A therapeutic, highly purified factor XI concentrate from human plasma. A highly purified factor XI (FXI) concentrate was prepared from human plasma by a process comprising a filter adsorption step and chromatography on a cation exchange resin. The freeze-dried FXI, which solubilized quickly, had high specific activity (130-150 U/mg protein), high potency (approx. 100 U/mL), and excellent stability for at least 24 hours at room temperature in the liquid state. The overall recovery was about 220 U of FXI per liter of plasma. Minor protein contaminants (C1-inhibitor, fibronectin, IgG, and alpha-2-macroglobulin) were found to be between 0.13 and 0.46 mg per 1000 U of FXI. Fibrinogen and relevant coagulation factors (factors II, V, VII, IX, X, XII, XIII, and VIII/von Willebrand factor) were undetectable, as evidenced by immunologic and immunoelectrophoretic data. Components of the kinin system were present in trace amounts or were undetectable. No evidence of activated factors such as factors Xa and IXa was found. Proteolytic activity, as assessed by S-2288 chromogenic substrate, was negligible and thrombin was undetectable. A solvent-detergent treatment was included prior to chromatographic purification to enhance viral safety against lipid-enveloped viruses. In vitro and in vivo animal studies demonstrated the absence of thrombogenic, hypotensive, or toxic effects. No thrombogenic activity was found in the Wessler model in rabbits at doses of 900 to 1100 U of FXI per kg of body weight. This FXI preparation could be beneficial in substitution therapy of congenital or acquired FXI deficiency, especially as a way to avoid the use of fresh-frozen plasma.


Evolution by acquisition: the case for horizontal gene transfers. One of the most debated questions in the field of molecular evolution is the possible role of horizontal transfer in evolution. Of all the claims that have been made over the years, those reporting transfers between eukaryotes and prokaryotes are the most controversial. Here we present the cases for and against several such possible gene acquisitions.


Direct identification of Yersinia enterocolitica in blood by polymerase chain reaction amplification. Primers based on the nucleotide sequence of the virF gene in the pYV plasmid and the chromosomal ail gene were used in polymerase chain reaction (PCR) amplifications to directly identify Yersinia enterocolitica in blood. Approximately 500 bacteria seeded into 100 microL of blood can be extracted and amplified by PCR to yield positive results. PCR analyses of seven Y. enterocolitica isolates previously implicated in blood contaminations showed that only one isolate harbored the plasmid-borne virF gene; however, all seven isolates were identified effectively by the PCR product amplified from the chromosomal gene. The PCR assay has the potential for use in the identification of Y. enterocolitica contamination in stored units of blood or in the rapid diagnosis of transfusion-related bacteremia caused by Y.


14-3-3 proteins: a highly conserved, widespread family of eukaryotic proteins. A family of proteins known as 14-3-3 is currently receiving increased attention by investigators studying a broad range of biological systems, including plants and invertebrates. The outstanding feature of this family is the extraordinarily high sequence conservation observed. Current thinking indicates that these proteins may function as regulators in signal transduction/phosphorylation mechanisms.


Regulation of sugar utilization by Saccharomyces cerevisiae. There are several kinds of regulation that enable microbes to cope with rapidly changing supplies of nutrients. This is exemplified by sugar metabolism in Saccharomyces cerevisiae. Some readily reversible controls affect the activity of enzymes, either by allosteric activation and deactivation, which often occur within seconds, or by covalent modification, within minutes. Other controls regulate the amount of enzyme present in the cells, either by irreversible proteolytic inactivation of the enzyme, or by influencing enzymic synthesis. The nomenclature of these processes is often confused.


[Pelvic insufficiency during pregnancy. Is pelvic girdle relaxation an unambiguous concept?]. Pelvic insufficiency during pregnancy, pelvic girdle relaxation, is defined as a condition with pain at the pubic symphysis and/or the sacroiliac joint developing in connection with pregnancy or delivery. No unambiguous criteria for the diagnosis of pelvic girdle relaxation exist but the following findings occur: Direct tenderness at the pubic symphysis and/or sacroiliac joint, waddling gait, pain on change of position, positive Trendelenburg's sign, iliac compression test, iliac gapping test and sacral pressure test. The frequency is 7.6-18.5 per 1000 deliveries. The incidence is increased in multiparae and women with occupations which strain the back. Recurrence occurs in 41-77%. The condition appears for the first time usually in the 5th-8th months of pregnancy. The majority of patients recover shortly after delivery but in some a condition of prolonged pain persists. The cause of pelvic girdle relaxation is unknown. Hormonal and biomechanical factors are considered to be of significance. No increased mobility in the pelvic joints nor general hypermobility have been demonstrated. Treatment is symptomatic and consists of information, instruction in relief and psychosocial support. Exercises and a trochanter belt may be useful. No controlled investigations of the value of treatment are available.


[Closed anesthetic systems].

[Closed anesthetic systems]. Anaesthesia with closed anaesthetic systems demands knowledge of the physiology of the patients and of how the various anaesthetic gases behave in the organism as only the gases which the patients produces and absorbs are eliminated and replaced. The system is educational as it provides knowledge of the genuine absorption of oxygen and anaesthetic gases. The method is favourable to the environment as only the gases which are used are supplied and it is thus economical in use although investment in monitoring equipment is necessary. In practice, induction and waking of the patient are complicated with this system and it requires an anaesthetist who constantly adjusts the gases in the circuit.


[Low-flow anesthesia systems].

[Low-flow anesthesia systems]. At present, when economy and environment receive high priority, the ideal anaesthesia system with inhalation anaesthetics is a closed circle system in which only the gases which the patient consumes or produces are replaced or eliminated. Low-flow (LF) anaesthesia in which the fresh gas flow which is employed in a closed system, provides a stable system compares with closed anaesthesia systems. Compared with open systems and circler systems with considerable fresh gas flow, the LF system provides advantages as regards economy, environment and exposure of staff to inhalation anaesthetics. The special conditions involved in LF anaesthesia are described in detail with the hope that the method will obtain more widespread distribution than is the case in Denmark today. If greater safety under anaesthesia is desired, eg by monitoring the concentrations of CO2, O2 and inhalation anaesthetics which the patients inspire and expire, this monitoring equipment can be financed by introduction of LF anaesthesia.


[A marked decline in the mortality from ischemic heart disease among middle aged Danish men in the 1980's and simultaneous changes of mortality because of other causes]. The mortality from ischaemic heart disease (IHD) in 35-64 year old Danish men has declined by 27% from 1981 to 1989. In the same period, a lesser increase in mortality from all other causes was observed. However, this is a heterogenous phenomenon, since the mortality from (in particular) infectious diseases (AIDS), diabetes mellitus, and a number of diseases related to heavy drinking has increased, whereas the suicide rate and mortality from lung cancer (in 1985-89) have decreased. It is not possible to evaluate the contribution of improved treatment of IHD cases and a decreasing incidence of disease, respectively, to the decline in mortality from IHD. A decreasing incidence is very probable, however, since both the percentage of smokers and the plasma cholesterol levels in middle-aged men have declined significantly since mid-1970s and leisure time physical activity has increased. The trend in IHD mortality in the 1980s points to a sustained decline in the 1990s and a levelling off in the increase in mortality from other causes. Thus total mortality is expected to decrease more rapidly in the 1990s, resulting in an increase in life expectancy of Danish men.


[Why do patients change physicians?].

[Why do patients change physicians?]. The purpose of this investigation was to describe why patients change their general practitioners (GP) by the means of questionnaires. Questionnaires were given 357 patients who had changed GPs in 1990 and 206 (58%) returned the questionnaire. The most common reasons were dissatisfaction with the quality of the service provided, too little time allowed or lack of communication between patient and doctor. Women accounted for approximately 75% of the total number and preferred female GPs, whereas men who changed doctors probably did so because they wanted to have the same GP as their families. The frequency of change was about 1% and most of the patients had stuck to the same GP for several years before changing.


[Acceptance of ambulatory laser conization under local anesthesia by Danish women]. The aim of the study was to evaluate the acceptability of CO2 laser excisional conization for cervical intraepithelial neoplasia under local anaesthesia in an outpatient setting. Seventy-seven patients, who underwent this procedure, were interviewed three months later concerning pain during treatment, pain and bleeding in the immediate postoperative period, and their general opinion about this procedure. The median duration of surgery was 11 minutes. The postoperative median observation time was 90 minutes. Seventy-one women experienced no discomfort during treatment. Thirty-one patients needed mild analgesics for an average of three days. Bleeding continued for a mean of 7.7 days after treatment and 73% experienced the bleeding as less, 8% as more as compared to menstrual bleeding. Ninety-two percent of the women would prefer this procedure if they had to undergo conization once again. In conclusion, we found a high acceptability in women treated with CO2 laser excisional conization under local anaesthesia in an outpatient setting.


[Treatment of central facial nerve paralysis with electromyography biofeedback and taping of cheek. A controlled clinical trial]. We studied 35 patients with facial palsy after stroke, admitted to a rehabilitation hospital. We examined the patients on admission and after one, two and six months with 1) clinical evaluation of the facial function using a modified House-Brackmann scale, 2) photographs of patients with six different facial expressions; these photos were evaluated by "blinded" observers using the modified House-Brackmann scale, 3) questionnaire about patients emotional reactions to the facial paralysis and 4) facial sensation. No differences were found between a control group of 12 and a group of patients (23) training facial function 2-3 times a week, each session of 15 minutes, with EMG-biofeedback and cheek taped between training sessions. A significant improvement in facial function occurred spontaneously after one month in rehabilitation unit in the total group. After six months 2/3 of the patients had normal facial function or mild dysfunction. Patients with right-sided facial palsy showed a significantly better improvement at six months as compared to patients with left-sided facial palsy. The questionnaire showed that only half of the patients were aware of the asymmetric face. We cannot recommend training with EMG-biofeedback to patients with facial paralysis after stroke. Spontaneous remission is to be expected.


