Factor VIIa/tissue factor-catalyzed activation of factors IX and X on a cell surface and in suspension: a kinetic study.

The kinetics of activation of factor IX and factor X by factor VIIa was studied in the presence of various sources of tissue factor: (1) a surface membrane of human ovarian carcinoma cell line, OC-2008 (2) the cell lysate (of OC-2008) and (3) reconstituted purified human tissue factor. The rates of activation of factors IX and X were monitored in activation peptide release assays using tritiated substrates. The results indicate that the apparent Km values for factor IX and factor X were similar for a given tissue factor, but varied with tissue factor source. The source of tissue factor greatly influenced the apparent differences in Vmax for factors IX and X. When a surface of monolayer provided tissue factor, the Vmax of factor IX was only 2-3 fold lower than factor X, but when either a cell lysate or purified tissue factor was the source of cofactor activity, the difference in Vmax rose to about 8-10 fold. Although, the tissue factor apoprotein in the cells was expressed entirely on the outer surface membrane, the activity of tissue factor on the intact cell surface was 50 to 100-fold lower than in the lysed cell preparation.


Defibrotide inhibits platelet activation by cathepsin G released from stimulated polymorphonuclear leukocytes.

Defibrotide is a polydeoxyribonucleotide with antithrombotic effects in experimental animal models. Most of the actions of this drug have been observed in in vivo test models but no effects have been reported in in vitro systems. In this paper we demonstrate that defibrotide interferes with polymorphonuclear leukocyte-induced human platelet activation in vitro. This effect was not related to any direct interaction with polymorphonuclear leukocytes or platelets, but was due to the inhibition of cathepsin G, the main biochemical mediator of this cell-cell cooperation. Since cathepsin G not only induces platelet activation but also affects some endothelial cell functions, the anticathepsin G activity of defibrotide could help to explain the antithrombotic effect of this drug.


A soluble recombinant factor VIII fragment containing the A2 domain binds to some human anti-factor VIII antibodies that are not detected by immunoblotting.

Human factor VIII (fVIII) inhibitors are pathologic antibodies that inactivate fVIII. A cDNA clone was modified to encode fVIII amino acid residues 373-740 for expression in a baculovirus vector in insect cells. The encoded protein fragment H2 was produced as a soluble, secreted protein, and it was used to test inhibitor plasmas for the presence of antibodies that were not detected by immunoblotting. Seven of 13 inhibitors that bound only to the fVIII light chain by immunoblotting also bound to fragment H2 in an immunoprecipitation assay. Thus multi-chain inhibitor reactivity of inhibitors is more frequent than previously reported. One of these inhibitors was shown to share the epitope for other inhibitors that bind to H2 within amino acid residues 373-541 in immunoblotting assays. The sensitive immunoprecipitation assay described allows determination of relative H2 binding capacity of the total IgG and epitope localization of inhibitors that cannot be similarly characterized by immunoblotting.


Comparison between a one-point dilute phospholipid APTT and the dilute Russell viper venom time for verification of lupus anticoagulants.

In the present study, the dilute Russell viper venom time (RVVT) and the dilute phospholipid activated partial thromboplastin time (PL-APTT), which are two assays used for the verification of lupus anticoagulants (LA), were modified to increase standardization. The modified assays were then compared with respect to sensitivity and specificity in detecting LA in plasmas from 72 patients with a prolonged APTT. Modifications included utilizing a single dilution of phospholipid that was either bovine brain thromboplastin (Thrombofax) or liposomes comprised of phosphatidylcholine/phosphatidylserine, and expressing the results as a ratio of the clotting times of the mixture of patient and normal plasma/clotting time of normal plasma. In the RVVT, the correlation coefficient between assay results for liposomes and Thrombofax was 0.88 and in the PL-APTT, the correlation was 0.68. A positive test for LA was defined as a ratio of greater than or equal to 1.3 for the PL-APTT with liposomes and greater than or equal to 1.2 for the PL-APTT with Thrombofax and the RVVT with Thrombofax or liposomes. Regardless of the phospholipid source in the test system, the PL-APTT demonstrated higher sensitivity and the RVVT showed greater specificity in detecting patient plasmas that contained antiphospholipid antibodies.


The role of phospholipids and the factor VII Gla-domain in the interaction of factor VII with tissue factor.

Whether or not the factor VII Gla-domain is involved in the high-affinity interaction of factor VII and tissue factor via calcium-dependent interactions with surrounding phospholipids is unknown. To investigate this, we have purified the factor VII Gla-peptide (FVII-GP) from digested recombinant human factor VIIa and assessed its effect on factor VII:tissue factor interactions. FVII-GP inhibited the activation of factor X by factor VIIa in the presence of either soluble or cell surface tissue factor half-maximally at 0.5 microM and 2.7 microM, respectively. However, FVII-GP failed to inhibit the specific binding of factor VIIa to cell-surface tissue factor, and did not inhibit the ability of tissue factor to stimulate the amidolytic activity of factor VIIa. Unrelipidated tissue factor apoprotein stimulated the amidolytic activity of factor VIIa to the same extent as relipidated tissue factor apoprotein. These findings suggest that the factor VII Gla-domain does not directly interact with tissue factor, but rather is important for calcium binding and concomitant expression of other factor VII epitopes necessary for tissue factor recognition and binding. To test this hypothesis, we have prepared a monoclonal antibody against a putative factor VII epitope that participates in the interaction of factor VII with cell-surface tissue factor (peptide 195-206) and assessed its ability to bind to factor VII in the presence and absence of calcium. Binding of this monoclonal antibody (PW-4) to intact factor VIIa was calcium-dependent and could be inhibited in a dose-dependent manner by peptide 195-206.(ABSTRACT TRUNCATED AT 250 WORDS)


Comparison of recombinant plasminogen activator inhibitor-1 and epsilon amino caproic acid in a hemorrhagic rabbit model.

A rabbit ear model of blood loss was developed to compare the effects of an active form of recombinant plasminogen activator inhibitor-1 (rPAI-1) with epsilon amino caproic acid (EACA) in antagonizing tissue-type plasminogen activator (r-tPA)-induced blood loss. The antagonism of both rebleeding, which occurs as a result of hemostatic plug degradation, and r-tPA-induced hemorrhage, where rabbits lose approximately 30% of their blood volume, was studied. rPAI-1 (1 mg/kg i.v.) or EACA (70 mg/kg i.v.) antagonized the rebleeding induced by r-tPA (10 micrograms kg-1 min-1) to a similar extent. In the hemorrhagic studies, rPAI-1 effectively antagonized the r-tPA-induced hemorrhage with an ED50 of 3 mg/kg i.v., while the ED50 obtained for EACA was 230 mg/kg i.v. rPAI-1 may be of value in reversing r-tPA-induced blood loss during thrombolytic therapy or in clinical situations where excessive fibrinolysis contributes to bleeding.


G4120, an Arg-Gly-Asp containing pentapeptide, enhances arterial eversion graft recanalization with recombinant tissue-type plasminogen activator in dogs.

The effects of G4120, a cyclic Arg-Gly-Asp (RGD) containing peptide which inhibits fibrinogen binding to the platelet receptor GPIIb/IIIa, on thrombolysis with recombinant tissue-type plasminogen activator (rt-PA) were investigated in a combined arterial and venous thrombosis model in heparinized dogs. The arterial thrombus model consisted of a 3 cm everted (inside-out) carotid arterial segment inserted into a transsected femoral artery which occludes within 30 min with platelet-rich material and which is resistant to recanalization with 0.5 mg/kg rt-PA. The venous thrombus was a 125I-fibrin labeled whole blood clot produced in the contralateral femoral vein. In 5 dogs given an intravenous bolus of 0.05 mg/kg G4120 followed by a continuous infusion of 0.05 mg/kg per hour for 3 h (group I), arterial occlusion persisted throughout a 4 h observation period and was still present at 24 h in all dogs; the extent of venous clot lysis after 120 min was 27 +/- 7%. In 5 dogs given the same infusion of G4120 in combination with 0.5 mg/kg rt-PA over 60 min, recanalization of the arterial graft occurred in all dogs, within 13 +/- 2 min and persisted throughout the observation period of 4 h (p = 0.01 versus G4120 or rt-PA alone); at 24 h, however, all grafts were occluded. Venous clot lysis in this group was 75 +/- 8% (p = 0.002 versus G4120 alone and p = NS versus rt-PA alone). Pathologic analysis revealed platelet-rich or mixed thrombus with platelet-rich and erythrocyte-rich zones.(ABSTRACT TRUNCATED AT 250 WORDS)


On the fibrinolytic system in aged rats, and its reactivity to endotoxin and cytokines.

Aged rats are more susceptible to endotoxin-induced effects, including microthrombosis and platelet aggregation, than are young rats. To investigate whether changes in the fibrinolytic system might be involved, we investigated the fibrinolytic activity in plasma euglobulin fractions and tissues (lung and heart) of young (6-months old) and aged (24-months old) rats under baseline conditions and after challenge with endotoxin. Aged rats had lower plasma levels of tissue-type plasminogen activator (t-PA) and of urokinase-type PA (u-PA) activity. PA inhibitor (PAI) activity was higher in the plasma of aged rats, as was t-PA activity in lung and heart. Rats were treated with either a low dose (1 microgram/kg) or a high dose (10 mg/kg) of endotoxin. Both treatments induced a transient phase of increased blood fibrinolytic activity, as evidenced by higher levels of tissue-type plasminogen activator (t-PA) activity and decreased levels of PA inhibitor (PAI) activity. Over time, the fibrinolytic activity decreased, probably due to increased levels of PA inhibitor. Both the early increase in t-PA activity, and the subsequent increase in PAI activity, were more pronounced in the aged rats, as compared with the younger rats, after the high dose of endotoxin. The aged rats also responded to an injection of interleukin-1 beta or tumor necrosis factor-alpha with a larger increase of PAI activity than did the younger rats. Together the data suggest that, compared to young rats, aged rats have a decreased base-line plasma fibrinolytic activity, while their fibrinolytic system is more responsive to challenge by endotoxin and cytokines.


Characterization of three alboaggregins purified from Trimeresurus albolabris venom.

