micrograms/ml) were found in the traumatized eyes in comparison to control eyes (P = 0.0001; P = 0.006). Cefazolin exhibited excellent penetration, achieving concentrations well above minimum inhibitory concentration values for most organisms. Gentamicin levels, however, were well below acceptable therapeutic levels. This study suggests that systemically administered cefazolin can achieve significant intravitreal penetration at minimum inhibitory concentrations after penetrating injury.


Subretinal perfluorocarbon liquids. An experimental study. Perfluorocarbon liquids (PFCL) are fully fluorinated, synthetic, transparent compounds with a high specific gravity. These compounds are being increasingly used as an intraoperative tool for repair of complicated retinal detachments. A known complication of their use, however, is liquid entering the subretinal space via a retinal break. The purpose of this study was to evaluate the effects of two of these liquids when placed subretinally in the rabbit eye. Vitrectomy, retinotomy, and subretinal injection of 0.03 cc of either perfluoroctane, perfluorotributylamine, or balanced salt solution (control eyes) were performed on 36 rabbit eyes. Animals were monitored clinically by indirect ophthalmoscopy and fundus photography for up to 21 days. After the 21-day observation period, electroretinograms (ERG) were taken before the rabbits were killed. Histopathologic studies were done at 3 hours, 24 hours, 3 days, 7 days, 14 days, and 21 days after injection. Three eyes demonstrated tearing of the retinotomy site due to downward migration of the PFCL droplet. Results of the ERGs were normal in all animals tested. Phagocytosis of PFCL droplets by the retinal pigment epithelium (RPE) was observed in 1 eye 3 hours after injection. Three of the eyes that received PFCL injections and all of the control eyes demonstrated moderate intracellular edema of both inner and outer nuclear layers as early as 24 hours after injection. In one eye injected with PFCL, these changes progressed to swelling and cystic formation of the inner nuclear layer and mild degeneration of the outer photoreceptor segments 3 days after injection. It was assumed that these effects occurred on a mechanical basis and were not related to PFCL toxicity.(ABSTRACT TRUNCATED AT 250 WORDS)


The effect of simultaneous internal tamponade on fluid compartmentalization and its relationship to cell proliferation. To determine whether the residual free spaces within the vitreous chamber that result after vitreoretinal surgery and internal tamponade may be avoided, and to verify whether such compartmentalization is of real importance in the recurrence of postoperative proliferative vitreoretinopathy (PVR), the use of simultaneous double filling with polydimethylsiloxane (PDMS) and fluorosilicone (FSiO) in the repair of complicated retinal detachment is evaluated in 12 selected cases. Initial retinal reattachment was achieved in all cases. PVR recurred in 10 patients (83%), 6 of whom showed partial retinal detachment. Inferior and superior postoperative residual free spaces were abolished by this procedure, but a new residual fluid space was created, lying horizontally between the bubbles and expanding in a triangular shape nasal to the optic disc and temporal to the macula. Overall, 9 of 10 eyes with PVR after surgery had proliferation involving these areas. These findings support the concept that compartmentalization is of major importance in determining postoperative cell proliferation.


Retinal detachment after refractive surgery for myopia. Refractive surgery has been used widely in some countries for the last 20 years for the correction of myopia. Radial keratotomy and keratomileusis, the most common procedures, may concur with retinal detachment. A total of 14 eyes in 12 patients, 7 after keratomileusis and 7 after radial keratotomy, which had either asymptomatic or symptomatic retinal breaks, subclinical and clinical rhegmatogenous retinal detachments, or both, are discussed here. Five eyes were treated with either laser photocoagulation or cryopexy alone, seven eyes with a scleral buckling procedure, one eye with vitrectomy, and one eye was not operated on. At the final follow-up examination, anatomic reattachment had been achieved in 12 of 14 eyes (85.7%). Visual acuity improved in 3 eyes (21.4%), remained stable in 9 eyes (64.3%), and was worse in 2 eyes (14.3%). The scleral buckling procedures used in the repair of retinal detachment induced refractive changes by modifying axial length and corneal curvature, with recurrence of myopia and astigmatism. Myopia increased a mean of -3.00 diopters in 6 of 7 eyes (86%). Myopic astigmatism power changed a mean of -1.00 diopter in 5 eyes (71%), and the astigmatic axes shifted in 3 eyes (43%). This situation could be prevented with an early peripheral search for and treatment of peripheral retinal degenerative pathologic changes, by avoiding encircling bucklings, or by using alternative methods of treatment.


Retinal detachment in eyes with congenital glaucoma. Five patients with congenital glaucoma were treated for complicated retinal detachment. All patients underwent a pars plana vitrectomy and fluid/gas or fluid/silicone exchange. The technical difficulties of operating on buphthalmic eyes are described. Due to subretinal reproliferation, corneal decompensation, and pressure elevation, the functional prognosis is still poor.


Management of threshold retinopathy of prematurity. The Cryotherapy for Retinopathy of Prematurity Study demonstrated the benefit of intervention for threshold disease. The authors reviewed their experience with cryotherapy, investigating the questions of treatment for bilateral disease. Between 1985 and 1990, 71 eyes from 41 infants with threshold retinopathy of prematurity were treated. Of the 65 eyes with a minimum of 3 months follow-up, only 7 eyes (11%) progressed to stage 4, although an additional 8 eyes (13%) developed a posterior retinal fold. Although the overall results are comparable to those repeated by the Cryotherapy for Retinopathy of Prematurity Study, the authors recommend treating both eyes if they reach threshold, and treating the two eyes at the same sitting.


