MRI gadolinium enhancement of bone marrow: age-related changes in normals and in diffuse neoplastic infiltration

 Objective: To quantify gadolinium-related enhancement in the bone marrow of the spine in normals and in patients with homogeneous diffuse malignant bone marrow infiltration. Design and patients: The patients consisted of two groups: group 1 comprised 94 healthy adults (18–86 years) without bone marrow disease and group 2 comprised 30 patients with homogeneous diffuse malignant bone marrow infiltration due to myeloma (n=20) or breast carcinoma (n=10). All patients received intravenous gadopentetate dimeglumine (Gd-DTPA), 0.1 mmol/kg body weight. Pre- and postcontrast signal intensity (SI) on T1-weighted spin-echo (SE) images (TR/TE: 572 ms/15 ms) was measured over a region of interest (ROI) and the percentage SI increase was calculated. The results were confirmed by bone marrow biopsy (n=20) and clinical parameters (n=10). Dynamic contrast-enhanced studies using a spoiled gradient-recalled-echo (GRE) sequence (TR/TE/α: 68 ms/6 ms 75°) were performed in 10 controls with normal bone marrow. Results and conclusion: Contrast material enhancement in healthy persons can vary greatly (range 3–59%, mean 21%, SD 11%). With increasing age there is a significant decrease in contrast enhancement (Pearson’s correlation, P<0.01). The percentage SI increase in patients with intermediate-grade (biopsy 20–50 vol%) and high-grade (biopsy >50 vol%) diffuse malignant bone marrow infiltration was significantly higher than in normals (mean 67%, SD 34%, P<0.001). Low-grade (biopsy <20 vol%) diffuse malignant bone marrow infiltration can not be assessed by non-enhanced T1-weighted SE images or Gd-DTPA application. In conclusion, contrast material enhancement in healthy persons can vary greatly and is dependent on age, while intermediate-grade and high-grade diffuse malignant bone marrow infiltration can be objectively assessed with SI measurements.     

Natürliche Familienplanung

The symptothermal method (STM) is the most effective method of natural family planning, if two parameters to determine the beginning as well as the end of the fertile phase are used (double-check). The main parameters observed by women are BBT and cervical mucus changes. The method-effectiveness is 0.3–0.5 pregnancies per 100 women years, if there is no unprotected intercourse in the self-detected fertile phase. The use-effectiveness is about 2 in Germany. These results are derived from large European databases. In developed countries, the STM replaces the old calendar and temperature methods and the Billings method.     

Zur Eliminationskinetik des Digoxin vor und während Spironolactonbehandlung

Zusammenfassung Im Tierversuch konnte unter hohen Spironolactondosen eine Beschleunigung der Digoxinelimination nachgewiesen werden, die auf eine vermehrte Metabolisierung des Digoxins nach Induktion mikrosomaler Leberenzyme zurückgeführt wurde. Deshalb wurde bei 8 Patienten die Eliminationskinetik des Digoxins vor Spironolactonbehandlung untersucht, wobei morgens nüchtern 0,1 mg³H-Digoxin intravenös als einmalige Dosis verabreicht wurde. Zur Messung der Digoxinkonzentration wurden venöse Blutproben zu bestimmten Zitpunkten bis zu 120 h entnommen, der Urin fraktioniert 5 Tage lang gesammelt. Zusätzlich wurde während der gesamten Versuchsperiode die im Stuhl ausgeschiedene Digoxinmenge bestimmt. Während der Messung der Digoxinelimination wurden gleichzeitig nicht-invasive Parameter des mikrosomalen Leberenzymsystems wie Antipyrinhalbwertszeit, Antipyrinclearance, Gamma-Glutamyl-transpeptidase im Blut und d-Glucarsäureausscheidung im 24 h-Urin gemessen. Danach wurde jedem Patienten 15 Tage lang eine therapeutische Erhaltungsdosis von 150 mg Spironolacton täglich verabreicht. 10 Tage nach Beginn der Spironolactonbehandlung wurde die oben beschriebene Untersuchung der Digoxinelimination zusammen mit den Parametern des mikrosomalen Leberenzymsystems wiederholt.Aufgrund der errechneten pharmakokinetischen Parameter ließen sich unter Spironolactonbehandlung keine Änderungen der globalen Eliminationskonstante respektive der Halbwertszeit des Digoxins nachweisen. Ebenso blieb das Verteilungsvolumen, die renale und metabolische Clearance unbeeinflußt, die Digoxinausscheidung im Faeces war während beiden Versuchsperioden nicht signifikant verschieden und betrug für die gemessene Zeitperiode etwa 15% der verabreichten Dosis. Außerdem zeigten die Parameter des mikrosomalen Enzymsystems der Leber keinerlei Änderungen vor und unter Spironolactonbehandlung. Aufgrund dieser Ergebnisse konnte unter den klinisch üblichen Spironolactondosen keine Veränderung der Digoxinelimination nachgewiesen und eine Enzyminduktion sicher ausgeschlossen werden. Deshalb sind die in der Literatur berichteten Änderungen der Digoxinausscheidung auf eine zu hohe Dosierung im Tierversuch zurückzuführen und haben für den Menschen keine therapeutische Bedeutung.Herrn Prof. Dr. E. Bauereisen zum 65. Geburtstag in Dankbarkeit gewidmet     