[Lateral cervical cysts as primary manifestation of tonsillar cancer]. Of 59 patients with tonsillar carcinoma, eight presented with a cervical cyst which was judged to be a branchial cyst clinically and after fine needle aspiration. In all cases, the cyst was removed and microscopic examination revealed malignancy. The correct diagnosis, carcinoma of the tonsil with cystic lymph node metastasis, was revealed during the primary operation in two cases, in four cases the diagnosis was made at a second operation where ipsilateral tonsillectomy was performed and in two cases the diagnosis was first made several years later. It is concluded that, in patients who are over the age of 40 years, the diagnosis of branchial cyst should not be accepted primarily even if fine needle aspiration does not give any suspicion of malignancy.


[Focal myositis].

[Focal myositis]. Focal myositis is a rare benign pseudotumor of skeletal muscle, of unknown cause. Clinically it presents as an enlarging mass within a muscle, usually in en extremity. Biopsy shows characteristic histological changes of inflammation, focal degeneration and regeneration. The natural course of this disorder is spontaneous regression. This report describes the case of a 17-year-old boy with focal myositis of the thigh and a review of the relevant literature.


[Doppler ultrasonography in arteriosclerosis of the lower extremities]. Arteriography, which requires resources and is not entirely without risk, has hitherto been a prerequisite for reconstructive surgery in cases of symptom-producing arteriosclerosis in the lower limbs. As an alternative, indirect Doppler ultrasonic examination has been employed but does not appear to be suitable in the clinical routine. On the basis of a review of the literature, it is suggested that, employing a combination of ultrasonic picture scanning and Doppler ultrasonic duplex scanning, it may be possible to diagnose significant solitary stenoses or short occlusions in the aorto-iliac segment and in the femoral artery but that this does not appear to be employable at present in cases of multiple lesions. Examination of the popliteal artery is still too unreliable and reasonably certain assessment of the crural arteries is not possible with the present technique. Duplex scanning can thus not replace arteriography as yet for examination of patients with ischaemia in the lower limbs.


[Relationship between distal systolic blood pressure and wound healing. A retrospective study of patients with crural ulcers]. To anticipate the need for ensuring quality in treatment of patients with ulceration of the lower leg and complicating arterial occlusive disease, three authors examined the files of 56 patients with systolic digital blood pressure (SDBP) below 60 mmHg, all admitted to the geriatric in-patient department over a 11-year period in a retrospective study. In 40 patients (71%) the ulcer healed. Eight patients (14%) required amputation, six patients (11%) died and two patients (4%) were unsolved. We found a significant correlation between SDBP and ulcer healing (p = 0.006). In patients with SDBP < or = 35 mmHg, healing on conservative pharmacotherapy was demonstrated even with critical ischaemia.


[Can Doppler ultrasound replace strain gauge in the measurement of ankle blood pressure?]. Traditionally, strain gauge technique is used in Denmark to measure ankle blood pressure, a method requiring both time and well-trained personnel. In a study involving 90 limbs in 45 patients, this method was compared with ultrasonic technique using a portable 5 MHz Doppler. The reproducibility of Doppler ankle pressure measurement was similar to that found in strain gauge based studies. Two consecutive measurements may differ by 20 mmHg or in terms of ankle-brachial index by 0.15 before this is considered significant. No systematic variation was found between the two methods. Increasing difficulties were encountered with the Doppler technique at pressures below 50 mmHg. It is concluded that Doppler is a good alternative to strain gauge for measurement of ankle blood pressure.


[Psychosocial factors and breast cancer. A review]. Cancer of the breast is the commonest from of cancer of women in Denmark and the incidence is increasing. At present, a series of risk and prognostic factors are recognised. These are primarily related to the endocrine system. Other factors, including the significance of psychological and social factors, have been investigated. A review of the literature concerning the significance of psychological and social factors as risk and prognostic factors, respectively, reveals that the methodological problems in these investigations are considerable and multifarious. On the basis of a review of the literature, it is concluded, that there is no proof that psychosocial factors influence the disease of cancer of the breast. Nevertheless, certain evidence exits in the literature suggesting a connection between inhibition of aggression and an introverted personality and the development of cancer of the breast while, in some investigations, ability to cope has a certain significance as a prognostic factor. Investigations of psychosocial intervention as the actual antineoplastic treatment are very few and the results are difficult to interpret. It may be concluded that no basis exists to justify employment of psychosocial intervention as an actual form of treatment with the object of improving survival.


[Fatal traffic accidents among the elderly in the county of Ringkøbing]. The cases of all persons aged 70 years or more who were killed in traffic accidents in the County of Ringkøbing during the period 1.1.1983-31.12.1990 were reviewed on the basis of the death certificates and the police reports. A total of 58 deaths were involved and this was significantly greater than in the age group 0-69 years (p < 0.01). Twenty-eight of the accidents (48.3%) were car accidents. The commonest cause of these car accidents was that "give way" signs had not been respected and there were thus no solo accidents. The next most frequent type of accident consisted of knocking down of pedestrians (25.9%), followed by bicycle accidents (15.5%) and moped accidents (8.6%). Out of the total of fatal accidents, only one of the fatally injured persons was under the influence of alcohol (1.7%). If passengers in motor vehicles were excluded, a total of 39 of the fatally injured persons (88.6%) were themselves the cause of the accident concerned. It is concluded that fatal traffic accidents among elderly persons in the County of Ringkøbing constitute a great problem and that the driving abilities of elderly persons should be investigated further.


[Why young women apply for abortion without permission from their parents]. Review of all of the abortion consultations from 1986 revealed that 46 of the young women under the age of 18 years utilised the possibility of applying for abortion without permission from their parents which the Danish legislation on termination of pregnancy in 1973 permits. Forty-two of the young women were granted permission for abortion without permission from the parents as it was considered that the relationship between the girl and her parents would otherwise deteriorate. This was not considered to be the case in the four girls for whom application for termination of pregnancy was refused. This material, which is focussed on a problem which has not previously been illustrated, is too limited to permit drawing of any conclusions but there is no information about whether the requirement of parental permission is beneficial or deleterious for the parent/daughter relationship. Relevant investigations are required.


[Demonstration of bacteriuria in elderly hospitalized patients. Comparison between leukocyte and nitrite strips and culture]. The purpose of this study was to assess the accuracy of test strips for urinary nitrite and leucocytes for detection of bacteriuria in elderly patients. The material consisted of 213 urine samples from 85 women and 26 men (median age 79 years, range 60-93 years) within the first two days in hospital. The results of the test strip reactions were read in the department and in the laboratory. The strip test results and symptoms of UTI were compared with culture results. 27% of the samples showed significant bacteriuria on culture (> or = 10(5) colonies/ml urine). 21% of the 102 patients who had submitted two urine samples within the first two days had significant bacteriuria in both samples. Less than half of these patients had symptoms of UTI. The false negative rate of test strips (defined as the number of proven laboratory UTIs not demonstrated by the test strips, expressed as a percentage of the total number of proven UTIs) was 29% in the department and in the laboratory it was 13%. 15% of the test strips at the laboratory failed to detect significant E. coli infections which were predominant. In conclusion, we found that it is advisable to perform urine culture if symptoms of urinary tract infections are present.


[UV cured acrylates--potent contact allergens in the occupational environment]. Allergic contact dermatitis is still an important disease in occupational medicine. Acrylic compounds are known to be potent contact sensitizers causing allergic eczema after occupational exposure. To illustrate the problem and the need for preventive arrangements the authors present an unusual clustering of allergic contact dermatitis in three technicians who produced hearing aids using ultraviolet cured akrylate compounds. All three technicians developed eczema on their fingers few months after introduction of the new acrylate compounds in the production. Skin patch testing with the products confirmed that sensitization.


[Injuries due to fireworks].

[Injuries due to fireworks]. This investigation is a review of the injuries due to fireworks seen in five casualty departments in Denmark over a period of four years. These casualty departments have a total catchment population of 675,000 (13% of the population of Denmark). The review is based on data from the Danish section of EHLASS-project. (Europea Home and Leisure Accident surveillance system). During the period of observation, 358 injuries due to fireworks were observed. 60% of the injuries occurred in persons under the age of 18 years. In 51%, the mechanism of the injury consisted of direct heat while 33% of the patients were hit by flying fireworks and 10% had small foreign bodies in the eye. The regions most frequently injured were the hands/fingers (40%) or the eyes (24%). 6% of the patients required admission to hospital. The estimated number of injuries due to fireworks in Denmark is 690 annually. The majority of injuries due to fireworks were due to incorrect use of fireworks of absence of protective measures.


[Burns due to fireworks. A 4-year study of the incidence and causes with suggestions for prevention]. During the period around New Year 1991-1992, significantly more patients were admitted to the burns units in Denmark with burns caused by fireworks, compared to the previous three years. All patients were males and 88% under 18 years of age. The areas burned were localized primarily to the thighs and the front of the body. The main causative fireworks were whistles. Analyses revealed the fuses to be highly combustible. New directives have been issued, requiring whistles to be equipped with safety fuses. Although 70% of the patients were aware that fireworks should not be carried close to the body, the message has not been sufficiently stressed. A campaign for the oncoming New Year, informing about burns, eye and hand injuries caused by fireworks is under preparation. Although sale of fireworks to persons under 18 years of age is prohibited, more than 80% of the children had purchased the fireworks themselves. We recommend reinforcement of the law.


[Genetic counseling. Past time, present time, future]. Recent literature concerning the effects of genetic counselling is reviewed. Although the vast increase in our knowledge about the human genome has opened new possibilities for genetic diagnosis, few scientific investigations consider the questions of the social and individual impact. In general, there is an international consensus that genetic counselling is and should be non-directive, and analyses of reproductive decisions following counselling conclude that it seems to reinforce decisions already made by the families, and that objective genetic risks only play a limited role for the decisions, but the availability of prenatal diagnosis may contribute to the families' desire to have more children.


[Granulocyte-macrophage colony-stimulating factor. Treatment of patients with highly malignant lymphomas and acute lymphoblastic leukemias after autologous bone marrow transplantation]. We have evaluated the effect of intravenous infusions of granulocyte-macrophage colony-stimulating factor (GM-CSF) in ten patients undergoing autologous bone marrow transplantation after total body irradiation (11 Gy) and cyclophosphamide (120 mg/kg) conditioning for malignant lymphomas or acute lymphoblastic leukaemias. Mild side effects related to GM-CSF were seen in six patients, of whom one chose to discontinue treatment. Compared to a historic control group consisting of six patients treated with an identical conditioning regimen, a tendency was seen towards a more rapid neutrophil regeneration and a decreased need for erythrocyte transfusions. Moreover, a statistically significant improvement in thrombocyte related parameters was demonstrated. In contrast, there were no significant differences in severe toxicity, days on i.v. antibiotics, septic episodes or duration of hospitalization. In conclusion, it seems that GM-CSF treatment is of value in patients undergoing AKMT.