Applications and limitations of vitreoretinal biopsy techniques in intraocular large cell lymphoma. The cases of 4 patients with clinical signs of intraocular large cell lymphoma are described. Initial cytopathologic examination of vitrectomy specimens failed to establish the malignant character of the vitreous infiltrates. Three of the four patients eventually developed solid central nervous system tumors, intracranial biopsy samples of which revealed large cell lymphoma, 13 months to 42 months after initial examination. In one patient, transscleral retinochoroidal biopsy confirmed the diagnosis at the same time as negative vitreous cytologic examination. Results of cytopathologic examination alone of vitreous biopsy specimens may not be sufficient to make a diagnosis in certain cases of large cell lymphoma that are subsequently documented by CNS biopsy. Careful attention should be paid to the handling, processing, and interpretation of vitrectomy specimens from patients suspected of having intraocular large cell lymphoma. Consideration should be given to immunocytologic staining and interpretation by centers that are highly experienced in vitreous cytopathology.


Giant retinal tears. Surgical techniques and results using perfluorodecalin and silicone oil tamponade. Intraoperative use of perfluorocarbon liquids in the management of giant retinal tears was introduced about 4 years ago. Twenty-four patients were operated on for giant retinal tears using perfluorodecalin and silicone oil tamponade. All patients underwent pars plana vitrectomy, unfolding of the giant retinal tears by perfluorodecalin, perfluorodecalin-silicone oil exchange, and endophotocoagulation. The lens was removed in 10 of 14 phakic patients, and encircling scleral buckle was placed in 18 cases. Twenty-three of 24 retinas remained successfully attached with a minimum of 6 months of follow-up. Short-term results of intraoperative use of perfluorodecalin and silicone oil tamponade in the management of giant retinal tears are encouraging. Perfluorodecalin offers the advantage of low cost compared with other perfluoro-carbon liquids like perfluoro-n-octane. The exchange with silicone oil offers the advantages of easy removal of perfluorodecalin and absence of posterior slippage of the retinal tear.


An overview of potential applications of heparin in vitreoretinal surgery. Heparin is a naturally occurring complex polysaccharide with properties that lend themselves to the potential treatment of proliferative ocular disorders. The biochemistry of heparin and its effects on the eye and cultured ocular cells under varied experimental conditions are discussed.


The lowest effective dose of tissue plasminogen activator for fibrinolysis of postvitrectomy fibrin. Tissue plasminogen activator (tPA) has been shown to be effective at a dose of 25 micrograms in the treatment of severe postvitrectomy fibrin. However, a recent report based on an animal model indicates that retinal toxicity may occur at doses as low as 25 micrograms. This study uses a low dose (1.5 micrograms to 3 micrograms) of tPA for 34 injections in 26 eyes, and determines the lowest effective dose to be between 1.5 and 3 micrograms. Complete fibrinolysis was achieved in all 28 eyes in which 3 micrograms of tPA was administered within 10 days of vitrectomy, whereas partial fibrinolysis was achieved in eyes treated with 3 micrograms of tPA 27 days and 82 days after vitrectomy. Complete fibrinolysis occurred in only 1 of 4 eyes that receive 1.5 micrograms of tPA. A dose of 3 micrograms of tPA is recommended for treatment of severe fibrin after vitrectomy, as it has a wider margin of safety than do higher doses.


Can the diode laser (810 nm) effectively produce chorioretinal adhesion? In this study, argon green (514 nm), krypton red (647 nm), and diode (810 nm) lasers were used to produce transpupillary photocoagulations on rabbit chorioretina to simulate a retinal buckle treatment. To evaluate the efficacy of the diode laser in creating a retinopexy effect, the morphologic aspects of the acute lesions and scar development were compared. The study of the acute lesions revealed that the chorioretinal thermal damage produced by the argon green laser involved all the retinal layers and the retinal pigment epithelium. The use of the krypton red and the diode lasers resulted in deeper chorioretinal thermal damage. Two months after the treatments, all the lesions resulted in adhesive chorioretinal pigmented scars. However, the diode lesions produced a deeper scar, characterized by marked chorioretinal atrophy.


A new device for pupillary dilatation in vitreous surgery. A completely new surgical technique to obtain pupillary dilatation is presented. It permits achievement of a mydriasis sufficient to observe the vitreous cavity in both phakic and aphakic eyes during vitreous surgery. Miotic immobile pupils not dilatable pharmacologically are enlarged by means of a silastic ring with a C-shaped groove on its outer part. This is introduced into the eye through a limbic opening. When in place, the external sulcus of the ring hosts the pupillary rim. Twelve patients (three phakic and nine aphakic) were treated. In two patients operated upon previously with silicone oil tamponade, some difficulties were encountered during the insertion of the device owing to the lubricating effect of the oil. After the removal of the ring, all the pupils returned to a round shape, with no apparent damage to the iris structure.


Artificial iris diaphragm and silicone oil surgery. In order to avoid contact between silicone oil and the cornea and subsequent painful corneal dystrophy in aniridial eyes, an artificial iris diaphragm was constructed. It consists of polymethylacrylat (PMMA) and simulates the situation of the iris with a central pupillary opening and inferior iridectomy. To date, these diaphragms have been implanted in 11 cases of the severest ocular trauma with accompanying aniridia and proliferative vitreoretinopathy. In the presence of sufficient residual secretion of the ciliary body (9 cases), the diaphragm assumes the function of normal iris and prevents the silicone oil from coming into contact with the corneal endothelium. The transparent diaphragm ensures a view through to the fundus. In the early postoperative period, there was, as anticipated, a fibrinous reaction in the area of the anterior segment.


