Biomedical subjects
Publications and source records attributed to P B Nielsen.
We report a case of severe early congenital syphilis in the infant of a mother who acquired syphilis in mid pregnancy. The mother had received full antenatal care including serological screening for syphilis. Congenital syphilis is re-emerging in a number of industrialised countries and this report demonstrates that some of the most serious cases cannot be prevented by routine antenatal screening.
alpha-Tocopherol is an excellent solvent for many poorly soluble drugs. The aim of this work was to study whether or not the presence of alpha-tocopherol has an influence on the solubilisation of poorly soluble drugs in simulated intestinal fluids (SIF). The solubilizing capacity of mixed micelles containing alpha-tocopherol towards three lipophilic drugs was investigated. The solubilisation of alpha-tocopherol in an aqueous micellar phase was increased by the addition of monoglycerides (MG) and free fatty acids (FFA), preferably of medium chain length, as compared to a simple bile salt solution. The addition of alpha-tocopherol to mixed micellar solutions seems to have an effect on the solubilizing capacity, which can be correlated to the partition coefficient of the drug to be solubilised. A positive effect on the solubilisation of griseofulvin and felodipine was found. For a highly lipophilic drug (Lu28-179), a positive effect on solubilisation was observed only in media containing MG and FFA of medium chain length. Generally, alpha-tocopherol cannot be considered an important factor for the solubilisation of highly lipophilic drugs in SIF. The presence of lipolytic digestion products (LDP) of the proper chain length in relation to the drug to be solubilised is much more important.
The applicability of alpha-tocopherol as a lymphotropic carrier for a highly lipophilic drug has been evaluated. Transport to the intestinal lymph of the highly lipophilic model drug, Lu28-179, in rats after administration to the stomach in an alpha-tocopherol emulsion was compared with lymphatic transport after administration of a sesame oil emulsion and an alpha-tocopherol/sesame oil emulsion. Lymphatic transport of the triglycerides and of alpha-tocopherol was determined. A conscious rat model was used, and the mesenteric lymph was collected. There was no significant difference between the cumulative masses of triglyceride from the two emulsions containing triglyceride 24 h after administration. Administration of an alpha-tocopherol emulsion seemed to induce mobilization of endogenous triglyceride. The lymphatic transport of alpha-tocopherol was less than 1 mg 24 h after administration of both emulsions containing alpha-tocopherol. The absorption of Lu28-179 from the alpha-tocopherol emulsion was very low, with a lymphatic recovery of 0.05%. When administered in an alpha-tocopherol/sesame oil emulsion, the recovery of Lu28-179 increased sevenfold to 0.35%. However, after administration of Lu28-179 in a sesame oil emulsion, the lymphatic recovery increased a further 13-fold to 4.5%. In conclusion, the study showed that alpha-tocopherol did not promote lymphatic absorption of Lu28-179 and thus was not a good lymphotropic carrier, as compared with sesame oil. Alpha-tocopherol in combination with sesame oil was not a good lymphotropic carrier either. The non-absorbed alpha-tocopherol fraction in the intestine might be able to prevent the absorption of Lu28-179.
Twenty-four PCR primer pairs were designed for the detection of porcine microsatellites. Polymorphism was investigated in 76 unrelated animals from four different breeds: Duroc, Landrace, Hampshire, and Yorkshire. Compared with human microsatellites, a general lower heterozygosity was detected; however, for each microsatellite a significant variation between breeds in number of alleles and heterozygosity was seen. Mean heterozygosity was found to be significantly higher (P < 0.01%) in the Yorkshire breed than in the other three breeds. Linkage analyses with the CEPH linkage packet were performed in a backcross family comprising 45 animals, of which 43 had informative meioses. Ten of the microsatellites could be assigned to six different linkage groups, demonstrating that linkage mapping with microsatellites can be carried out with great efficiency in a relatively small number of animals. Four of the linkage groups represent Chromosomes (Chrs) 4, 6, 7, and 8 respectively, while two linkage groups are unassigned.
The present study compared ofloxacin and erythromycin in a double-blind study with parallel groups for clinical efficacy and the number and severity of adverse reactions in patients treated in general practice for acute or chronic sinusitis. All patients lived in medium-sized to large towns and rural districts in the northern and western parts of Sealand, Funen and eastern Jutland, Denmark. Three hundred and nineteen patients were enrolled in the study, of whom 280 were clinically evaluable. From this total number, 136 patients were treated with ofloxacin (31 males and 105 females) and 144 patients were treated with erythromycin (40 males and 104 females). Following administration of either ofloxacin 400 mg once daily or erythromycin 500 mg twice daily for 7-14 days, 94.9% of the ofloxacin-treated group and 94.4% of the erythromycin-treated group were cured of their infections. There was no difference in clinical efficacy. Complications occurred in 18 of 155 patients in the ofloxacin-treated group and 32 of 164 in the erythromycin-treated group (P < 0.05), corresponding to 27 and 45 symptoms respectively (P < 0.01). This difference in adverse reactions principally involved gastrointestinal symptoms, i.e. 19 in the ofloxacin-treated group and 41 in the erythromycin-treated group (P < 0.01). Present findings show that the two antibiotics are comparable as to clinical efficacy, but the frequency of adverse reactions is significantly higher in the erythromycin-treated group due to the greater incidence of gastrointestinal adverse reactions.