Alboaggregins (AL-A, AL-B, AL-C) isolated from Trimeresurus albolabris snake venom represent a new family of proteins which bind to platelet glycoprotein Ib (GPIb). These alboaggregins were purified to homogeneity with ion exchange HPLC (Mono-Q column) and hydrophobic HPLC (TSK Phenyl-5PW column). On SDS-polyacrylamide gel electrophoresis, apparent molecular weights of AL-A, AL-B and AL-C were 52 kDa, 26 kDa, and 121 kDa respectively, under nonreducing conditions. Upon reduction, each alboaggregin showed two types of chains with apparent molecular weights in the range of 15-20 kDa. All three alboaggregins agglutinated formalin-fixed platelets. Agglutination activities and binding of labeled alboaggregins to GPIb were specifically inhibited by the monoclonal antibody AK2 which is directed against the 45 kDa N-terminal region on GPIb, but not by monoclonal antibodies against other epitopes on GPIb. 125I-alboaggregin binding to platelets was not altered by the presence of thrombin. Alboaggregins did not bind to GPIIb/IIIa. Alboaggregins were competitive inhibitors for 125I-bovine vWF binding to platelets. Mutual competition studies between AL-A, AL-B and AL-C for the binding of labeled bovine vWF and AL-B to platelets demonstrated that AL-B and AL-C had a significantly higher affinity than AL-A.


Prolonged bleeding time of Chediak-Higashi cats corrected by platelet transfusion.

Cats with the Chediak-Higashi syndrome (CHS) have a platelet storage pool deficiency (SPD). Ten CHS cats were transfused with a concentrate of 51Cr-labeled platelets prepared from normal donor cats. One hour after transfusion, the donor platelet count in CHS recipient cats was 40,000-60,000/microliters. Bleeding time before transfusion was 9.1 +/- 3.0 min. When donor platelet count in CHS cats was 50,000/microliters, bleeding time was 1.7 +/- 0.2 min. Bleeding time of normal cats was 1.4 +/- 0.3 min. Bleeding time increased to 3.3 +/- 0.2 min and to 5.3 +/- 0.2 min when the platelet count was 30,000/microliters, and 15,000/microliters, respectively. The close inverse relationship between bleeding time and number of donor platelets in CHS cats (r = -0.92), suggests that prolonged bleeding time is due to a platelet abnormality, that platelet transfusion can effectively correct prolonged bleeding time in an animal model of platelet SPD and that CHS cats may be an appropriate animal model to evaluate hemostatic capabilities of transfused platelets.


Effects of heparin and endothelial cell growth supplement on haemostatic functions of vascular endothelium.

Heparin in combination with endothelial cell growth factor (ECGF) affects physiological responses and growth of human umbilical vein endothelial cells (HUVEC). We have examined the effect of heparin, crude ECGF (endothelial cell growth supplement [ECGS]), or both on the basal and thrombin challenged output of metabolites by HUVEC. The supernatant and/or cell lysate was assayed for released prostacyclin, von Willebrand factor, tissue plasminogen activator, plasminogen activator inhibitor and thrombospondin. Heparin modified release of all these metabolites when in combination with ECGS, and in general these responses were the opposite of those generated by inflammatory mediators such as interleukin-1. It has been postulated that heparin acts by potentiating the effect of ECGF, but heparin inhibited thrombospondin release and enhanced that of von Willebrand factor in the absence of ECGS, while ECGS alone inhibited release of plasminogen activator inhibitor. Thus, under our experimental conditions it would appear that heparin and crude ECGF can affect HUVEC independently of one another.


[Decision to withdraw cardiopulmonary resuscitation at Norwegian hospitals].

We present a survey on the use of do-not-resuscitate orders in Norwegian hospitals based on mailed questionnaires. 559 doctors, at least one from every somatic hospital in Norway responded. Do-not-resuscitate orders were issued by 92% of these doctors. There were large differences, however, as to who made the decision, who was involved in the decision-making, the consequences of a do-not-resuscitate order, and how the orders were documented. Formal rules for do-not-resuscitate orders are needed.


[Use of the R-concept in a medical department].

Do-not-resuscitate orders issued in a medical department were studied by retrospective evaluation of 195 consecutive deaths in the department in 1991. No attempt at resuscitation was recorded in 171 patients. In these cases, do-not-resuscitate orders were documented in 67 only. For more than half of the orders, no reason was given in the medical record, and partial orders not to resuscitate were found in five patients only, none of whom were resuscitated. No difference was found in use of do-not-resuscitate orders between intensive-care units and regular wards, between patients above and patients below 80 years of age, or between patients with and patients without cancer. We suggest extended use of do-not-resuscitate orders in our department, and better documentation of the orders. Written guidelines have been established for this purpose.


[Computer tomography after reconstructive vascular surgery of the abdominal aorta. Can fluid around the aortic prosthesis be considered a normal finding?].

15 patients who had elective aortic reconstruction for infra-renal aortic aneurysm (nine patients) or aortoiliac occlusive disease (six patients) were evaluated using postoperative computerized tomography. The assessment was performed 1-2 weeks, 6-8 weeks and 6-8 months after implantation of woven Dacron graft. All patients were without clinical or laboratory signs of infection. The presence or absence of retroperitoneal air or fluid collections was assessed. In patients operated on for aneurysms, perigraft fluid was present in two cases 6-8 weeks after operation, but had disappeared within 6-8 months. Even after only 1-2 weeks, no accumulation of periprosthetic fluid was found in patients operated on for occlusive disease. Retroperitoneal air was not seen in any of the cases. It is concluded that perigraft fluid may be a "normal" phenomenon during the early postoperative period in patients operated on for abdominal aortic aneurysm.


[New therapeutic possibilities with drugs affecting serotonin receptors].

The past decade has seen important progress in understanding the localization, pharmacology, and function of serotonin (5-HT) receptor subtypes. At least seven subclasses have been shown to exist, and evidence is emerging to suggest further subclassification. Serotonin is involved in numerous physiological processes (e.g. feeding, sleep, pain, sexual behavior, temperature regulation) and pathophysiological ones. Serotonin reuptake blockers have been found effective in the alleviation of depression and attacks of panic, and are at varying stages of clinical evaluation in the treatment of obsessive compulsive disorder, chronic pain, and bulimia nervosa. Selective potent serotonin receptor agonists and antagonists show promise in the treatment of migraine, nausea and vomiting, schizophrenia, anxiety, hypertension, and Raynaud's disease.


[Mucosal lesions associated with antiphlogistics--treatment and prevention].

Gastrointestinal side effects associated with nonsteroidal, anti-inflammatory drugs are well known, but recent data suggest that the small and large bowel are target organs in addition to the gastroduodenal mucosa, although the clinical significance of changes in permeability and of mucosal inflammation is unknown. Inhibition of prostaglandin synthesis remains the major pathogenetic hypothesis for the entire gastrointestinal tract, but additional mechanisms are probably involved. Ulcers that occur during non-steroidal anti-inflammatory drug therapy can be treated in the same way as other peptic ulcers, but the duration of treatment should be extended if the non-steroidal anti-inflammatory drug cannot be withdrawn. Prophylactic therapy with H2-antagonists or prostaglandin analogues may be justified in selected high risk individuals.


[Treatment of acute hypergranular promyelocytic leukemia with all-trans-retinoic acid].

Two patients with relapsed hyper-granular promyelocytic leukemia were treated with all-trans-retinoic acid. Both obtained complete remission with minimal transfusion requirements, no haemorrhagic complications or serious infections, and involving short periods of hospitalization. This course of events corresponds well with previously published information from larger patient materials, which are also discussed in the article.


[Attitude of blood donors towards cholesterol measurement].

In analyses of cost-effectiveness it is customary to count knowledge of having a high serum cholesterol level as a negative factor. There is little support for this practice in the literature. We have studied the attitude of 305 Norwegian blood donors towards cholesterol testing. 63% stated that they were interested in their serum cholesterol level, and 40% said they knew their own serum cholesterol level. The attitude towards cholesterol testing was clearly positive, both among men and among women, regardless of age. Only one donor stated that she did not want to have her serum cholesterol tested in conjunction with blood donation.


[Treatment of relatives].

The article addresses the physician's relationship to the next of kin of multi-traumatized patients. The various phases of grief are discussed:phase of shock, lack of emotion, disturbance of the imagination, sense of guilt, as well as aspects connected to donation of organs. Finally three case reports are presented to further illustrate the points made in the article.


[Neurobiological aspects of addictive drugs].

Increasing insight into the molecular and cellular mechanisms of drugs of abuse has been obtained during the last decade. Such drugs exert several of the effects related to their abuse potential by interacting with the mesocorticolimbic dopaminergic system. Single doses of several drugs of abuse increase dopamine activity in nucleus accumbens, which is related to reward and reinforcement. Repeated administration may result in development of tolerance, but also in behavioral sensitization and conditioning. These processes alter subsequent drug-related behaviours and may contribute to relapse to drug taking.


[Contact tracing in genital chlamydia infections].

Only one in five general practitioners in Norway initiates notification of partner(s) after diagnosing a case of genital chlamydial infection. In order to increase the use of this efficient case-finding method we review the aims of notifying partners and the judicial, ethical and economical aspects of the method. We describe both provider-referral and patient-referral methods. The first approach is chosen when the index patient wants to remain anonymous. General practitioners are advised not to give the index patient medication for the contacts. Instead, the contacts should be examined and informed by qualified personnel. Notification of partner will be a cornerstone in the struggle to control the current epidemic of genital chlamydial infection in Norway.


[Infection problems in the leukopenia phase after autologous bone marrow transplantation].

Between 1986 and 1991, 29 patients with malignant lymphomas were treated with total body irradiation and high-dose chemotherapy followed by autologous bone marrow transplantation at the Norwegian Radium Hospital. Owing to treatment-induced bone marrow toxicity, the leucocyte count in peripheral blood rapidly fell to zero. The aplastic phase lasted for 25 days (median). All patients experienced fever in the posttransplant period and needed broad-spectrum antibiotics. 12 patients had documented bacteremia, mostly with Gram-positive isolates. There were seven cases of documented focal infections, and antibiotic-associated colitis was seen in two cases. Other complications included bleedings and skin rashes. Four patients died in the post-transplant period from complications related to the cytotoxic treatment. We discuss guidelines for antimicrobial treatment of suspected and confirmed infections in neutropenic patients.


[Contact tracing routines for genital chlamydia infections used by Norwegian physicians. A questionnaire study].