Discharge of pulmonary rapidly adapting stretch receptors during HFO ventilation. High-frequency oscillatory ventilation (HFOV) has been shown to stimulate slowly adapting pulmonary stretch receptors (PSR) and thereby to inhibit spontaneous breathing, i.e. HFOV prolongs expiration or even elicits normocapnic apnea. However, during HFOV respiratory effects possibly mediated by pulmonary rapidly adapting receptors (RAR) have also been observed, e.g., diaphragmatic activation or augmented breaths. Therefore, we analyzed HFOV-induced changes in RAR activity in anaesthetized rabbits by mean of single fibre preparations of vagal RAR afferents. HFOV was applied in several combinations of airway pressure (Paw) and oscillation frequency (fOsc). In the sample of 60 RAR fibres prepared in 20 rabbits we found a wide spectrum of discharge patterns during HFOV. The inspiratory discharge rate during HFOV was increased in 38, decreased in 10, and unchanged in 12 RAR. The expiratory discharge rate was increased in 34, decreased in 17, and unchanged in 9 RAR. The effects of gradually changing Paw or of fOsc during HFOV were different in different fibres. In 17 fibres both inspiratory and expiratory discharge rates rose with increasing Paw during HFOV, whereas 19 fibres were not affected by increasing Paw. In some fibres either the inspiratory (12) or the expiratory (9) activity was inhibited in proportion to increasing Paw. From these results we conclude, that (a) the changes of RAR activity during HFOV are heterogeneous and the reflex effects of RAR stimulation may be balanced by RAR with decreased activity; (b) this heterogeneity of RAR discharge patterns explains the dominancy in the control of breathing during HFOV of the homogeneously stimulated PSR; and (c) depending on HFOV ventilatory parameters used the overall RAR stimulation may be strong enough to overrule the inspiration-inhibiting effects of PSR.


Ontogenetic modification of the hypercapnic ventilatory response in the zebra finch. We investigated the effect of exposure to CO2 during development on the adult ventilatory response to CO2 of zebra finches. Developing zebra finches were exposed to chronic hypercapnic respiratory environments as embryos, as nestlings or during both developmental periods. Their responsiveness to CO2 was then measured following a 125-135 day post-fledging deacclimation period. At a FICO2 of 0.06, mean ventilation of adult finches in the three groups was 74.8, 61.3 and 65.8%, respectively, of that of finches reared under normocapnic conditions. These data indicate that adult acute ventilatory responsiveness to CO2 in birds may be in part determined by CO2 exposure during early development and may help explain the observation that fossorial and semifossorial species of birds and mammals, that naturally encounter high CO2 conditions in their burrows, have a blunted hypercapnic ventilatory response.


Reduced tidal volume increases 'air hunger' at fixed PCO2 in ventilated quadriplegics. The act of breathing diminishes the discomfort associated with hypercapnia and breath-holding. To investigate the mechanisms involved in this effect, we studied the effect of tidal volume (VT) on CO2-evoked air hunger in 5 high-level quadriplegic subjects whose ventilatory capacity was negligible, and who lacked sensory information from the chest wall. Subjects were ventilated at constant frequency with a hyperoxic gas mixture, and end-tidal PCO2 was maintained at a constant but elevated level. VT was varied between the subjects' normal VT and a smaller VT. Subjects used a category scale to rate their respiratory discomfort or 'air hunger' at 30-40 sec intervals. In 4 of 5 subjects there was a strong inverse relationship between breath size and air hunger ratings. The quality of the sensation associated with reduced VT was nearly identical to that previously experienced with CO2 alone. We conclude that afferent information from the lungs and upper airways is sufficient to modify the sensation of air hunger.


Molecular adaptation of hemoglobin function in mammals. Vertebrate hemoglobins are tetramers made of two pairs of alpha and beta subunits each containing a hydrophobic pocket where a heme molecule binds tightly and allows for the reversible binding of oxygen. Both tertiary and quaternary structures are ideally suited for the loading and unloading of oxygen necessary for the metabolic requirements of the organisms. Starting from a single ancestor hemoglobin subunit, evolutionary processes have led to heterologous tetramers exhibiting a moderate oxygen affinity due to heme-heme interaction (allosteric mechanism) which may be further modulated through electrostatic interactions with chloride and/or organophosphate anions present in the red cells. These effectors, which bind preferentially to the deoxy-Hb tetramers at a distance from the heme groups, play a major role in the adaptation of the respiratory properties of hemoglobin to either allometric-dependent oxygen needs or to various hypoxic environments such as altitude, burrowing, or foetal life. In most cases the existence or the strength of the effector-Hb complexes, hence the changes in the allosteric equilibrium, may be ascribed to one or a few mutations of residues at the effector binding sites. Typical examples of these mechanisms are described.


Respiratory-associated rhythmic firing of midbrain neurons is modulated by vagal input. We recorded phrenic nerve activities and single unit firings of mesencephalic neurons in 19 decerebrate, paralyzed and ventilated cats, in which the spinal cord had been transected at C7-T1 and carotid sinus nerves cut but vagus nerves left intact. After we had found neurons with respiratory-associated rhythmic activity, we tested the effect of changing pulmonary vagal input by (1) stopping and restarting the ventilator; (2) changing the ventilator's tidal volume; (3) progressively cooling the vagus nerves to 6-7 degrees C; and (4) vagal section. All methods of testing yielded results that showed that vagal input, probably from pulmonary stretch receptors, tonically inhibits the respiratory-associated firing of the mesencephalic neurons by a direct mechanism that is independent of a vagal effect on medullary respiratory drive. We have suggested that these neurons are involved in the mechanism that conveys information about respiration to the cortex where it may be interpreted as the sensation of dyspnea. If so, movement and increased expansion of the lungs can be expected to lessen the sensation.