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The quality of training given by the security department has a direct impact on the job performances of each security officer. The author discusses how on-the-job training can be a vital part of the training effort when done properly and effectively.
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The public immunization program against diphtheria, established in 1941, has almost eradicated the disease in Denmark, and 1956 became the first year without any notified cases. Since then, toxigenic strains have only been isolated five times--three cases of clinical diphtheria due to Corynebacterium diphtheriae biovar. mitis and two cases of tonsillitis/pharyngitis due to Corynebacterium ulcerans. The source of the infection was not identified in any of the cases. The first case of diphtheria in 1968 was imported from abroad. The following two cases in 1983 and 1985 were due to strains of the same phage type and peptide profile as the strains isolated during the epidemic in Sweden in 1984-1986. This indicates that the Danish cases and the Swedish epidemic derived from the same source. The diphtheria immunity of the Danish population is decreasing, and the level of protection is approaching the Swedish level. The impact is that a situation like that in Sweden may be anticipated with diphtheria epidemic in the lowest socio-economical groups--the skid row dwellers, alcoholics and drug abusers--if the immunization program against diphtheria is not intensified.
A retrospective survey of non-typhoid Salmonella bacteraemia in the period 1984 to 1988 was carried out by the five departments of clinical microbiology in Greater Copenhagen. A total of 168 patients were identified. A gradual increase was observed from 11 cases in 1984 to 58 cases in 1988. The corresponding incidence per 100,000 inhabitants in Copenhagen rose from 0.9 in 1984 to 5.0 in 1988. During the same period the total registered incidence of human Salmonella infections in Denmark increased from 17.6 to 67.4 per 100,000 inhabitants. The serotype most often isolated from bacteraemic patients was Salmonella dublin followed by Salmonella enteritidis and Salmonella typhimurium. Salmonella dublin demonstrated enhanced invasive and pathogenic properties. Predisposing factors were present in 56% of the patients; the most common was malignant disease. A fatal or complicated course of the bacteraemia was observed more frequently in patients with underlying diseases than in persons who had previously been healthy. A total of 17% of the patients died; one-fifth of these had a ruptured aortic aneurysm. It is concluded that the substantial increase in the number of cases and the often serious course taken by the infection demonstrate a need for increased efforts at prophylaxis.
1. Species specific problems complicating the measurement of prorenin and renin concentrations were studied in bovine, hog and horse plasma. 2. In contrast to horse renin, bovine and hog renin reacted with rat angiotensinogen, allowing measurement of the plasma renin concentration in cattle and hog with rat angiotensinogen as exogenous substrate. 3. Trypsin treatment of plasma in order to activate prorenin generated an interfering angiotensin I immunoreactive material in all three species, most extensively in horse plasma. 4. This material could be removed in bovine and hog plasma by a cation-exchange resin, allowing an assay of the plasma prorenin concentration to be constructed in these species. 5. Another strategy has to be followed in order to measure prorenin and renin concentrations in horse plasma.
By means of a new antiserum, Mm, the Mae phenotype can be shown to be controlled by the Maem allele, the Mef phenotype by either the original Mef or a new Mefm allele, and the Mbe(f) phenotype by the Mbe(f)m allele. The complexity of the porcine M system is now extended to 13 internationally recognized blood group factors controlled by at least 19 alleles.
During a 21-month period, 65 consecutive patients admitted with ascites were included in a prospective study of the incidence of spontaneous bacterial peritonitis, and paracentesis was performed on admission. The ascitic fluid was cultured, ascitic leucocytes were counted and pH was measured. Bacterial growth was found in five patients with chronic liver disease, who were diagnosed as having spontaneous bacterial peritonitis (SBP), since no intra-abdominal focus could be demonstrated. Thus, the incidence of SBP in this material was 7.7% (95% confidence limits: 2.5-17%). SBP was caused by Escherichia coli (n = 3), coagulase negative staphylococcus (n = 1), and Bacteroides species (n = 1). Abdominal tenderness, abnormal intestinal sounds, fever and hepatic encephalopathy were equally frequent in the group with SBP and in patients with sterile ascites. Infection was not anticipated in any of the patients with SBP. In contrast to several previous studies, neither ascites pH nor ascites leucocyte counts were any help in obtaining a rapid diagnosis. Survival time of patients with SBP was significantly shorter than of patients without SBP.
