[Sleep disorders and use of psychotropic drugs in 6-year-old children].

The purpose of this prospective survey, conducted over a two years period, was to study the use of psychoactive drugs among six year-old children in the Bas-Rhin administrative "département", of eastern France. The factors analysed were family environment, after-school time, the child's sleep, the locality where the child lived and the drugs used. The child was examined by school doctors, in the presence of the parents, at the compulsory consultation at the start of first-year infant school. The study was exhaustive. Of the 11,274 children examined, 12.1% used a psychoactive drug, although only 1% were considered by their parents to be suffering from insomnia. Of the children using drugs, 32% had used them for more than a year, 24% for more than two years and 11% for more than three years. Consumption was also shown to vary greatly between different localities; in some areas the proportion of children using drugs was more than 50%.


[Clinical and molecular basis of androgen resistance].

Androgen resistance is responsible for the development of a spectrum of abnormalities of male sexual differentiation, and can be broadly divided in two categories: deficiency of 5-alpha-reductase and defects in the androgen receptor. Recent developments in the field on molecular biology have allowed the cloning and characterization of the genes responsible for both syndromes and have made it possible to detect the subtle molecular defects underlying these diseases. This discussion will review some of the most recent development in this field of research.


[Recent diagnostic and therapeutic aspects in male sexual impotence].

Male sexual impotence is the symptom of an alteration of central and peripheral mechanism neuropsychoendocrine, vascular and neurological. Nowadays it affects 8-10% of sexually active population. In some diseases, like diabetes and uremia, it can reach very high percentages of incidence. At our Andrology Center 35% of referrals are represented by sexual complaints. In the last years the diagnostic accuracy has increased, narrowing the percentage of unknown causes. Vasculopathy represents the most relevant pathological condition associated with impotence: it can affect both arterial and venous vessels. The new medical technologies and procedures permit an increase of the life span but often affecting the quality of life. Therefore, the iatrogenic causes of impotence, both pharmacological and surgical, are growing. A modern diagnostic approach starts with an accurate clinical history and physical examination, followed by an NPT (nocturnal penile tumescence) test and/or ICI (intracavernosal injection) with a standard dose of PGE1 and Doppler flowmetry of penile arteries. An endocrine evaluation (LH, testosterone and prolactin) is also performed. Further investigation of a vascular dysfunction is represented by more invasive procedures, like arteriography, cavernosography and cavernosometry. A suspect of neurological disease is confirmed by sacral evoked potentials. According to the findings of these examinations, a correct therapeutical approach can be applied in 100% of cases. An endocrine treatment is adequate only when a clear reduction of T plasma level or hyperprolactinemia are present. The treatment of other central disorders causing psychoneuroendocrine impotence is promising, but still under investigation. The intracavernosal injection of vasoactive drugs, apart from having revolutionized the diagnostic approach to the impotent patient, represents a clear standpoint in medical management of impotence, particularly in vascular and neurological diseases. The great advancement in the technology of penile prostheses has allowed the development of valuable and reliable tools to be used in selected cases.


[Hyperthyroidism during pregnancy].

The authors review the current knowledge of fetus and woman thyroid physiology during pregnancy. They analyze the abnormalities related to hyperthyroidism, and clinical and therapeutic aspects of thyrotoxicosis; in detail possible fetal complications. They suggest the practical management of thyrotoxicosis during pregnancy.


Therapeutic strategies in a male with delayed puberty.

Therapeutical strategies in male with delayed puberty. Delayed puberty (absence of pubertal modifications after 14-15 years of age) due to transitory deficit of LHRH secretion often constitutes a difficult differential diagnostic problem for conditions of permanent LHRH deficit which can be identified only after 18 years of age in the idiopathic hypogonadotropic hypogonadism. After a period of clinical observation short-term therapy with pulsatile LHRH administration may take place. Therapy can be necessary: to document the functional integrity of the pituitary-gonadal axis; to promote pubertal modification such as to improve and physiologically sustain the patient; to tray a neuroendocrine activation of endogenous LHRH-LH secretion. Also delayed puberty linked to uremia seems to respond to short-term pulsatile LHRH administration. Pulsatile LHRH administration is the most physiological therapeutical approach to subject with delayed puberty. It seems to constitute a valid alternative to the therapy with testosterone or gonadotropins.


[Respiratory inductive plethysmography in the functional evaluation of patients undergoing coronary by-pass surgery].

The functional respiratory changes following coronary by-pass surgery were previously evaluated with the traditional spirometric method. Aim of this work is to introduce the respiratory inductive plethismography (RIP), a well known non-invasive technique, into the study of those volumetric and ventilatory modifications. Eight cardioischemic patients were selected: all but one were free from pulmonary disorders. The tidal volume, the respiratory rate, the minute ventilation, the vital capacity and the relation between the abdominal and the thoracic part of the ventilatory act, were measured in the pre-intervention session and in the 1st, 3rd and 7th day after the operation of coronary by-pass. In the same sessions, except the 1st day after surgery, the maximal respiratory pressures were evaluated with traditional manometers. The functional changes of the examined parameters, statistically studied with the variance analysis, closely resemble the spirometric modifications registered by other authors. Furthermore the relative contributions of the thoracic and abdominal compartments of the pulmonary ventilation were evaluated, thanks to the non-invasive plethysmographic method. Rip makes it possible to measure the ventilatory pattern and some pulmonary volumes in the very early phases after thoracic surgery, without any trouble for the patient and in a non-collaborative state of consciousness, too.


[Diet manipulations and nickel sulphate-induced contact dermatitis evaluated in 24 cases].

The wide distribution of nickel in the environment as well as in animal and vegetable foods has led a large number of authors to investigate the oral absorption of nickel. The aim of this study was to evaluate the effect of a free-nickel diet in 24 patients affected by nickel sulphate-induced contract dermatitis. The diagnosis was made on the basis of their past history and of Patch test. A complete remission of symptoms was obtained with a nickel-free diet for two months; Patch test became partial negative in 50% of patients and completely negative in 33%. In conclusion our results confirm the relationship between nickel-induced dermatitis and oral nickel absorption and suggest that diet manipulations can be useful in cases of refractory skin manifestations.


[Microparticulate aerosols and respiratory allergy].

The assessment of allergenic activity in submicronic particles could explain some unknown aspects of pollinosis pathogenesis. Twenty-five 0.5 discs have been obtained using a high volume sampler (Hi Vol Andersen) equipped with 0.3 micron Whatman paper filters. These discs have been challenged with a concentrated pool of sera of Parietaria allergic patients by RIA in order to evaluate the presence of allergenic activity on filters. Discs of non sampled filters and discs of sampled filters challenged with serum pool of patients sensitized to house dust mites were used as controls. The percentage of bound radioactivity was detected by gamma-counter. The radioactivity bound to sampled discs with Parietaria sera was 2.3 +/- 0.55 (Standard Deviation); radioactivity detected on control discs was comparable to background values detected by counter. These preliminary date might suggest that submicronic particles of Parietaria can retain some allergenic activity.


[An unusual chronic microvasculitis: Goodpasture's syndrome with late myocardial involvement].

We describe a disease, started in a female young adult patient as an apparent pulmonary siderosis, followed nine years later by an extracapillary proliferative nephritis, which developed to uremia in a few months. Later an intra-myocardial vasculitis, responsible of heart failure, appeared. Immune-histochemistry and serological tests exclude a disease mediated by anti-GMB antibodies, and pathologic features suggest a vasculitis mainly affecting lungs and kidneys.


A case of vascular purpura with scurvy.

A case of vascular purpura of the lower limbs in a 67 year old man is described. A diagnosis of scurvy was made in consideration of the absence of signs of vasculitis on skin biopsy, the history of a diet extremely poor in vitamin C and the prompt resolution of clinical picture with administration of vitamin C. The authors emphasize the importance of taking into consideration scurvy in the differential diagnosis of vascular purpura: this may spare expensive investigations and a dangerous delay in appropriate therapy.


[Can alpha-interferon exacerbate a case of mixed cryoglobulinemia?].

We describe a case of exacerbated mixed cryoglobulinemia in a patient previously treated with alpha-interferon, for chronic active hepatitis. The possible pathogenesis of this exacerbated mixed cryoglobulinemia and the relationship between cytokines, hepatitis viral infections and immune reactions is discussed.


Migration stimulation factor (MStF), from murine B cells, constitutively produced by a T-B hybridoma.

Hybridomas were established between murine spleen B cells and the thymoma cell line BW5147, to purify the migration stimulation factor (MStF), a molecule likely involved in immunosuppression. The parental B cells were from Lo/PHA mice previously shown to produce high levels of MStF after immunization by appropriate (tolerogenic) doses of ovalbumin. Among the positive clones, B9 was selected, since it produced high levels of MStF constitutively, and no immunoglobulin. This clone was shown to contain the genome of the B-cell fusion partner, since one of its L chain genes had undergone a VK-JK rearrangement. Isolation of MStF by size-exclusion chromatography showed 2 major peaks of activity, one of which eluted in a 20-kDa, almost protein-free fraction. This elution is unlikely to correspond to the true molecular mass, since MStF was found not to be a protein. Indeed, MStF was TCA-soluble, thermoresistant, highly hydrophobic and protease-resistant, but activity was abolished by neuraminidase digestion. The possibility of its being a small molecule transported by a protein carrier was also ruled out. These results suggest that MStF is a complex molecule containing both sialic residues and a lipid moiety. Experiments are planned to further investigate the chemical structure of this unusual B-cell factor.


[Lymphoproliferative syndrome with granular lymphocytes of CD8+ phenotype: a clonal pathology with a chronic course].

The syndrome of CD8 hyperlymphocytosis with neutropenia is a heterogeneous disorder ranging from reactive benign state to neoplastic pathology. The prognosis for LGL (Large Granular Lymphocyte) leukemia depends likely on its phenotype:-NK phenotype, extremely poor prognosis and rapidly fatal-T phenotype (CD8+), chronic disease with slow progression. Here, we report four cases of CD8+ hyperlymphocytosis with neutropenia, which are CD2+/-, CD3+, CD4-, CD8+, CD16-, CD56+/-, CD57+ phenotype. These lymphocytic proliferations were associated with clonal rearrangement of T-cell receptor b gene. In two cases, characteristic blood hyperlymphocytosis appeared only after splenectomy, but retrospective bone marrow analysis showed that the CD8+, CD57+ lymphocyte proliferation previously existed. These lymphocytes had a low natural killer activity against K562 cell line. HTLV1 proviral sequence was not integrated in leukemic cell DNA. This monoclonal pathology has a chronic clinical course, with a thirteen year evolution in one case. Splenectomy did not correct neutropenia but allowed the control of hemolytic anemia and auto-immune thrombocytopenia in one case.