Phrenicotomy in the rat: acute changes in blood gases, pH and body temperature. Adult male rats were used to compare blood gases, pH and body temperature (Tb) before and after acute bilateral phrenicotomy. Under anaesthesia a femoral artery was catheterised and ties were placed round the phrenic nerves of seven rats (PNX group), while in five rats the ties were placed in the vicinity of the phrenic nerves (SHAM group). Twenty-four hours after surgery arterial blood samples were collected during quiet wakefulness (QW) and grooming (G), before and 1 h after the ties were pulled, and analysed for PO2, PCO2 and pH. No changes were detected in the SHAM samples taken before and after the ties were pulled. In the PNX group a significant decrease in Tb occurred (QW, 0.6 degrees C; G, 1.5 degrees C). Following PNX PaO2 decreased by 11.2 mmHg (QW) and 10.0 mmHg (G); PaCO2 increased by 2.6 mmHg (QW) and 2.4 mmHg (G) and pH fell by 0.04 (QW) and 0.03 (G). All changes except in PaCO2 (QW) were significant. It is concluded that the changes in Tb, blood gases and pH which follow phrenicotomy in the rat are due to an increase in dead space ventilation (VD) and a small reduction in alveolar ventilation (VA) associated with a faster, shallower pattern of breathing.


Afferent innervation and receptors of the canine extrathoracic trachea. The aim of this study was to establish the cranio-caudal distribution of slowly (SAR) and rapidly (RAR) adapting receptors of the extrathoracic trachea (ETT) as well as their innervation and response to water solutions of different compositions. Experiments were carried out on anesthetized dogs breathing spontaneously through a low cervical tracheostomy. Eighty percent of SARs and 76% of RARs with fibers in the superior laryngeal nerve (SLN) were found in the cranial third of the ETT. Fifty-seven percent of SARs and 45% of RARs with fibers in the cervical vagus and/or recurrent laryngeal nerve (RLN) were localized in the caudal third of the ETT. Instillation of water into the tracheal lumen had no effect on the activity of any SAR tested, but stimulated 41% of the RARs with fibers in the SLN and 23% of the RARs with fibers in the cervical vagus. Some of the RARs with fibers in the SLN (24%), but none of those with fibers in the cervical vagus/RLN, responded also to iso-osmotic dextrose solutions. Trachealis muscle contraction failed to stimulate the RARs tested. The blocking temperature for SAR and RAR fibers was similar and well within the range of myelinated fibers. We conclude that the SLN provides the innervation of the cranial ETT while the RLN has fibers for the caudal ETT with some overlap in the middle. The responses to water solutions indicate that tracheal RARs constitute a more heterogeneous group than laryngeal RARs.


Phase differences between chest and mouth flows in patients suffering from pulmonary disease. The phase difference (PD) between mouth flow and chest flow during rest breathing was measured in pulmonary diseased patients using a body box and the results were compared with normal subjects. Whereas the PD increased in patients with chronic pulmonary obstructive disease (COPD) compared to normal subjects, PD was found to be normal in patients with interstitial pulmonary fibrosis (IPF) (Normal: 2.94 +/- 1.25, COPD: 11.32 +/- 4.17*, IPF: 2.62 +/- 1.67 degrees; *P < 0.01). PD correlated well with FEV1.0/VC%, PFR, RV/TLC, VTG and Ra (r: -0.759, -0.672, -0.788, 0.666, 0.606). From an in-depth analysis of the results, we suggest that the factors which increase PD in COPD patients include hyperinflation of the lung, increases in airway resistance and increases in the parallel inhomogeneity of airway resistance accompanied by an unevenness of alveolar pressures. PD was thought to be clinically useful for the evaluation of the pathological stages of COPD because it reflects the overall clinical manifestations in COPD patients.


Mechanical characteristics and functional length of canine expiratory muscles. The expiratory muscles of the abdominal region actively contribute to breathing. In dogs, the transversus abdominis appears to be the main abdominal muscle of expiration. The in vitro mechanical properties of the transversus abdominis have not been reported to date, and formed the basis of the present investigation. Moreover, in order to understand better the nature of the mechanical interplay between the various abdominal muscle groups, we also evaluated the effects of posture on the operational length of canine transversus abdominis and external oblique muscles and related their in situ length to optimal length. The experiments were performed on twelve mongrel dogs, anesthetized with pentobarbital sodium. Contractile properties of excised transversus abdominis muscle strips were evaluated at 37 degrees C and revealed similar twitch, force-frequency and length-tension properties as previously reported in canine external oblique (Farkas and Rochester, J. Appl. Physiol. 65: 2427-2433, 1988). In the supine posture, we noted that external oblique was operating at 88% Lo, while the transversus abdominis was operating at a significantly shorter length of 74% Lo. Thus, in the supine posture, the external oblique is better situated than the transversus abdominis to generate tension. In the prone posture, however, we noted that both abdominal muscles were located at similar positions along their length-tension curve, operating at a length of roughly 77% Lo. Since both muscles share common length-tension characteristics, the present results indicate that the tension generating potential of both muscles in prone dogs is equal for a given neural input. However, we conclude that the preferential recruitment of the transversus abdominis in prone animals must be related to factors other than simple tension generation.


Respiratory-associated thalamic activity is related to level of respiratory drive. We recorded phrenic nerve activity and thalamic single unit firing in unanesthetized, suprathalamically decerebrated, paralyzed and ventilated cats, in which vagi and carotid sinus nerves (CSN) had been ablated. Seventy-six (14%) of 545 neurons in regions of the thalamus related to the ascending reticular system, which had been tonically firing at low respiratory drives, developed rhythmic increases of firing associated with each respiration when drive had been increased by CSN stimulation or hypercapnia. The increases of neuronal firing occurred in late inspiration/post-inspiration but sometimes lasted into expiration; the magnitude of change was graded according to the magnitude of respiratory activity. Thalamic neurons also fired with a rhythm related to ventilator-induced chest expansion, some units showing both the respiratory-associated and the ventilator-related rhythms. Simultaneously recorded mesencephalic and thalamic neurons developed similar rhythms when drive was increased. We suggest that these neuronal activities reflect the conveyance of information about respiration to the cortex, where it may lead to the sensation of dyspnea and perhaps to arousal.