Notification of partner(s) is recommended as a measure to control the epidemic of genital chlamydial infection. We surveyed a random sample of Norwegian general practitioners and privately practising gynaecologists. Only one in five general practitioners initiated notification of partner(s) after diagnosing a patient with genital chlamydial infection. A proposed new Communicable Diseases Act will make it mandatory to notify the partner in the event of such infections. 49% of general practitioners are in favour of the proposal, 21% oppose it while 30% remain uncertain. After implementation of similar legislation, Sweden has experienced a decline in the incidence of genital chlamydial infection. We believe increased notification of partner would help to control the Norwegian epidemic.


[The calendar as criterion--duration of sick leave and physicians' work conditions].

This paper addresses physicians' tendency to allot standardized, "rounded off" sick leave. Of the 401 sick leaves reviewed, 64.3% lasted for one or two weeks, one or two months, or to the end of the week or month. The patients' presumed wish for an extended leave, and the practitioners' strained work situation were examined as possible influential factors. A scrutiny of general practitioners' and company practitioners' working conditions, and employees' current inclination to work, does not support these ideas. Dialogue between physician and patient should be improved and we also suggest a change to "vaguer" durations of sick leave.


[Systemic mycoses. Epidemiology, clinical aspects, diagnosis].

Systemic mycoses are serious, often life-threatening, infections that are encountered with increasing frequency in many countries. These infections are most often seen as a result of advanced medical treatment leading to profoundly immuno-suppressed patients. In Norway, most systemic mycoses are caused by Candida, followed by Aspergillus, Cryptococci and Mucorales. This paper deals with the pathogenetic and immunologic mechanisms underlying these infections. The different agents are described, and the various clinical manifestations. A discussion of the diagnosis of systemic mycoses is followed by some general considerations regarding treatment.


[Reduction mammaplasty in breast hypertrophy].

Between January 1984 and November 1990 a total of 292 patients underwent reduction mammaplasty for hypertrophic breasts. Of these patients, 233 had a superomedial pedicle (Orlando's method) and 36 an inferior pedicle (Robbins' method). 23 had various other operations. The patients operated on by Orlando's and Robbins' method were compared retrospectively. It was found that Robbins' method was superior in younger women, owing to increased sensitivity of the nipple-areola complex, and lactation. In the physicians' opinion, wide scars developed in 32% of the patients. In our opinion closing the wound with intracutaneous suture might improve the quality of the scar. Of the patients assessed, 98% were satisfied with the physical outcome of the operation and 86% with the cosmetic outcome. The operative technique of the two methods is described.


[Ferritin concentration in serum in health adults. Significance for blood donation].

Serum ferritin levels were measured in 613 women and 376 men included in our Blood Donor Registry in 1990, prior to their first donation. The mean serum ferritin was 34 micrograms/l in females and 98 micrograms/l in males. For men less than 20 years of age mean serum ferritin was 52 micrograms/l which is significantly lower than for the other age groups. For women greater than or equal to 50 years of age mean serum ferritin was 61 micrograms/l, which is significantly higher than for the younger age groups. In 22% of the women and 1.3% of the men serum ferritin was less than 15 micrograms/l upon registration. Female blood donors with an initial serum ferritin of less than 10 micrograms/l had donated on average 1.2 times 11 to 23 months later, and 56% were temporarily or permanently deferred from donation. Females with an initial serum ferritin of between 30 and 39 micrograms/l had donated 2.5 times, and 26% were deferred.


[Catecholamine release--unpredictable side effects of calcium antagonists].

Animal and in vitro studies have shown that calcium antagonists release noradrenaline from sympathetic nerves. Several calcium antagonists interact with the catecholamine storage vesicles in a way that reduces the ability of the vesicles to take up and store catecholamines. Clinical studies indicate that verapamil and nifedipine increase release of noradrenaline from the heart during ischemia. Calcium antagonists thus have a direct catecholamine-releasing effect that may be clinically relevant (may induce negative side effects).


[Congenital myotonic dystrophy].

Congenital myotonic dystrophy is a distinct entity causing severe hypotonia and other neuromuscular manifestations. The disease is usually inherited from the mother and shows a more severe course than the adult form of dystrophia myotonica. Congenital myotonic dystrophy is associated with increased perinatal mortality. We describe a case with this disorder and discuss the differential diagnosis in relation to other neuromuscular disorders causing hypotonia in early life.


[Intestinal lymphoma presented as multiple intestinal polyposis].

Primary gastrointestinal lymphoma is a rare condition. It constitutes approximately 5% of all lymphoid malignancies. Primary lymphomas of the intestinal tract rarely present as multiple polyposis. We describe such a patient who was treated with chemotherapy. The treatment of choice is surgery when possible. Chemotherapy is used in addition when high grade non-Hodgkin lymphoma is revealed. Chemotherapy should be used for patients who are unable to undergo curative resections. Prognosis is poor for patients with a non-resectable disease.


[Poisoning with long-acting anticoagulants].

Until last year, all rodenticides that could be marketed freely in Norway contained anticoagulants. In recent years rodenticide manufacturers have replaced warfarin by so-called "superwarfarins" as the active substances in their products. The latter are more toxic, also in a human context. One single intake can produce an anticoagulatory effect which may last for 50 to 60 days, and the intake of larger quantities over a period of time can induce the same effect for close to seven months. We describe two patients who were poisoned with bromadiolone. One of them had to be treated with vitamin K1 for six months. Reference is further made to similar casuistics described in the literature. Finally, the authors outline a recommended method of treatment.


[Fluconazole--a new antifungal agent].

Fluconazole (Diflucan) is a new triazole antifungal agent that is effective against a wide range of fungi and has a favourable pharmacokinetic profile. Fluconazole is absorbed well after oral intake independent of food intake. Fluconazole is given once daily, in a dose of 50-400 mg. The dosage is the same for oral and parenteral administration. Tissue penetration is good, as is the concentration in cerebrospinal fluid. Fluconazole should not be given to children under 16 years of age, nor to pregnant or breast-feeding women. In Norway, fluconazole is indicated for treatment of candida vaginitis that is resistant to other treatment, invasive candida infection, candida stomatitis in immunocompromised hosts, and cryptococcal meningitis.


[Treatment of gynecologic bleeding disorders].

Conclusions reached at an expert meeting arranged by the Medical Products Agency (Läkemedelsverket) in Sweden on the treatment of gynaecological bleeding disorders are presented. An active approach to endometrial diagnosis is recommended when bleeding is protracted and does not respond to medication, and when bleeding occurs more than one year after menopause. A period of expectation is permissible in women younger than 45 years. Exfoliative endometrial diagnosis is highly sensitive and specific and, in recent years, the traditional curettage has been reappraised as the first method of choice. Bleeding during anovulatory cycles is usually managed by treatment with progestagens. Menorrhagia may be diminished by oral contraception, tranexamic acid or NSAID. Endometrial resection offers a promising alternative to hysterectomy. Genital infection is another common cause of irregular bleeding in sexually active women and must be treated before invasive procedures are undertaken. Abnormal bleeding in patients with endometriosis often improves as a result of the treatment given to alleviate other symptoms such as pain. Bleeding irregularities caused by gynaecological malignancy, particularly contact bleeding in cancer of the cervix, are seen during the reproductive years and are accessible for diagnosis. The authors also discuss irregular bleeding caused by coagulopathia or treatment with hormones, as well as the effect of antifibrinolytic drugs.


[Expert witness in cases of rape].

The decision to try a rape case in court may depend on the medico-legal evidence documented by a doctor. Generally, doctors have little knowledge of expectations and requirements in court regarding testimony and expert opinion. In 1990, the Norwegian Directorate of Health recommended that victims of rape and violence all over the country--independent of police notification--be offered a medical and a medico-legal examination and follow-up. The Oslo Emergency Hospital has practised this health service for six years. The article describes the Oslo routine as a basis for doctors with little or no knowledge of the subject. Rape trauma, a variant of post-traumatic stress disturbance, manifests over time as physical, psychological and social reactions which influence the patient's health. The doctor must therefore follow the patient over time in order to apply this diagnosis. Rape trauma may be unknown to the court; a reason why the doctor should inform the prosecutor if it is decided that the case is to be tried in court. In order to document rape trauma as evidence the doctor must be called as an expert medical witness and not as an ordinary witness.


[Are silicone breast prostheses dangerous?].

Since 1964 silicone breast prostheses have been implanted in 5 million women for breast reconstruction after cancer operations, to correct congenital deformities and for cosmetic reasons. There is no evidence in the literature of a correlation between silicone implants and breast cancer. Some authors claim that silicone implants reduce the reliability of mammography. Autoimmune diseases in patients with silicone mammary implants are reported in less than 40 cases. Most of these are localized or systemic scleroderma. An association with silicone implants has been suggested, but this suggestion has not been confirmed by scientific data.


[A cerebrovascular unit. Experiences after 8-years of activity].

The authors review experience gained from developing and running a non-intensive stroke unit during the years 1983-91. The number of patients treated per year has increased from 65 to 149. The average length of stay in hospital has dropped from 21 to 15 days. About 87% of the patients had verified stroke, 7% had transient ischemic attacks (TIAs). Other intracranial diseases were found in 3.3%. The mortality rate was low (5%) 48% of the patients were transferred to a rehabilitation centre, 37% were discharged to their homes, with or without out-patient care, and 10% were discharged to nursing homes. Early and systematic investigations and multi-disciplinary rehabilitation in a specialized stroke unit increases the quality of care for patients suffering from stroke. A shorter stay in hospital gives a bonus in the form of reduced health expenditures.


[Gingival hyperplasia induced by calcium channel blockers. Rare or frequent in Norway?].

Sales statistics indicate that the number of Norwegians treated with calcium channel blockers increased from about 50,000 in 1986 to about 83,000 in 1991 (last year: nifedipine 39%, verapamil 27%, amlodipine 21%, diltiazem 10% and felodipine 3%). In spite of widespread use, only one report on gingival hyperplasia induced by calcium channel blockers has been received by the Norwegian Adverse drug reaction committee. The incidence of this adverse reaction is uncertain, but the few controlled studies that have been performed indicate that it may be as high as 15% in patients on long-term treatment, at least with nifedipine. This corresponds to nearly 5,000 cases among the about 32,000 users of nifedipine. Norwegian physicians and dentists are asked to report cases of gingival hyperplasia induced by calcium channel blockers. Although the voluntary report system is fraught with uncertainty, it is hoped that, in a relatively small and surveyable drug market as the Norwegian, the reporting may provide some relevant information, e.g. to allow comparison of the potential of the various calcium channel blockers to induce this adverse effect. A Norwegian controlled study on gingival conditions among long-term users of calcium channel blockers is in its initial stage. It may be of interest to compare the results of this study with the indications obtained from the spontaneous reporting on the incidence of this adverse effect, which is relatively easy to diagnose.