[Incidence of cholesterol embolisms in 70 atheromatous patients hospitalized for cardiovascular evaluation].

Cholesterol crystal embolization must be considered in all atheromatous patients hospitalized for cardiovascular evaluation. Because this is a difficult and often belated diagnosis, between June 1989 and June 1990 a prospective study was conducted on 70 patients. Clinical monitoring, including examination of the fundus oculi, was performed before, and on the 5th day of cardiovascular investigations. The incidence of systemic emboli (12.8%) detected in this way corresponds to that reported in rare published series. Funduscopy is a simple, rapid and little expensive examination which should improve the investigative procedures and point to the best treatment.


[Prognostic factors and monitoring of myeloma].

An improved knowledge of the initial prognostic factors of multiple myeloma and regular monitoring of the disease should result in the choice of the most effective treatment. The conventional prognostic factors have been divided into three stages by Durie and Salmon. These stages are based on the proportion and type of the monoclonal component, on haemoglobin, calcium and creatinine blood levels and on the extent of bone lesions. However, this widely used classification has certain disadvantages: the size of the tumoral mass is evaluated mainly from the proportion of monoclonal gammopathy, the bone lesions are difficult to determine and the kinetics of cell proliferation are not taken into account. Parameters with high prognostic value have recently been demonstrated; they include beta 2-microglobulin, LDH, interleukin-6, C-reactive protein, serum albumin and kinetic of cell proliferation. When associated, these data allow to establish prognostic staying that are at least as relevant as those of the Durie-Salmon's classification. Monitoring of patients with multiple myeloma by means of a time-related curve of either the tumoral mass or the amount of monoclonal gammopathy leads to the best possible treatment.


[Physiopathology of human obesity].

Our knowledge of hunger and bodyweight regulation is gradually increasing. There are wide interindividual variations in nutritional needs and therefore in susceptibility to gross overweight. Obesity is associated with disturbances in neurosensorial, hormonal and metabolic regulations which are now much better understood. Studies of certain ethnic groups in which obesity is particularly prevalent contribute to the genetic approach to the condition. As in animals, where obesity models correspond to mono- or polygenic transmissions, it is probable that in human beings obesity is a syndrome with multiple causes.


[Acute non-obstructive necrotizing enterocolitis in adults].

Acute non-obstructive necrotizing enterocolitis in adults is characterized by pathological features: it is an intestinal necrosis beginning in the mucosa, without obstruction of the mesenteric vessels. The disease occurs in a variety of circumstances which may be roughly divided into infections and fall in proximal or distal mesenteric flow rate, the infectious and circulatory mechanisms often coexisting. Little information on the diagnosis is provided by clinical and paraclinical data. Management is medical and/or surgical; it includes alleviation of the symptoms in intensive care unit, attempts at producing local vasodilation whenever possible and resection of the intestinal segment affected. In many cases the diagnosis is made at exploratory laparotomy. The prognosis is poor; it depends on the patient's age, on the extent of the lesions which sometimes require wide intestinal resections, and on the time to diagnosis.


[Pyogenic osteomyelitis in Gaucher's disease].

Gaucher's disease is a sphingolipidosis which may be accompanied by severe pain in the bones. We report a case of Bacteroides fragilis osteomyelitis consecutive to surgical biopsy. The bone pain may be due to ischaemia of the bone or to a pyogenic osteomyelitis which is iatrogenic in most cases. The clinical and paraclinical features of these two entities are described after a review of the literature, and the main complementary examinations leading to their diagnosis are presented.


["Spontaneous" hematoma of the psoas in Gaucher's disease].

The authors report a case of iliac muscle haematoma responsible for inguinal pain in a patient with Gaucher's disease type I. This exceptional cause of pain must now be considered side by side with the classical femoral head osteonecrosis and infectious coxitis. Magnetic resonance imaging appears to be the most sensitive and most specific examination for the aetiological diagnosis of hip pain in Gaucher's disease. In the absence of thrombocytopenia and franck abnormality of coagulation, the spontaneousness of the haematoma is discussed.


[Septicemia associated with the presence of a pacemaker with endocavitary electrode].

Septicaemia on endovenous pacemaker electrodes is infrequent and difficult to detect. We report the case of a 64-year old woman with a diagnosis of prolonged fever that dragged on for several months before infection of her pacemaker was considered, then confirmed. Repeated Staphylococcus epidermidis isolates from blood cultures were no longer regarded as contaminations, and transoesophageal echocardiography revealed the presence of a "mass" on her endocavitary electrode, which had not been visualized on several previous échocardiographies. Surgical removal of the electrode was soon required in view of multiple septic emboli despite a bacteriologically effective antibiotic therapy. The outcome is favourable after a 6-month follow-up. The authors review the diagnostic and therapeutic problems created by infections on electrosystolic exciting electrodes.


[Sarcoidosis and leukemia/T-cell lymphoma associated with HTLV-1 virus infection in adults (apropos of a case)].

The HTLV-1 virus causes a disturbance of the immune system, the evaluation of which is often difficult. We report a case of sarcoidosis in a 49 year old woman of Martinique as evidenced by bilateral hilar adenopathy, hypercalcaemia, uveitis and granulomatous lesions on histological examination. Serological was positive for HTLV-1 antibodies. Three years later she developed an adult T-cell leukemia/lymphoma. The relationships between the HTLV-1 retroviral infection and different pathologies observed are discussed.


[Inflammatory rheumatism flare-up after surgical treatment of Cushing's disease: two cases].

The anti-inflammatory effect of natural glucocorticoids is often overlooked, as shown by these two cases of inflammatory rheumatism flare-up which occurred after surgical treatment of Cushing's syndrome. The disorder in the first case was exacerbation of a probable rheumatoid arthritis; in the second case an unlabelled inflammatory rheumatism appeared in a context of postoperative corticotropic deficiency. In both cases a purely substitutive hydrocortisone therapy resulted in dramatic regression of the articular symptoms. It is well known that rheumatismal manifestations may occur in patients with slow adrenal failure. The determinant factor seems to be a glucocorticoid deficiency, either isolated or associated with others, since cortisol exerts and anti-inflammatory activity. In patients with corticotropic deficiency following surgical treatment of Cushing's disease, the endogenous corticosteroid therapy of hypercortisolism is interrupted, allowing the aggravation or emergence of inflammatory rheumatism.


[Circulating lupus coagulation inhibitor in two sisters, one with disseminated lupus erythematosus and the other with immunologic thrombocytopenic purpura].

Familial cases of lupus anticoagulant were rarely described. We report the observation of two sisters with lupus anticoagulant, one with thrombocytopenic purpura and the other with systemic lupus erythematosus.


[Antiphospholipid antibodies (aPL): detection and clinical significance].

Phospholipid-binding antibodies are heterogeneous immunoglobulins of G and/or M and/or A class which can be detected in association with a variety of pathologies. However they can also occur in the absence of any clinical manifestations. Despite their paradoxical in vitro anticoagulant activity, phospholipid-binding antibodies, either primary or secondary, are frequently associated with venous and/or arterial thrombotic events. Hence, their detection has to be performed in several major clinical situations, cerebral attack, myocardial infarction, recurrent fetal loss, deep vein thrombosis ... Their course has to be controlled at least every six months. Since the incidence of phospholipid-binding antibodies in auto-immune pathologies is high, immunological disorders should also be considered. As yet there is no standardized assay of phospholipid-binding antibodies, either functional with respect to their anticoagulant activity, or immunological (ELISA). It is not established whether they possess an own pathogenic potential or appear as a secondary response following cellular alterations known to be thrombogenic. However it has been suggested that they could participate in the disruption of the hemostatic balance towards procoagulant tendency resulting in thrombosis.


[Treatment and monitoring of primary hypothyroidism].

Treatment of primary hypothyroidism requires a long-term hormonal therapy with levothyroxine which restores a normal TSH value. In a series of 192 patients followed up for at least 3 years we tried to evaluate the variability of maintenance dosage and to analyse the factors predictive of replacement dosage. The L-T4 dosage varied from one individual to the other, from 0.6 to 3.2 micrograms/kg. The mean maintenance dosage (118 +/- 38 micrograms/day) was similar in men and women weight for weight, but it was higher in subjects aged under 60 and in those with Hashimoto's or congenital hypothyroidism. There is a positive linear relation between the equilibrium dose and the TSH value (n = 0.84; p < 0.001) and a negative relation with the L-T4 concentration (n = 0.71; p < 0.001). The yearly variation of dosage in each individual was small (about 3.5%) and of the same order as the variation of weight. We conclude that the L-T4 maintenance dosage depends on the cause of hypothyroidism, on the importance of biochemical abnormalities and on the patient's age, sex and weight. In practice, however, the necessary dosage is difficult to predict. In the equilibrium phase the need for replacements is remarkably stable. A yearly assay of baseline TSH seems to be sufficient to evaluate the quality of hormonal compensation in the absence of intercurrent events.


Who gets care? Access to health care as an arena for nursing action.

Access to health care in the United States is undeniably inequitable. What should nurses do in the face of increasing gaps in availability of services? The author addresses this question by framing access to health care in its broadest sociopolitical context, positing that access to care is an essential dimension of nursing theory, research, and practice. By offering a conceptual definition of equitable access, providing rationale for the significance of this concept, and critically exploring conditions that limit access to affordable, high quality, nondiscriminatory health care in the U.S., the author lays theoretical groundwork for more effective investigatory and practical action to assure equitable access.


Qui bono? Nursing education in the context of nursing's agenda for health care reform.

Stevens' question "Who Gets Care?" is in the tradition of those arguing for increased access and a more equitable distribution of society's benefits. As such, it provides a framework for nursing scholarship concerned with social as contrasted with individual interventions. Nursing's Agenda for Health Care Reform advances the argument still further by questioning the ideology reinforced by the current system, and offering an alternative system, alternative services and agents. In so doing, the proposed agenda questions the dominant ideology and is, therefore, more accurately a radical departure from the status quo than a reform. While there are some implicit assumptions of both reform and radical change embedded within the work of those addressing a "curriculum revolution," the discussion would benefit from explicit expositions of both the social construction and social function of higher education.


Diagnosis of human parvovirus B19 infections by polymerase chain reaction.