[Cancer research in clinical practice. The attentive physician and the family anamnesis]. Astute physicians play an important role in the detection of cancer causes. Their most powerful tool is the family history. It permits the identification of families with unusual cancer clusters. The members of such families can be recruited for research in prevention and molecular genetics. The potential of research in medical practice should be exploited more extensively in the future.


[Indications for, technique and interpretation of arterial Doppler sonography from the vascular surgeon's viewpoint]. Doppler sonography is one of the most important diagnostic tools for angiologists and vascular surgeons and also for general practitioners with an interest in vascular disease. It can be carried out easily and at low cost and, at the same time, provides reproducible, quantitative data on which further diagnostic and therapeutic decisions can be based. First, systolic arterial pressures in the anterior and posterior tibial and in the peroneal arteries are measured, with the Doppler probe placed at ankle level. A cuff is wrapped around the lower leg and inflated until the Doppler signal disappears. The highest value measured in each leg is termed ankle pressure. Division of the latter by systolic brachial pressure results in the so-called ankle-brachial index or "ABI". Ankle pressure and ABI correlate well with clinical findings. In normal individuals it is greater than 1. In claudication it ranges between 0.3 and 0.9, in patients with resting pain between 0.1 and 0.5 and with ischemic tissue loss between 0.0 and 0.2. After angioplastic or surgical revascularization procedures, a fall of the ABI by 0.15 or more is an indication of relevant hemodynamic deterioration and, therefore, calls for further investigation by arteriography or color duplex sonography.


[Manual medicine of the spine--indication, diagnostic and therapeutic possibilities]. Manual medicine developed rapidly during the last 40 years and became an integral part of standard medicine. The basic idea behind the methods used is that several acute and chronic disorders the spine and peripheral articulations are caused by functional disturbances in one or more spinal motion segments, and also in peripheral joints, always accompanied by reflectory muscular reactions. These changes must be detected and treated specifically. The diagnosis for manual therapy is always complementary to general medical examination. Knowledge of absolute and relative contraindications is the basis for every manual therapy. Therapeutically, apart from the actual mobilization with or without impulse, the so-called neuromuscular techniques are used; these are acting together with the muscle force of the patient and with the thereby triggered reflex-mechanisms. Whereas the latter techniques are also used in physiotherapy, mobilization with impulse should be practised nowadays only by trained physicians and chiropractitioners, since the risks involved are considerable. It is of great importance that the therapy is not limited just to the manipulation of the functionally disturbed motion segment but that in addition muscular disbalance is treated.


Multiple sleep latency tests during the constant routine. The "post-lunch dip" is a common behavioral phenomenon, though perhaps a misnomer. Biphasic models of the human sleep tendency rhythm suggest an alternative explanation for the afternoon decline in alertness. Sleep tendency was measured with the Multiple Sleep Latency Test (MSLT) at 2-hour intervals in 16 volunteers from three age groups (ages 10-12, ages 16-17, ages 62-74 years) during a constant routine in which small meals were given each hour. Baseline scores showed no significant Time of Day effect, although a trend for an afternoon dip was present in the eldest group. During the constant routine, a significant Time of Day effect was found for the two older groups and not for the prepubertal group. The results indicate a midday increase in sleep tendency that is unrelated to food intake but that may be related to developmental or maturational processes.


Precise conservation of NREM period 1 (NREMP1) delta across naps and nocturnal sleep: implications for REM latency and NREM/REM alternation. The delta integrated amplitude (DIA) in nonrapid eye movement period 1 (NREMP1) of daytime naps was precisely subtracted from the NREMP1s of ensuing nocturnal sleep, indicating that the brain can retain a record of DIA expressed in sleep episodes initiated 12.5 and 8.5 hours before nocturnal sleep onset. The DIA subtraction was primarily accomplished by reduced NREMP1 duration [earlier rapid eye movement (REM) onset], suggesting that the timing of REM period 1 (REMP1) onset is controlled by delta need. This result is consistent with the hypothesis that REM sleep occurs when a stimulus for NREM has been partially depleted.


Spontaneous ventilation and respiratory motor output during carbachol-induced atonia of REM sleep in the decerebrate cat. Microinjections of carbachol into the pons induce a state that resembles rapid eye movement (REM) sleep in intact cats and, in decerebrate, artificially ventilated cats, produce postural atonia accompanied by a powerful depression of the respiratory motor output. In this study, pontine carbachol was used in decerebrate, spontaneously breathing cats to assess the effects of mechanical and chemical respiratory reflexes on the magnitude and pattern of the carbachol-induced depression of breathing, and to determine whether the depression is altered in those animals in which rapid eye movements are present. Phrenic nerve activity and tidal volume were only transiently depressed at the onset of the carbachol-induced postural atonia, whereas the decrease in respiratory rate and the depressions of hypoglossal and intercostal activities persisted until the response was reversed by a pontine microinjection of atropine 15-101 minutes after the onset of carbachol response. Ventilation was reduced to 70% of control during the steady-state conditions. The irregularity of breathing, characterized by the inter-quartile ranges of the distributions of the peak phrenic nerve activity and respiratory timing, did not increase following pontine carbachol. Neither vagotomy nor vigorous eye movements were associated with increased breathing irregularity. This contrasts with the irregular breathing (with minor average changes in ventilation) typical of natural REM sleep. We propose that the carbachol-injected decerebrate cat provides a useful model of the depressant effects that neural events associated with REM sleep may have on breathing.