[Intravenous drug users and the HIV epidemic].

Data are taken from a study of 1,765 arrested intravenous drug users at the Oslo Central Police Station. Intravenous drug users in Oslo seem to get themselves tested for HIV regularly. In 1990-91 the average number of HIV-tests was 5.3, and the time since last test was, an average, between eight and nine months. Most intravenous drug users do not share needles and syringes. The most important source of needles and syringes in Oslo is an ambulant bus which can be found in city centre at night. HIV-seropositive drug users seem to have more regular contact with treatment programmes than those who are HIV-seronegative. Most of the HIV-seropositive drug users who are under treatment are to be found in a few institutions.


[What symptoms and complaints result in sick-listing? ICPC-coding of patients' own opinion in general practice].

The aim of this study was to describe which complaints patients themselves regard as the cause of sickness certification. During one week in April 1986, 1,379 patients in Buskerud county, Norway, filled in a form after receiving an initial certificate of illness or a continuation certificate from a general practitioner. International Classification of Primary Care (ICPC) no. 1-29 was used to classify the patients' symptoms and complaints. More than half of the patients (53%) considered pain in the musculoskeletal system, particularly back pain (22%), as the reason for their sickness certification. Physical work load was assumed to be a contributory cause to the complaints by 66% of the patients certified sick because of back pain, 58% of those certified sick due to cervical spine and shoulder symptoms, and 72% of those with myalgia, fibrositis (ICPC no. L18, L19). 29% of the patients meant that their health problems could have been prevented, and 15% reported that they could have continued work if their jobs had been adjusted because of their condition.


[The question of compensation for animal epidemics--general legal principles and discussion of selected verdicts].

A summary is given of general and specific aspects and jurisdiction in connection with sections 66-71 (compensation for damages of the German animal epidemic law). The author can be contacted for specific details.


[An elephant tusk with a spear injury].

This tusk specimen contains a metal spear with a wooden component, which is surrounded by a quiver-like osseous encasement. The injury was probably caused by a drop-spear trap. The spear entered the tusk through the base of the pulp. The osseous encasement is constructed by pulpocytes which turned to odontoblasts after stimulation and are responsible for the development of secondary dentine. Secondary dentine is characterized by its irregular arrangement of dentine tubules, in contrast to those of true ivory.


[Cellulose acetate electrophoresis, radial immunodiffusion and nephelometry--comparative methods for the determination of albumin].

Different methods for the determination of albumin in dogs and cats are compared. Nephelometry was found to be the method of choice, due to its excellent precision, the immediate test results and the wide measuring range. The advantage of the radial immunodiffusion method is that expensive equipment need not be acquired, which makes the test profitable for small amounts of samples. At the expense of accuracy, electrophoresis enables the simultaneous evaluation of all protein fractions.


[The effect of environmental factors on the occurrence of udder diseases].

The influence of housing factors on udder diseases was investigated in 2156 tiestall barns with 41893 cows and in 98 loose housed herds with 4126 cows. In loose housed herds less teat injuries were observed and also less mastitis than in tiestall barns. Within the different tiestall systems there was a trend to more udder diseases in short standings with a dung grid than in other systems. The ordinary neck chain and the "Grabner"-tethering system showed better results than the horizontal chain and the yoke tying system. Stall partitions between the cows caused a marked reduction of udder diseases. The installation of a cow trainer showed advantages regarding udder diseases. Inaccurate standing measurements (length and width) caused more udder diseases. When the metal grid was in poor condition, the incidence of teat injuries as well as udder diseases of heifers increased. Teat injuries and udder infections were more frequent when limb or digit injuries were found. Regular hoof care twice a year reduced the udder disease rate. Bedding material influenced the incidence of udder diseases positively. On farms where the cows were on pasture, the incidence of udder infections was higher than on farms where the cows were permanently housed. Heifers that were tied as calves or as juveniles showed significantly less udder diseases than those that were raised in groups. Faults in milking, defects in milking machines and deficits in milking hygiene showed a negative effect on udder diseases.


[Infection with Leptospira interrogans, serovar mozdok, in cattle].

In East Germany the same serovar, Leptospira mozdok, of the Pomona serogroup is found in cattle as well as in swine populations (Zieris 1989). Nowadays cases of bovine leptospirosis caused by infection with L. pomona have no significance. There are marked epizoological differences between infection with L. mozdok and L. pomona. The main source of infection with L. mozdok for cattle is the black striped field mouse (Apodemus agrarius). Secondary homonomous transmission occurs among the cattle. The clinical course of both infections is the same--including peracute, acute and chronic forms. Important prophylactic measures are effective rodent control and optimising hygiene conditions both in housing and on pasture. Veterinarians in abattoirs must consider leptospirosis in the differential diagnosis in cases with icteric signs, especially when the meat is derived from emergency slaughter.


[The clinical effectiveness of FSH-P for induction of superovulation in cattle].

The clinical efficacy of FSH-P for the initiation of superovulation in cattle was examined on 1000 animals of the Deutsche Schwarzbunte and Rotbunte breeds of RPN Verden during the years 1988 and 1989. In untreated cattle only one embryo is found (R. J. Mapletoft 1983, Roselius 1989). In the group of the FSH-P treated animals, the number of transferable embryos was 5.8 +/- 3.6. The 25% percentile was 3 and the 75% percentile was 8. A seasonal dependence was not found.


[Rumen fluid studies in calves with abnormal and normal sucking behavior].

Ruminal fluid and blood samples were analysed in 39 calves with poor suckling behaviour and reduced milk intake (group 1) and in 21 calves with normal suckling behaviour (group 2). The pH level and chloride concentration was determined in the ruminal fluid as well as in the blood. In addition Gram stains and subsequent microscopical examinations of the ruminal fluids were carried out. Blood samples were submitted for blood gas analysis. Notable differences were found between the two groups. The pH level of the ruminal fluid was less than 5.5 in 29 of the 39 calves in group 1 (74.4%); in contrast, the pH was always above 5.5 in group 2. In group 1, 22 calves with a pH of less than 5.5 also revealed a metabolic acidosis of the blood. Mainly gram-positive bacteria were found in the ruminal fluid of 74.4% of the calves in group 1. On the other hand, 76.2% of the calves in group 2 revealed a mainly gram-negative flora. There was no difference in the chloride concentration, either in the blood or in the ruminal fluid and the values showed a high range of scatter.


[Selenium poisoning in fattening swine].

A case of selenium toxicosis was observed in fattening pigs. Intoxication was caused by high levels of selenium in a commercial mineral premix. Instead of the recommended dose of 16 ppm Se, the mineral feed contained selenium at concentrations of 657 and 1059 ppm. The ration in use was found to contain more than 14 ppm selenium. Clinical symptoms were observed 5 to 6 weeks after the pigs began consuming the contaminated feed mixture. Feed intake was markedly reduced and animals showed severe lameness due to separation and necrosis of the hoof wall at the coronary band. Some pigs were reluctant to stand. In some cases alopecia was detected. At histopathological examination one animal with paralysis of the hind limbs revealed a focal bilaterally symmetric poliomyelomalacia in the lumbar segment of the spinal cord. Diagnosis was confirmed by high selenium contents of liver, kidneys and blood. After removing the incriminated feed no further pigs developed signs of intoxication. New horn growth was present and lame animals recovered slowly.


[Restraint methods for bird patients. Theoretical principles and practical implementation. Part 1].

In avian medicine an adequate diagnostic and therapeutic procedure is not possible without restraint. Accidents result most often from the ignorance of certain bird-specific physiological and anatomical characteristics. On the basis of theoretical principles, the different restraint techniques are described and demonstrated by figures in detail.


[The use of tiletamine/zolazepam/romifidine for distant immobilization of wild boars].

The immobilisation of 25 wild boars with a combination of tiletamine/zolazepam/romifidine is described. The applied dose was 3-6 mg/kg BW Tilest 500 and 100 micrograms/kg BW Sedavet. The mean recumbency time was 5-10 min. There were no critical moments during anesthesia, even with pregnant sows. Anesthesia was supervised with a pulse oximeter and a respiration frequency monitor. The oxygen saturation was between 92% and 96%, pulse and respiration rate remained normal.


[Surgical removal of a pedunculated uterine tumor in a donkey mare].

The unusual incidence of a pedunculated fibrosarcoma in the uterus of a donkey is reported. The tumor caused colic-like symptoms and blood tinged vaginal discharge. The diagnosis was made by ultrasound and rectal examination. The patient was successfully treated surgically, by ovariohysterectomy.


[Lens-induced uveitis (endophthalmitis phakoanaphylactica) in domestic animals].

In this paper ophthalmological and clinical results as well as the literature on lens-induced uveitis (LIU), a relatively unknown pathological syndrome in domestic animals, are presented. Out of all ocular material sent to the Institute of Pathology, GSF, from 1970 until 1990 (n = 864), 40 individual cases of LIU (14 cases in dogs, 13 in cats, 10 in rabbits, 1 in a horse and 2 in birds) were diagnosed. The histology of the eyes of the cases is characterized by a lesion of the lens capsule and a consequent reactive phacogenic inflammation of the anterior segment of the eye in the region of the anterior uvea. A comparison of the history and ophthalmological diagnosis indicates that 36 lens-induced uveitis cases occurred following a (spontaneous) traumatic injury to the eye, whereby the anterior lens capsule was perforated with the result of the lens material being exuded into the anterior uvea (iris-ciliary body region). The strongly vascularized anterior uvea is used as a carrier and a connecting link to the immune system. None of the histologically examined cases of LIU were diagnosed as such clinically. This can be explained by the fact that the uveitis is difficult to recognize on account of overlying secondary alterations in the eye. Nevertheless the morphological substrate of LIU is considered to be pathognomonic. The inflammatory and cellular reactions leading to a release of the lens material observed in domestic and laboratory animals exhibit only slight parallels to those observed in man. The case history of animals usually reveals a traumatic injury and an endophthalmitis (with or without secondary glaucoma) which cannot be controlled therapeutically. The therapy for promptly diagnosed cases should be a lens extraction to save the affected eye and its sight. In advanced cases the enucleation of the bulbus is the therapy of choice.