The polymerase chain reaction (PCR) was used for detecting parvovirus B19 DNA in clinical specimens. A pair of oligonucleotide primers spanning the PstI-fragment of the B19 virus genome was used for PCR, and a PCR product of 727 bp was amplified. B19 virus DNA was detected in all sera (n = 26) of individuals in the incubation period and acute phase of infection. PCR was useful for detecting viral B19 DNA in amniotic fluid and fetal blood of hydropic fetuses, confirming fetal B19 virus infection.


The AIDS epidemic in Tanzania: rate of spread of HIV in blood donors and pregnant women in Dar es Salaam.

The prevalence of antibodies to HIV in population groups in Dar es Salaam, Tanzania has been monitored from late 1984 through 1991. In the pregnant women and blood donors the doubling time was about 2 years. If, however, the doubling time is calculated from reported cases of AIDS of the whole country, an average doubling time of 10 months is obtained. We point out factors that may bias calculations of the rate of spread of the virus and thus give rise to erroneous projections for the nearest years, especially the so-called transient effect. It is recommended that serosurveys of representative population groups are carried out at regular intervals.


Sexually acquired HIV infections: an analysis of epidemiological data concerning cases reported in Sweden 1988-90.

536 Swedish residents who during the years 1988-90 were reported as having contracted HIV through sexual contacts were asked about circumstances regarding the transmission. Answers were received in 411 (76.7%) of the cases (285 homosexual men, 68 heterosexual men and 58 heterosexual women). In 282 (69%) of the cases the persons were without symptoms and in 231 (56%) cases the infection was considered to be < 3 years old. Among homosexual men and heterosexual women the infection was usually acquired in Sweden or Europe whilst heterosexual men more often acquired their infection at casual contacts on other continents.


A six-year follow-up of HIV seroprevalence among 300 intravenous drug users in Stockholm.

As HIV tests became available in 1984, 300 intravenous drug users (IVDUs) admitted to treatment centres in Stockholm were tested and asked questions regarding their drug use and other risk factors with regard to HIV. At this initial testing, 33 persons (11.0%) were seropositive. Among the 79 heroin users, 28 (35.4%) were positive. The cohort has been followed until 1990 at which time a further 12 seroconversions had taken place. Annual seroconversion rates fell during the study period. The findings support the official statistics showing a fall in new HIV diagnoses among IVDUs during the second half of the 1980's.


Clinical and immunological follow-up of previously hospitalized HIV-2 seropositive patients in Bissau, Guinea-Bissau.

A follow-up study was done in Bissau on 113 HIV-2 seropositive patients and 97 HIV-2 seronegative patients 3-15 months after hospitalization. Follow-up totalled 63.5 person years for seropositive patients and 62 for seronegative patients. The mortality during the follow-up period was 43.3% among the seropositive patients (rate 72/100 person years; p.y.) and 25.8% among the seronegative patients (40/100 p. y.). Among 25 HIV-2 associated AIDS cases the mortality was 80% (rate 117/100 p. y.). The median survival time for the AIDS patients was 8 months. Among 48 HIV-2 seropositive patients who lacked signs or symptoms included in the WHO case definition for AIDS at the time of hospitalization 6 patients (12.5%) developed AIDS related symptoms (ARS) during altogether 31.5 person years of follow-up (rate 19/100 p. y.). Tuberculin anergy was demonstrated in 83.3% (15/18) of HIV-2 seropositive patients with AIDS or ARS, in 14.3% (6/42) of seropositive patients without HIV-related symptoms and in 6.9% (5/72) of seronegative patients. A low CD4 T-lymphocyte count in combination with a low CD4/CD8 T-cell ratio was found significantly more often in HIV-2 seropositive patients with AIDS or ARS (62.5%, 10/16) than in HIV-2 seropositive patients without HIV associated symptoms (6.9%, 2/29) or in seronegative patients (2.7%, 1/37). Thus the mortality among recently hospitalized HIV-2 seropositive patients was high and a high proportion of seropositive patients with HIV-related symptoms had evidence of immunodeficiency.


Multiresistant Shigella species from African AIDS patients: antibacterial resistance patterns and application of the E-test for determination of minimum inhibitory concentration.

The antibacterial resistance pattern and minimum inhibitory concentrations (MIC) of 25 Shigella flexneri, 5 S. boydii, 8 S. sonnei, and 3 strains of S. dysenteriae type 2 isolated from Kenyan prostitutes with bacillary dysentery and AIDS were determined, and the applicability of the E-test for MIC determination evaluated. All strains were resistant to > or = 3 of 9 different antibacterial agents tested. All strains were resistant to tetracycline and erythromycin, 95% to trimethoprim/sulfonamide, 93% to streptomycin, 54% to ampicillin, 39% to chloramphenicol, 2% to nalidixic acid and none to gentamicin and ciprofloxacin. Six different resistance patterns were observed. The most common pattern was resistance to tetracycline, erythromycin, trimethoprim/sulfa and streptomycin (39%). The E-test was shown to be well-suited for susceptibility testing of multiresistant Shigella spp.; the reproducibility was excellent and the correlation with the microtiter dilution method and the disk diffusion method were 98% in both instances. The MIC measured with E-test and the microdilution method were within +/- 1 dilution step for 94.4% of the combinations tested.


Clinical features of sporadic Campylobacter infections in Norway.

To assess risk factors and clinical impact of campylobacteriosis in Norway, a case-control study of sporadic cases of infection with thermotolerant Campylobacter spp. was conducted. This report describes: (1) the frequency and duration of signs and symptoms, antimicrobial treatment, hospitalization, and faecal carriage among the study patients; (2) diarrhoeal illness and campylobacter carriage among their household members; and (3) antimicrobial susceptibility pattern among bacterial isolates. A total of 135 patients with bacteriologically confirmed campylobacter infection were enrolled in the study. Of these, 58 (43%) were domestically acquired while 77 (57%) were acquired abroad. If the study enrollees are representative of the cases reported to the national surveillance system, the reported infections led to an estimated annual average of at least 8590 days of illness, 78 admissions to hospital, 329 days of hospital stay, 2236 days lost at work or at school, 1000 physician consultations, and 96 antimicrobial prescriptions among the 4.2 million Norwegians. Convalescent carriage of campylobacter was detected in 16% of the patients who submitted follow-up stool specimens; the organism was carried for a mean of 37.6 days (median 31, range 15-69) after the onset of illness. Antimicrobial treatment appeared to have reduced the likelihood of carriage once symptoms had resolved. Diarrhoeal illness was more commonly reported in members of case households than control households (OR = 5.44, p < 0.0001). Cases were more likely than controls to report antecedent recurrent diarrhoea (OR = 6.00, p = 0.034). Two cases of neonatal infection, probably acquired from the mother at the time of delivery, were detected.(ABSTRACT TRUNCATED AT 250 WORDS)


Vaccine immunity to diphtheria: a 20-year follow-up study.

A cohort of close to 70 children born in 1967-68 was followed for estimations of serum antitoxin levels against diphtheria. During the first 3-year-period after vaccination the mean level declined from 0.05 international units (IU) to 0.03. From the year before to the year after the booster of 0.5 LF of toxoid was given at the age of 8 years, the mean level raised from 0.01 to 0.06 IU. At 18 years the mean was again down to 0.01. Between 18 and 23 years of age a difference between the sexes was seen (higher levels in men). The explanation of this phenomenon must be the extra booster given to those young men who have done their compulsory military service.


Immunoglobulin- and complement-coated bacteria in middle ear effusions during the early course of acute otitis media.

We used an immunofluorescence assay to investigate the content of secretory IgA- (SIgA), IgG-, IgM- and C3b-coated bacteria in middle ear effusions obtained within 12-72 h after the onset of acute symptoms of purulent otitis in 28 patients (37 ears). Simultaneously we analyzed the bacteria, both qualitatively and quantitatively, using standard culturing methods and fluorescein conjugated (FITC) antibodies to Haemophilus influenzae and Streptococcus pneumoniae. The ages of the patients were in the range of 5 months to 17 years; 18 were males and 10 females. 73% of the samples harboured no antibody- or C3b-coated bacteria, and particularly those of young patients (< 20 months). 92% of the samples were culture-positive, while 8% showed dormant bacteria. The predominant species were S. pneumoniae and H. influenzae. In 8% of the samples there was heavy and in 11% slight peripheral SIgA-coating of the 5% showed heavy and 19% slight peripheral IgG-coating. Only 3 samples were intensely opsonized, i.e. the bacteria were coated with IgG and C3b simultaneously. In most cases of acute purulent otitis media, the middle ear cavity of young individuals is not able to coat pathogens with SIgA, IgG, IgM and C3b during the early course of infection.


Lactic acid isomers and fatty acids in sinus secretion: a longitudinal study of bacterial and leukocyte metabolism in experimental sinusitis.

Concentrations of the two optic isomers of lactate (D- and L-form) as well as glucose, succinate, acetate, butyrate, isovalerate and valerate were examined in purulent sinus secretions. The samples were obtained from rabbit maxillary sinuses, experimentally infected with Streptococcus pneumoniae or Bacteroides fragilis. More soluble acids such as acetate displayed relatively low levels in the secretion, despite a high microbial production. A substantial increase in D-lactate concentration was found in secretions only the first day after induction of pneumococcal sinusitis, and not in bacteroides sinusitis. L-lactate levels were particularly high in secretions of a marked purulent character, and this isomer can be considered as indicator of anaerobic glycolysis in the leukocytes. Less diffusible fatty acids such as butyrate and isovalerate accumulated in the secretion, in spite of a relatively lower production rate, and are thus more reliable indicators of bacterial metabolism.


Fungal gut colonization with Candida or Pityrosporum sp. and serum Candida antigen in preterm neonates with very low birth weights.

To evaluate the diagnostic value of gut colonization by yeasts and of candida antigen in serum for predicting fungal infection in very premature neonates, faecal and serum samples were obtained biweekly from 27 newborn babies treated at our neonatal intensive care unit. Altogether 82 sets of serum and faecal samples were obtained. 17 babies were followed for > or = 4 weeks. Blood cultures, both by routine and lysis centrifugation techniques, were performed for bacteria and fungi if infection was suspected. All children were given systemic broad-spectrum antibiotic treatment. Five of the children died, all without evidence of fungal infection. No systemic antifungal treatments were given. Quantitative faecal cultures demonstrated Candida albicans in 3 (11%) (10(3)-10(5) colony forming units/g) and Pityrosporum sp. in 8 (30%) of the preterm neonates. Candida antigen in titre 4 was detected in 1/82 serum samples. The child subsequently died with no other evidence of candida infection. In 56 full term neonates treated at the intensive care unit during the same period and tested by 1 set of samples, faecal colonization with Candida sp. was detected in 2 (4%) and with Pityrosporum sp. in 4 (15%). None were positive for candida antigen. Fungal gut colonization did not lead to clinical infection in the preterm neonates studied. The false positivity rate of the candida antigen test was low (0.7%). The predictive value of the test could not be determined in this study group with no systemic fungal infections. The role of pityrosporum as an inducer of neonatal infections remains to be evaluated.


