Biomedical subjects
Publications and source records attributed to M Neuman.
Presented is a case of pneumococcal peritonitis in the presence of an IUD. The bacteriological identification was made by culturing material obtained via culdocentesis on admission. Treatment was conservative. The English literature is reviewed.
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The effect of total abdominal hysterectomy as treatment for benign conditions on the postoperative incidence of urinary symptoms and abnormal urodynamic findings was evaluated in 16 premenopausal women who lacked urinary symptoms preoperatively. The urodynamic evaluation was performed preoperatively, at 4 weeks, and again at 4 months after surgery. No clinical symptoms of frequency, nocturia, urgency, or urge or stress incontinence were found postoperatively. There were no significant differences from the preoperative values for cystometry, uroflometry, and urethral pressure profiles. Urinary dysfunction should not be a consequence of an uncomplicated total abdominal hysterectomy for benign conditions in women who were previously free of urinary symptoms.
A 27-year-old, previously healthy normotensive woman was admitted for hyperemesis gravidarum and treated with intravenous fluids and metoclopramide. Thereafter, a neuropsychiatric syndrome developed, with acute asymmetrical axonal motor-sensory polyneuropathy and marked anxiety, depression, irritability, and memory and concentration difficulties. Raised porphyrin precursors were found in the patient's urine, but not in her feces. Although the association of acute porphyria and pregnancy is rare, the pregnancy itself, combined with a state of starvation, and the administration of metoclopramide, could have precipitated the acute attack in this case. Thiamine deficiency, Guillain-Barré syndrome, and an obstetric complication producing closely related symptoms were excluded. The drug was stopped and the patient was treated with a high-carbohydrate diet and physiotherapy. A normal infant was delivered spontaneously at term.
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Ventricular antiarrhythmic therapy is aimed traditionally at preventing arrhythmias and ventricular fibrillation. Recently, a new approach has been introduced, where drug therapy facilitates the ability of the heart for spontaneous defibrillation. The chemical features and the electrophysiologic properties are discussed below. The introduction of this new group of defibrillating antiarrhythmic drugs implies the extension of the common classification of antiarrhythmic drugs.
A 16-year-old patient with Behçet's syndrome had massive hemoptysis due to a ruptured aneurysm of a segmental artery of the left lung. Emergency left lower lobectomy was performed. The patient is well 12 months after operation. There have been no further episodes of hemoptysis.
The effect of concomitant hysterectomy during colposuspension on the cure rate of genuine stress incontinence was evaluated prospectively in 45 patients. Twenty-two women underwent a colposuspension only (no-hysterectomy group) and 23 had a concomitant abdominal hysterectomy and cul-de-sac obliteration (hysterectomy group). Twenty-five months postoperatively, no differences were found in the cure rate for urinary stress incontinence between the two groups (95.5 and 95.7% for the no-hysterectomy and the hysterectomy group, respectively). In the no-hysterectomy group, three patients (13.6%) had enterocele formation after surgery; this complication did not occur in any of the patients in the hysterectomy group.