[Cells in the cerebrospinal fluid of dogs and cats. Part 2].

Three groups of cerebrospinal fluid (CSF) cells can be formed: 1. cells of the normal CSF, such as monocytes, small lymphocytes and occasionally cells of the ventricle system, 2. cells found in dogs and cats with neurologic disorders, such as reactive monocytes and lymphocytes, macrophages, neutrophils and eosinophils in addition to cells of the first group, 3. neoplastic cells. The different cells are introduced and their origin, function and occurrence are discussed. Mitotic figures, degenerated cells and artefacts are also mentioned.


[Fresh water aquariums and veterinary practice. 1. Principles of fresh water aquariums].

Although aquarium fish belong to the most frequently-kept pets they are very rare as patients in veterinary clinics. Besides the fact that the cost of the single fish is usually low, one reason might be that a sick fish has always to be seen in the context of its aquarium conditions, and that most veterinarians lack knowledge of required parameters. The following summary is intended to give an overview of the factors that are important for an optimal functioning aquarium, and with that for the health and well-being of the animals. Knowledge of these factors will help in the recognition and prevention of diseases resulting from management faults.


Effect of calcium and phosphate ions on hemolysis induced by Pyrularia thionin and Naja naja kaouthia cardiotoxin.

Pyrularia thionin is a strongly basic bioactive peptide of 47 amino acids isolated from nuts of Pyrularia pubera. It is hemolytic, cytotoxic and activates an endogenous phospholipase A2 in 3T3 cells. Earlier studies have shown that the cardiotoxin from Naja naja kaouthia has similar activities and binds to the same site as Pyrularia thionin. Since the peptides appear to bind to the phospholipids of cell membranes to elicit their cellular responses, the effect of modifying the electrostatic environment was studied by separately adding phosphate ion and Ca2+, and by removing Ca2+ from the membrane by treatment with EGTA. Analysis of erythrocyte hemolysis for both Pyrularia thionin and cardiotoxin shows that the reactions follow Michaelis-Menten kinetics, with the peptides serving as the substrate. The basal rate of hemolysis in physiological saline is markedly increased by the addition of phosphate in the 5-10 mM range and also by removing membrane-bound Ca2+ by incubation of the cells with 10 mM EGTA. These treatments do not change the apparent K(m) values, but increase the V(max), indicating that more binding sites are made available by these treatments. On the other hand, added Ca2+ in the 5-10 mM range competitively inhibits the reaction by inhibiting the binding of the peptide to the membrane.


Binding properties of Pyrularia thionin and Naja naja kaouthia cardiotoxin to human and animal erythrocytes and to murine P388 cells.

Pyrularia thionin and snake venom cardiotoxin are strongly basic peptides which induce hemolysis, depolarization of muscle cells and activation of endogenous phospholipase A2. An earlier study of the hemolysis reaction indicated that the two peptides bind to and compete for the same site on human erythrocytes. A recent study examined the hemolysis induced by both peptides as the phosphate and Ca2+ content of the reaction mixture was varied. The results of the recent study (VERNON, L. P. and ROGERS, A., Toxicon 30, 701-709) agree with this companion study on the binding of 125I-labeled pyrularia thionin and cardiotoxin to erythrocytes under the same conditions. Added phosphate ion at 5 mM and removal of membrane-bound Ca2+ by treatment with 10 mM EGTA make more binding sites of the same affinity available to both peptides, which are shown to bind in a competitive fashion to the same site. Addition of 10 mM Ca2+ to the medium decreases peptide binding due to competitive binding of Ca2+ to the same site on the membrane. For human erythrocytes the number of binding sites/cell for the thionin ranged from 0.7 to 1.7 x 10(5) and for cardiotoxin from 0.82 to 1.6 x 10(5). The calculated dissociation constants (Kd) from the Scatchard plots ranged from 0.43 to 1.1 microM for the thionin and from 0.40 to 0.98 microM for the cardiotoxin. The binding sites for thionin and cardiotoxin with sheep erythrocytes were 1.7 and 2.0 x 10(4) sites/cell, respectively, and both cow and horse erythrocytes demonstrated 2.7 x 10(4) sites/cell for the thionin. Binding studies with murine P388 cells showed 7.0 and 9.5 x 10(6) sites per cell for Pyrularia thionin and cardiotoxin, respectively.


Mojave toxin affects fusion of myoblasts and viability of myotubes in cell cultures.

Mojave toxin is a neurotoxic, heterodimeric phospholipase isolated from the venom of Crotalus scutulatus scutulatus. Responses of primary rat muscle cell cultures and clonal muscle cell lines to treatment with Mojave toxin and its constituent subunits were examined. Continuous exposure of cells to 0.5 microM or 1.0 microM Mojave toxin or the basic subunit, added 24 hr after plating, prevented fusion of primary myoblasts and C2 myoblasts to multinucleate myotubes. Under the same experimental conditions, some myotube formation was observed when RMo cells were used, but the number and size of the myotubes were reduced substantially compared to untreated controls. The addition of Mojave toxin to established myotubes that arose from differentiation of primary myoblasts or C2 myoblasts essentially led to total disappearance of the myotubes from the cell layer within 48 hr. Myotubes from RMo cells treated in the same manner, however, did not disappear, but they were smaller and less numerous than comparable controls. Similar results were generated by exposure of myotubes to the basic subunit of Mojave toxin under the same conditions. The underlying layer of mononucleate cells was retained in both instances. Toxin-free cultures continued to develop in the usual manner. Treatment with 1.0 microM concentrations of the acidic subunit, pancreatic phospholipase A2 or a non-neurotoxic phospholipase from Naja naja atra gave results indistinguishable from untreated control cultures.


Morphology of the large granular alveoli of the parotid glands in toad (Bufo ictericus) before and after compression.

The parotid glands of toads are constituted by an accumulation of venom-producing granular alveoli. Parotid glands of Bufo ictericus were manually compressed and immediately excised. Normal glands (not submitted to compression) were also excised and processed for histological and ultrastructural observations. The glandular body of large granular alveoli in parotid glands is formed by a myoepithelial layer, internally covered by a syncytial secretory layer. In the normal parotid gland this layer is very electron dense, thus preventing clear visualization of organelles. Large secretion granules are located in the main secretion mass, near the syncytium. In the compressed parotid gland, the myoepithelium shows a number of alterations, including presence of myelin figures and foci of degradation in the cytoplasm. The organelles of the syncytial cytoplasm are easily observed. The mitochondria are swollen; the cristae are shortened or absent. Syncytial secretion granules and lengthened structures linked to the syncytial matrix are to be seen. A large amount of smooth endoplasmic reticulum is present, while the rough endoplasmic reticulum is reduced. This large quantity of smooth endoplasmic reticulum suggests enhanced synthesis of the cardiotoxic steroids of the venom. Alterations in the mitochondria and the presence of myelin figures and degenerative foci in the cytoplasm may probably be regarded as consequences of the cellular injury provoked by compression.


Synthesis and characterization of a disulfide bond isomer of omega-conotoxin GVIA.

Solid phase peptide synthesis and air oxidation of omega-conotoxin GVIA yielded, in addition to the desired product, an isomeric peptide which could be completely separated from the native toxin by repeated HPLC. A chymotrypsin-trypsin digest of this peptide, when subjected to HPLC peptide mapping, provided peptides identical with synthetic disulfide containing peptides predicted for the omega-conotoxin isomer containing C1-C2, C3-C5, C4-C6 cystinyl pairings. The 'shaking' potency (ED50 = 1500 pmoles/kg, i.c.v.) of the isomeric peptide upon cannulated rats was 1.3% of the potency of native conotoxin (ED50 = 20 pmoles/kg). Considering that all three disulfide pairings in the isomer are different from the native toxin, its retention of biological activity is of interest.


Renin and aldosterone levels and hypertension following envenomation in humans by the yellow scorpion Leiurus quinquestriatus.

Renin activity and aldosterone blood levels were measured in ten patients following scorpion envenomation by the scorpion Leiurus quinquestriatus. All patients were hypertensive on admission, with clinical signs of systemic intoxication. The blood renin and aldosterone levels were elevated in all ten patients. The observation of high blood pressure and elevated levels of renin suggests that in addition to increased circulating catecholamines following scorpion envenomation, sympathetically induced renin release may play an important role in the pathogenesis of hypertension. This observation re-emphasizes the importance of afterload reduction in the treatment of the cardiovascular manifestations of scorpion envenomation.


Fate of a single dose of the 14C-labelled mycotoxin, fumonisin B1, in rats.

The fate of the mycotoxin, fumonisin B1, (FB1) dosed to rats by i.p. injection and by gavage was traced using 14C-labelled FB1. Twenty-four hours after i.p. injection, 66% of the radioactivity was recovered in faeces, 32% in urine, 1% in liver and trace amounts (less than 1%) in kidney and red blood cells. When dosed by gavage, all (101%) radioactivity was recovered in faeces and trace amounts were found in urine, liver, kidney and red blood cells. The bulk of the radioactivity recovered was unmetabolized FB1.


Structure of the low molecular weight protein copurified with alpha-latrotoxin.

Some samples of latrotoxin purified from the black widow spider venom contain two components: alpha-latrotoxin (M(r) approximately 130,000) and a low mol. wt protein with M(r) about 8000. Clones carrying the cDNA sequence for the low mol. wt protein copurified with alpha-latrotoxin were isolated from spider venom glands. Nucleotide sequence analysis of the cloned cDNA revealed the primary structure of the polypeptide to be 18 amino acids signal peptide and 70 amino acids protein chain with mol. wt of 7947 and pI of approximately 4.0. The protein exhibits certain structural homology with erabutoxin-a from the sea snake.


Effects of Duvernoy's gland secretions from the eastern hognose snake, Heterodon platirhinos, on smooth muscle and neuromuscular junction.

Duvernoy's gland secretions (100 micrograms/ml) from the eastern hognose snake, Heterodon platirhinos, induced a neuromuscular blockade in the isolated frog sciatic nerve-gastrocnemius muscle preparation and effectively antagonized acetylcholine and histamine responses of the rat duodenum preparation. The Duvernoy's secretions (100 micrograms/ml) produced a reversible, excitatory effect in the guinea-pig ileum in vitro. Mice administered the secretions (100 mg/kg, i.p.) exhibited minor, transient signs of toxicity. These preliminary observations provide evidence for toxicity of H. platirhinos Duvernoy's gland secretions but do not warrant categorizing the potential toxicity of this species with that of proteroglyphous, solenoglyphous, or the more venomous opisthoglyphous species.