[Prevention of postoperative thromboembolism in Denmark. A questionnaire study on principles of prevention of thrombosis at hospital surgery departments]. In a questionnaire survey among surgical hospital departments in Denmark (1990), we assessed the attitudes and practices of use of postoperative thrombosis prophylaxis (TP). Replies were obtained from 92% of departments. Otological and odontological departments seldom used TP. Among departments performing major surgery a total of 88% used TP routinely (general surgery: 91%, orthopedic surgery: 94%, gynecology: 84%). 68% of these departments used TP according to written instructions. Indications for TP, and methods used, are in accordance with the literature, except for the use of TP in emergency surgery (routine in 36% of departments only), or for the continued use of aspirin for TP in 13% of departments.


[Pernicious anemia. A study of initial forms of the disease and diagnostic significance of determination of the intrinsic factor antibody and parietal cell antibody]. In a prospective study of thirty five consecutive patients with decreased plasma cobalamine (P-Cbl), twenty-two (63%) were diagnosed as having pernicious anaemia (PA) (no age or sex differences) on basis of the B12-absorption test and/or megaloblastic changes in the bone marrow. In this group ten patients were anaemic (six of whom were characterized as macrocytic), sixteen of nineteen examined had megaloblastic changes in the bone marrow, and all of thirteen examined had achlorhydria with positive correlation to Parietal Cell Antibodies (PCA). Two patients with PA had normal Cbl-absorption and two had malabsorption at the time of diagnosis. Twenty-one patients (95%) had PCA and thirteen (59%) were Intrinsic Factor Antibody (IFAb) positive. Three patients IFAb-seroconverted within a year. Among the remaining thirteen patients (37%), one had PCA but not IFAb and three were IFAb-positive all of whom had normal Cbl-absorption. Of the three patients with IFAb one had also PCA, one IFAb-seroconverted within three months, and one had microcytic anaemia with iron depleted bone marrow due to coecal cancer. Among twenty two healthy adult controls four (18%) had PCA while none had IFAb. This investigation shows that at the debut half of PA patients (55%) do not have anaemia, some have normal Cbl-absorption and some have malabsorption. 95% have PCA and 59% have IFAb. So, IFAb-negative PA is often seen (41%) and seroconversion can take place. Diagnosis is even more reliable, when achlorhydria is present in PCA-positive persons. Healthy PCA-positive persons are probably predisposed to develop PA. Patients with cbl-deficiency, IFAb and/or PCA must be considered as having latent PA even if they have normal haemoglobin and normal Cbl-absorption. These patients should be followed and, in case of anaemia or signs of neuropathia, treated.(ABSTRACT TRUNCATED AT 250 WORDS)


[Behçet's syndrome: an unusual cause of genital erosion]. A case of incomplete mucocutaneous Behçet's disease is presented. In spite of weekly to monthly attacks of genital pain for fifteen years, this diagnostic entity had been ignored. We wish to emphasize that Behçet's disease may be the cause of otherwise unexplained genital erosions. A set of clinical criteria according to an international study group serves to establish the diagnosis. Treatment is controversial. This case has been successfully treated with systemic tetracycline for more than six months.


Tubuglomerular feedback control in long-looped nephrons. Topical minireview. The tubuloglomerular feedback mechanism is highly activated in juxtamedullary nephrons and considered to play a major role in intrarenal regulation of glomerular filtration rate. The vasculature of juxtamedullary nephrons is highly vasoreactive with a high ability for vasodilation. This vasoreactivity is a prerequisite for an important influence of the tubuloglomerular feedback mechanism on the medullary blood flow and its regulation.


Airway pressures during positive pressure ventilation with superimposed oscillations before and after lung injury in the cat. This study was made to determine how oscillations superimposed on intermittent positive pressure ventilation (IPPV) influence the arterial blood gases, pH and the airway pressures during adequate alveolar ventilation i.e. at inhibition of inspiratory activity, before and after experimentally induced lung injury in the anaesthetized cat. Two IPPV frequencies were studied. The lung was injured by instillation of xanthine oxidase into the upper airways during IPPV. The peak, mean and end-expiratory intrapleural and airway (intratracheal) pressures at two levels were measured and the arterial blood gases and pH were determined at inhibition of inspiratory activity with and without superimposition of oscillations on the ventilatory pattern. Before lung injury, superimposed oscillations lowered the airway pressures only at an IPPV rate of 15 breaths per minute (b.p.m.). After lung injury, such oscillations increased the airway pressures only at 15 b.p.m. The airway pressures were always lower at 60 than at 15 b.p.m.


Afferent activity in pulmonary stretch receptors before and after lung injury. This study was undertaken to determine the effect of a lung-injury on the activity of slowly adapting pulmonary stretch receptors. Comparisons of receptor activity were made at inhibition of inspiratory (phrenic nerve) activity. The inspiratory activity of these receptors was found to be decreased after lung-injury.


Airway obstruction, obesity and CO2 ventilatory responsiveness in the sleep apnea syndrome. In 32 patients with sleep apnea syndrome (SAS), pulmonary function, blood gases and the ventilatory response to CO2 (CO2 VR) were studied before and 6 months after uvulopalatopharyngoplasty. Nine of the SAS patients had airway obstruction (AO-SAS), defined as FEV1.0 < or = 72% of the predicted value. They had a significantly higher PaCO2, lower PaO2 and a lower CO2 VR than the remaining SAS patients. Preoperatively 4 SAS patients were hypercapnic (PaCO2 > 5.8 kPa) and compared with the normocapnic ones they were more obese; in 3 of them FEV1.0 was < or = 72%. The hypercapnic SAS patients had a significantly lower CO2 VR. The CO2 VR was significantly correlated to AO and the degree of oxygen desaturation during sleep, but not to the number of episodes of apnea and hypopnea nor their length. The VR to CO2 did not predict the postoperative outcome. Postoperatively 2 hypercapnic obese AO-SAS patients showed a large decrease in episodes of apnea and hypopnea and an increase in CO2 VR, and became normocapnic. Other patients showed no consistent changes in CO2 VR postoperatively.


Intravenous theophylline after beta 2-agonist treatment in severe acute asthma. Effect on patients who are not pre-treated with theophylline. The effect of i.v. theophylline after high-dose beta 2-agonist treatment in severe acute asthma was studied in 30 patients from a multicentre study who reported not having taken theophylline during the last 24 hours. One hour after the start of inhaled or i.v. salbutamol treatment, all patients received 6 mg/kg of i.v. theophylline. The plasma concentration 30 minutes after the start of the theophylline infusion was 78 +/- 13 mumol/l (mean +/- SD). The mean change (delta) in peak expiratory flow (PEF) was 8 +/- 6% of the predicted 30 minutes after the theophylline infusion and 7 +/- 5% 60 minutes after it. The increase in PEF was greater in this patient group than in a group of 101 patients from the same multicentre study who were on theophylline medication and were therefore given a reduced dose (3 mg/kg) (7 +/- 5 vs. 4 +/- 6% of the predicted value, p < 0.01). The proportion of patients with an increase in PEF of > or = 10% of the predicted at discharge was 27% (8/30) in the patient group in this investigation and 14% (14/101) in the group who was on theophylline treatment.


Effects of omeprazole and ranitidine on plasma gastrin concentration and stomach gastrin content in rats. Prolonged fasting and longer time between dosing and sampling reduced the plasma gastrin concentrations after omeprazole (80 mumol/kg x 2 for 14 days) treatment in male rats whereas the amounts of tissue gastrin were essentially unchanged during these initial experiments. After 28 days omeprazole (80 mumol/kg x 2) or ranitidine (375 mumol/kg x 4) that produced corresponding inhibition of acid secretion, increased the tissue gastrin content by 114 and 59%. A low dose of omeprazole (20 mumol/kg x 2) also raised the gastric gastrin content (41%), whereas no change was noted on treatment with a low dose of ranitidine (125 mumol x 4). Following recovery for 28 days no significant increases in gastrin were observed. 1, 3, 7, 14 or 28 days of treatment with omeprazole (80 mumol/kg x 2) gradually increased the gastric gastrin content being significantly raised already after 3 days. We conclude that a) measuring the tissue gastrin content may be the preferable method when changes in gastrin following long-term treatment with acid inhibiting drugs are to be determined, b) the amount of gastrin in the stomach increases rapidly following treatment with omeprazole and is approximately doubled following 28 days of treatment and c) after treatment for 28 days omeprazole was found to cause greater elevations in the tissue gastrin content than ranitidine despite similar degrees of basal acid inhibition.


Treatment of non-union after tibial shaft fracture with a full cortical thickness inlay bone graft. Twenty-seven non-infected delayed union or non-union fractures of the shaft of the tibia in 26 patients were operated on with a full cortical thickness inlay graft taken from the injured leg. The initial trauma was moderate in 9 fractures and severe in 18. Fifteen fractures were closed injuries and 12 open. The fracture pattern was longitudinal in 5 cases, transverse in 11 and communited in 11. Surgery was performed 12 to 72 weeks (mean: 30 weeks) after the fractures had been sustained. All fractures healed after the bone grafting procedure. The time until union was established after surgery ranged from 6 to 37 weeks (mean: 17 weeks). The healing time was neither influenced by the initial type of fracture pattern (p > 0.05) nor by the fracture age at surgery (r = -0.21). Of 13 patients re-examined 8 to 16 years after surgery, the clinical results were classified as excellent in 8, as fair in 2, and as poor in 3 patients.


Sternocostoclavicular hyperostosis. Presentation and long-term follow-up of three cases. Sternocostoclavicular hyperostosis is a rare disease characterized by recurrent pain and skeletal swelling in the upper part of the chest. The clinical manifestations are closely linked to pustulosis palmo-plantaris but the etiology is still obscure. We present three cases of sternocostoclavicular hyperostosis with a follow-up period of 9-22 years at our department.