Cerebrospinal fluid levels of IL-6 in patients with acute infections of the central nervous system.

Interleukin-6 (IL-6) activity was measured in the cerebrospinal fluid (CSF) of patients with acute bacterial or viral meningitis and in AIDS patients with various cerebral disorders. Increased levels of IL-6 were detected in the CSF of patients with bacterial meningitis. On the contrary, most of the samples from patients with viral meningitis (predominantly caused by mumps virus) had no detectable IL-6 activity in CSF. A moderate increase of IL-6 levels was detected in the CSF of AIDS patients with AIDS dementia complex (ADC), progressive multifocal leukoencephalopathy and cerebral toxoplasmosis. Moreover, higher levels of IL-6 were detected in the CSF of patients with cryptococcal meningitis. We conclude that the initial events of CSF inflammation in patients with acute viral meningitis are different from those in patients with acute bacterial meningitis, and the role of IL-6 is less critical to the process.


Salmonella paratyphi C osteomyelitis: report of two separate episodes 17 years apart.

Osteomyelitis secondary to salmonella infection is well documented in the literature. Infection in more than one focus has also been described. To the best of our knowledge this is the first report of recurrent osteomyelitis in a normal host (a 35-year-old man) with the same organism (S. paratyphi C) in different sites 17 years apart.


Long-term oral ciprofloxacin in the treatment of prosthetic valve endocarditis due to Pseudomonas aeruginosa.

Prosthetic valve endocarditis caused by Pseudomonas aeruginosa is refractory to medical treatment alone and early valve replacement is necessary. We describe a 40-year-old patient in whom endocarditis developed in the early postoperative period, and reoperation was not considered feasible. Ciprofloxacin was administered orally in order to suppress bacteremia for 36 months. Long-term oral ciprofloxacin may provide an opportunity in the treatment of prosthetic valve endocarditis caused by Ps. aeruginosa in patients who are unfavorable candidates for reoperation.


Peritonitis with Mycobacterium fortuitum in a patient on continuous ambulatory peritoneal dialysis.

A 35-year-old man on continuous ambulatory peritoneal dialysis (CAPD) developed peritonitis due to Mycobacterium fortuitum and coagulase-negative staphylococci, following an unsuccessful renal transplantation. Infection subsided after removal of the dialysis catheter and treatment with amikacin. Clinicians and microbiologists should be aware of M. fortuitum as a potential cause of peritonitis in patients with debilitating underlying diseases. It is able to grow on ordinary culture media, but detection requires prolonged incubation, and it may be confused with poorly characterized diphtheroids.


Aspergillus flavus wound infection following repair of a ruptured duodenum in a non-immunocompromised host.

Aspergillus flavus is generally considered to be an opportunistic organism, rarely causing clinical infections in the immunocompetent host. We present a case of a 79-year-old man without history of immunocompromise who developed a severe aspergillus wound infection in an open wound following repair of a traumatic duodenal perforation. Despite aggressive treatment, this invasive infection contributed significantly to his eventual demise.


Acquired bisalbuminemia in staphylococcal endocarditis treated with dicloxacillin.

An albumin fraction with increased anodal mobility was observed on cellulose acetate electrophoresis, isoelectric focusing, and immunoelectrophoresis of serum obtained 1 month after a 68-year-old male patient had been treated with dicloxacillin for Staphylococcus epidermidis endocarditis. The patient also suffered from rheumatoid arthritis demanding hospital treatment. Normal albumin results from several earlier runs were thus available, and follow-up showed reversion to normal albumin mobility. Treating albumin with dicloxacillin in vitro produced a corresponding mobility increase.


Isolated severe thrombocytopenia and bleeding caused by piperacillin.

Bleeding and severe thrombocytopenia developed in a 71-year-old man who had been receiving piperacillin 5 g intravenously every 8 h for 9 days for the treatment of Pseudomonas aeruginosa septicemia. After piperacillin was discontinued, the platelet counts became normal. Rechallenge was made with 2 g of piperacillin intravenously resulting in thrombocytopenia within 6 h of piperacillin administration. The platelet count normalized after 3 days when no further piperacillin was given.


Chloramphenicol-resistant typhoid fever: an emerging problem in Oman.

Until recently multiply drug-resistant Salmonella typhi was uncommon in the Sultanate of Oman. In 1990 the first isolate of chloramphenicol-resistant S. typhi from an Indian expatriate was reported. In 1991, 58 cases of typhoid fever were diagnosed, of whom 19 (33%) were resistant to chloramphenicol. All patients with chloramphenicol-resistant S. typhi are either Indians or Omani with a history of recent travel to India. Chloramphenicol may not be the appropriate blind therapy for such patients. Ciprofloxacin may be the alternative.


Increased rate of survival in Streptococcus pneumoniae-infected rats treated with the new immunomodulator Pidotimod.

Wistar rats infected with Streptococcus pneumoniae (type III ATCC) rapidly develop an acute form of experimental lobar pneumonia (ELP) with death of 80-90% of the animals by 6 days after the infection. Prophylactic treatment of these animals with the novel immunomodulator Pidotimod, at the dose of 25 mg/kg bw, significantly increased their rate of survival as compared to the control group (50 vs. 90% respectively). Recovery from the infection appeared definitive since all the Pidotimod-treated survivors were alive and in good condition at the end of the observation period (45 days post infection). Prophylactic treatment with higher or lower doses of the drug was ineffective. Therapy with Pidotimod was not effective. This preliminary study suggests that Pidotimod may have contributed to activation of specific and non-specific immune effectors involved in the host response to S. pneumoniae infection.


Self-appraisal and coping in out-patients with chronic disease.

Self-appraisal, coping efforts, muscle function, and activity and severity of disease were examined in out-patients with rheumatoid arthritis, osteoarthrosis or diabetes mellitus. Factor analysis of a 31-item self-appraisal and coping questionnaire yielded eight factors (self-appraisal, acceptance, minimization, planful problem-solving, avoidance, persistence, attribution of responsibility, and support seeking). For the factors of avoidance, minimization, and persistence, as well as for measures of activity and severity of disease, significant differences between the diagnostic groups were found. For patients with rheumatic arthritis, hierarchical regression analysis indicated disease duration to be associated with acceptance and with attribution of responsibility, and disability measures to be associated with self-appraisal. For patients with osteoarthrosis, they showed disability in muscle function to be associated with avoidance, and more negative self-appraisal as well as lower levels of support seeking to be associated with long disease duration. Results are discussed in terms of structural and adaptive defence forms and of adherence to a coping model ("medical model") which tends to foster acceptance and dependency.


Coping behavior of Finnish adolescents: remarks on a cross-cultural comparison.

As part of a larger cross-cultural project, the present study analyses the coping styles of Finnish adolescents. A sample of 548 adolescents aged 15 to 17 years was investigated. Coping styles were defined by a matrix of 20 coping strategies applied across eight different developmental areas. Factor analysis revealed a three-dimensional structure of coping styles. The first dimension involves activities such as seeking support or taking advice (Active Coping), the second emphasizes the adolescent's appraisal of the situation and the search for a compromise (Internal Coping/Compromising) and the third includes defenses like denial and withdrawal (Withdrawal) and may be regarded as dysfunctional. The Finnish adolescents most frequently employed functional forms of coping like Active Coping and Internal Coping/Compromising: dysfunctional coping style such as Withdrawal was used less often. In addition, significant main effects for age and gender were found. Girls favored more Active Coping and support seeking behavior, as compared to boys. Both functional coping modes showed an increase with age. A comparison of coping styles across eight different problem areas revealed situation specific influences, too. The discussion compares the coping styles of Finnish adolescents with results of two parallel studies focussing on German and Israeli adolescents, using the same instrument. In spite of the considerable impact of environmental and historical conditions in the three countries, the similarities in coping behavior were impressive.


Adolescents' alcohol use related to perceived norms.

A questionnaire survey was carried out among 898 Norwegian adolescents age twelve to twenty. The study focused on the relation between adolescents' alcohol use on one side and estimated drinking norms (peers' drinking) together with attributed opinion norms (parents' and friends' acceptance of adolescents' alcohol use) on the other. On average, 5% of students in 7th, 8th, and 9th grade reported weekly alcohol use. They overestimated the number of fellow students using alcohol every week seven-fold. Students' estimates were significantly related to self-reported alcohol use. Even in high-school (10th, 11th and 12th grade) where 29% reported weekly alcohol use, students overestimated number of weekly drinkers among friends and fellow students by two-fold. Contrary to the results from a previous study conducted in Norway, in this study opinions attributed to both friends and parents about adolescents' alcohol use were significantly related to the students' own alcohol use. Estimated behavior norms and attributed opinion norms explained 46% of the observed variance in students' self-reported frequency of drinking. In a health promotion context, these results point to the importance of correcting student misconceptions about how often friends and fellow students drink alcohol.


Struggling with self: the personal projects of students seeking psychological counseling.

Personal projects can be described as self-articulated goals and related sequences of actions. In order to investigate what kind of personal projects people with psychological problems have, and how they work on them, 28 counselling client students, 44 students of psychology, and 45 students of technology completed a Finnish version of Little's (1987) Personal Project Inventory. The results showed that the clients scored lower on project accomplishment than other groups. Their personal projects were frequently self-related, while those of the technology students were often task-related. The higher their sense of coherence, self-esteem, mental health and life satisfaction, the more subjects expected to accomplish their projects, the more frequently they described task-related projects, the less negative affect they reported, and the less frequently they described self-related projects. These results suggest that psychologically distressed individuals struggle with self-related projects and have problems in accomplishing their projects.


Time perception: effects of sex and sound intensity on scales of subjective duration.

Six women and six men reproduced ten time intervals varying in logarithmic steps between 1.3 and 20 s. The durations were indicated by white noise of 10, 25, 40 and 55 dB SL, different sound intensities in different sessions. It was found that (i) greater sound intensity entails shorter reproductions, and (ii) reproductions by male observers are shorter than those by female, although for both (i) and (ii) there is an interaction with the standard durations. The data were treated in accordance with the "parallel-clock model" (Eisler, 1975), whereby the parameters of the psychophysical power function are determined from duration reproduction data. As in previous experiments (Eisler, 1975), the data showed a break in the function entailing two segments. The effect of sound intensity could be attributed to the exponent, which was lower for stronger noise, and the effect of sex to the weight coefficient of the upper relative to the lower segment of the psychophysical function, the coefficient being lower for men.