What is tityustoxin?

Tityus serrulatus scorpion venom was fractionated by gel filtration affording two heterogeneous toxic fractions, T1 and T2; the latter was further fractionated by ion-exchange chromatography. The fraction of T2 eluted with 0.15 M ammonium acetate buffer, originally named 'tityustoxin', was shown to be a pool of several proteins. One of them, TsTX, as well as T1, was also named 'tityustoxin'. The major and perhaps most potent toxin of the venom, gamma-toxin, was eluted with 0.30 M buffer as a highly purified protein and shown to be different from TsTX. gamma-Toxin is contained in both T1 and T2.


Effect of the cyanobacterial (blue-green algal) toxins from Microcystis aeruginosa on isolated enterocytes from the chicken small intestine.

Livestock deaths, and clinical reports of human injury, follow the consumption of toxic blue-green algae. The experiments described show that isolated intestinal enterocytes from chicks are both deformed and killed by exposure to Microcystis toxins, in a dose-dependent and time-dependent manner. The enterocytes were protected from toxicity by deoxycholate, bromosulphothalein and rifampicin. It was concluded that the gastroenteritis clinically associated with accidental Microcystis ingestion is likely to reflect enterocyte injury by Microcystis toxins, and that the therapeutic use of bile acids or transport inhibitors may be of value in treatment.


Effects of sea water pollution on chicken embryos.

Organic matter and heavy metal contamination in sea water obstruct vital functions of chicken embryos and interrupt their growth. Histological examination of contaminated fetuses showed a menacing growth of abnormal protuberances in the lungs as well as highly impeded formation of capillaries, although the windpipes exhibited normal expansion. Compared with controls, liver tissue also showed retarded growth accompanied by decrease in liver weight. Consequently, vital metabolic functions were impaired, hydropsy and evisceration developed, and fetuses were deformed.


Evaluation of enzymuria as an indicator of amikacin-induced renal damage in guinea pigs.

Guinea pigs were injected subcutaneously for 10 days with amikacin (AK) at a dose of 0, 100, 200 or 400 mg/kg body wt. per day. The total daily dose was administered in either a single injection or divided equally and given as two daily injections. After the 10 days of AK treatment, uptake of the organic cation, tetraethylammonium (TEA) into renal cortical slices was inhibited in a dose-related manner. Changes in renal tubular morphology also increased with higher doses. The urinary excretion of the enzymes, N-acetyl-beta-D-glucosaminidase (NAG), and alkaline phosphatase (ALP) significantly increased during the course of AK treatment, however, due to the large intragroup variability, the daily fluctuations and the absence of any distinct trends in urinary enzyme excretion it was difficult to establish a dose-relationship between AK-induced renal damage and the resultant enzymuria. At doses of 100 and 200 mg/kg body wt., the two-injection regimen resulted in the greater renal accumulation of AK and damage as reflected by a greater inhibition of TEA uptake and greater changes in renal tubular morphology. In contrast, this difference in toxicity could not be detected with enzymuria again due to the large intragroup variability and the absence of discernable excretion patterns of NAG and ALP. Thus, neither NAG nor ALP appear to be suitable quantitative markers of AK-induced nephrotoxicity.


Inhalation toxicity of chromium from Whetlerite dust in rats.

The acute inhalation toxicity and metabolic fate of chromium and copper from Whetlerite dust in rats were investigated. Groups of male and female, Sprague-Dawley rats were exposed to Whetlerite dust and base carbon dust as outlined in the OECD Limit Test guidelines. At 14, 28 and 180 days post-exposure, rats were evaluated for gross pathological changes and tissues were collected for chromium and copper determination. Four deaths occurred during or post-exposure, but did not appear to be compound related. No gross pathological changes were observed at necropsy in either group. Organ chromium concentrations were below detection limits of 0.5 micrograms Cr/g dry tissue in both exposure groups. According to OECD guidelines, neither Whetlerite dust nor base carbon dust demonstrated an acute inhalation toxicity.


Mesenteric mast cell degranulation in acute T-2 toxin poisoning.

T-2 toxin-induced alterations in rat mesenteric mast cell granulation were measured by cytophotometric analyses of the metachromatic reaction of mast cell granules with azure B. Hypogranulation (diminution of metachromatic material) was observed 8 h following injections of T-2 toxin (0.5-1.5 LD50, i.p.). These data suggest that mast cell activation occurs during acute T-2 intoxication and raise the possibility that mast cell mediators may contribute to toxin-induced cardiovascular collapse.


Brain energy metabolites in mice intoxicated with acrylamide: effects of ischemia.

Concentrations of phosphocreatine, creatine, ATP, ADP, AMP, glucose and lactate in the whole brain did not differ between the mice intoxicated with acrylamide and the controls. When the brain was made ischemic, these concentrations changed to the same extent in both groups. The only difference was the lower pyruvate in acrylamide-intoxicated mice under the ischemia. Thus, as far as the whole brain is concerned, acrylamide does not cause gross alterations of energy metabolites, even under ischemia.


Teratological assessment of diiodomethyl p-tolyl sulfone in rats.

Pregnant rats were given diiodomethyl p-tolyl sulfone (DIMPTS) at a dose of 0, 0.125, 0.25, 0.5 or 1.0% in the diet on days 6-15 of pregnancy. Maternal body weight gain and food consumption during the administration period were significantly lowered in the 0.25, 0.5 and 1.0% groups. No significant changes induced by DIMPTS were detected in the number of resorptions and dead fetuses, and body weight of live fetuses. Morphological examinations of fetuses revealed no evidence of teratogenesis. It could be concluded that DIMPTS has no teratogenic effects on rat offspring, even at doses which induced maternal toxicity.


Detection of contact sensitivity of metal salts using the murine local lymph node assay.

The local lymph node assay (LLNA) is a predictive test for the detection of contact allergens. Nickel and chromium sensitization are common cases in man. However, in a previous study topical application of nickel sulfate and potassium dichromate in aqueous solution failed to induce activation in the draining lymph node. This study describes the application of LLNA to evaluate the contact sensitivity of metal salts. The metal salts were applied in dimethylsulfoxide or aqueous ethanol solution. In some experiments, the skin of the ears was gently abraded using a needle prior to application of metal salts. The ability of seven metal salts to induce lymph node cell (LNC) proliferation was compared. Nickel, cobalt, chromium and copper salts increased LNC proliferation, whereas zinc, manganese and iron salts failed to induce LNC proliferation in this assay.


Modification by phenobarbital of decreased glutathione content and glutathione S-transferase activity in livers of lead-treated mice.

Lead acetate (100 mg/kg) administered i.p. to male mice decreased hepatic glutathione (GSH) content and also glutathione S-transferase (GST) activity. However, the liver GSH content of mice treated with both lead and phenobarbital (80 mg/kg, i.p.) remained unchanged, whereas their GST activities were higher than the controls. Phenobarbital antagonized the Pb-induced decrease in liver adenosine triphosphate content. Additionally, phenobarbital shortened the half-life of hepatic GSH determined using buthionine sulfoximine, an inhibitor of GSH synthesis. Acceleration of hepatic GSH turnover by phenobarbital possibly diminishes the Pb-induced impairment of GSH-conjugation of xenobiotics.


Effect of cadmium and/or selenium on liver mitochondria and rough endoplasmic reticulum in the rat.

This study was conducted to investigate the effect of cadmium (Cd) and/or selenium (Se) on hepatic mitochondria and rough endoplasmic reticulum (RER). Male Sprague Dawley derived rats (150-200 g) received sodium acetate (NaAc; 1.23 mg/kg), Cd (0.84 mg/kg), and/or Se (1.6 mg/kg) intraperitoneally. Livers were perfused with 2% glutaraldehyde at 48 h, 72 h, or 96 h after treatment and prepared for electronmicroscopy. Results indicate that Cd and/or Se are capable of inflicting mitochondrial and RER structural changes, and the damage by Cd alone is more severe than Se alone or with Cd.


Curvi-linear relation between acetone in breathing zone air and acetone in urine among workers exposed to acetone vapor.

An occupational health study was conducted on 45 acetone-exposed male workers in combination with 343 non-exposed men to examine the quantitative relationship between the intensity of acetone vapor exposure and the concentration of acetone in urine. The time-weighted average acetone concentrations were measured by means of diffusive samplers with water as absorbent, whereas urine samples were collected at the end of the shift as well as before the shift on the next morning. Acetone concentration in shift-end urine did not increase when the workers were exposed to acetone up to approx. 15 ppm, and this was followed by a gradual increase at a higher atmospheric acetone concentration, in a manner dependent to acetone vapor concentration. The comparison in acetone concentrations between the urine samples collected at the shift-end and those before the shift of the next morning showed that the levels in two sets of samples were the same among those exposed to 15 or less ppm acetone, whereas acetone in the shift-end samples was significantly higher than the counterpart levels in the pre-shift samples among those exposed to acetone at more than 15 ppm.


Modification of metal-induced micronuclei formation in mouse bone marrow erythrocytes by Phyllanthus fruit extract and ascorbic acid.

The comparative efficacy of Phyllanthus emblica fruit extract, and its main constituent, ascorbic acid, in modifying the cytotoxic action of lead and aluminium was evaluated in vivo in bone marrow cells of Mus musculus. Oral administration of Phyllanthus emblica fruit extract for 7 days before exposure to the metals through intraperitoneal injections reduced the frequency of micronuclei induced by all doses of both metals. Priming with comparable doses of synthetic ascorbic acid reduced micronuclei formation induced by both doses of aluminium and only the lower dose of lead. With the higher dose of lead (20 mg/kg body wt.) priming with ascorbic acid increased the frequency of micronuclei when compared with mice administered lead alone. The greater efficacy of Phyllanthus fruit extract in alleviating metal-induced clastogenicity may be due to the combined action of all ingredients in the crude extract, rather than to ascorbic acid alone.


Oxidative and non-oxidative metabolism of ethanol by the rabbit lung.