Pulse pressure, mean blood pressure and impaired glucose tolerance--a study in middle-aged subjects. In a study of 695 middle-aged subjects, without antihypertensive agents, and without more pronounced obesity, both pulse pressure (PP) and mean blood pressure (MBP) were strongly related to 2-h blood glucose in 75 g OGTTs (p < 0.001). All hypertensives (DBP > or = 90 mm Hg) were separated into 39 with higher PP (> or = 60 mm Hg) and 137 with lower PP (< 60 mm Hg). The high PP hypertensives, compared with the low PP hypertensives and all 519 normotensives, had higher frequency of impaired glucose tolerance (IGT; WHO-criteria), 33%, 6%, and 4%, respectively (p < 0.001), and also higher mean 2-h blood glucose, 5.9, 4.5, and 4.2 mmol.l-1, respectively (p < 0.001). These differences were independent of MBP levels. Similarly, all 54 hypertensives with higher MBP (> or = 110 mm Hg) had more IGT and higher 2-h glucose than the 122 hypertensives with lower MBP (< 110 mm Hg) or the normotensives, 30%, 5% and 4%, respectively (p < 0.001), and 5.8, 4.4, 4.2 mmol.l-1, respectively (p < 0.001), independently of PP. Thus, both high PP and high MBP were related to IGT, independently of each other.


The diagnosis of abdominal neuroblastoma: relative roles of ultrasonography, CT, and MRI. Abdominal neuroblastoma is reviewed in terms of its diagnosis, including in utero, at birth, and through infancy into childhood. Age at diagnosis remains the best predictor of survival, with infants under 1 year of age having almost 100% cure. Ultrasonography and magnetic resonance imaging (MRI) are the recommended diagnostic modalities to stage the abdominal primary, although computed tomography (CT) (including myelography) is still widely and efficiently used. Examples are given of each stage.


Magnetic resonance imaging for diagnosis and follow-up of genitourinary, pelvic, and perineal rhabdomyosarcoma. Magnetic resonance (MR) imaging, ultrasound, and computed tomography (CT) were performed for diagnosis and follow-up of rhabdomyosarcoma (RMS) arising from the genitourinary tract in five children, pelvic musculature in one, and the perineum in three others. MR imaging performed at 1.0 T included the following: spin-density-, T1-, and T2-weighted images in all nine patients; gadopentatate dimeglumine (Gd-DTPA)-enhanced T1-weighted images in five; and short TI inversion recovery (STIR) images in two children. Longitudinal T1-weighted images were of additional help in localizing the primary tumor at diagnosis and detecting local spread. Residual or recurrent disease within the bladder was best detected by spin-density images. Gd-DTPA enhancement improved contrast in two studies, but paramagnetic artifacts obscured intravesical lesions in three other studies. STIR images disclosed pelvic and retroperitoneal lymphadenopathy. MR imaging is recommended as the key method of diagnosis and follow-up of pelvic RMS.


Imaging the pediatric pelvis: the normal and abnormal genital tract and simulators of its diseases. Imaging of the pediatric pelvis has proven of great use in defining the normal and abnormal genital tracts. Sonography is the key screening tool and often the only tool necessary for the diagnosis of problems related to ambiguous genitalia, ovarian and uterine masses, amenorrhea, and abdominal and pelvic pain. Computed tomography (CT) and magnetic resonance imaging (MRI) have key roles in the global assessment of the pelvis particularly with regard to the assessment of tumor spread.


Renal cystic disease in infants and children. Renal cystic disease is a common abnormality of the kidney in the pediatric age group. Cystic disease may occur as a sporadic dysplasia or, somewhat more commonly, represent a genetic disorder. Establishment of an accurate diagnosis, prognosis, and treatment requires a broad approach to the problem, including radiologic imaging, renal function testing, and occasionally surgical biopsy. Interpretation of the imaging studies requires understanding of the patterns of renal cystic disease in the pediatric age group.


Primary megaureter in infants and children: a review. Primary megaureter is a common cause of obstructive uropathy in children. The imaging studies and records of 75 infants and children with primary megaureter seen at Children's Hospital were reviewed. We describe our findings and illustrate the clinical presentations, diagnosis, and treatment of this entity.


Ambiguous genitalia: diagnosis, evaluation, and treatment. The pediatric radiologist plays a significant role in the evaluation and the treatment of infants with ambiguous genitalia. On the first day of life, an investigation should be initiated that includes studies, in particular a sonogram, to demonstrate the presence or absence of a uterus, and a genitogram to define the presence of a vagina. Once gender assignment has been made, information regarding the size of the vagina and its position in regard to the urogenital sinus becomes essential to the pediatric urologist when planning a course for reconstruction. Herein we break down intersex states into four major categories: female pseudohermaphroditism, male pseudohermaphroditism without müllerian structures, and male hermaphroditism with müllerian structures and true hermaphroditism. The role of the radiologist in each of these states is discussed.


Radiographic and radionuclide lung perfusion imaging in healthy calves and calves naturally infected with bovine respiratory syncytial virus. Nine calves between three and 18 weeks old with serologically confirmed natural bovine respiratory syncytial virus infection were examined clinically, radiographically and by radionuclide lung perfusion imaging. The results were compared with those from seven healthy calves. The diseased calves were euthanased and examined pathologically, virologically and bacteriologically. The clinical signs indicated that the disease was in an acute stage. Radiography of the diseased animals revealed cysts, corresponding morphologically with bullous emphysema, and infiltrations roughly corresponding in distribution with atelectatic and, or, pneumonic areas. Radionuclide lung perfusion imaging revealed no perfusion shifts between the left and right lungs and a normal perfusion pattern in five of the nine diseased calves. The abnormalities in the perfusion patterns of three calves were probably caused by anatomical disorders such as cysts and pleural adhesions, but no cause of the abnormality could be found in one calf. These findings suggest that in calves infected with bovine respiratory syncytial virus, the normal perfusion pattern is maintained until anatomical disorders occur. The pathological examination and radiography revealed that the cranioventral lung fields were particularly poorly ventilated. This finding and the normal perfusion pattern indicate that these parts of the lungs are probably the sites where shuntings and perfusion-ventilation mismatchings occur.


Risk factors associated with hydropericardium syndrome in broiler flocks. A prospective study was undertaken to identify the epidemiological factors associated with the development and spread of the hydropericardium syndrome in broiler flocks. Data were collected between July 1989 and April 1990 from 131 flocks in 105 broiler production units pertaining to their demography, management practices, prophylactic procedures and concurrent diseases. The incidence rate of the syndrome in the whole population was 46.6 per cent. There were significant associations between the incidence in a flock and visits by a poultry vaccination crew (P = 0.014), the number of flocks raised (P = 0.004) and the source of light and heat (P = 0.007). Flocks that had one or more visits by a poultry crew were 15 times more likely to be affected by the syndrome than flocks that had no such visits. Premises where one flock was raised were nearly three times more likely to be affected than premises where two flocks were raised, and the use of electricity as a source of light and heat entailed a much lower risk of hydropericardium syndrome than kerosene oil.


Corticoid production by four dogs with hyperfunctioning adrenocortical tumours during treatment with mitotane (o,p'-DDD). In two dogs with hyperadrenocorticism due to an adrenocortical tumour, treatment with o,p'-DDD was started. Their hormonal response was monitored by measurements of the urinary corticoid/creatinine ratio. In one dog, two courses of 10 days treatment with o,p'-DDD were ineffective, whereas in the other dog the urinary corticoids decreased to very low levels after only six days of treatment, and corticosteroid supplementation had to be started. Two other dogs received o,p'-DDD according to a protocol used for the treatment of pituitary-dependent hyperadrenocorticism which aims at the complete destruction of the adrenal cortices, with substitution for the induced hyperadrenocorticism. Both dogs made a good recovery and their urinary corticoid/creatinine ratio decreased to within the reference range. In one of them the tumour had decreased considerably in size by five weeks after the start of the treatment.


[The epidemiological surveillance of HIV infection in Russia in 1987-1991]. The data on the occurrence of HIV in Russia in 1987-1991 are presented and the effects of the epidemiological surveillance system used at that time on the epidemiological process of HIV infection in the Russian Federation is evaluated. The most important features of that system included the centralized registration of all cases of HIV infection irrespective of the degree of clinical symptoms, large-scale obligatory examination of the population for antibody to HIV, epidemiological investigation of all reported cases of HIV infection. The occurrence of HIV infection in 1987-1991 in Russia remained very low, 0.335 per 100,000, showing no trend for increase. Owing to that system of the epidemiological surveillance of HIV infection in the USSR, nosocomial outbreaks were discovered which gave a rise in the number of recorded cases in 1989. In 1990-1991, changes in the structure of the epidemic process occurred. In those years, HIV transmission among homosexuals became most important, increasing from 22.4% to 47.8% which characterized the beginning of a new stage of the epidemic. On the whole, the epidemiological surveillance system for HIV in the USSR, 1987-1991, was effective, although it needs improvement including reconsideration of the population groups to be obligatorily examined for HIV antibody.


[The prevalence of the markers of viral hepatitis B and delta among the population in regions differing in the level of morbidity]. From two regions differing by the levels of incidence of hepatitis B, 2019 blood serum specimens from normal population were examined for markers of HBV infection. In Moscow, among 1040 samples examined HBsAg was found in 2.0%, anti-HBs in 10.0%, anti-HBc in the absence of HBsAg and anti-HBs in 4.5%. In the Osh Province of Kirgizstan, among 979 subjects examined the same markers were found in 10.3%, 22.4%, and 14.0%, respectively. In this area, HBsAg was detected most frequently among infants (14.9% in infants under 1 year), in whom HBs-antigenemia was combined with the presence of HBeAg in 54.5% and with anti-HBc-IgM in 69.2%. Antibody to delta antigen (anti-delta) was found in 24 (25.8%) out of 93 HBsAg-positive subjects in the Osh Province but in none of 21 subjects with HBs-antigenemia in Moscow.


