Inactivation of diaminopyrimidines and sulfonamides in Barbour-Stoenner-Kelly medium for isolation of Borrelia burgdorferi.
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Anti-Bacterial Agents↗
Biomedical subjects
R Gasser
Publications and source records attributed to R Gasser.
Roxithromycin in the treatment of Lyme disease--update and perspectives.
Spirochaetal infections have been successfully treated with penicillin; more recently, erythromycin has been used in cases with known penicillin allergy. The discovery of the spirochaete Borrelia burgdorferi and the elaboration of a new generation of macrolides with properties that differ from older macrolides have led to new ways of treating spirochaetal disease with these compounds. This paper presents data on the in vitro and in vivo efficacy of a combination of roxithromycin and co-trimoxazole against B. burgdorferi. In vitro (checkerboard technique; B. burgdorferi strain B31; modified BSK II medium) it was found that while roxithromycin showed excellent efficacy against B. burgdorferi (MIC 0.031 mg/l), co-trimoxazole had no effect. However, the combination of both chemotherapeutics led to a minor synergistic effect, decreasing the MIC for roxithromycin by one dilution step at concentrations of co-trimoxazole from 256 to 8 mg/l. In addition, a clearly reduced growth of microorganisms was seen at concentrations of roxithromycin as low as 0.015 mg/l in combination with 256 to 4 mg/l co-trimoxazole, when compared to the positive controls. Most interestingly, however, the motility of B. burgdorferi was markedly reduced even when the two drugs were combined at very low concentrations. In an in vivo, non-randomised, open, prospective pilot study it was found that of 17 patients with confirmed late Lyme borreliosis (stage II/III), treated with combined roxithromycin (300 mg b.i.d.) and co-trimoxazole for 5 weeks, 13 (76%) recovered completely by the end of treatment, and four continued to have symptoms on follow-up at 6 and 12 months. This success rate is similar to that seen with i.v. penicillin and ceftriaxone. It appears that the reduced motility of B. burgdorferi makes the pathogen more accessible to the immune system.
Administration, Oral↗
Transvaginal sacrospinous colpopexy: anatomic landmarks to be aware of to minimize complications.
Transvaginal sacrospinous colpopexy is currently used to repair varying degrees of vaginal vault prolapse. It involves placing a stitch from the vaginal cuff to the sacrospinous ligament approximately 2 cm medial to the ischial spine to correct the defect. This may be associated with pudendal artery and nerve (pudendal complex) along with sciatic nerve injury if the procedure is not carefully performed. This study was designed to emphasize the anatomic landmarks that make the sacrospinous ligament a potentially dangerous zone that surgeons must be aware of to minimize complications. Twenty-four female cadavers were obtained from the Louisiana State University Medical School anatomy laboratory. They were carefully dissected to expose the anatomic structures of interest. The following measurements were then obtained: the distance from the ischial spine to the medial border of the sacrum, the medial and lateral aspects of the pudendal complex, and the sciatic nerve. The obstetric conjugate of the pelves was also obtained. The pudendal complex and sciatic nerve were found to be 0.90 to 3.30 cm medial to the ischial spine. After the six smallest and largest pelves were compared, it was noted that the larger the obstetric conjugate the longer the sacrospinous ligament and vice versa. Also, the distance from the ischial spine to the sciatic nerve correlated with the size of the obstetric conjugate. The pudendal complex and sciatic nerve travel underneath the lateral third of the sacrospinous ligament. Therefore we recommend that the placement of the stitch be made medial to that portion of the ligament. More importantly, the stitch must be placed as superficial as possible and never across the entire thickness of the sacropinous ligament. This should decrease the rate of complications associated with this type of colpopexy.
Cadaver↗
[Coronary aneurysm in a 69-year-old patient. Transthoracic echocardiography].
This case report is on a 69-year old male patient treated with cephalosporins because of suspected myocarditis due to borreliosis. Using transthoracic echocardiography a big aneurysm of the proximal part of the left coronary artery was detected. Coronary angiography revealed an aneurysm 1.2 cm in diameter at the origin of the left anterior descending branch and confirmed the initial diagnosis. In addition, coronary three-vessel disease with reduced left ventricular function was found. Coronaritis due to Lyme borreliosis could not be ruled out with certainty. The patient was relatively asymptomatic, and hence conservative therapy was recommended. The case described here serves as a basis for a discussion on the aetiology, clinical manifestation, diagnosis and therapeutic management of coronary aneurysms.