Prevalence studies of problematic behaviors in four-year-olds.

Prevalence rates for specific behaviors in the Problem Behavior Questionnaire (PBQ; Behar & Stringfield, 1974) and for four psychosomatically related behaviors (soiling, day and night wetting, and complaints about bodily aches) were estimated in a sample of 377 Swedish 4-year-olds described by their parents (mainly mothers). The results showed that several of the behaviors classified as outgoing conduct problems were common in this age group; boys showed more problematic behaviors than girls, as did children with older siblings. Firstborn children with younger siblings were more fearful and worried. No systematic differences between children in different types of day care were found. Maternal education had no relationship to reported child behaviors. The findings were discussed in terms of the four-year-age period as a period of transition and with regard to different family situations.


Preventing childhood accidents in the home: parental behavior to reduce household hazards.

The parents of all children between 6 and 18 months in four Norwegian municipalities participated in an investigation to assess to what extent parents take actions to reduce household hazards their children are exposed to, and to identify factors associated with such behaviors. The Health Belief Model was used as a theoretical framework guiding the selection of variables. The results indicate that most parents take considerable action to reduce household hazards. The constructs derived from the Health Belief Model accounted for only a small part of the variance in parental behavior to reduce hazards in the home.


Maze-running and thigmotaxis in mice: applicability of models across the sexes.

Both male (n = 244) and female (n = 223) Swiss albino mice displayed a U-shaped pattern of thigmotaxis (wall-seeking) in a circular open-field (OF) before and after a daily maze-running. A significant increase of mice's tendency to occupy the inner partitions of the OF after the maze trial on the last three out of five days of training was observed. When factor analyzed, the variables indicating the wall-seeking behaviour of both sexes were divided into two factors interpreted as "spontaneous" in conjunction with the first three to four maze trials and as "learning-related thigmotactic behaviour" during the subsequent trials in the course of the learning process.


Single lung transplantation. Surgical experiences with the first seven patients.

Seven single lung transplants are reported. The patients were severely disabled and oxygen dependent below sixty years of age with a poor prognosis. Diagnosis were alfa 1-antitrypsin deficiency (3), sarcoidosis (3) and idiopathic emphysema (1). Multiorgan-harvesting including six hearts, was performed in local or distant hospitals (3). Partial cardiopulmonary bypass simplified transplantation. The surgical procedure was modified with a direct transpericardial approach. Soft tissue wrapping by a vascularized pedicle secured the bronchial anastomosis. The four drug immunosuppressive regimen included cyclosporin A, azathioprine, steroids and antithymocyte globulin. Primary graft function was excellent. Six patients survived the postoperative period and are alive 5-19 months post transplant. Transbronchial biopsies and lung function studies have been helpful in detecting pulmonary rejections. Patient rehabilitation is satisfactory in most patients with improvement in physiologic parameters.


Decreased blood loss after cardiopulmonary bypass using heparin-coated circuit and 50% reduction of heparin dose.

In a randomized, double-blind study of patients undergoing elective coronary artery grafting, the effect of heparin-coated circuit combined with 50% reduction of systemic heparin bolus was investigated. Ten patients comprised group HC (heparin-coated) and ten group C (controls). The mean total doses of heparin were 172 IU/kg in group HC and 416 IU/kg in group C and the respective protamine doses were 0.96 and 3.96 mg/kg (both p < 0.001). Activated clotting times during cardiopulmonary bypass were significantly shorter in group HC, and both intra- and postoperative bleeding was significantly less than in group C (7.7 vs. 11.7 ml/kg, p = 0.036, and 6.9 vs. 9.7 ml/kg, p = 0.004). Hemoglobin loss via the drains was 22.5 g in group HC and 43.7 g in group C (p < 0.005). Hemolysis at the end of bypass was significantly greater in group C. Apart from one perioperative myocardial infarction in group HC the postoperative course was uneventful. Use of a heparin-coated circuit is concluded to permit complication-free reduction of heparin and protamine doses and to decrease both intra- and postoperative bleeding, which may favorably influence the outcome of coronary artery grafting.


Factors influencing return to work after aortocoronary bypass surgery.

Factors influencing the effect on employment status were investigated in 250 patients (males: females 224:26) who underwent coronary artery bypass surgery between March 1983 and November 1985. The median age at operation was 57.9 (range 36.6-69.4) years and the median follow-up time 32 (19-52) months. Preoperatively 149 patients (59.6%) were receiving sick pay or disability pension because of their heart disease. Only 64 (25.6%) were gainfully employed, in contrast to 97 (38.8%) at follow-up. Of those who were working at the time of operation, all but eight returned to work postoperatively. At follow-up 183 (80.3%) were free from symptoms or much improved, with degree of improvement somewhat greater in those who were working postoperatively. The period of sick leave and the preoperative waiting time were significantly shorter for patients who were working postoperatively than for those who were awarded disability pension. Age, previous myocardial infarction, duration of preoperative angina and type of work were also found to influence postoperative employment status.


Procainamide conversion of acute atrial fibrillation after open-heart surgery compared with digoxin treatment.

In 30 patients who developed atrial fibrillation after open-heart surgery the efficacy of intravenous procainamide was evaluated and compared with standard acute digoxin digitalisation. The patients were randomized to two groups of 15. One group received procainamide intravenously at a rate of 25 mg/min and with maximum dose 15 mg/kg. In the other group digoxin 0.75-1.0 mg was given intravenously according to renal function and body weight. Conversion to sinus rhythm occurred during or immediately after the infusion in 87% of the procainamide group, but only in 60% of the digoxin group (p < 0.05). The mean time from start of treatment to conversion was 40 min in the procainamide vs. 540 min in the digoxin group (p < 0.002). There were no serious complications of the procainamide treatment. Intravenous procainamide conversion of postoperative atrial fibrillation is concluded to be effective and safe and can be recommended as the treatment of first choice in awake and nonintubated postoperative cardiac patients.


Nonpharmacologic treatment of supraventricular and ventricular tachyarrhythmias. A review of 249 consecutive patients.

Incapacitating or life-threatening tachyarrhythmias were treated nonpharmacologically in 249 patients from 1982 to 1991. Among 92 patients surgically treated for supraventricular tachycardia the cure rate was 93% and the complication rate 12%. Radiofrequency catheter ablation gave an equal cure rate in 51 patients, but with no major complications or mortality. Direct-current catheter ablation of the His bundle was successful in 96% of 27 patients with drug-refractory atrial fibrillation or other supraventricular tachyarrhythmias. Among 64 patients undergoing surgery for ventricular tachycardia/ventricular fibrillation, the perioperative mortality was 9%, estimated 5-year survival 69% and estimated 5-year freedom from the preoperative arrhythmias 72%. Of 18 patients treated with implantable cardioverter defibrillator, three (18%) died of heart failure during follow-up. Nonpharmacologic treatment of tachyarrhythmias is concluded to be effective and often definitively curative. The safety-risk ratio is improving as new treatment modalities are developed.


Myocardial protection by retrograde cardioplegic perfusion in the presence of acute coronary artery obstruction. An experimental study.

To investigate retrograde delivery of cardioplegic solutions as a means of enhancing myocardial protection in the presence of coronary artery occlusion, a two-part experimental model was devised. In part 1 (in vitro) the possibility of retroperfusing the entire myocardium during acute occlusion of the left anterior descending artery (LAD) was assessed. In part 2 (in vivo) acute LAD occlusion was performed in dogs, and during 2 hours of aortic cross-clamping crystalline cardioplegic solution was infused at 20-minute intervals. In group I the infusion was antegrade, via the aortic root, and in group II it was retrograde, via the coronary sinus. Thereafter the LAD snare was released and the dogs were weaned from bypass. Delivery of cardioplegia through the aortic root was associated with depression of ventricular function, poor myocardial cooling and severe cellular damage. With the retrograde procedure there was significantly improved recovery of left ventricular function, uniform myocardial cooling and better preservation of cellular morphology.


Folded lung: a masquerader of malignancy.

Four cases of folded lung were observed over an 8-year period up to 1990. Because of suspected malignancy, three patients underwent exploratory thoracotomy, without subsequent morbidity or mortality, but the fourth patient declined surgery. Although folded lung may have characteristic computed tomographic features, these may be mimicked by carcinoma. If the patient is fit enough, exploratory thoracotomy is advisable in order to establish the diagnosis and permit resection of the lesion, if indicated, while avoiding the risks entailed by false negative CT scan and needle biopsy.


Continuous extrapleural intercostal nerve block and post-thoracotomy pulmonary complications.

To evaluate the effects of continuous extrapleural intercostal nerve block on post-thoracotomy pain and pulmonary complications, a randomized, double-blind, placebo-controlled study was conducted on 80 patients undergoing elective thoracotomy for pulmonary (n = 47) or oesophageal (n = 33) procedures. In patients who received continuous bupivacaine infusion, the requirement for intramuscular opiate and rectal diclofenac was less, the score on a visual linear analogue pain scale lower and recovery of pulmonary function more rapid than in saline-infused controls. Postoperative pulmonary complications occurred in 35% of the saline group, but only 10% of the patients with bupivacaine infusion (p < 0.01). In patients with chronic obstructive airways disease (COAD), the incidence of postoperative pulmonary complications was 54.5% in the saline group and only 4.5% in the bupivacaine group (p < 0.01). Among the patients without COAD there was no significant intergroup difference in such complications. We conclude that continuous extrapleural intercostal nerve block is effective for post-thoracotomy analgesia and reduces pulmonary complications of thoracotomy in patients with COAD.


Posterolateral diaphragmatic hernia in adults--acute symptoms, diagnosis and treatment. Case report.

Acute herniation through a posterolateral diaphragmatic defect is rare in adults. Two cases in which such herniation occurred by sudden inversion, a 29-year-old man and a 17-year-old girl, are presented. The symptoms, diagnosis and treatment are discussed.


MRI as guide to surgical approach in tuberculous pericardial abscess. Case report.

In a 30-year-old man with tuberculous pericardial effusion and symptoms of constrictive pericarditis, 2-D echocardiography indicated localized effusion. Subsequent magnetic resonance imaging showed the effusion to be posterior and compressing the left ventricle. Guided by this information, pericardial resection with drainage of tuberculous abscess was performed via left anterior thoracotomy.