[The experimental infection of bats with lyssavirus serotypes 1 and 4]. The results of intramuscular inoculation of 111 bats (Myotis daubentoni, Myotis brandtii) with three strains of Lyssaviruses--Yuli, Stade, and 1150 are presented. Bats were found to have low susceptibility, especially to strains of serotype 4. After infection with serotype 4 viruses, fewer bats died but within shorter periods than after infection with serotype 1. After inoculation with strain 1150, 60% of bats yielded virus, whereas only 9-24% did after inoculation with type 4 strains. The survival time after inoculation was 32.2 and 19.0 days, respectively. Manifestations of the disease, virus distribution in viscera, and the results of examinations of specimens from bats by express methods are described.


Unilateral seminal vesicle cyst presenting as hematospermia; diagnosis established by transrectal prostatic ultrasound. A case report of a unilateral seminal vesicle cyst presenting as painless hematospermia in a 44-year-old patient is presented. Ultrasound-guided needle aspiration of the cyst demonstrated a markedly elevated LDH level in the cyst fluid of unknown significance. Antibiotic injection under ultrasound guidance into the seminal vesicle cyst was accomplished. Laboratory evaluation on the cyst fluid is suggested.


[The comparative characteristics of the peroxidase conjugates used in Soviet immunoenzyme test systems for detecting HIV antibodies]. Five lots of peroxidase conjugates were studied in enzyme immunoassay systems "Recombinant-HIV" and "Peptoscreen-2" for detection of antibody to HIV. The conjugates differed from each other by the source of generation and methods of preparation. The conjugates were studied in biochemical tests and ELISA. When panels of sera from HIV-infected children and adults were employed, the advantages of using the anti-immunoglobulin conjugate over protein A-peroxidase conjugate were demonstrated, as the former increased the sensitivity of the test systems to HIV antibody detection.


Empowering physicians to respond to domestic violence. Despite the progress of the last 15 years in combating family violence, some individuals, community agencies and institutions still support a man's "right" to control, and they often disregard the physical violence he uses. Because threats and assault are in fact against the law, a man who physically or sexually assaults his wife or girlfriend couldn't keep doing it without this support from the very people who are supposed to enforce the law and help the victims of crime-namely, police, prosecutors, judges, clergy, psychologists, social workers and doctors. Some let him get away with it, look the other way, or--unsure of what to do to stop it--do nothing at all. Thus, they reinforce his "right" to use force, even if they never say, "Go ahead, hit her." The police officer who walks a man around the block or fails to show up when called, the clergyman who advises a woman to go home and pray, the doctor who gently patches her injuries but avoids asking who inflicted them, all cooperate with the abusive man in several ways. He comes to understand that no one will stop him from doing what he does. He learns that there are no consequences to his actions--even his violent actions. He can beat up "his woman" if he wants to and get away with it.


A needs assessment survey of HIV-infected patients. Few studies have surveyed HIV-infected patients to determine how adequately medical, legal, psychological, social service, and financial needs are being met through current treatment services. Fifty HIV-infected men seen at a county medical facility were surveyed to determine which of 17 needs were being met and the importance rating attributed to those needs. Five needs were reported by more than 30% of the sample as not being met: 1) being able to talk about fears of the future, illness, or death; 2) being occupied and having things to do; 3) having up-to-date information about HIV; 4) having someone to help them with their feelings of depression, helplessness, anxiety, or anger; and 5) help for the patient's family. Three of these five needs involve better access to psychological services. Although patients felt they had knowledgeable medical staff and good health care, they wanted more up-to-date information on HIV treatment.


A multi-institutional analysis of perinatal cocaine use. The frequency of cocaine abuse in pregnant women has increased markedly in the United States during the last decade. This increased abuse has lead to recognition of potentially negative perinatal outcomes. The purpose of this study is to determine the incidence of positive cocaine-specific screens in pregnant women and delivered infants at two Milwaukee area sites: an urban teaching hospital with a delivery base of 5,500 births annually and a suburban hospital with a delivery base of 1,700 births. A prospective, blinded analysis of urine specimens was performed at both sites over a 3-month period. All delivered infants, all women who presented to the labor and delivery unit and were discharged undelivered, and women who presented to the urban hospital's obstetrical clinic had urine samples obtained for toxicology analysis. Demographic data was also collected to include age, race, gestational age, and history of drug abuse. Results of the urine screen and demographic data were analyzed for frequency distribution. The overall incidence of positive cocaine screens was 3.5% in the urban population and less than 1% in the suburban population.


Lack of correlation between aortic calcification and bone density. Previous radiographic studies have suggested a positive relationship between two degenerative processes associated with aging: calcification of the abdominal aorta and osteoporosis. Such a relationship has not been studied using modern quantitative densitometry. Aortic calcification was quantified on spinal radiographs from 112 elderly men. Bone mineral density was determined at six scanning sites using photon densitometry. There was no significant correlation between aortic calcification and bone mineral density at any of the scanning sites when the effect of age was held constant in the statistical analysis.


Dose-range finding study with the proton pump inhibitor pantoprazole in acute duodenal ulcer patients. Pantoprazole is a newly developed benzimidazole derivative with strong inhibitory actions on gastric acid secretion by blocking H(+)-K(+)-ATPase. This randomized double-blind multicenter trial investigated the efficacy of 20 mg, 40 mg and 80 mg pantoprazole o.m. on ulcer healing and symptomatic relief in 219 out-patients with endoscopically assessed acute duodenal ulcer. After 2 weeks complete ulcer healing was achieved in 58%, 89% and 82% of the patients with 20 mg, 40 mg and 80 mg pantoprazole o.m., respectively. After 4 weeks, corresponding figures were 93%, 99% and 100%; the difference of the healing rates between the 20 mg and 40 mg groups at 2 weeks was statistically significant (p < 0.0001). A rapid pain relief was achieved in all treatment groups: 72% of the 20 mg group, 89% of the 40 mg group, and 84% of the 80 mg group were pain-free after 2 weeks. The difference between 20 mg and 40 mg was statistically significant (p < 0.05). Pantoprazole was well tolerated. Adverse events occurred in 13 patients; headache, skin alterations, and diarrhea were reported most frequently. Severity and frequency of adverse events did not reveal any dose-dependence. In conclusion, pantoprazole provides fast healing of acute duodenal ulcer as well as rapid improvement of ulcer symptoms. For further clinical trials in peptic ulcer disease a daily dose of pantoprazole 40 mg o.m. is recommended.


Two weeks treatment with amoxicillin/omeprazole for eradication of Helicobacter pylori. In an open study, 62 patients with Helicobacter pylori-associated ulcer disease or functional dyspepsia were treated for two weeks with 2 x 20 mg omeprazole preprandially and 4 x 500 mg amoxicillin suspension one hour before meals and at night. 57 patients (active ulcer disease: n = 53, functional dyspepsia: n = 4) completed the study without contravening the protocol. The rate of eradication of the bacteria at least 4 weeks after cessation of study medication was 82.5% (47/57 patients). Three patients experienced side effects during the treatment period (stomatitis, self-limiting diarrhea, allergic exanthema). In one case allergic exanthema led to discontinuation of therapy. 11 patients with H. pylori-associated ulcer disease received 2 x 20 mg omeprazole for two weeks. In this group no eradication of bacteria was observed.


Repeated isovolemic large-volume erythrocytapheresis in the treatment of idiopathic hemochromatosis. In order to assess the effectiveness of cytapheresis as a possible alternative therapy for iron depletion, we performed a prospective study on eight unrelated patients with idiopathic hemochromatosis (HC). Isovolemic large-volume erythrocytapheresis (EA) (1000 ml apherisate) was carried out every four weeks until serum ferritin levels dropped below 300 micrograms/l (initial therapy). In all patients iron depletion was achieved after a mean of 8.5 months (8.9 EA with a total removal of 9.41 RBC). Serum ferritin levels decreased during initial therapy from 2596 +/- 399 to 168 +/- 83 ug/l. Serum iron level (240 +/- 35 to 125 +/- 48 ug/dl) and transferrin saturation (91 +/- 6 to 19 +/- 10%) declined accordingly. Clinical reexamination after initial therapy revealed improvement of clinical symptoms, normalization of hepatic iron, but liver histology remained unchanged. Reaccumulation of iron was prevented by maintenance EA therapy every five to six months (follow-up 18-36 months). Isovolemic large-volume EA is an effective, fast and safe method to remove excessive stored iron in patients with HC. Compared to phlebotomy, EA can selectively remove RBC, while saving plasma proteins, platelets, and clotting factors. Although, the need for special equipment and trained personnel as well as the relatively high costs are limiting factors of EA so far, it can be of crucial advance in some patients with HC.


[Liver function tests in a clinical comparison]. Various liver function tests were evaluated in regard to a quantitative estimation of the impairment of liver function related to the Child-Pugh classification in 32 patients with cirrhosis. Only the ICG-test revealed significant differences between healthy subjects and cirrhotic patients in stadium Child A, B and C. When ICG-dye retention values were plotted as a function of the individual score units of the Child-Pugh classification, a linear relationship with a correlation coefficient of 0.7 was obtained. In contrast to the ICG-test, the MEGX- and galactose elimination capacity (GEC)-test as well as static parameters of liver function (cholinesterase activity, prealbumin concentration, coagulation factor V and VII) resulted in less significant differentiation of the various Child classes. The MEGX-test, GEC, concentration of prealbumin, coagulation factor V and VII were only weakly correlated to the score units of the Child-Pugh index. The results of this study indicate that of all evaluated parameters only the ICG-test is suitable for objective and graduated analysis of liver function in patients with cirrhosis.


[Differential diagnostic value of occult blood in stool in hookworm infection in the Third World. Study from Papua New Guinea]. In 633 persons of the Madang province in Papua-New Guinea hookworm-infection, blood hemoglobin and the presence of blood in stools were studied. 60% of the subjects were infected with hookworm (Necator americanus). There was a significant linear correlation between the intensity of hookworm infection and blood haemoglobin level. The Colo-Rectal test gave positive results in 17% of the cases without worm-infection. In infected persons, the Colo-Rectal test gave an increasing rate of positive results as the parasite infection increased: 24% for subjects with low levels of infection, and 57% and 67% for moderate and high levels, respectively. The mean blood-haemoglobin level was lower in persons with positive Colo-Rectal-Test and hookworm infection (11.8 g%) than among those with negative Colo-Rectal-Test and hookworm infection (15.0 g%, p < 0.01). In young populations with a known high prevalence of hookworm infection, Colo-Rectal test is therefore suitable for the detection of moderate or severe hookworm infections. It may serve as a simple and useful method to work up anaemia is such populations.