Pulmonary ethanol metabolism in the rabbit was investigated in vitro by examining oxidative (alcohol dehydrogenase) and non-oxidative (fatty acid ethyl ester synthase) pathways. Pulmonary alcohol dehydrogenase (ADH) activity was very low when measured at close to normal physiological conditions but increased at higher pH, although it was lower than that in the liver. Significant esterification of oleic acid was detected using rabbit lung homogenates, with the rate being intermediate to that of the other tissues examined. The results indicate that oxidative metabolism of ethanol (via ADH) by the rabbit lung is minimal compared to other tissues, but non-oxidative metabolism of ethanol leading to FAEE formation occurs at significant rates that may alter lipid metabolism or membrane composition.


Sex, light and carotenes: the development of Phycomyces.

Phycomyces blakesleeanus is known for the elaborate behaviour of its sporangiophores (fruiting bodies). Sporangiophore development is exquisitely sensitive to blue light, easy to describe quantitatively, pliable to genetic and biochemical research, and reminiscent in many details of other photoresponses in the same and in other organisms. The developmental and behavioural processes of Phycomyces share a number of genes. A combinatorial use of gene expression appears to be the basis for the complexities observed in this fungus.


Cell polarity and cell diversification during early mouse embryogenesis.

At the eight-cell stage of mouse development, the organization of blastomeres changes from radially symmetrical to polarized. This acquisition of cell polarity, followed by asymmetric divisions, leads to the formation of two phenotypically different cell types, which give rise to the first two cell lineages of the mouse blastocyst embryo, trophectoderm and the inner cell mass. Cell fate, controlled by positional information, is not irreversibly fixed during differentiation, providing the embryo with considerable developmental flexibility.


Continuous conversion of neuron phenotype in hydra.

All neurons in adult hydra are constantly changing their location. This poses interesting problems for the maintenance of the organization of the hydra nervous system. The solutions provide a different perspective on the development of nervous systems.


The TATA-binding protein: a central role in transcription by RNA polymerases I, II and III.

The TATA-box-binding protein, first noted for its association with the general transcription factor TFIID, has recently been shown to be required for transcription by all three classes of nuclear RNA polymerase found in eukaryotes. As such, it plays a unique and pivotal role in gene expression in higher organisms.


Microsatellites for linkage analysis of genetic traits.

Microsatellites are tandem repeats of simple sequence that occur abundantly and at random throughout most eukaryotic genomes. Since they are usually less than 100 bp long and are embedded in DNA with unique sequence, they can be amplified in vitro using the polymerase chain reaction. Microsatellites are easy to clone and characterize and display considerable polymorphism due to variation in the number of repeat units. This polymorphism is sufficiently stable to use in genetic analyses. Microsatellites are therefore ideal markers for constructing high-resolution genetic maps in order to identify susceptibility loci involved in common genetic diseases.


Use of in vivo apparent pA2 analysis in assessment of opioid abuse liability.

Abuse liability testing of opioid drugs was originally motivated by attempts to separate the analgesic effects of opioids from their likelihood for abuse. It has become apparent that the human population group likely to abuse opioids has little overlap with the population group requiring opioids to treat pain, therefore there is no longer a need to separate these two properties of opioids. This is fortunate, since, as reviewed here by Jim Woods and colleagues, the results of the plethora of studies that have attempted to distinguish these two properties in known opioids strongly indicate that they are inseparable. Evaluation of the abuse potential of novel opioids remains, however, critically important in deciding on governmental restrictions on their accessibility. In addition, opioid abuse liability testing contributes enormously to our understanding of the behavioral mechanism of action of these drugs, and in surprising and helpful ways has increased our appreciation of the various test systems used to garner information about them.


Cytokines and neuropathology.

Inflammatory processes in the brain require the cooperation of immunocompetent cells and glial cells, which communicate by secreting bidirectional mediators. Resident cells within the nervous system can synthesize and secrete inflammatory cytokines, as well as neuropeptides, contributing to the response within the CNS to injury or immunological challenge. Although the mechanisms of cell activation and immune interaction are poorly understood, accumulating evidence implicates these pathways in neuropathogenesis, as described here by Sharon Wahl and colleagues. For example, in the acquired immune deficiency syndrome (AIDS), HIV-1-induced nervous system dysfunction and dementia are associated with the presence of infiltrating leukocytes and the release of inflammatory cytokines. Defining the pathways of cytokine dysregulation and neurotoxicity invoked by the infiltrating leukocytes, as well as the contribution of the neural cells themselves, may help to identify mechanisms of intervention in this and other debilitating CNS diseases.


IgG subclasses in symptomatic IgA deficiency.

We evaluated IgG subclass levels in 11 symptomatic patients (ages between 3 and 22; mean 7.5 years) with IgA deficiency, seven with selective IgA deficiency, and four with low IgA levels. All patients had experienced three or more episodes of sinopulmonary infections a year. Combined IgG2-IgG4 deficiency was detected in two patients, IgG2 deficiency in one patient and IgG4 deficiency in two patients. Elevated IgG1 and IgG3 levels were detected in most of the IgG subclass deficient and sufficient patients. It is known that gammaglobulin replacement therapy reduces the frequency of infections significantly in IgG subclass deficiency. Although immunization against IgA is a risk in IgA deficiency, these patients can be treated with gammaglobulins containing low IgA.


Evaluation of the hypercoagulable state by measuring protein C and antithrombin III levels in nephrotic syndrome and in familial Mediterranean fever-related amyloidosis.

The levels of protein C (PC) and antithrombin III (AT III) antigens (ag) were measured in the plasma of 39 patients with various histologic types of primary nephrotic syndrome (NS) and in 12 patients with amyloidosis secondary to familial Mediterranean fever (FMF). The controls comprised 15 healthy children. Normal or elevated PC levels were observed in primary NS patients (mean 64%, range 36-98%) and in amyloidosis patients (mean 58%, range 48-70%). There was no difference found between PC ag levels in primary NS and in amyloidosis patients. In addition, no correlation existed between protein selectivity and the PC ag levels in the primary NS patients. Normal and decreased levels of AT III were observed (mean 29 mg/dl, range 11.1-39 mg/dl) in the patients with primary NS and amyloidosis (mean 31 mg/dl range, 21-39 mg/dl). The AT III ag levels of these two groups did not differ and no correlation was found between protein selectivity and AT III levels in primary NS patients. These results suggest that in patients with primary NS, or amyloidosis secondary to FMF, hypercoagulability is not related to a deficiency in PC ag levels due to a dynamic balance between urinary losses, increased rate of hepatic synthesis, catabolism and the distribution of PC in the body compartments. Patients with low AT III levels may be more susceptible to thromboembolic complications than patients with normal levels.


Standard and low birth weight formulas compared for effects on growth of preterm infants.

The study population consisted of 22 infants hospitalized for low birth weight or prematurity at the Maternity and Children's Hospital in Samsun. Eleven infants were fed the low birth weight formula and the rest were fed the standard formula. Weight gain, increases in length and occipitofrontal circumference were higher in the low birth weight formula group than in the standard formula group. In cases which require it, a low birth weight formula should be given instead of the standard formula.


A rare entity among childhood malignant lymphomas (large anaplastic T-cell Ki-1 +).

A case of peripheral type T-cell lymphoma is presented to underline the difficulty in distinguishing the initial clinical findings of an inflammatory neoplastic disorder since the diagnosis could only be arrived at after several repeated lymph node biopsies. An 11 10/12-year-old boy admitted to the hospital with inguinal lymph node enlargement was diagnosed as having adenitis and periadenitis. The disease had progressed and the patient had remittent fever rising to 39 degrees C, and another biopsy was taken. Cervical lymphadenomegaly was present, A diagnosis of chronic lymphadenitis with lymphocyte loss and fibrosis was established. The diagnosis could only be made from biopsy material taken from the deep cervical (jugularis interna) and axillary lymph nodes one year later, which showed Ki-1 antigen positive large T-cell lymphoma. The disease showed continuous activity in spite of chemotherapy and the child survived only 17 months.


[Use of compulsory measures in psychiatry after introduction of the new psychiatric law].

Investigation of compulsory treatment and mechanical restraint in the Psychiatric Hospital in Arhus reveals that no great changes in the employment of compulsory measures in psychiatry during the period around introduction of the new Danish legislation on October 1 1989 have occurred. The total duration of mechanical restraint constituted 0.3% of the entire duration of psychiatric hospitalisation in acute admission wards after the introduction of the legislation. The mean duration of mechanical restraint was 4.3 hours (5 minutes-5.3 days) and was similar in men and women. In 55.5% of the cases of mechanical restraint, a waist-belt alone was employed while, in the remaining cases, wrist or ankle cuffs were employed in addition. A doctor was present in 48.9% of the cases when mechanical restraint was applied. No differences were observed between the sexes in the extent of mechanical restraint but female patients were seen by a doctor prior to restraint more frequently than male patients. A tendency to employ a waist-belt alone was observed as the first form of restraint in women whereas men were frequently restrained by means of wrist or ankle cuffs also. The most frequent reason for restraint was that the patients constituted a danger to themselves and others.


[Deprivation of liberty in psychiatry after introduction of the new psychiatric law].

This investigation shows that the rate of commitment to mental hospitals in Denmark increased from the year before the introduction of the new Danish psychiatric legislation when it was 24.4 (23.1-25.8) per 100,000 of the population till the year after when it was 28.4 (27.0-29.9) of the population. The increase in the commitment rate may, wholly or partially, be the result of the fact that the deprivation of liberty, which was previously more or less informal, was now registered. The results do not suggest that commitment of non-psychotic patients is employed more frequently than previously. The commitment rates for men and women were found to be identical after introduction of the new legislation. On the basis of data from the closed wards in the Psychiatric Hospital in Arhus, which receives approximately 11% of all committed patients in Denmark, it was found that the total number of admissions where patients were deprived of their liberty was nearly twice that of the number of involuntary admissions in the period immediately after introduction of the legislation. The average duration of involuntary detainment for committed patients was 20 days (1-101 days) and for patients admitted voluntarily but detained involuntarily 10 days (1-104 days). Involuntary detainment of patients admitted voluntarily occurred on an average two days (0-144 days) after admission. Following involuntary admission, significantly more women (51.5%) as compared with men (15.6%) were detained involuntarily whereas men had an excessive risk for deprivation of liberty for more than three days without formal involuntary detainment.


Beta-ketothiolase deficiency. A case report.