Primary chondroblastic osteogenic sarcoma of the left atrium. Case report.

A case of chondroblastic osteogenic sarcoma of the left atrium is presented. The malignant nature of the tumour was not revealed until surgery. It was considered to be nonresectable. At autopsy the tumour was found to be confined to the atrial septum. The possibility of preoperatively establishing the diagnosis and determining the extent of the tumour is discussed.


Assessment of the lifetime accumulated cadmium intake from food in Kempenland.

Research in 1984 indicated that the cadmium body burden was higher in a village where the soil is contaminated with cadmium (Luyksgestel) than in a control village (Zeeland). The distribution of kidney function parameters also differed between the two villages. The aim of this study is to estimate the lifetime accumulated cadmium intake from food for the people from both villages. Various data sets describing dietary patterns in the Netherlands were used. The assessed average lifetime accumulated cadmium intake from food by the study subjects (aged 30-69 years) was 435 mg (+/- 131 mg) in Luyksgestel and 394 (+/- 113 mg) in Zeeland. The estimated lifetime accumulated cadmium intake for a hypothetical allotment gardener of 55 years was 520 mg from vegetables grown on uncontaminated soil, and 655 mg for lifelong consumption of vegetables from contaminated soil. The Luyksgestel subjects' estimated cadmium intake from food was well below the provisional tolerable weekly intake as proposed by the WHO, of 400-500 micrograms or 1124-1404 mg for the lifelong intake by a 55-year-old man.


[The value of magnetic resonance tomography in diagnosis and follow-up of cervical spine injuries].

We report upon 12 cases of magnetic resonance imaging of cervical spinal cord injuries, in 8 cases done within 24 h after the injury. We found haemorrhages in the spinal cord in 3 cases, compression of the spinal cord in 3, swelling of the spinal cord in 2, and transsection of the spinal cord and hematoma in the epidural space in 1 case each. A normal MR image was seen in a patient with a complete transverse lesion of the spinal cord. The other 4 MR examinations were carried out between 2 weeks and 8 months after injury or operation. In 2 of these trauma victims interbody fusion of the cervical spine was performed, and the neurological deficit was subsequently worse in both. In 1 patient the course of a haemorrhage within the spinal cord was monitored by MR imaging: 1 image revealed the treatment of a burst fracture of C-7 with an interposed flap from the greater omentum.


[Vertebral fractures and abdominal trauma. A retrospective study based on 415 documented vertebral fractures].

415 spinal fractures were analysed retrospectively. A simultaneous occurrence of vertebral fracture and abdominal trauma was found in 14 patients (3.4%). The mechanism of injury was a fall from a considerable height in 9 cases, a car accident in 3 and a motorcycle accident in 2. Isolated fractures of the transverse processes and rotational injuries of the spine were found to be associated particularly frequently with an abdominal trauma (3 of 14 isolated fractures of the transverse processes = 22%, 5 of 61 rotational injuries = 8.2%), while compression injuries only showed such a simultaneous abdominal injury in 2% of the 300 fractures of this type. We never encountered the combination of distraction injury/abdominal trauma. This is probably because two-point lap-type seat belts are only rarely used in our country. In 2 patients with rotational injuries neurological deficits were observed. The abdominal injuries encountered in our patients were: massive concussion of the kidney (6 cases), rupture of the spleen (3 cases), rupture of the liver (2 cases), rupture of the mesocolon (2 cases), rupture of the caecum (1 case), rupture of a pre-existent aneurysm of the aorta (1 case), rupture of a renal artery (1 case), massive retroperitoneal haematoma (1 case). Other injuries were present in 12 of the 14 patients: 3 craniocerebral injuries, 7 fractures of the long bones, 6 injuries to the thorax and 3 to the pelvis. In conclusion, a simultaneous finding of vertebral fracture and abdominal trauma is rare in our patients.(ABSTRACT TRUNCATED AT 250 WORDS)


[Ultrasound assessment of reconstructed rotator cuffs].

The evaluation of recurrent shoulder symptoms in patients who have had rotator cuff repair is a diagnostic challenge. Pain and limitation of motion may be caused by a recurrence of the rotator cuff tear. Arthrography is not considered to be helpful in postoperative cases, since it is false-positive in most of them. Pre-operative ultrasonography of the shoulder is regarded as a highly accurate diagnostic tool for rotator cuff tears. The diagnostic criteria used are: the continuity of the rotator cuff, its contour, its thickness and its echogenicity. Our study was aimed at determining which ultrasonographic criteria were significant for a retear. In addition, the "normal" postoperative sonographic appearance of the rotator cuff was established. Of 133 patients with a full thickness rotator cuff tear, 110 were evaluated 4-48 months (mean in 21 months) after surgery. A total of 85 cuffs were reconstructed, in 46 cases by direct suture, in 33 cases by suture to the major tubercle and in 6 cases by tendon transfer (Cofield technique). In 25 cases cuffs the could not be reconstructed. Subacromial decompression was performed routinely. The patients were evaluated clinically by range of movement, force and isometric and impingement tests. The subjective outcome was assessed by the algo-functional index of Patte. Ultrasonography was performed using a 7.5-MHz linear scanner. Each sonographic criterion was referred to the clinical and subjective findings. Ultrasonographic evaluation of the rotator cuffs that could not be reconstructed revealed non-visualization of the tendons. In 13 of the 85 patients in whom reconstruction of the cuff was possible a normal sonographic pattern was seen.(ABSTRACT TRUNCATED AT 250 WORDS)


[Surgical treatment of dislocated 3 and 4-segment fractures of the proximal humerus].

Twenty-eight three- and four-segment fractures of the proximal humerus were treated by plate fixation (n = 22), screw or Kirschner wire stabilization (n = 5), and primary endoprothesis (n = 1). There were no early postoperative complications. Fourteen months after the operation, 80% of the patients examined showed good results; 4 cases had poor results. In comparison to other reports our results are positive and support plate fixation as the method of choice in these situations.


[Osteochondrosis dissecans of the elbow joint].

Thirty-one elbow joints in 29 patients (28 males, only 1 female), operated on for osteochondritis dissecans, were available for follow-up after an average of 10 years. The mean age at diagnosis was 24.4 years, but 11 patients were younger than 20. In 23 out of 29 patients the right elbow was involved, including 2 cases with bilateral involvement. In 20 cases removing the free bodies was the only surgical procedure performed, but in 2 cases it was combined with resection of the radial head. At follow-up, only one-third of the patients had no complaints. Nevertheless, daily activity was not restricted for any of the cases. Degenerative arthritic changes were found in only a few cases. These results are illustrated by means of three typical cases, which are compared with six similar cases in the international literature.


[Interlocking nailing of the femur--analysis of problems and errors based on 80 fractures].

A series of 79 patients with 80 femoral fractures stabilized by the Grosse-Kempf interlocking femoral nail system (Howmedica) were critically evaluated for the frequency of problems and technical mistakes during surgery. Problems with patient positioning were negligible. In patients with fractures at a suitable site, the Wittmoser table proved useful. Closed reduction should not be attempted at all costs: in borderline cases, open reduction should be given preference to prevent complications. Radiologically relevant problems included: twisted nails, 27.5% of all cases; broken nails, 2.5%; bent nails, 1.2%. Proximal screws were too long in 18.7%, too short in 1.5%, placed too far cranially in 29.6%, shifted (with damage to the thread) in 3.1%. Distal screws were too short in 11.7%, too long in 16.1%, protruding laterally in 2.9%, malpositioned in 1.4%; affected by ectopic calcifications in 4.4%, by cortical fragmentation in 8.8%, and loosing in 10.2%; both screws broke in one case. Technical mistakes during surgery were faulty assessment of the fracture pattern in 7.5%, a wrong impaction site in 23.7%, and bursting of the proximal fragment in 11.2%. Leg shortening was observed in 8% (16 mm, on average) and lengthening in 11.2% (6.2 mm, on average). Rotational malalignment was seen in 23 of 35 patients followed up clinically: inappropriate external rotation (12.5 degrees, on average) in 12 patients and inappropriate internal rotation (10 degrees, on average) in 11. Implant damage was seen in 8.7%. A breakdown of the complications by the operating surgeons involved clearly shows where the problems lies: 80 fractures were treated by 25 surgeons.(ABSTRACT TRUNCATED AT 250 WORDS)


[Effects of different intramedullary stabilizing procedures of the femur on lung function in polytrauma].

We investigated the effects of primary (< 24 h) intramedullary femoral nailing on lung function and pulmonary hemodynamics in multiple trauma patients. The standard procedure following reaming of the medullary canal (AFN) was compared with a new procedure using a small, solid nail without prior reaming (UFN). Pulmonary hemodynamics were determined using a pulmonary artery catheter. Global lung function was assessed by means of the oxygenation ratio (PaO2/FiO2). Concentrations of elastase and the platelet count as a general parameter of the clinical course were determined from central venous blood during and 3 days after surgery. The lung function was stable in UFN patients (n = 6), but decreased significantly in AFN patients (n = 10) from 353 +/- 24 (PaO2/FiO2 preoperative) to 260 +/- 28 (PaO2/FiO2 postoperative) and did not improve until 48 h later. Pulmonary artery pressure (Pap) remained within normal limits in UFN patients, whereas in AFN patients Pap increased from 27.4 +/- 3 mm Hg (preoperative) to 37 +/- 3 mm Hg during reaming and did not normalize until 1 h after insertion of the nail. The platelet count remained unchanged in UFN patients and dropped in AFN patients from 143 +/- 25 x 1000 cells/ml blood (preoperative) to 87.5 +/- 15 x 1000 cells/ml blood 2 days after surgery. Our measurements did not show an increase in central venous triglycerides in the AFN group, probably because bone marrow does not become immediately soluble. There was no significant difference between the increase of elactase levels in the two groups. The femoral nailing procedure with reaming in multiple trauma patients involves a potential risk to the lung.(ABSTRACT TRUNCATED AT 250 WORDS)


[Candida infection in the severely burned patient--a successful treatment concept with liposomal amphotericin B].

Candida sepsis is a very serious complication in severely burned patients. This mainly affects patients whose immune system is weakened by illness and/or by drugs. Often diagnosis is difficult because candida sepsis occurs after an initial infection, but therapy is always difficult. Good fungicidal drugs are available, but their side effects limit their effectivity. Two severely burned patients who were suffering from a gram-negative sepsis confirmed by clinical and laboratory data developed candida sepsis. Conventional therapy failed, and both patients suffered from renal failure with constantly high candida-latex-antigen titre. By means of the liposomal encapsulated amphotericin B, which has the same fungicidal effect as amphotericin B, but without its limiting side effects, both, patients could be saved. The kidneys functioned as normal again, the laboratory findings were normal when the patients were discharged.