Mitochondrial DNA sequences reveal close relationships between social parasitic ants and their host species

In the tribe Leptothoracini, the phylogenetic relationship of socially parasitic ants (Doronomyrmex kutteri, D. goesswaldi and Harpagoxenus sublaevis) and their host species Leptothorax acervorum has been controversial. Even more controversial is the relationship between the socially parasitic ant Chalepoxenus muellerianus and its host species Leptothorax unifasciatus, L. nigriceps, L. interruptus and L. recedens. On the basis of morphological, ecological and ethological criteria it has been argued that socially parasitic ants and their respective hosts always evolved from common ancestors, and hence it has been postulated that these species should be included in common taxonomical groups. This would require the division of the tribe Leptothoracini into two subgroups, one comprising the subgenus Leptothorax (s. str.) and the other the subgenus Myrafant, together with their respective parasitic genera. We have used the polymerase chain reaction (PCR) to compare a 360-bp sequence of the mitochondrial cytochrome b gene of 14 species belonging to the tribe Leptothoracini and an outgroup species Tetranorium impurum (Tetramoriini). The results generally agree with the morphological studies which suggest that a common ancestral species differentiated into host and parasite species. This relationship is very obvious within the Leptothorax (s. str.) group but less pronounced in the species belonging to the Myrafant group. Leptothorax (Temnothorax) recedens shows a greater sequence divergence than the outgroup species T. impurum.     

Antibody- and complement-mediated lysis of HIV-infected cells and inhibition of viral replication

HIV-1-positive antisera were tested for their ability to lyse HIV-1-infected cells in the presence of active complement. Cytolytic effects caused by sera derived from infected humans were slower than those observed with sera from immunised chimpanzees. Lytic but also negative sera were found among HIV-1-infected asymptomatic men as well as among clinical AIDS cases. Human antisera that lysed infected cells reacted similarly irrespective of whether the complement was heterologous or autologous. Analysis of complement-mediated lysis using defined antisera against recombinant HIV-1 env or core antigens suggested that gp160/gp120 and p24 can act as target antigens for an antibody- and complement-mediated cytolysis of infected cells. Complement alone reduced the spread of HIV-1 infection in CD4+ cells and the ability of HIV-1 and HIV-2 to form plaques in CD4-transfected HeLa cells. Co-operative effects of specific antibodies and complement were the most effective in inhibiting HIV infections.     

RECOMBINATION FRACTIONS IN THE HLA SYSTEM BASED ON THE DATA SET ‘PROVINCES FRANÇAISES’: INDICATIONS OF HAPLOTYPE-SPECIFIC RECOMBINATION RATES

In the large genetic survey ‘Provinces Françaises’ the recombination fractions in the HLA system have been estimated by a family analysis programme (FAP). A total of 1332 families were analysed and in general the findings were in agreement with recombination fractions reported previously. The maternal recombination rates were on average 1.8 times higher than the corresponding ones for males. The comparison of the recombination fractions with the corresponding physical distances suggests the existence of hot spots of recombination. The analysis did not show deviations from expected values for HLA-A and B alleles on HLA-A/B recombinant haplotypes. However, analysis of HLA-B/DR recombinant haplotypes showed a skewed distribution of B and DR alleles. The significance of the findings is difficult to evaluate as all results are estimated numbers and frequencies but a manual analysis of the recombinant families confirmed the observations. HLA-B/DR recombinant haplotypes carried often HLA-DR3 and DR11 whereas DR2 and DR7 were more rarely present on recombinant haplotypes. DR4 had an increased incidence on BF/DR recombinant haplotypes but not on A/B or B/BF recombinant haplotypes. Some of the haplotypes with the strongest linkage disequilibria as A1, B8, DR3 and A3, B7, DR2 seem to be less frequently involved in recombinations than other haplotypes. Variations of recombination rates depending on certain alleles or haplotypes might partially explain the conservation of some haplotypes or part of haplotypes in Caucasoids.     

Ciprofloxacin in the treatment of acute exacerbations of chronic bronchitis

Eighty hospital patients with acute purulent exacerbations of chronic bronchitis associated withHaemophilus influenzae, Streptococcus pneumoniae, Branhamella catarrhalis orPseudomonas aeruginosa were treated with ciprofloxacin. The patients were divided into four groups of 20 patients each and administered either 500 mg, 750 mg (two different batches of tablets) or 1000 mg twice daily for ten days. Most of the patients withHaemophilus influenzae andBranhamella catarrhalis infections were treated successfully but the results in patients withStreptococcus pneumoniae andPseudomonas aeruginosa infections were less satisfactory. Although the ciprofloxacin MICs for the latter organisms were relatively low, mean serum and sputum concentrations measured on the first day of treatment did not exceed 2–3 mg/l and 1–2.3 mg/l respectively. The overall clinical results for all dosage regimes were only fair, mainly due to failure to eradicateStreptococcus pneumoniae andPseudomonas aeruginosa. Adverse effects (nausea, stomach pain or hallucinations) were seen in eight patients, causing treatment to be discobtinued in five. It is concluded that ciprofloxacin is only of limited use in the treatment of respiratory tract infections unlessStreptococcus pneumoniae is absent.