Splenic lesion as a complication of laparoscopy. Case report. A case of splenic lesion is reported in a 48-year-old female patient who underwent an uneventful diagnostic laparoscopy. Symptoms suggesting massive intraabdominal bleeding occurred 5 hours later. Intraoperatively, a small posterior splenic lesion was found, which could be repaired using fibrin glue. This protracted complication must have occurred while establishing the pneumoperitoneum; its cause is unclear, but distortion and stretching of small adhesions of the spleen with the abdominal wall may have played a role. Although rare, this complication should be considered when a patient deteriorates after an uneventful laparoscopy.


[Jejunogastric invagination--a rare complication of stomach surgery]. The jejunogastric intussusception is a rare complication of gastric surgery. An acute and a chronic form of intussusception can be distinguished. Three anatomical types of jejunogastric invagination have been classified. Endoscopy is the diagnostic procedure of choice, early operative desinvagination the therapy of choice. The effectiveness of different operative procedures to prevent reinvagination is contested.


[Oxygen radicals and acute pancreatitis]. Oxygen-derived free radicals mediate an important step in the initiation of experimental acute pancreatitis. Thereby these reactive oxygen metabolites are generated at an early stage of disease. The source of the enhanced production of oxygen radicals remains unclear. Experimentally, the efficiency of scavenger treatment varied between different models, whereby these differences were depending on the experimental model and not on the form of pancreatitis which was induced. Most studies pretreated the experimental animals before inducing acute pancreatitis. This does not mirror the clinical reality, since patients are admitted to the hospital after onset of the disease. It was shown in Cerulein-pancreatitis, however, that scavenger treatment also mitigated the pancreatic tissue damages after induction of acute pancreatitis. Moreover, antioxidant treatment also attenuated the extrapancreatic complications, thus improving the final outcome of the disease. The first indirect observations also suggest that in human acute recurrent and chronic pancreatitis oxygen free radicals are generated and add to the damages seen. Therefore, well-defined controlled clinical studies with patients suffering from acute pancreatitis are needed to validate the role of oxygen radicals in this disease.


[Successful high-frequency current ablation of three accessory conduction pathways in a single session]. A case is presented of a 25-year-old symptomatic male with Wolff-Parkinson-White syndrome and three overt accessory atrioventricular connections which were all diagnosed and ablated during the same session. A discordant preexcitation pattern between delta wave and QRS axis was found on the surface electrocardiogram, indicating the presence of two or more accessory pathways. During atrial pacing the appearance of a changing QRS morphology and alternating delta wave suggested the presence of an additional left-sided pathway. After ablation of a right anteroseptal pathway, a second pathway was found located in the left lateral position and was successfully ablated. The final pathway became evident only after the ablation of the first two and was found to be located in a right midseptal position. This pathway was also ablated during this session. There were no complications and the patient remained asymptomatic during an 11-month follow-up.


[Wolff-Parkinson-White syndrome: regional endocardial potential and efficacy of high frequency ablation]. The aim of the study was the evaluation of results of radiofrequency (RF) catheter ablation in relation to characteristics of regional endocardial potential morphology. 418 RF current deliveries in 26 patients with anterogradely conducting left-sided accessory pathways (AP) were investigated. A large regional atrial deflection (> 1/4 of ventricular potential) prior to RF discharge is a prerequisite for ablation success using the ventricular approach. A failing or extremely short (< 10 ms) isoelectric interval between atrial and ventricular deflections of the regional potential predicts a block of the AP. A persistent block can be expected if the regional electrogram contains an AP potential and the AP block occurs early (< 5 s) during onset of RF current.


[Myocardial function before and after reopening of chronic coronary occlusion]. To assess the myocardial function before and after reopening of chronic coronary artery occlusions, 20 patients were investigated at rest and during exercise with ECG and equilibrium radionuclide ventriculography. The recanalisation of the chronically occluded vessel was carried out by means of Rotacs-catheter in 17 patients, of a guide wire enforced by recanalisation-catheter in 2 patients and of a thin guide wire alone in 1 patient, always followed by conventional balloon angioplasty. After successful PTCA the average coronary artery stenosis diameter decreased from 100% to 34 +/- 6%. Angina pectoris and/or dyspnea observed during exercise were improved in 83% of the patients. The radionuclide global left ventricular ejection fraction at rest increased from 55 +/- 9% to 59 +/- 10% (p < 0.05), and during exercise from 52 +/- 12% to 61 +/- 12% (p < 0.05). The improvement in global ejection fraction at rest was more pronounced in 5 patients, who suffered from angina pectoris at rest before PTCA (from 56 +/- 4% to 65 +/- 9%, p < 0.05). It is concluded that reopening of chronically occluded coronary arteries in properly selected patients leads to a significant improvement of the global left ventricular function at rest and during exercise.


[Hibernation, stunning, ischemic preconditioning--new paradigms in coronary disease?]. Myocardial ischemia has traditionally been characterized as an imbalance between energy supply and demand. In the initial seconds after a sudden reduction of coronary blood flow, myocardial energy demand most certainly exceeds the reduced energy supply. This temporary mismatch, however, is an inherently unstable condition because regional contractile dysfunction ensues. The mechanisms responsible for the rapid reduction in contractile function of the acutely ischemic myocardium are still poorly understood. If some residual blood flow exists, a state of "perfusion-contraction matching" can be maintained without the development of irreversible damage. The metabolic status of such hypoperfused myocardium improves as myocardial lactate production is attenuated and creatine phosphate, after an initial reduction, returns towards control values. The hypoperfused myocardium can respond to inotropic stimulation by dobutamine with increased function. The recruitment of an inotropic reserve implies increased energy utilization. In fact, the partially normalized lactate production is again increased, and creatine phosphate is decreased again. Apparently, the inotropic challenge once again precipitates a supply-demand imbalance which had been at least partially corrected by the ischemia-induced decrease of regional contractile function. A situation of chronic contractile failure in viable myocardium which normalizes upon reperfusion has been termed myocardial "Hibernation". Myocardial "Stunning" is characterized by a reversible post-ischemic contractile dysfunction despite full restoration of blood flow. The underlying mechanisms are not clear in detail. An inadequate energy supply and an impaired sympathetic neurotransmission have been excluded. Potential mechanisms, which are not mutually exclusive, may include (1) damage of membranes and enzymes by free radicals, (2) an increase in free cytosolic calcium during ischemia and reperfusion, and (3) a decrease of the calcium sensitivity of the myofibrils. The equally pronounced increases in regional contractility in normal and "stunned" myocardium during intracoronary calcium infusion, postextrasystolic potentiation and the infusion of the calcium-sensitizing agent AR-L-57, however, suggest an unchanged calcium sensitivity of reperfused myocardium. Interventions to reduce free radical formation or to increase their elimination attenuate myocardial stunning. Likewise, pretreatment with calcium antagonists before ischemia attenuates myocardial stunning. This effect is probably related to an attenuated myocardial calcium overload during early ischemia. The potential benefit from calcium antagonists when given after established reperfusion remains controversial.(ABSTRACT TRUNCATED AT 400 WORDS)


[Left ventricular dimensions and functions in the acute and chronic phase after myocardial infarct--comparison of cine-magnetic resonance tomography, angiocardiography, 2D-echocardiography and technetium ventricular scintigraphy]. To study left ventricular morphological and functional changes in the first six months after acute myocardial infarction, 37 patients (28 male, 9 female, age 42-78 years) underwent cardiac Cine-MRT 1 week, 4 weeks and 6 months after their first myocardial infarction. MR-tomograms were oriented to left ventricular true long and short axis. For comparison, contrast angiocardiographic, radionuclide and echocardiographic left ventricular studies were performed. LV-volume was calculated with the Simpson method for long axis images and by summation of slices for short axis images. Cine MRT results showed the following correlation to angiocardiography: in long axis r = 0.945 for LVEDVI, r = 0.958 for LVESVI, r = 0.869 for LVEF and r = 0.885 for cardiac index; in short axis r = 0.956 for LVEDVI, r = 0.965 for LVESVI, r = 0.917 for LVEF and r = 0.844 for cardiac index. For LVEF correlation to technetium radionuclide ventriculography was r = 0.760 in long and r = 0.861 in short axis. Correlation between Cine-MRT and echocardiography was poor as a consequence of the great variance of echogenity in the study patients. We conclude that Cine-MRT is an excellent method for morphological and functional left ventricular investigation, still limited in clinical praxis by costs and duration. As known from earlier investigations the development of left ventricular dilatation and functional disturbance was influenced by the size and location of the infarction with infarct size being the primary factor in the early and infarct location in the late post-infarction period. Outcome was worst following large anterior infarction.