A four-month-old boy with beta-ketothiolase deficiency is described in this report. Presenting symptoms and signs were vomiting, irritability and acidotic respiration. Laboratory investigations revealed hyperglycinemia, metabolic acidosis and ketosis. Subsequent urinary GC-MS analysis of the patient's urine sample showed the typical pattern of beta-ketothiolase deficiency. Our experience with this case indicates that accurate diagnosis and early treatment of inborn errors might be lifesaving.


Echocardiographic findings in endomyocardial fibrosis.

An 18-month-old infant diagnosed as having endomyocardial fibrosis by echocardiography is presented. Most patients with endomyocardial fibrosis reported in the literature are either older children or adults. To our knowledge, our patient was the youngest ever to have been reported. Echocardiographic studies showed obliteration of the left ventricular apex and increased echo reflectance at the left ventricular endocardium and subendocardium. The left atrium and right ventricle were significantly enlarged. Doppler echocardiography showed minimal mitral, but significant tricuspid regurgitation. In regard to the contribution of echocardiography in the diagnosis, we recommend this method for suspected cases. Contrary to the other patients reported, there was no thickening of the atrioventricular valves. Mitral valve insufficiency was related to the restriction of the ventricular filling rather than to valve involvement occurring with the disease.


Effects of cortisol and growth hormone on the metabolism of liver and bone in children with malnutrition.

A protein-energy deficit produces stress in the organism affecting all systems. Proportional to the degree of disease, cortisol and GH are mostly responsible for some of these effects. To investigate the effects on liver and bone, cortisol, GH, AST, ALT, ALP activities and Ca(T) and P(i) in serum were measured in 21 marasmus, nine kwashiorkor and 34 control children. In the marasmus group, we found a positive correlation between cortisol and AST, ALT and Ca(T) and a negative correlation between cortisol and ALP. In the kwashiorkor group there were positive correlations between the same parameters, although, they were of a lesser degree. Furthermore, in the kwashiorkor group we established a positive correlation between GH and ALP. Cortisol stimulates transaminases directly and suppresses ALP activity, thus indirectly increasing Ca(T), whereas GH has no direct effect on these enzymes. As the disease progresses and as liver functions deteriorate, AST, ALT and ALP increase in serum.


[Compulsory measures in psychiatry. A review of the first year after introduction of the new law].

A prospective survey of all registered treatment or measures carried out against the wishes of the patients during the first year after enforcement of the new Danish legislation in 1989 in the Psychiatric Hospital in Aalborg is presented. A total of 376 treatment situations and measures were registered. These involved 235 patients. It was found that 79 forced admissions had occurred together with 36 situations where patients who had been admitted voluntarily were forced to remain in hospital. The survey does not demonstrate any major change in the pattern of enforced measures and treatment after introduction of the new legislation. The working conditions for the new advisors for patients prescribed by the new law are described. These were found to be badly paid, idealistic and hard working. The daily administration of the law has been found to be quite bureaucratic. In addition, complains by patients concerning enforced measures and treatment are described. It is found that no verdicts contradict the steps taken by the hospital.


Immunofluorescence study of childhood renal amyloidosis.

In this paper, the findings of immunofluorescence (IF) studies of 57 patients with childhood biopsy-proven renal amyloidosis are presented. All specimens were investigated by the direct IF technique and the simultaneous use of antisera to human IgG, IgM, IgA, fibrinogen and C3. Antisera to C1q, C4, HbsAg, IgE (in each of ten cases), kappa and lambda light chains of immunoglobulins (Igs) and albumin (in each of five cases) were also used. AA type amyloidosis was determined in all patients by Wright's potassium permanganate reaction. In thirty-four of these patients (60%), Familial Mediterranean Fever (FMF) was found to be the underlying disease for renal amyloidosis. In 39 cases (68.5%), renal biopsy showed positive fluorescence staining while in 18 cases (31.5%), fluorescence staining was negative. The immunofluorescence pattern of glomerular deposits was neither granular nor linear but large isolated or confluent masses which were located in the mesangium and in the capillary walls, and were similar in all cases whatever the antisera used. The areas showing immunofluorescence staining almost corresponded to the locations of amyloid deposits. Immunoreactants showed various combinations of deposition with the exception of IgE, HbsAg and albumin antisera which yielded continuously negative reactions. C3 was the immunoreactant most commonly encountered. Kappa and lambda light chains of lgs were demonstrated in one of five biopsy specimens tested. Although it was not diagnostic, this IF pattern was found to be rather characteristic. Demonstration of immunoglobulins and other components of the humoral immune system is not a rare occurrence in renal amyloidosis, and passive absorption of plasma proteins does not simply explain these immunohistologic findings.


[Compulsory admission for treatment--an interview study of patients. 1. Admission procedure, use of restraint and treatment].

Forty-three patients committed for treatment in Copenhagen county were interviewed on their discharge from hospital. Half of the patients felt better after hospitalization, while one fourth of the patients were dissatisfied. Food, changes in housing and human contact were given as examples of the positive outcome. One half of the patients were given compulsory medication and one fourth were physically restrained. The patients experienced many adverse effects of the medication. It is recommended, that psychiatrists are involved to a higher degree in evaluation and treatment before decisions for compulsory hospitalization are taken. Investigations are needed to find predictors for a positive outcome in involuntary hospitalization. Unnecessary hospitalization should be avoided in order not to harm the patient-doctor relationship.


HLA and leukemia: is it a simple allelic association?

The first association between a disease and MHC antigens was established for viral leukemogenesis in mice. Since then, numerous studies in humans have been carried out and the data obtained suggest that Cw3 and Cw4 may be markers for leukemia susceptibility genes. Given the relatively weak relevance of HLA-C locus antigens in immune response, unrecognized properties of Cw3 and Cw4 should be considered to explain this association. Family studies have consistently revealed limited heterogeneity of HLA antigens in those families, increased parental HLA antigen sharing resulting in increased homozygosity among offspring and high frequency of recombinations within the MHC. Furthermore, the HLA genotype of leukemic patients was found more frequently among their siblings than the anticipated 25 percent. Another significant deviation from the Mendelian expectation was increased HLA-DR identity of offspring to that of their mother in those families. These and other observations imply that in leukemia families unknown MHC-linked recessive factors linked to Cw3 and Cw4 alleles may be susceptibility genes which also cause segregation distortion of HLA genes and probably developmental errors.


[Compulsory admission for treatment--an interview study of patients. 2. Rights, guardianship and attitudes to commitment].

Forty-three patients committed for treatment in Copenhagen County were interviewed about their rights, protection of rights and consequences of the commitment. Very few patients felt they had been properly informed about their rights and they knew very little about how to complain to the authorities about their commitment. Attorneys were found to have too little competence and insufficient training, and patients felt insecure about their attorneys' role. One forth of the patients agreed that they had to be committed, while one forth never accepted their commitment. Difficulties in giving information to the psychotic patient with disturbances in cognition and on unrealistic way of thinking are discussed. It is concluded, that there is a need to strengthen patients' rights, but not at the expense of the possibility of delay in administering treatment.


[Compulsory admissions at the Frederiksberg hospital during the period 1 Nov 1987 to 30 Sep 1989. 1. Characteristics of the compulsory admissions and the admitted persons].

During a period of 23 months from 1 Nov. 1987 to 30 Sep. 1989, before the new Danish legislation came into force, there were 64 compulsory commitments to the Psychiatric Department in Frederiksberg Hospital. These comprised 3.6% of all the admissions which corresponds to the national average in Denmark. Equally many were admitted on health grounds (yellow admission papers) and on account of danger (red admission papers). Women were admitted more frequently than men. The distribution corresponds to the sex distribution of all psychiatric admissions in Frederiksberg and reflects a sex distribution in the municipality with preponderance of women as compared with the national Danish average. On the Danish national basis, the majority of these admissions are men. One fourth of the admission papers did not contain an adequate description of the reasons for presuming mental illness and/or the danger or health criteria. There is thus reason to encourage meticulous care in completion of the medical certificates in cases of compulsory commitment. On discharge from hospital, 14% had a "non-psychotic" diagnosis, which corresponds to the national Danish average. One month after discharge from hospital, 40% were attending outpatient treatment in the department and one year later, 38% of those followed-up were receiving outpatient treatment. In more than one third, compulsory commitment was thus followed by a prolonged period of voluntary treatment. 33% were readmitted during the subsequent year and this was compulsory in 13%.


[Compulsory admissions at the Frederiksberg hospital during the period 1 November 1987 to 30 September 1989. 2. Patients' assessment and experiences of the admissions].

The object of this prospective, descriptive investigation was to illustrate how the committed patients assessed and experienced the actual compulsory commitment and their assessment of the Danish legislation concerning mental illness by means of an interview investigation on discharge. During the period of investigation of 23 months, there were 64 compulsory admissions. Of these, 31 were on account of danger (red admission papers) and 33 on health grounds (yellow admission papers). Thirty-three (52%) patients were interviewed and of these 13 were admitted on account of danger and 20 on health grounds. Twenty-two (67%) of the patients did not realise that they were undergoing compulsory admission until the police came to fetch them. The majority considered that the functions of the police (68%), admission staff (55%) and the remainder of the staff (79%) had been good or satisfactory. 46% did not know who had demanded admission and did not ask the interviewer. 30% were satisfied with information about complaints. 42% were satisfied with the function of the supervisory committee but just under 30% did not realise that it existed. 61% considered that compulsory admission could have been avoided if other help had been offered. 61% were satisfied with the hospitalization. 64% considered that it is necessary to have legislation which permits compulsory admission. Relatively more of the patients admitted with red admission papers expressed satisfaction with, and accept of, their own compulsory admission and accept of compulsory admission in general. The present investigation will form a basis for comparison of the conditions under the new Danish legislation concerning mental illness.


[Acute uremia after renal cholesterol embolism].

A case of acute uraemia caused by cholesterol emboli in the kidneys in a sixty-six year old male with arteriosclerosis is presented. No effective treatment is available, but recognizing the condition may save the patient from otherwise time-consuming extensive diagnostic programmes.


[Bilateral symmetrical stress fracture of the ulna].

Good documentation is available concerning the prevalence, localisation and treatment of stress fractures. Stress fractures are much less common in the upper extremities than in the lower limbs. An unusual case of bilateral stress fractures in the ulnae in a patient aged 95 years is reported. These fractures are attributed to the use of a walking aid for a period of one year. The clinical features of stress fractures are discussed on the basis of the case history.