Aged↗
Effects of treadmill exercise protocol with constant and ascending grade on levelling-off O2 uptake and VO2 max.
In order to investigate the effect of an exercise protocol on the levelling-off O2 uptake and VO2 max values, ten male subjects aged 28 +/- 5 yrs, height 1.8 +/- 0.05 m, body mass 76 +/- 6 kg performed two treadmill exercise protocols: 1) constant grade (CG) of 5%, with increasing running speed starting at 6 km.h-1 and increments of 2 km.h-1 every 3 minutes. 2) ascending grade (AG) starting at 0% and increments of 5% every 3 minutes, with constant running speed of 5 km.h-1. During each protocol oxygen uptake (VO2), pulmonary ventilation (VE), tidal volume (Vt), and breathing rate (BR) as well as blood lactate concentration (La) and heart rate (HR) were measured. In CG a levelling-off phenomenon of VO2 in all cases was observed. Aerobic capacity expressed as VO2 max in CG was 46.2 +/- 6.0 ml.min-1.kg-1. In contrast, VO2 max was 35% higher in AG (62.6 +/- 7.2 ml.min-1.kg-1). The behaviour of VO2 indicates a lower efficiency with increasing work load in AG as compared to CG. Regarding maximum performance it can be concluded that VO2 in CG seems to be limited by a mechanical or neuromuscular constraint on the depth of breathing, which is confirmed by a distinct flattening of Vt. The levelling-off of the VO2 in CG, something which is not observed in AG, can be explained plausibly this way.
Adult↗
Cases of Lyme borreliosis resistant to conventional treatment: improved symptoms with cephalosporin plus specific beta-lactamase inhibition.
We present four cases of verified late Lyme borreliosis with persistent symptoms and positive serology despite repeated courses of high-dose intravenous penicillin G and/or cephalosporins (including cefoperazone). The patients were now treated with cefoperazone 2 g plus sulbactam 1 g bid iv for 14 days. At the end of treatment, patients were symptom free and have remained so for the following 12 months. By then, IgG against Borrelia burgdorferi had decreased. It is concluded that the addition of beta-lactamase inhibitors to intravenous treatment could be beneficial in Lyme disease refractory to conventional treatment.
Cefoperazone↗
Changes in thyroid hormone parameters after acute myocardial infarction.
Abnormalities in circulating thyroid hormone levels are very common in systemic nonthyroidal illnesses, such as acute myocardial infarction. In this study, thyroid parameters were determined in a series of 16 consecutive infarction patients treated by thrombolysis. Blood samples were taken before therapy as well as 2, 4, 6, 8, 12 and 72 h following admission. Total and free serum thyroxin and triiodothyronine decreased and reverse T3 increased significantly showing no major variations up to 72 h, whereas thyroid-stimulating hormone values remained almost unchanged during the observation period. Subjects with CK-MB levels of more than 150 ng/ml (n = 10) revealed similar changes in thyroid parameters in comparison to those with lower values (n = 6; NS). Thus, although hormone modifications very often occur following acute infarction, thyroid status may not serve as a marker for the extent of left ventricular dysfunction in the early phase of myocardial infarction.
Aged↗
[Hypertension and hemorheology].
A number of epidemiologic studies have provided evidence for an increased blood viscosity in hypertensive patients. Increased viscosity could result either from hemoconcentration, thus constituting a secondary phenomenon, or, alternatively, result directly from increased intracellular calcium concentrations in erythrocytes. The latter would augment the aggregating potential of these cellular blood compounds. This currently hypothetic view remains to be elucidated. Enhanced viscosity, however, may result in increased peripheral resistance and lead to hypertensive complications. The evaluation of antihypertensive therapy should therefore take possible effects upon blood viscosity into account.
Antihypertensive Agents↗
[Recent molecular and pharmacologic aspects of ACE inhibitors].
ACE-Inhibitors are well established in the treatment of hypertension and heart failure. Other indications, that are under discussion, are coronary artery disease, renal failure and diabetes mellitus. The mechanism of action of ACE-Inhibitors is not only the reduction of angiotensin II and accumulation of bradykinin but also an increase of the action potential of the heart muscle, increase in glucose uptake in skeletal muscle, inhibition of platelet aggregation and opening of the K-ATP-channels.
Angiotensin II↗
Cyclic phenomena in early myocardial infarction.