The five departments of clinical microbiology in Greater Copenhagen have together carried out a retrospective review of bacteraemia caused by the zoonotic Salmonella serotypes in the period 1984-1988 in the municipalities of Copenhagen and Frederiksberg and in the County of Copenhagen. A gradual increase in frequency was observed from 11 cases in 1984 to 58 cases in 1988. The serotype most commonly isolated was Salmonella dublin followed by Salmonella enteritidis and Salmonella typhimurium. S. dublin was found to be more invasive and more virulent than the other serotypes. Predisposing factors were present in 56% of the patients; the commonest of these was malignant disease. Fatal or complicated course of the disease were observed more frequently in predisposed patients than in persons who had previously been healthy. A total of 17% of the patients died and one fourth of these had ruptured aortic aneurysm probably on account of Salmonella arteritis. 20% developed recurrence of bacteraemia while in the remaining patients the disease ran an uncomplicated course. It is concluded that the marked increase in the number of cases and the serious course taken by the infection demonstrate a definite need for increased prophylactic efforts in the food industry.
Type I allergy directed against Pneumocystis carinii (PC) has been investigated in 14 patients with AIDS. The Pneumocystis carinii pneumonia often shows a rapid and severe course, and type I allergy against the parasite might be a pathogenic co-factor in the interstitial lung inflammation. In twelve of the AIDS patients the clinical symptoms and course of illness indicated a PC pneumonia. The basophil histamine release test was used as a sensitive test to detect type I allergy against PC. Eight of the patients showed significant histamine release when stimulated with PC. In contrast, only two patients in the group of 12 HIV antibody-positive homosexual men and none in the control group of 13 heterosexual men released histamine. The histamine release was mediated by an immunological reaction, since the release was abolished and regained by removal from and refixation to the cell surface of the cell-bound immunoglobulins before the antigen challenge. The results suggest an involvement of type I allergy as a pathogenic co-factor in Pneumocystis carinii pneumonia.
An ELISA to measure Pneumocystis carinii-specific IgG, IgM, and IgA has been developed. The antigen was prepared from purified cysts by sonication and ultracentrifugation. Antigen particles with sedimentation coefficients less than 165 S were used. The technique has been compared with indirect immunofluorescence, using whole cysts as antigen. Ninety human sera were assayed. The results were significantly correlated. The ELISA-technique was more sensitive, and owing to the soluble antigen the daily variation was less than 1 per cent. The technique is useful for quick and reliable detection of Pneumocystis carinii antibodies in a routine laboratory.
The titers of IgG and IgA to Pneumocystis carinii in 36 AIDS patients did not differ significantly from those in 31 controls. Only 2/15 patients (13%) with P. carinii pneumonia (PCP) had titers of IgM antibodies greater than or equal to 5, which is significantly less frequent than in 32 controls (62%) and in 21 AIDS patients without PCP (43%). The risk of PCP was 5 times higher in patients without IgM antibodies to P. carinii than in patients who had these antibodies. A significantly higher percentage of those without PCP (57%) showed increasing titers of IgM antibodies to P. carinii in the second of paired samples taken about 6 months apart, compared with whose with PCP (9%; p = 0.05). All patients had high titers of antibodies to CMV and HSV and normal total concentrations of immunoglobulins. None of the patients responded in lymphocyte transformation to P. carinii, CMV, or HSV antigens. There is no obvious explanation to the selective lack of IgM antibodies to P. carinii in patients with PCP. Lack of IgM antibodies may be a marker for an immunodeficiency to P. carinii.
To identify factors that may predict the development of the acquired immune deficiency syndrome (AIDS) or AIDS related symptoms various immunological measurements were studied in a group of homosexual men attending screening clinics for AIDS in Copenhagen. Fifty seven men whose ratio of T helper lymphocytes to T suppressor lymphocytes (CD4:CD8 ratio) was less than 1.0 before the study began were included. Forty two were positive for antibody to the human immunodeficiency virus (HIV), of whom 38 were reinvestigated after a median observation period of 10 months. Among the seropositive men the transformation responses to pokeweed mitogen and cytomegalovirus and the absolute count of CD4 positive lymphocytes were the most common abnormal values. In particular, a low relative response to pokeweed mitogen on initial investigation correlated with a worsened clinical condition on reinvestigation. The risk of a worsened clinical condition was 55 times higher in seropositive men whose responses to pokeweed mitogen were low than in other seropositive men. The corresponding relative risks for low transformation responses to cytomegalovirus and for a decreased absolute count of CD4 positive lymphocytes were 18 and six. The relative response to pokeweed mitogen is therefore a very sensitive short term predictive marker of the clinical condition of seropositive patients who have a CD4:CD8 ratio of less than 1.0.