Regulation of G418 selection efficiency by cell-cell interaction in transfection.

We attempted to establish the optimum conditions for the calcium phosphate (CaPO4) precipitation protocol by counting G418 resistant (G418r) colonies after transfection of pSV2-neo DNA into BALB 3T3 cells. The amount and molecular size of carrier DNA, number of plating cells, treatment period of DNA-CaPO4 precipitates and expression time of G418 selection were found to be important factors in the induction of G418r colonies. Six G418r clones were derived from BALB 3T3, NIH 3T3 and FRSK cells, and cocultured with G418 sensitive (G418s) parent cells in G418 medium. The colony formation capacity of all G418r cell clones decreased with the increasing number of plated G418s cells. Cell-cell contact appeared to be necessary to reduce the colony formation of G418r cells, and contact-dependent G418r cell killing was probably not related to gap junction formation. Contact-mediated cell killing is a likely explanation for the observation that induction of G418r colonies is often reduced under conditions of high-density plating, long treatment of DNA-CaPO4 precipitates, and long expression time of G418 selection. These results suggest that in some instances transfection efficiency using pSV2-neo DNA should be carefully evaluated because culture conditions can mask the induction of G418r colonies.


Characterisation and correction of a mammalian cell mutant defective in late step of base excision repair.

An Indian muntjac cell line, SVM, is unusually sensitive to cell killing induced by a range of alkylating agents. Cells transfected with the Escherichia coli ada gene or human genomic DNA have allowed the response of SVM to alkylating agents to be dissociated into two distinct components. Thus, in SVM, which expresses very low levels of alkyltransferase (AT), O6-alkylguanine appears to be the major cytotoxic, clastogenic, and recombinogenic lesion following exposure to agents such as methylnitrosourea (MNU). However, SVM is also very sensitive to agents such as dimethylsulfate (DMS), which produce only very low levels of O6-methylguanine damage. Sensitivity to DMS resides in an inability to complete base excision repair, with the appearance of persistent single-strand DNA breaks (SSBs), and does not appear to involve defects in glycosylase, apurinic/apyrimidinic endonuclease, or DNA ligase activities. Another, possibly related, phenotypic trait in SVM is its limited ability to ligate transfected linear plasmid DNA. Transfectants of SVM, harboring human DNA sequences, show a significant correction of DMS-induced cytotoxicity and clastogenicity and a reduction in the levels of DMS-induced DNA SSBs. The DMS-resistant transfectants have an increased ability to ligate linear plasmid DNA, and also express AT, making these lines resistant to alkylating agents such as MNU. These results suggest that cells possess a mechanism that regulates AT expression, plasmid break-joining ability, and certain aspects of base excision repair. Transfectants of SVM containing human DNA provide a means to isolate genes involved in a coordinate response to alkylation damage.


Novel method for isolating mammalian cells defective in fluid-phase endocytosis.

A new method for isolating mutants defective in fluid-phase endocytosis has been developed based on the observation that endocytosed horseradish peroxidase can be made lethal to cells. The method was used to isolate a mutant from Chinese hamster ovary cells, termed HRP-1, that was temperature-sensitive for viability and had a 70% reduction in the rate of horseradish peroxidase endocytosis at the restrictive temperature. At high temperature, HRP-1 cells were also defective in the secretory path and their Golgi complex disappeared at the resolution of fluorescence microscopy. These properties are similar to two previously described mutants of CHO cells, DS28-6 and V.24.1. In complementation tests, mutants HRP-1, DS28-6, and V.24.1 all appeared to be in the same complementation group.


Efficient selection of mu m-mutants from mu m-expressing myeloma cells by treatment with ricin A-conjugated anti-mu antibody.

We have developed an efficient system for obtaining myeloma mutants defective in trans-acting factors required for immunoglobulin (Ig) gene expression. The system consists of a myeloma cell line designed for this purpose and an efficient method for selecting mutants from it. The cell line is X63.653 transfected with the mu gene, whose tailpiece sequence was replaced with the transmembrane sequence of human EGF receptor to hold mu on the cell surface and whose CH1 sequence was removed to prevent mu from being retained in the endoplasmic reticulum. It efficiently and stably expressed mu chains of IgM on the cell surface (mu m+) without light chains. To obtain mutants lacking mu m (mu m-) from the mu m+ cell line by selectively killing mu m+ cells, a method with ricin A-conjugated anti-mu antibody was more reliable than complement lysis mediated by anti-mu antibody. Applying the system, we obtained a variety of mu m- mutants.


Targeted delivery of antisense oligonucleotides by molecular conjugates.

Antisense oligonucleotides efficiently inhibit gene expression in vitro; however, the successful therapeutic application of this technology in vivo will require the development of improved delivery systems. In this report we describe a technique that efficiently delivers antisense oligonucleotides into cells using molecular conjugates. This technique, which was initially developed for the delivery of eukaryotic genes, is based on the construction of DNA-protein complexes that are recognized by the liver-specific asialoglycoprotein receptor. Binding of poly(L-lysine)-asialoorosomucoid (AsOR) protein conjugates with phosphorothioate antisense oligonucleotides to chloramphenicol acetyltransferase (CAT) led to the formation of 50- to 150-nm toroids. Exposure of the antisense molecular complexes (3 microM oligonucleotide) to NIH 3T3 cells genetically modified to express both the AsOR receptor and CAT, inhibited CAT expression by 54%, which was completely blocked by excess AsOR. Equivalent inhibition of CAT activity with purified oligonucleotide alone was observed at a 30 microM concentration. Furthermore, examination of the cells using indirect immunofluorescence for the presence of CAT protein showed 28% of cells exposed to the molecular conjugates lacked any detectable CAT enzyme. Cells exposed to oligonucleotide alone showed a highly variable staining pattern, and only a few of the cells were completely void of CAT protein. Together these data demonstrate that molecular conjugates provide a highly specific and efficient system for the delivery of antisense oligonucleotides.


Hepatitis B screening in pregnancy: practical aspects.

Hepatitis B may be acquired at birth from a mother who is a chronic carrier and may result in debilitating liver disease later in life. Screening of pregnant women and preventive measures have been shown to be clinically effective and at least marginally cost-effective. The Centers for Disease Control recommends universal screening of pregnant women. Cost-effectiveness has been evaluated using estimated costs and assuming patient compliance. The practical aspects of screening a high-risk population are described in the context of a single program, with discussion of excess costs and problems with implementation.


Use of moderate hypothermia during elective craniotomy.

Use of moderate hypothermia as an adjunct to elective craniotomy is described in 21 patients. Systemic hypothermia to 32 degrees C was induced by cooling blankets at a mean cooling rate of 1.6 degrees C/min. Patients were rewarmed at the same rate prior to closure of wounds. There were no hypothermia-related complications and the method increased brain relaxation. The rationale for use of this therapy in elective craniotomy and severe head injury is reviewed.


Relationships between haemostatic factors and capillary morphology in human diabetic neuropathy.

We have examined haemostatic factors in 15 diabetic patients with peripheral neuropathy and 10 diabetic patients without clinical complications. Plasma and blood viscosity, fibrinogen, factor VIIIc, von Willebrand factor activity, spontaneous platelet aggregation and fibrinolytic activity were not significantly different between diabetic patients without clinical complications and diabetic patients with peripheral neuropathy. Platelet aggregation was enhanced in diabetic patients with neuropathy compared with those without complications. In the 15 patients with neuropathy and 3 without complications, who underwent biopsy of sural nerve, skin and muscle, associations were found between haemostatic variables and measures of nerve capillary pathology, notably: plasma fibrinogen and nerve capillary basement membrane thickness (r = 0.70, p < 0.001); thromboxane B2 production and nerve capillary basement membrane thickness (r = -0.61, p < 0.01); plasma fibrinolytic activity and endoneurial capillary lumen size (r = 0.60, p < 0.01) and endothelial cell outer perimeter (r = 0.65, p < 0.01). The main associations of skin and muscle capillary abnormalities were with measures of in vitro platelet aggregation, and the correlations found with nerve capillary measurements were not echoed in the overlying muscle and skin. The results are supportive of the involvement of haemostatic abnormalities in the pathogenesis of diabetic neuropathy.


Treatment of venous thromboembolism in patients with congenital deficiency of antithrombin III.

The treatment course of all thromboembolic events in the patients with congenital deficiency of antithrombin III (AT III) in the national Swedish register was reviewed in order to assess the appropriate medical therapy in this situation. The medical treatment of 70 events of venous thromboembolism was evaluated. There were eight cases with signs of clinical progression. The risk of therapeutic failure with heparin could be as low as 1.5% or as high as 9.2%. It would not be cost-effective to substitute with concentrates of AT III in every case with congenital deficiency thereof in connection with acute venous thromboembolism. "Heparin resistance" does not seem to be a problem in the vast majority of these patients.


Effects of heparin, dermatan sulfate and of their association on the inhibition of venous thrombosis growth in the rabbit.

This study compares the ability of unfractionated heparin, of dermatan sulfate, and of their simultaneous administration delivered as continuous intravenous infusion or as a single bolus injection to inhibit the growth of a standardized venous thrombosis in the rabbit. When delivered as continuous intravenous infusion for 4 h, heparin and dermatan sulfate inhibited thrombus growth in a dose dependent manner. The maximum antithrombotic effect of heparin was achieved at the dose of 0.15 mg kg-1 h-1 (25 U kg-1 h-1) which generated a mean plasma concentration of 1.8 micrograms ml-1 (0.31 U ml-1) and a 1.8 fold prolongation of the activated partial thromboplastin time (APTT) in comparison to the pretreatment value. A comparable antithrombotic effect was obtained with dermatan sulfate at the dose of 2 mg kg-1 h-1. This dose generated a mean plasma concentration of 30 micrograms ml-1 and a 1.3 fold APTT prolongation. Increasing these doses up to 10 fold did not improve the antithrombotic effect which did not overpass 60-70% of the controls. When the compounds were delivered simultaneously, the maximum antithrombotic effect (64%) was obtained with the following association: 0.06 mg kg-1 h-1 (10 U kg-1 h-1) for heparin and 1 mg kg-1 h-1 for dermatan sulfate. Increasing these doses up to 4 to 5 fold did not improve the antithrombotic effect. Heparin, dermatan sulfate and the association of both were also delivered as single bolus injections and the resultant antithrombotic effect was determined 4 h after saline infusion.(ABSTRACT TRUNCATED AT 250 WORDS)


Tissue factor localization in non-human primate cerebral tissue.