DQB1-0602 (DQw1) is not present in most nonDR2 Caucasian narcoleptics. Human narcolepsy is a genetically determined disorder of sleep strongly associated with the human leucocyte antigens (HLA) DR2 and DQw1. In black narcoleptic patients, susceptibility for narcolepsy is more closely related to a specific gene subtype of DQw1, DQB1-0602, than to DR2. About 30% of black narcoleptic patients are nonDR2, but all carry the HLA DQB1-0602 gene. In the present study, we have tested caucasian nonDR2 cataplectic patients (6 sporadic cases and 7 familial cases from 3 multiplex families) for the presence of the HLA DQB1-0602 and DQA1-0102 (DQw1) using a specific polymerase chain reaction (PCR)-oligotyping technique. None of the patients was DQB1-0602 or DQA1-0102 positive, thus proving that, in caucasians, DQB1-0602 and DQA1-0102 (DQw1) are not prerequisites for the diagnosis of narcolepsy. Further studies with more patients are warranted to exclude the possibility that a few caucasian patients carry rare haplotypes with DQB1-0602 independently of DR2.


Plasma renin activity and sleep-wake structure of narcoleptic patients and control subjects under continuous bedrest. In order to determine if renin release would be affected by a dysfunction of the circadian and ultradian organization of sleep, 24-hour profiles of plasma renin activity (PRA) concomitant with sleep stages were established in 10 normal subjects and nine narcoleptic patients, with 10-minute blood sampling intervals. Mean PRA levels were similar in control subjects and narcoleptic patients. Individual 24-hour profiles revealed that the previously described association between renin oscillations and sleep stage alternations was preserved. Increased PRA release was observed during the transition from rapid eye movement (REM) sleep or waking periods to nonrapid eye movement (NREM) sleep, and REM sleep occurred as PRA levels were decreasing. Thus, PRA curves exactly reflected the irregularities and disturbances in the sleep structure of the narcoleptic patients. The 24-hour PRA profiles of the patients did not show the general upward trend during nighttime sleep, which is probably induced in the control subjects by the repetitive recurrence of longer episodes of undisturbed NREM sleep. Because of marked sleep fragmentation in the patients, the duration of NREM sleep was often insufficient to allow for the occurrence of a significant PRA increase. Because sleep onset REM (SOREM) episodes, characteristic of narcolepsy, are not preceded by NREM sleep and its associated increase in PRA, no relative PRA decline occurred during this type of REM sleep. In conclusion, the 24-hour PRA profiles of the narcoleptic patients reflected exactly their sleep stage distribution, confirming previous findings that PRA oscillations appear to be inseparable from the NREM-REM sleep cycle.(ABSTRACT TRUNCATED AT 250 WORDS)


Sleepiness/alertness on a simulated night shift schedule and morningness-eveningness tendency. This study examined the influence of morningness-eveningness on night shift sleepiness in 15 subjects. Sleepiness was assessed during a five-night protocol involving the multiple sleep latency test (MSLT), repeated test of sustained wakefulness (RTSW) and the Stanford Sleepiness Scale (SSS). Daytime sleep was estimated by sleep diaries and wrist actigraphy. The sample was divided by median score on the Horne and Ostberg Morningness-Eveningness Questionnaire. Physiological sleep tendency was significantly worse between 0030 and 0430 hours for the Morning Tendency group than for the Non-Morning Tendency group. The Morning Tendency group reported obtaining less daytime sleep than the Non-Morning Tendency group; however, there was no difference between groups in total daytime sleep estimated by actigraphy. This preliminary study suggests that morning types are sleepier during night shift hours than non-morning types.


Melatonin rhythms in night shift workers. For some time, it has remained uncertain whether the circadian rhythms of permanent night shift workers are adapted to their night-active schedule. Previous studies of this question have often been limited by "masking" (evoked) effects of sleep and activity on body temperature and cortisol, used as marker rhythms. In this study, the problem of masking was minimized by measuring the timing of melatonin production under dim light conditions. Nine permanent night shift workers were admitted to the Clinical Research Center (CRC) directly from their last work shift of the week and remained in dim light while blood samples were obtained hourly for 24 hours. Melatonin concentrations were measured in these samples using a gas-chromatographic mass-spectrometric method. Sleep diaries were completed for two weeks prior to the admission to the CRC. Overall, the onset of the melatonin rhythm was about 7.2 hours earlier (or 16.8 hours later) in the night workers compared to day-active controls. It was not possible to know whether the phase of the melatonin rhythm was the result of advances or delays. In night shift workers, sleep was initiated (on average) about three hours prior to the onset of melatonin production. In contrast, day-active subjects initiated sleep (on average) about three hours after their melatonin onset. Thus, the sleep times selected by night shift workers may not be well-synchronized to their melatonin rhythm, assumed to mark the phase of their underlying circadian pacemaker.


Comparison of EEG sleep measures in healthy full-term and preterm infants at matched conceptional ages. Continuous electroencephalogram (EEG) sleep studies were obtained on healthy full-term and preterm infants at matched conceptional ages. Studies were recorded under environmentally controlled conditions. Eighteen healthy preterm infants were matched to 18 full-term infants based on conceptional age, sex, race and socioeconomic class. The initial 3 hours of a 12-hour recording were simultaneously recorded on paper and computer. The visually scored data based on the paper recordings for sleep architecture and continuity measures were studied. Differences in each sleep organization for the preterm infants included the following: a longer ultradian sleep cycle (70 minutes vs. 53 minutes, p = 0.02) was noted. More abundant tracé alternant (34% vs. 28%, p = 0.02) and less abundant low-voltage irregular active sleep (13% vs. 17%, p = 0.05) were noted. Although no differences were observed for sleep latency and efficiency, the preterm infants had fewer numbers and shorter durations of arousals, fewer body movements and rapid eye movement (REM) (p < 0.01), particularly during quiet sleep. The extrauterine experience or the earlier birth of the preterm infant may influence specific sleep architecture and continuity measures when compared with the sleep of full-term infants who experienced a complete intrauterine gestation.