[Noninvasive quantification and classification of the severity of aortic stenosis using Doppler echocardiography]. The exact determination of the severity of valvular heart disease represents the basis for the indication for surgery. Apart from the clinical findings, the estimation of the severity has, up to now, been based on the chest x-ray, the electrocardiogram, and the carotid pulse curve. By means of cardiac catheterization, the aortic valve gradient is determined and the aortic valve area is calculated using the Gorlin equation. Doppler echocardiography allows for a noninvasive gradient assessment. The peak and mean pressure gradients as well as the aortic valve area can be calculated. Echocardiography provides additional information about the severity of the left-ventricular hypertrophy, the heart size, as well as about secondary complications. Doppler echocardiography was performed in 95 patients to determine the peak pressure gradient. This Doppler-derived gradient correlated well with the catheterization-derived invasive gradient. The correlation coefficient was r = 0.81, for the mean gradient r = 0.77, and for the aortic valve area r = 0.87. Based on the classical determination of the severity of aortic stenosis by means of cardiac catheterization, a Doppler-derived mean pressure gradient > 54 mm Hg or a peak pressure gradient > 89 mm Hg and an aortic valve area > 0.7 cm2 are specific for severe aortic stenosis. A mean pressure gradient between 40 and 54 mm Hg or a peak pressure gradient of 67 and 89 mm Hg and an aortic valve area of 0.7 and 1.3 cm2 indicate moderately aortic stenosis.(ABSTRACT TRUNCATED AT 250 WORDS)


[Doppler echocardiography imaging of construction-induced regurgitation of technical heart valve prostheses]. The normal leakage flow in modern technical heart valve prostheses can be visualized by color-coded Doppler-echocardiography, provided that an adequate ultrasonic image quality can be achieved. Sometimes it may be difficult, however, to distinguish such a normal leakage flow from pathological regurgitation. We therefore mounted new specimens of five different types of prostheses (Bjørk-Shiley monostrut, Medtronic-Hall, Omnicarbon, Saint Jude Medical, Duromedics) into an invitro model, where the leakage flows could directly be visualized as emerging water jets. When the system was completely filled, the jets could also be registered by two-dimensional Doppler-echocardiography. For each valve, characteristic patterns for the localization of the principal jets were found. Besides the relative broad central jet in the Medtronic-Hall valve, all other jets arose mainly at the ring. They were detected at the hinges or the basis of the larger struts, respectively, and with asymmetrical mono-disc valves at the side of the smaller opening. The length and the orientation of the jets were found to change significantly with minimal variations of the position of the closing discs. This variability could be confirmed, when in a separate model the overall leakage flows were repeatedly measured. For patient examinations it seems useful to refer mainly to the localization of the jet origins. The comparison with reference values of jet-dimensions in Doppler images will rarely enable the examiner to distinguish between normal and pathological jets.


[Malignant hemangioendotheliosarcoma in the area of the right coronary artery: imaging by selective coronary angiography]. We report on a case of a malignant hemangioendotheliosarcoma in the right coronary artery. The first manifestation was a pericardial tamponade from a hemorrhagic pericardial effusion. The diagnosis was established only by selective coronary angiography of the right coronary artery, other imaging procedures did not lead to the diagnosis. During follow-up, multiple angiosarcoma developed in the liver, the spleen and, finally, in the lungs. Despite multichemotherapy, the patient died 7 months after the first manifestation.


European Vaccine Manufacturers: present status and future trends. The majority of the vaccines used in the world are supplied by companies grouped in the European Vaccine Manufacturers, a specialized group within the European Federation of Pharmaceutical Industries Associations. The vast supplies of vaccine to developing nations now represent too large a fraction of output, sold at low prices, that causes a drag on profitability. This situation needs to be addressed, to allow vaccine manufacturers to continue to provide quality vaccines at reasonable prices, and to foster research and development for improved and new vaccines.


Contribution to rabies prevention.

Contribution to rabies prevention. After the end of the Second World War, an outbreak of fox rabies invaded Europe. For the immunization of human populations and domestic animals against the risk of rabies transmitted by infected wild animals, it appeared necessary to replace the first generation of rabies vaccines (nerve tissue vaccines) by more potent and safer vaccines. The European vaccine manufacturers, in close collaboration with the research institutes engaged in rabies research, soon and quickly developed a second generation of rabies vaccines, produced in cell cultures including continuous cell lines grown in bioreactors of industrial scale. The third generation of rabies vaccines is already available: the vaccinia-rabies glycoprotein recombinant vaccine is presently applied on a large scale in some European countries for immunization of wildlife. The canarypox recombinant vaccine has already been considered and successfully tested for human immunization.


Contribution to hepatitis B prevention.

Contribution to hepatitis B prevention. Hepatitis B is widely recognized as an important public health problem. The only effective way to control hepatitis B is by vaccination. First generation plasma-derived hepatitis B vaccines have limitations. Advances in recombinant DNA technology have led to the development of yeast-derived recombinant hepatitis B vaccine which is now used extensively in the developed world. This article reviews the development of this new generation vaccine and the efforts to facilitate universal vaccination programmes particularly in the developing world. The issue of the cost of new generation vaccines, in relation to the major investment required for research and development and also the quality of the final product, is discussed.


The Children's Vaccine Initiative and vaccine supply: the role of the public sector. 'Children represent the most vulnerable segment of every society--and they are our present and future. Good health, especially of children, promotes personal and national development. Scientific progress, matched with improved capacities of all countries to immunize their children, provides an unparalleled opportunity to save additional lives and prevent additional millions of disabilities annually through a Children's Vaccine Initiative.' (The Netherlands Minister for Development Co-operation.)


An oral B subunit: whole cell vaccine against cholera. During the last decade there has been a rapid progress in the development of new, much improved vaccines against cholera. These vaccines, which are given orally to stimulate the gut mucosal immune system, are based on either a combination of purified cholera toxin B (binding) subunit and killed cholera vibrios of Inaba and Ogawa serotypes and El Tor and classical biotypes (B subunit-whole cell vaccine, B-WC) or on a live attenuated mutant strain of Vibrio cholerae producing the B subunit (CVD 103-HgR). The safety of the oral B-WC cholera vaccine and the immunogenicity and protective efficacy of this vaccine against both cholera and diarrhoea caused by enterotoxigenic Escherichia coli have been extensively documented, e.g. in a large randomized, placebo-controlled field trial in 90,000 persons living in a cholera endemic area. The potential for inexpensive large-scale manufacturing of the B-WC vaccine has recently been much facilitated by the introduction of recombinant DNA technology for production of the B subunit component. This now gives promise that this vaccine could become a useful, cost-effective tool in future strategies to control cholera both in endemic situations and in relation to acute epidemic outbreaks.


Immunopotentiating reconstituted influenza virosomes (IRIVs) and other adjuvants for improved presentation of small antigens. Synthetic peptides, purified subunits or inactivated small virus particles require immunopotentiation if they are to be effective vaccines. A large range of procedures to enhance immunogenicity has evolved over the last decades: aluminium salts, proteosomes, immunostimulating complexes (ISCOMs), liposomes, conjugation with bacterial products or derivatives, combination with surface-active agents or application of cytokines have been the most described classes of adjuvants. We describe here the design of an inactivated hepatitis A vaccine adjuvanted with immunopotentiating reconstituted influenza virosomes (IRIVs). The formalin-inactivated hepatitis A particles are attached to reconstituted protein-lipid complexes consisting of a mixture of phospholipids and influenza virus glycoproteins. With this new vaccine design we combined different immunostimulating effects: immunopotentiation by phospholipid vesicles, recognition of the haemagglutinin (HA) epitopes by the immune system, binding capacity of HA to sialic acid-containing receptors of macrophages and immunocompetent cells and mediation of entry into the cytoplasm of macrophages by a membrane-fusion event triggered by HA. Hepatitis A seronegative human volunteers received one intramuscular injection with this new vaccine. There were only few mild local reactions and 14 days after vaccination 100% of the subjects were seropositive. Among the individuals (control group) who received an alum-adsorbed vaccine, 88% developed local reactions. The seroconversion rate was 44%. We conclude from these results that the IRIVs provide a new approach to the future design of adjuvanted vaccines.


Strategies for the development of an antimalarial vaccine. Susceptible Aotus monkeys were immunized with Escherichia coli-derived fusion proteins containing partial sequences of the proteins MSAI, SERP, HRPII and with a group of three recombinant antigens isolated by screening with an antiserum raised against the protective 41 kDa protein band. HRPII, the combination of the fusion proteins of the 41 kDa group and a mixture of two sequences of SERP conferred significant protection against a challenge infection with Plasmodium falciparum blood stages. Based on the protective capacity of these recombinant antigens we have expressed two hybrid proteins (MS2/SERP/HRPII and SERP/MSAI/HRPII) in E. coli containing selected partial sequences. In two independent immunization trials it was shown that immunization of Aotus monkeys with either of the two hybrid proteins can protect the animals from an experimental P. falciparum infection.


The concept of herd immunity and the design of community-based immunization programmes. The paper focuses on the concepts of transmission success and herd immunity and their relevance to the design of community-based immunization programmes for the control of infectious diseases. Recent work in a number of areas is reviewed, including the influence of mass vaccination on the average age of infection and the incidence of morbidity due to infection and vaccination, the age window of susceptibility and the problems of vaccine programme design in developing countries, the interaction between vaccine efficacy and vaccine safety and the design of vaccination programmes for the control of sexually transmitted infections. Discussions centre on the interplay between an understanding of the transmission dynamics of an infection and the design of community-based control programmes.


Benefits and costs of vaccination.

Benefits and costs of vaccination. Vaccination programmes supported by the WHO and other organizations have dramatically reduced disease in developing countries, but there remains a need to extend coverage rates and expand the number of vaccines included. In industrialized countries, where paediatric vaccination is almost universal, there will be an increasing opportunity to protect against diseases which occur in later years.


EPI for the 1990s. The Expanded Programme on Immunization Team. This paper highlights the achievements, lessons learned, goals, policies, strategies and approaches for the Expanded Programme on Immunization for the 1990s. The Programme's Global Advisory Group endorsed the paper in October 1991, together with actions proposed for the 1990s. Figures showing immunization coverage and estimates of prevented and current mortality and morbidity are included.


The cold chain from manufacturer to vaccinator: experiments and experiences. Biological substances are temperature sensitive. Most vaccines must be constantly kept at temperatures between +2 to +8 degrees C (cold chain). To test the conditions of a long distance transport of vaccines in an 80 l cool box the temperature in the correctly packed box was monitored. The temperature remained between zero and +8 degrees C for more than 90 h, the ambient temperature during this test reached 37 degrees C for 5 h. It can be concluded that the currently used transport boxes are well suited for safe transport of sensitive products such as vaccines.


Availability of vaccines of an assured quality. In establishing standards of quality for vaccines used in vaccination programmes, it is necessary to protect the recipients without demanding unnecessarily high specifications and standards of purity. Such standards reduce profitability, jeopardizing further vaccine supplies and future research, and also diminish the probability of vaccine manufacture outside the industrialized countries. Funds will be needed to encourage research and local manufacture, and internationally accepted procedures of quality assurance must be established.


The countries' point of view.

The countries' point of view. Several important factors in the supply of quality vaccines to developing countries are explained. These include central purchasing, establishment of a National control authority and local vaccine production.