Tissue factor (TF), the principal procoagulant of human brain, resides in specific regions of the non-human primate central nervous system. Immunohistochemical studies employing murine anti-human TF monoclonal antibodies (MoAbs) detected TF antigen in the cortex, basal ganglia, cerebellum, and cervical spinal cord in three normal baboon subjects. Although significantly less prominent than human cortical gray matter, a distinct partition of TF in gray matter > white matter was noted. The gray matter predilection of TF was confirmed in primate temporal and parietal lobe cortex by both sandwich ELISA and one-stage coagulation assay. Variation in the relative quantity of TF antigen was observed by ELISA among the three subjects studied. Procoagulant activity followed the pattern of TF antigen (cortical gray matter > basal ganglia > or = cerebellum > cortical white matter), and was 96.5-98.5% inhibitable by a function inhibiting anti-human TF MoAb combination. TF antigen was associated with the microvasculature of all cerebral tissues studied, and spared capillaries most selectively in the cerebral cortex, basal ganglia, and cerebellum. These findings suggest a highly specific ordering of TF antigen and related procoagulant activity in the central nervous system of the baboon, confined primarily to gray matter parenchyma, and to the non-capillary microvasculature.


Recurrent, isolated factor X deficiency in myeloma: repeated normalization of factor X levels after cytostatic chemotherapy followed by late treatment failure associated with the development of systemic amyloidosis.

We describe the case of a 64-year-old woman with isolated severe factor X deficiency associated with kappa light chain myeloma. At the time of diagnosis there was no evidence for amyloidosis. Complete remission (CR) of myeloma as well as normalization of factor X levels were achieved after cytostatic chemotherapy. Subsequently, factor X deficiency recurred twice without any evidence for relapse of myeloma. The first time factor X normalized again following cytostatic treatment, the second time, however, factor X deficiency was refractory to chemotherapy. Finally, relapse of myeloma became evident associated with rapidly progressing, systemic amyloidosis, which was fatal within a few months. Initially, factor X infusion studies showed a normal recovery, but when amyloidosis became overt the recovery decreased to 0%. We assume that factor X deficiency was due to a binding of factor X to kappa light chains associated with the proliferation of the malignant myeloma cell clone.


Lysing patterns of retracted blood clots with diffusion or bulk flow transport of plasma with urokinase into clots--a magnetic resonance imaging study in vitro.

Fresh retracted clots are known to be poorly lysable by fibrinolytic agents. We have studied whether lysis of retracted clots could be enhanced by bulk transport in comparison to pure diffusion of plasma containing urokinase (400 IU/ml) into the clots. Cylindrical retracted blood clots were occlusively glued by a polyester into plastic tubes and put in contact with plasma through the clot bases. One group of clots (perfused clots, n = 10) was placed under a pressure difference of 6 kPa (60 cm H2O) which resulted in an average plasma flow of 0.97 +/- 0.34 microliters/min through the clot during the first hour. Another group of clots (non-perfused clots, n = 10) was incubated in the lytic plasma without a pressure difference. Clot sizes were measured during lysis by magnetic resonance imaging (MRI). Channels representing lysed areas penetrated into perfused clots with a velocity of 5.4 +/- 1.6 mm/h (n = 10), whereas the boundaries of non-perfused clots subsided with a velocity of less than 0.1 mm/h. Eight of the 10 perfused clots were recanalized after 8 h and the sizes of the perfused group were reduced to 64.0 +/- 10.7% of the initial values. The relative sizes of non-perfused clots after 8 h remained significantly higher: 95.0 +/- 1.3%, p < 0.005. In a separate experiment good agreement was obtained between the measured clot sizes by MRI and the residual radioactivity of 125I-fibrin in the clot.(ABSTRACT TRUNCATED AT 250 WORDS)


Recombinant variants of tissue-type plasminogen activator containing amino acid substitutions in the finger domain.

Tissue-type plasminogen activator (t-PA) is a fibrin-specific agent which has been used to treat acute myocardial infarction. In an attempt to clarify the determinants for its rapid clearance in vivo and high affinity for fibrin clots, we produced five variants containing amino acid substitutions in the finger domain, at amino acid residues 7-9, 10-14, 15-19, 28-33, and 37-42. All the variants had a prolonged half-life and a decreased affinity for fibrin of various degrees. The 37-42 variant demonstrated about a 6-fold longer half-life with a lower affinity for fibrin. Human plasma clot lysis assay estimated the fibrinolytic activity of the 37-42 variant to be 1.4-fold less effective than that of the wild-type rt-PA. In a rabbit jugular vein clot lysis model, doses of 1.0 and 0.15 mg/kg were required for about 70% lysis in the wild-type and 37-42 variant, respectively. Fibrinogen was degraded only when the wild-type rt-PA was administered at a dose of 1.0 mg/kg. These findings suggest that the 37-42 variant can be employed at a lower dosage and that it is a more fibrin-specific thrombolytic agent than the wild-type rt-PA.


Von Willebrand factor, plasminogen activator inhibitor-1 and C-reactive protein are markers of thrombolytic efficacy in acute myocardial infarction.

Plasma von Willebrand factor, plasminogen activator inhibitor activity and C-reactive protein were assessed as markers of coronary recanalisation in 30 patients with acute myocardial infarction receiving tissue-type plasminogen activator (t-PA). Blood samples were taken before t-PA (time 0), 4-hourly for 24 h and daily up to 72 h. A continuous electrocardiogram was recorded in the first 24 h. Coronary arteriography was performed 90 min and 24 h after the start of t-PA. Patients with a patent infarct artery (n = 17), compared to those with occluded artery (n = 13), showed a fall in von Willebrand factor from 0 to 24 h (p = 0.001), a greater fall in plasminogen activator inhibitor from 24 to 48 h (p = 0.04) and a fall in C-reactive protein from 48 to 72 h (p = 0.002). The accuracy of these indices compared favourably with time to peak plasma MB creatine kinase and > or = 50% resolution of maximal ST-deviation on the electrocardiogram. Thus, changes in plasma von Willebrand factor, plasminogen activator inhibitor and C-reactive protein during the first 3 days of myocardial infarction are indicative of thrombolytic efficacy. Their concordant behaviour may reflect a common regulatory mechanism.


Treatment of hypertension induces a fall in platelet basal cytoplasmic calcium concentration without influencing platelet aggregation.

The relationship between blood pressure and platelet basal cytoplasmic calcium concentration ([Ca2+]i) and platelet sensitivity to aggregating agents in hypertension has been investigated in hypertensive patients and normotensive subjects. Ten severely hypertensive patients whose blood pressures were poorly controlled with metoprolol, were given calcium antagonist (either nifedipine or felodipine) as a second line agent. Venous blood samples were collected at each treatment phase for measurement, in whole blood, of platelet aggregation in response to ADP and collagen, and of basal [Ca2+]i using fura-2. Control of blood pressure by the combination of metroprolol and a calcium antagonist induced a significant decrease in median [Ca2+]i from 116 (76-181) to 73 (60-83) nM, which was similar to the median value of 70 (61-80) nM obtained in 14 normotensive subjects. Overall [Ca2+]i correlated with mean blood pressure (r = 0.51). Treatment of hypertension with calcium antagonist did not change the response of platelets to collagen or ADP. The results confirm that effective treatment of hypertension significantly reduced basal [Ca2+]i in platelets but raise doubts whether elevated basal [Ca2+]i is necessarily the sole mechanism by which the sensitivity of platelets to aggregatory agents is increased in hypertension.


Inhibition of platelet adhesion to fibrin(ogen) in flowing whole blood by Arg-Gly-Asp and fibrinogen gamma-chain carboxy terminal peptides.

We have employed synthetic peptides with sequences corresponding to the integrin receptor-recognition regions of fibrinogen as inhibitors of platelet aggregation and adhesion to fibrinogen- and fibrin-coated surfaces in flowing whole blood, using a rectangular perfusion chamber at wall shear rates of 300 s-1 and 1,300 s-1. D-RGDW caused substantial inhibition of platelet aggregation and adhesion to fibrinogen and fibrin at both shear rates, although it was least effective at blocking platelet adhesion to fibrin at 300 s-1. RGDS was a weaker inhibitor, and produced a biphasic dose-response curve; SDRG was inactive. HHLGGAKQAGDV partially inhibited platelet aggregation and adhesion to fibrin(ogen) at both shear rates. These results support the identification of an RGD-specific receptor, most likely the platelet integrin glycoprotein IIb:IIIa, as the primary receptor responsible for platelet:fibrin(ogen) adhesive interactions under flow conditions, and indicate that platelet adhesion to surface bound fibrin(ogen) is stabilized by multivalent receptor-ligand contacts.


The residues AGDV of recombinant gamma chains of human fibrinogen must be carboxy-terminal to support human platelet aggregation.

The carboxy-terminus of the gamma chain of fibrinogen contains a sequence which is believed to be one of the domains that interacts with glycoprotein (GP) IIb/IIIa to support platelet aggregation. A normal variant of fibrinogen exists in which the four carboxy-terminal amino acids are replaced by 20 amino acids. This variant, known as gamma', has been reported to bind less effectively to platelets. The purpose of the present study was to engineer novel proteins to determine what differences in amino acid sequence between the gamma and gamma' chains influence the interaction of the carboxyterminus with GPIIb/IIIa. In this regard, the gamma chain cDNA in a bacterial plasmid expression vector was modified by oligonucleotide-directed mutagenesis to produce recombinant gamma chains with amino acid changes in the carboxy-terminus which reflect the differences between gamma and gamma'. The recombinant gamma chain with an unmodified carboxy-terminus supported adenosine diphosphate (ADP)-induced platelet aggregation to the same extent as intact fibrinogen. In contrast, the ability of gamma' 427 (the recombinant gamma' variant) and gamma 427 (where the 16 amino acid gamma' extension [412-427] was added to the carboxy-terminus of gamma) to support platelet aggregation was markedly reduced. In addition, the extent of ADP-induced platelet aggregation was decreased in the presence of gamma' 411 (where amino acids 408-411 in gamma were replaced with amino acids 408-411 in gamma'), while gamma 407 (where the four carboxy-terminal amino acids were deleted) was not capable of supporting aggregation. These findings demonstrate that the four residues AGDV are not only required but must be carboxy-terminal to support platelet aggregation.