Structural modification of the so-called 'first-generation' or 'urinary' quinolones has led to a considerable increase in their intrinsic antibacterial activity, together with marked changes in the pharmacokinetic properties. Tissue penetration is the most notable change, and the newer quinolones are comparable with the newer broad spectrum beta-lactams in their clinical spectrum of activity. Marketed compounds in the 4-quinolones group include pefloxacin, ofloxacin, enoxacin, ciprofloxacin and norfloxacin; many more compounds are in various stages of research and development. The 4-quinolones act by inhibition of bacterial DNA gyrase, a process which is pH and concentration dependent. The bactericidal activity can be partly abolished if protein synthesis is inhibited by chloramphenicol, or if RNA synthesis is inhibited by rifampicin (rifampin). The antibacterial spectrum of activity includes methicillin- and gentamicin-resistant staphylococci, multiresistant non-fermenters, all Enterobacteriaceae, Legionella, Neisseria species, Branhamella and Haemophilus influenzae. With the exception of norfloxacin, which is only 30 to 40% bioavailable from the oral route, the 4-quinolones are 80 to 100% bioavailable, absorption occurring within 1 to 3 hours. Food does not significantly alter Cmax, AUC or elimination half-life, although tmax, may be increased. The 4-quinolones are widely distributed throughout the body, with volumes of distribution greater than 1.5 L/kg. Protein binding is less than 30% in most cases. Penetration into most tissues is good. With the exception of ofloxacin and lomefloxacin (NY 198), which are metabolically stable, metabolism of the 4-quinolones occurs primarily at the C7 position in the piperazinyl ring. Biotransformation is extensive (85%) with pefloxacin, medium (25 to 40%) with ciprofloxacin and enoxacin, and low (less than 20%) with norfloxacin. Elimination half-lives vary between 3 and 5 hours (ciprofloxacin) and 8 to 14 hours (pefloxacin). Biliary concentrations of the 4-quinolones are 2 to 10 times greater than those in serum or plasma, with several compounds undergoing enterohepatic circulation. There is some evidence that ciprofloxacin, norfloxacin, ofloxacin and enoxacin have an active renal tubular excretion pathway. In impaired renal function, reduction of the glomerular filtration rate below 30 ml/min (1.8 L/h) is associated with an increase in elimination half-life and AUC, and a decrease in renal and total clearance of the 4-quinolones, and a decrease in 24-hour urinary recovery.(ABSTRACT TRUNCATED AT 400 WORDS)
The gaps in the present piperazinyl-substituted fluoroquinolones include: (a) gaps in their antibacterial spectrum, varying from one fluoroquinolone to another for streptococci-pneumococci-enterococci (SPE), some Gram-negative and Gram-positive anaerobes, Nocardia, Pseudomonas maltophilia, Ureaplasma urealyticum, slow-growing mycobacteria; (b) a pH dependence of their antibacterial activity (low activity at acidic pH for piperazinyl-substituted fluoroquinolones); (c) a rapid development of bacterial resistance for some bacteria (staphylococci, pseudomonas) in prolonged treatment of cystic fibrosis, intensive care units; (d) some gaps in the pharmacokinetic parameters such as incomplete oral bioavailability, short half-life, intensive biotransformation, unwanted interactions with other antibiotics or other drugs. The prospects for fluoroquinolones are trying to eliminate these gaps. The 7-piperazinyl or pyrrolidinyl, 1-cyclopropylfluoroquinolones have improved activity on SPE, anaerobes and pseudomonas-acinetobacter. Two categories can be distinguished: (i) with increased activity on SPE, but keeping also the activity on pseudomonas (A-62824, A-62254, A-65846, A-60969, AT-3295, AT-3765); (ii) with increased activity on SPE but with a loss of activity on pseudomonas (CI-934, PD-117558, S-25932). The pharmacokinetic parameters are modified by the N-methylation of the piperazine ring (bioavailability), modification of the hydrophilic or lipophilic character, conditioning half-life, metabolic biotransformation, diffusibility into the spinal fluid, crossing the blood-brain barrier, tubular reabsorption and neuropsychic adverse effects.
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Previously, it has been shown that following occlusion of the left anterior descending artery (LAD) in cats, i.v. administration of tricyclic antidepressants (TCAD) significantly decreases the incidence of ventricular fibrillation (VF), which terminates spontaneously upon appearance. Furthermore, this treatment significantly decreases the size of the unperfused ventricular muscle (ischemic myocardium) from 44%-84% (mean 61%) to 17%-56% (mean 34%). This latter effect was demonstrated by using color demarcation of the perfused myocardium with the injection of a dye into the left atrium after 2 h of LAD occlusion in both control and treated cats. It was assumed that reduction of the unperfused area was due to an increase of collateral blood supply to the ischemic area. Although the beneficial effect of TCAD on the collateral blood supply has been clearly demonstrated in cats randomly assigned to two groups, the present study was designed to investigate the changes in the size of the ischemic area in the same animal by using two different dyes. Both dyes were injected into the left auricle after the LAD occlusion: The first was injected before the TCAD treatment and the second after the treatment. Two days after fixation in 4% formaldehyde, the hearts were sliced into three or four transverse sections. Examination of the sections indicated that there were three types of myocardial markings: (a) totally unperfused myocardium; (b) an area perfused by both colors; (c) an area perfused only by the second dye, indicating an increased collateral blood supply, the effectiveness of which was increased by the TCAD treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
One case of primary hepatic tumor and four cases of metastatic liver disease which were treated by intra-arterial infusion are reported herein to demonstrate the importance of monitoring the perfused parenchyma by imaging in at least two views (anterior and lateral) after the injection of radiolabeled macroaggregates into the infusion system.