It has been shown by a number of authors that early myocardial infarction constitutes a dynamic process of cyclic oscillation between coronary occlusion and spontaneous coronary reopening. Infarct-markers, such as ST-segment elevation, serum-creatine kinase isoenzyme MB, the atrionatriuretic peptide (ANP) and serum-myoglobin (Mb) exhibit cyclic behaviour pattern during early AMI and thus reflect episodes of intermittent, spontaneous reperfusion. The latter have recently been verified by angiography. The mechanism underlying the phenomena seen in early myocardial infarction is likely to be based on a constant vasoconstrictive stimulus, deriving from aggregating platelets. The vasoconstriction subsequent to platelet aggregation produces an initial episode of myocardial ischemia. This episode is followed by a hypoxia of the artery wall. Reactive coronary dilation secondary to ischemia is than promoted by the release of vasoactive by-products of anaerobic glycolysis as well as changes in the open propability of certain transmembrane ion channels. Thereafter, the initial coronary occlusion is interrupted by transient vasodilation. A wave of reperfusion follows and leads to reoxygenation and wash-out of ischemia-induced vasodilative components as well as biochemical markers. The vasoconstrictive forces then take over again. This results in repeated waves of reperfusion. A number of arguments in favour of this concepts are discussed in this paper.
Atrial Natriuretic Factor↗
Coronary artery aneurysm in two patients with long-standing Lyme borreliosis. Borreliosis Study Group.
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Aged↗
Human liver arylacetamide deacetylase. Molecular cloning of a novel esterase involved in the metabolic activation of arylamine carcinogens with high sequence similarity to hormone-sensitive lipase.
Microsomal arylacetamide deacetylase (DAC) competes against the activity of cytosolic arylamine N-acetyltransferase, which catalyzes one of the initial biotransformation pathways for arylamine and heterocyclic amine carcinogens in many species and tissues. Activity determination and immunoblot analysis of DAC in human target tissues for arylamine carcinogens revealed that in extrahepatic tissues, additional enzymes are responsible for any deacetylation activity, whereas a single enzyme predominantly catalyzes this hydrolytic reaction in liver. We isolated and characterized a full-length cDNA from a human liver lambda gt11 library. This clone encodes an open reading frame of 400 amino acids with a deduced molecular mass of 45.7 kDa and contains two putative glycosylation sites. The 3'-untranslated region contains two putative polyadenylation signals. The cDNA was confirmed to be that for DAC in tryptic peptides from the purified human liver protein. Highest sequence similarity of DAC was found in a series of prokaryotic esterases encompassing the putative active site. Two extended regions of significant sequence homology with hormone-sensitive lipase and with lipase 2 from Moraxella TA144 were identified, whereas similarity to carboxyl esterases was restricted to the region encompassing the putative active site, indicating that DAC should be classified as esterase. This cDNA provides an important tool to study deacetylation and its effects on the metabolic activation of arylamine and heterocyclic amine carcinogens.
2-Acetylaminofluorene↗
Relationship of initial chorionic sac diameter to abortion and abortus karyotype based on new growth curves for the 16th to 49th post-ovulation day.
In order to determine whether initial chorionic sac diameter is related to subsequent abortion, abortus karyotype, or birth weight and length, chorionic sac diameter was prospectively measured by transvaginal ultrasound in 700 singleton pregnancies before post-ovulation day 31, the latest day cardiac activity becomes detectable in normal pregnancy. Results were compared to values for the 10th to the 90th centiles, determined from 227 measurements of in-vitro fertilization and gamete intra-Fallopian transfer pregnancies. The abortion rate was 23.9% [95% confidence interval (CI) 19.2%, 28.6%] when initial chorionic sac diameter was below the 50th centile, compared to 6.9% (95% CI 4.9%, 9.4%) when equal to or above the 50th centile. Chorionic sac diameter was below the 50th centile in all anembryonic abortions and in 62% of embryonic abortions. Triploidy, trisomy 47 + 16, or trisomy 16 and the presence of satellite bodies on chromosome 22 were the only abortus karyotypes significantly associated with small chorionic sac diameter. Initial chorionic sac diameter was not associated with birth weight or length. We conclude that chorionic sac diameter is decreased in anembryonic and embryonic abortion and that normal pregnancy outcome may be expected in 90-95% of pregnancies in which initial chorionic sac diameter is equal to or above average.
Abortion, Spontaneous↗
Species-specific expression of CYP4B1 in rabbit and human gastrointestinal tissues.