A longitudinal study of sleep stages in young women during pregnancy and postpartum. We conducted a longitudinal polysomnographic study in five healthy primiparous subjects, whose sleep was first recorded between 8 and 16 weeks of gestation, then every 2 months until parturition and at 1 month postpartum. The first 6 hours of sleep were used for statistical analysis. In contrast to previous studies, we found no reduction in stage 4 sleep with pregnancy. Slow-wave sleep (comprising stages 3 and 4), was significantly higher at 27-39 weeks of gestation than at 8-16 weeks, as predicted by the restorative theory of sleep. There was no significant difference in rapid eye movement (REM) sleep time. When compared to a group of normal ovulating women, however, REM sleep time decreased during the last two months of pregnancy and, although there was no change in sleep onset latency, the time spent awake during the first six hours of sleep was increased. Future research into the effects of cortisol and progesterone is indicated.


Automatic sleep/wake identification from wrist activity. The purpose of this study was to develop and validate automatic scoring methods to distinguish sleep from wakefulness based on wrist activity. Forty-one subjects (18 normals and 23 with sleep or psychiatric disorders) wore a wrist actigraph during overnight polysomnography. In a randomly selected subsample of 20 subjects, candidate sleep/wake prediction algorithms were iteratively optimized against standard sleep/wake scores. The optimal algorithms obtained for various data collection epoch lengths were then prospectively tested on the remaining 21 subjects. The final algorithms correctly distinguished sleep from wakefulness approximately 88% of the time. Actigraphic sleep percentage and sleep latency estimates correlated 0.82 and 0.90, respectively, with corresponding parameters scored from the polysomnogram (p < 0.0001). Automatic scoring of wrist activity provides valuable information about sleep and wakefulness that could be useful in both clinical and research applications.


[Different varieties and anatomopathological description of primary tumors of the liver]. The different types of primary hepatic tumors are examined, focusing on their macroscopic and histologic features. A large variety of neoplasms can be observed, derived from the different components of the liver. Benign (adenoma, focal nodular hyperplasia) or malignant (hepatocellular carcinoma) epithelial tumors of hepatocellular origin are very common. Hemangioma is the most common mesenchymatous-derived tumor. However, the frequency of each type of tumor varies considerably in the different age and sex groups. Some special entities recently reported, such as epithelioid hemangioendothelioma or fibrolamellar carcinoma are detailed.


[Clinical symptomatology and radiological aspects of primary cancers of the liver]. Hepatocellular carcinoma is a malignant tumor derived from hepatocytes. It is the most frequent of primary liver cancers. In 90% of the cases, it occurs in a cirrhotic liver and is now more and more detected by ultrasonographic screening of cirrhotic patients. Hepatocellular carcinoma can also be diagnosed at a more advanced stage, when complications, such as ascites, jaundice or digestive hemorrhage, occur. CT scan and magnetic resonance imaging are useful to confirm ultrasonographic findings, but angiography with infusion of Lipiodol in hepatic artery followed by CT scan remains the most sensitive method for diagnosis. Intrahepatic cholangiocarcinoma is derived from intrahepatic bile duct cells and does not occur in a preexisting cirrhotic liver. Diagnosis is usually late. Clinical features are those of hepatic malignancy with jaundice and abdominal pain. Morphological examination of the liver shows an intrahepatic tumor, sometimes associated with a dilatation of the surrounding bile ducts. Other primary malignancies are very rare. Fibrolamellar carcinoma presents as an abdominal mass occurring in a young adult with a non cirrhotic liver. Prognosis is better than that of hepatocellular carcinoma. Cystadenocarcinoma is a cystic tumor of bile ducts that can develop in a preexisting cystadenoma. Angiosarcoma is a highly malignant tumor derived from sinusoidal endothelial cells. Exposure to various carcinogens is found in 30% of the cases. Epithelioid hemangio-endothelioma differs from angiosarcoma by its occurrence in young adults and a more favorable prognosis.


[Advantages and difficulties of aerosol therapy]. Aerosolization of drugs may be designed to treat lower respiratory tract and bronchial diseases and more recently infectious diseases of the lungs. The use of drug aerosol has been limited by the relative lack of knowledge about the fate of inhaled drugs. It depends on the specifications of the aerosol, the drug itself, the conditions of aerosolization, and the presence of lung disease. The advantage of the airways route is that treatment effects are obtained without systemic effects.


[Vasomotricity of normal and atheromatous coronary arteries]. In order to fulfil, at any time, the myocardium requirements for oxygen and energy, the coronary circulation must be able of extremely intense and rapid vasodilation. This circulation undoubtedly is the body's regional circulation that "works" in the most difficult anatomical and physiological conditions. Coronary vasomotricity is regulated by three different systems operating synchronously. Metabolism-mediated vasodilatation, with adenosine as principal mediator, essentially concerns the small-caliber intramyocardial arterioles and is the predominant regulatory system in normal subjects. Nervous regulation (sympathetic and parasympathetic systems) exclusively concerns the wide, epicardial coronary arteries; it plays a modest, but non-negligible, role in normal subjects but becomes very important in patients with stenosis of the epicardial coronary arteries. Endothelium-mediated regulation, discovered about 10 years ago, seems to play a crucial role. Under the influence of haemodynamic and humoral stimuli, the endothelium synthesizes and releases substances which stimulate the underlying vascular smooth muscle. Nitric oxide (NO), or EDFR1, is the best known, but not the only messenger of vasodilatation; beside its relaxant effect on the smooth muscle, it exerts a potent platelet antiaggregating action. The functioning of these regulatory systems is deeply perturbed by atheroma of the coronary arteries: in addition to the fixed haemodynamic obstacle due to atheromatous stenosis, there is a diffuse decrease of endothelial functions and a rise in sensitivity to nervous vasoconstrictor stimuli.