Availability of quality vaccines: the industrial point of view. Availability of vaccines may be temporarily affected by sudden peak demand, coming on top of the vast increases of regular demand that the world has witnessed; this must be addressed by sound planning, and flexibility both from manufacturers and users. Temporary shortages are not structural in nature, and capacity is at hand to meet demand. Transfer of technology to developing nations is not likely to make the supply of vaccines of good quality any easier, faster or substantially cheaper, as the constraints that determine vaccine manufacture will not change merely by locating a production unit in a developing nation.


Availability of quality vaccines: policies of a non-government organization. The availability of vaccines, or any other health service, depends upon, first, the existence of a reliable system of delivery, and the effective management of this system to reach the target population and, second, the acceptance by parents or guardians of the value of the vaccine in preventing death and disability in young children and their mothers. This system must be fully funded and resourced for the foreseeable future if the service is to be sustainable. Today the major obstacles to effective immunization of young children in developing countries is the inadequate, insecure and unpredictable availability of funds and their management. Unless these problems are addressed and solved, the immunization targets set by the World Health Assembly (WHA) will not be met.


Biostatistical manual (BIOSTAT) for potency control and for evaluation of effectiveness of the WHO-EPI vaccines: software for personal computers. In accordance with WHO requirements, a specialized software has been developed for personal computers to analyse the potency data of the EPI vaccines and to evaluate the effectiveness of the vaccination. The software has three parts and allows users to create files from control data (BIOSTAT), to check the function of the software and statistical formulae (BIOSDEMO), and to understand the logic and structure of the data processing system and the statistical models (BIOSDOC).


Synthetic immunoadjuvants: application to non-specific host stimulation and potentiation of vaccine immunogenicity. It is well recognized that immunoadjuvants mainly play two roles; non-specific stimulation of host resistance against infections and cancer, and the potentiation of vaccine immunogenicity. This article reviews the recent results of the development of synthetic immunoadjuvants in our laboratory with special reference to muramyldipeptide (MDP), trehalose dimycolate (TDM), lipid A, chitin and their related compounds. The usefulness of MDP derivative MDP-Lys(L18), which has recently gone on the market as a haematopoietic agent for restoration of leukopenia in cancer patients treated with radiotherapy and chemotherapy, is reviewed. The various approaches to application of synthetic immunoadjuvants to the potentiation of vaccine immunogenicity, including adjuvant formulation, are also discussed.


Progress towards the development of new vaccines against whooping cough. Acellular vaccines against whooping cough are in the final stage of clinical testing and are likely to become available for mass immunization in the near future. Over a dozen vaccines of similar composition have been developed by vaccine companies and research laboratories; all of them contain a detoxified form of pertussis toxin (PT) that may be present alone or combined with one or more other non-toxic proteins, such as filamentous haemagglutinin (FHA), pertactin (69 kDa), and the agglutinogens (AGG). Most of the vaccines contain a PT that has been inactivated by chemical treatment, a process that reduces the immunogenicity of the molecule and may not completely eliminate the risk of reversion to toxicity. To avoid these problems, we have constructed by genetic manipulation a mutant of Bordetella pertussis that produces a non-toxic form of PT. This molecule (PT-9K/129G) contains two amino acid substitutions in the S1 subunit (Arg9-->Lys and Glu129-->Gly) which abolish the enzymatic activity of the S1 subunit and all the toxic properties of PT, without changing the immunological properties of the wild-type toxin. Following extensive preclinical studies, which have shown that PT-9K/129G is safe and more antigenic than the toxin treated with chemical agents, this molecule was tested for safety and immunogenicity in adult volunteers, 18-month-old children and 2-month-old infants. The molecule has been tested alone, combined with FHA and pertactin and also combined with diphtheria and tetanus toxoids.(ABSTRACT TRUNCATED AT 250 WORDS)


Pertussis: the trials and tribulations of old and new pertussis vaccines. The mortality from pertussis in unvaccinated infants is significantly greater than that reported. Most present day whole-cell pertussis vaccines are efficacious. Although they cause frequent reactions, studies during the last 15 years reveal no evidence that they cause brain damage. Acellular pertussis vaccines have been used successfully in Japan since 1981. In spite of this, five vaccine efficacy trials in three countries are presently in progress. Of the six vaccines being studied, three seem to be less than optimal choices for study because they are similar to the two vaccines evaluated in the original Swedish efficacy trial which had disappointing efficacy. The lessened reactions associated with acellular pertussis vaccines make routine adult booster immunization possible. A future immunization programme with vaccines that elicit antibodies which completely block bacterial attachment to ciliary epithelial cells, and which includes universal childhood immunization and adult booster doses can be expected to have a dramatic effect upon disease incidence and the circulation of Bordetella pertussis in the community.


Impediments, imponderables and alternatives in the attempt to develop an effective vaccine against AIDS. A personal view is presented that current successful vaccines against 'ordinary' viruses do not provide the guidelines needed for development of effective vaccines against the 'extraordinary' viruses that cause AIDS. Present 'candidate' AIDS vaccines fail to recognize the special attributes that are needed to make them successful. There is an urgent need for intensive studies of pathogenesis to seek and find the clues needed for vaccine attack that are at present unknown. Also needed is a targeted Research and Development organization comprising a cadre of capable scientists of requisite disciplines in adequate facilities, dedicated solely to the development of a vaccine against AIDS. The urgency imposed by the AIDS pandemic merits a new dedication to targeted basic research discovery and an effectively concentrated and coordinated applied research initiative.


Bacterial vaccines: old and new, veterinary and medical. Developments in veterinary and medical bacterial vaccines are outlined. In the former case, economic considerations are paramount, and cruder, less purified products of proven efficacy continue to be employed. For human use, however, safety and absence of side effects are increasingly demanded. Various examples of human and veterinary vaccines are discussed, and interaction between the two fields is illustrated by reference to the pig-bel disease in New Guinea and the possible aetiology of Sudden Infant Death Syndrome.


Synthetic approaches to vaccines for infectious and autoimmune diseases. The development is outlined of some synthetic vaccines against infectious diseases, in particular cholera, shigella and influenza. In the last case, use of the synthetic adjuvant MDP in combination with a haemagglutinin peptide has led to a synthetic vaccine with built-in adjuvanticity. The production of vaccines both by chemical synthesis and genetic engineering is described. The successful use of the synthetic amino acid copolymer COP-1 as an immunomodulatory vaccine to suppress the onset of allergic encephalomyelitis in experimental animals has led to clinical trials with patients suffering from exacerbating remitting multiple sclerosis. T-cell vaccination is an alternative approach to immunization against autoimmune diseases.


[Possibilities and limits of daily coping with illness by patients with chronic polyarthritis]. A central problem of persons with chronic polyarthritis is the necessary adaptation to deteriorating health in everyday activities. Difficulties and burdens of this adaptation are parts of the study undertaken in the Unna Model, which was part of the research on "Local Services for CP-Patients". In the first part two female patients are described with regards to these everyday problems of "normalization", i.e., including health conditions resp. daily activities. An important element is the microsocial context: mutual expectations and support in the family and at the work place. In the second part some quantitative results of interviews with 93 cP-patients are presented. They show the importance that is given by these interviewed persons to these daily adaptations, self help, and support.


[Developing occupational integration of patients with chronic polyarthritis during productive years]. Rheumatoid arthritis is a common disorder that depends on the activity of the disease, the severeness of the functional losses, and the degree of suffering from pain. In a study of 817 RA patients it could be shown that the occupational status depends as much on the severing of the disease as on the job status, educational status, and income.


[The role of the family physician in cooperation and coordination management of chronic rheumatic patients]. Rheumatoid arthritis (RA) is a disease that confronts the primary care practitioner with medical and organizational problems. There are only few experiences in diagnosis and therapy of (early) RA because of the low prevalence rate. Especially in rural districts there is a deficit in physiotherapists, ergotherapists, and psychologists with knowledge in rheumatology. The cooperation with rheumatologists is an organizational problem. In a study of 817 RA patients it could be shown that organizational help and, the offer of complementary therapy in the vicinity of a patient's home led to an increase of well-being and decrease in costs and severity of the disease.


["Mobile occupational therapy" for rheumatic patients: development of the service, utilization and management with aids and braces]. The development and utilization of occupational therapy as a home care service for patients with rheumatic diseases is examined. This new service was implemented in Schleswig-Holstein by local branch of the German League against Rheumatism, an organization devoted to the promotion of help and self-help for patients. The data for this study are based on standardized documentations within a comprehensive evaluation of model-intervention, and also accounting records. From July 1, 1986 until June 31, 1991, there were 1120 prescriptions issued by 293 physicians at 86 locations. 529 patients could be served with a total amount of 6778 time-units of care. The development of the service shows a slowly but steady and region wide growing acceptance by the practitioners and, accordingly, an increasing utilization associated with an increasing inclusion of non-rheumatic diagnoses. The supplies of support devices (included in 55% of all prescriptions) and braces (included in 26% of all prescriptions) are described separately, since patient counseling and assistance--particularly in connection with support devices and aids for everyday life--are of great importance.


[The "Hannover Chronic Polyarthritis School": development of a curriculum and implementation of a controlled study for educating patients with chronic polyarthritis]. Patient education is an important and necessary tool to facilitate coping with a chronic disease. The existing studies about new approaches to patient education and their effects are reviewed and discussed. The interdisciplinary team of the MRH tried to improve the deficient situation concerning patient education in rheumatology in Germany. They elaborated the "cP-Schule Hannover", a curriculum for patient education in small groups in an outpatient clinic setting. The courses include eight sessions taught by a psychologist and performed by a team of health professionals. Four groups with a total of 31 RA-sufferers have been evaluated in a controlled prospective study over 3 months. The significant effects of this patient education program were an increase of knowledge and satisfaction which were still evident after a follow-up period of 3 months. Negative side-effects like worsening of psychological status were not observed. Based on these positive experiences and results a "patient education" working group was founded in late 1989. This working group is a member of the German Association of Rheumatology. It focuses on the elaboration of a structured, supra-regional standardized patient education program for rheumatoid arthritis consisting of several modules.