CYP4B1 is a P450 enzyme displaying tissue and species specific regulation. The rabbit CYP4B1 enzyme exhibits activity towards procarcinogenic aromatic amines. In the present study, CYP4B1 expression has been characterized in rabbit tissues using histological techniques, Northern blotting and Western blotting. Similar analyses were attempted using available human tissues. CYP4B1 mRNA and protein was demonstrated throughout the rabbit small intestine and colon. A unique 1.8 kb transcript, that is smaller than the transcript found in other tissues, was detected in rabbit stomach with a CYP4B1 specific RNA probe. No CYP4B1 protein was detected in this tissue. In rabbit liver, CYP4B1 was induced by phenobarbital primarily in zone 1 hepatocytes (periportal). In humans, CYP4B1 expression was demonstrated at low levels in human colon using in situ hybridization but not in liver or the small intestine. All rabbit gastrointestinal tissues other than stomach possess a high capacity for the activation of 2-aminofluorene compatible with CYP4B1 expression. In contrast, no activity was observed in human gastrointestinal microsomes. The present study therefore shows that CYP4B1 is an abundant P450 in the rabbit gastrointestinal tract and identifies species-specific differences in CYP4B1 expression and function.
Animals↗
A most unusual case of a whole family suffering from late Lyme borreliosis for over 20 years.
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Aged↗
Ophthalmic manifestations in Lyme borreliosis. A review.
Lyme borreliosis is an emerging tick-borne spirochetal infection characterized by a broad variety of symptoms, ranging from neurologic disorders and different skin manifestations to cardiac symptoms. Many ocular and neuro-ophthalmic symptoms have recently been attributed to Lyme disease. Especially in endemic areas ophthalmologists need to be aware of Borrelia burgdorferi as a possible causal agent. The aim of this paper is to present a short review of the literature of ophthalmic disorders resulting from Borrelia burgdorferi infections.
Eye Infections, Bacterial↗
[First aid measures by lay persons in cardiovascular arrest].
The efficiency of first aid resuscitation is affirmed by many publications. In a questionnaire of the division of Cardiology of the Department of Internal Medicine, Graz and the Styrian Heart Patient Society distributed during the course of the Graz spring fair 1993 the population was approached as to first aid in cardiac arrest. 550 subjects responded to answer this circular for assessment dividing the population statistically in 4 different age groups showing differences among male and female and country and city dwellers. It has been shown that general first aid resuscitation has been known sufficiently, whereas special cardiorespiratory procedures (such as artificial respiration or cardiac massage) were unknown to most.
Adolescent↗
Site-directed mutation studies of human liver cytochrome P-450 isoenzymes in the CYP2C subfamily.
Evidence from human studies in vivo and in vitro strongly suggests that the methylhydroxylation of tolbutamide and the 4-hydroxylation of phenytoin, the major pathways in the elimination of these two drugs, are catalysed by the same cytochrome P-450 isoenzyme(s). In the present study we used site-directed mutagenesis and cDNA expression in COS cells to characterize in detail the kinetics of tolbutamide and phenytoin hydroxylations by seven CYP2C proteins (2C8, 2C9 and variants, and 2C10) in order to define the effects of small changes in amino acid sequences and the likely proteins responsible in the metabolism of these two drugs in man. Tolbutamide was hydroxylated to varying extents by all expressed cytochrome P-450 isoenzymes, although activity was much lower for the expressed 2C8 protein. While the apparent Km values for the 2C9/10 isoenzymes (71.6-131.7 microM) were comparable with the range of apparent Km values previously observed in human liver microsomes, the apparent Km for 2C8 (650.5 microM) was appreciably higher. The 2C8 enzyme also showed quite different sulphaphenazole inhibition characteristics. The 4-hydroxylation of phenytoin was also more efficiently catalysed by the 2C9/10 enzymes. These enzymes showed similarities in kinetics of phenytoin hydroxylation and sulphaphenazole inhibition compared with human liver phenytoin hydroxylase. Also of interest was the observation that, among the 2C9 variants, small differences in amino acid composition could appreciably affect both tolbutamide and phenytoin hydroxylations. The amino acid substitution Cys-144-->Arg increased both the rates of tolbutamide and phenytoin hydroxylations, while the Leu-359-->Ile change had a greater effect on phenytoin hydroxylation. We conclude that: (1) although 2C8 and 2C9/10 proteins metabolize tolbutamide. only 2C9/10 proteins play a major role in human liver; (2) 2C9/10 proteins also appear to be chiefly responsible for phenytoin hydroxylation; and (3) subtle differences in the amino acid composition of these 2C9/10 proteins can affect the functional specificities towards both tolbutamide and phenytoin.
Amino Acid Sequence↗