Atrial natriuretic factor in cats subjected to acute myocardial ischaemia. Eighteen anaesthetized open chest cats were subjected to 10, 30, or 50 min occlusion of the left anterior descending coronary artery (LAD). Heart rate, left ventricular end-diastolic (LVEDP) and systolic pressure (LVSP), and dp/dt were continuously recorded during the experiments. Prior to LAD-occlusion, and just before termination of the experiments, blood samples were collected from the left femoral artery for measurements of atrial natriuretic factor (ANF), catecholamines, electrolytes, urea, and creatinine. Simultaneously, biopsies were collected from the right auricular wall. The tissue was embedded in Lowicryl K4M, and ultrathin sections were incubated with anti-ANF antibodies and secondary antibodies conjugated to gold particles. The density of ANF-containing atrial-specific granules labelled with gold particles was morphometrically calculated. LVEDP increased significantly in all three time groups, and when pooling the pre- and postocclusion values, there was an increase from 5.1 +/- 0.4 to 10.3 +/- 1.2 mmHg (p < 0.05). The noradrenaline level increased from 0.93 +/- 0.18 to 2.34 +/- 0.75 nmol l-1 (p < 0.05) after LAD-occlusion. Similarly, the mean plasma level of ANF in the 18 cats increased from 57.6 +/- 11.9 to 98.9 +/- 22.6 pmol l-1 (p < 0.05). Atrial granular density appeared to decline after 10 min of occlusion (from 0.141 +/- 0.017 to 0.127 +/- 0.022 granules-1 microns 2 sarcoplasm), and after 30 min there was a significant decrease (0.080 +/- 0.012 granules/microns 2, p < 0.05). However, after 50 min occlusion the granular density was almost restored (0.133 +/- 0.017 granules/microns 2). Plasma ANF showed a positive linear correlation to LVEDP and to the noradrenaline level.(ABSTRACT TRUNCATED AT 250 WORDS)


Rapid C-reactive protein (CRP) measurements in the diagnosis of acute appendicitis. C-reactive protein (CRP) has been measured in plasma of patients with acute appendicitis and in controls without appendicitis to test the accuracy and diagnostic performance of a new rapid test kit for CRP (NycoCard CRP). The values obtained for CRP by the rapid test correlated well (Rs = 0.92) with the reference method for measuring CRP. The sensitivity, specificity and predictive values were calculated at different cut-off values. At values > 10 mg l-1 a sensitivity of 58% and a negative predictive value of 72% were found. Higher values of sensitivity were observed for men than for women, 69% and 44% respectively. Patients with acute appendicitis who had had symptoms for more than 24 h, had elevated CRP values (cut-off > 10 mg l-1) in more than 80% of cases. Our study shows that the rapid CRP test and the reference CRP test gave an almost identical result.


Transcapillary filtration of plasma protein in long-term type 1 (insulin dependent) diabetic patients. To study the pathophysiologic mechanism leading to increased transcapillar sieving of albumin in patients with diabetic nephropathy, subcutaneous interstitial concentrations of albumin, transferrin, total IgG and IgG-4 was measured in 30 long-term type 1 diabetic patients using the skin suction blister method. Eight normal subjects served as controls. The patients were divided in groups according to their urinary albumin excretion: normal (n = 11), micro-albuminuria (n = 9), and clinical nephropathy (n = 10). Results were expressed as the blister to serum concentration ratio (Cb:Cs) of each macromolecule. Normoalbuminuric patients had lower Cb:CsIgG ratio than healthy controls (0.28 +/- 0.04 vs. 0.35 +/- 0.09, p = 0.03). The lowest Cb:CsIgG ratio (0.23 +/- 0.07) was found in patients with clinical nephropathy. The same trend could be demonstrated in the other Cb:Cs ratios, but differences there were not significant. No differences related to capillary charge- or size-selectivity could be demonstrated between the groups. The results might reflect an increase of intracapillary hydrostatic pressure or increased capillary hydraulic permeability in the diabetic state per se, augmented during the development of microvascular complications.


Serum concentrations and excretion of bile acids in cirrhosis. Bile acid concentrations in serum, and urinary and faecal excretion of bile acids have been studied in ten patients with liver cirrhosis as a consequence of alcohol abuse. Eight of the patients were categorized as Child group A, whereas the remaining two patients comprised Child group C. Individual bile acids were isolated and identified by gas chromatography coupled to mass spectrometry. Total fasting serum bile acid concentrations were elevated in all patients, but not correlated to conventional tests of liver function. Eight of the patients had increased urinary excretion of bile acids. Faecal bile acid-excretion was highly variable between patients, and also between Child's group A and C patients. Total fasting serum bile acid concentrations were not correlated to either urinary, faecal, or total bile acid excretion (= synthesis of bile acids) or to the ratio between urinary and faecal excretion of bile acids. The daily synthesis of bile acids showed a large overlap between Child's group A and C patients. The percentage of chenodeoxycholic acid and its metabolites relative to total daily excretion of bile acids did not correlate, indicating that the synthesis pathways for the primary bile acids does not systematically change in relation to the rate of synthesis. We conclude that even in mild cirrhosis, serum bile acid concentrations are elevated. However, no consistent changes in synthesis of bile acids or synthesis pathways was observed in such patients.


Biological variation of the leukocyte differential count quantities. The biological variation of the blood concentration and number fraction of the different kinds of leukocytes have been estimated, over a one-year period in a group of 19 women and 20 men, apparently healthy volunteers. All measurements have been performed with a Toa E-5000 haematological analyser. The medians of the within-subject biological coefficients of variation, separated by sex when significant differences exist, are the following for concentrations: 9.4% in men and 15.4% in women for the leukocytes, 16.9% in men and 26.9% in women for the neutrophils, 12.3% for the lymphocytes, 14.9 for the basophils+eosinophils+monocytes (as measured by Toa E-5000); and for number fraction are the following: 8.6% for neutrophils, 0% in men and 7.2% in women for lymphocytes, and 16.7 for basophils+eosinophils+monocytes (as measured by Toa E-5000). With these data the index of individuality, the critical difference for significant change detection and the desirable imprecision have been calculated.