Oral single-dose therapy with fosfomycin-trometamol (F-T) was used in 18 patients with lower urinary tract infections. The isolated bacterial strains presented a minimum inhibitory concentration of greater than 128 micrograms/ml in vitro. In spite of this 'resistance' in vitro, a clinical and bacteriological cure was obtained in 12 cases (66%). There were relapses in 2 cases, and clinical and bacteriological failure in only 2 cases. These results are due to the high urinary levels and prolonged bactericidal activity of urine after single-dose therapy with 3-5 g F-T. The clinical and biological tolerance was very good.
We describe a case of spontaneous infection of a renal hematoma complicating warfarin sodium anticoagulant therapy. The infected hematoma was successfully drained by sonar-guided fine-needle aspiration. All reported cases of renal hematomas complicating anticoagulant therapy are reviewed.
The recent piperazinyl-substituted mono-fluoroquinolones represent a family with some common characteristics on one side, and variable parameters on the other side. COMMON characteristics: same mechanism of action: DNA-gyrase inhibitors of the A subunit of topoisomerase; pH dependent antibacterial activity; a rather long post-antibiotic effect for both gram-positive and gram-negative bacteria; same physiochemical properties: organic acids, high pKa, lipophilicity. Some common pharmacokinetic parameters: low protein binding (less than 50%); high volume of distribution (greater than 1.5 l/kg) with good attainable tissue concentrations in lymph, blister fluid, renal tissue, prostate, bronchial secretions, saliva, aqueous humor, CSF, bone, bile; good intracellular penetration in macrophages, polynuclear neutrophils; high peak urinary concentrations markedly exceeding the MIC for virtually all bacterial urinary tract pathogens, even accounting for the increase in MIC in the urine, especially at lower (acidic) pH; low extraction ratio dialysis; similar adverse reactions; CNS, gastro-intestinal, photosensitivity, tendo-articular and cartilage toxicity. However, most other pharmacokinetic parameters are different from one fluoroquinolone to the other; oral bioavailability, peak serum levels (C max) as a measure of bioavailability, terminal half-life of elimination (t1/2) are all variable. The extent of metabolic biotransformation varies greatly, the two extremes being ofloxacin, showing a high metabolic stability, and pefloxacin, highly metabolized. The degree of antibacterial activity of different metabolites also varies greatly. The renal clearance of most fluoroquinolones, except pefloxacin, greatly exceeds normal glomerular filtration rate, suggesting additional renal tubular secretion. Renal elimination of most fluoroquinolones - except pefloxacin, is blocked by probenecid.(ABSTRACT TRUNCATED AT 250 WORDS)
The recent piperazinyl-substituted mono-fluoroquinolones represent a family with some common features on the one hand, and some variable parameters on the other. Some of the common features are: same mechanism of action (DNA-gyrase inhibitors of the A subunit of topoisomerase); pH-dependent antibacterial activity; a rather long post-antibiotic effect for both Gram-positive and Gram-negative bacteria; same physicochemical properties (organic acids, high pKa, lipophilicity). Common pharmacokinetic parameters include low protein binding (less than 50%); high volume of distribution (greater than 1 l/kg) with good tissue concentrations attainable in lymph, blister fluid, renal tissue prostate, bronchial secretions, saliva, aqueous humour, CSF, bone and bile; good intracellular penetration in macrophages and polynuclear neutrophils; high peak urinary concentrations, markedly exceeding the MIC for virtually all bacterial urinary tract pathogens, even accounting for the increase in MIC in the urine, especially at lower (acidic) pH; low extraction ratio dialysis; similar adverse reactions (CNS, gastrointestinal, photosensitivity, tendo-articular and cartilage toxicity). However, most other pharmacokinetic parameters are different from one fluoroquinolone to the other: oral bioavailability, peak serum levels (Cmax) as a measure of bioavailability, terminal half-life of elimination (t1/2) are all variable. The extent of metabolic biotransformation varies greatly, the two extremes being ofloxacin, showing a high metabolic stability and pefloxacin, highly metabolized. The degree of antibacterial activity of different metabolites also varies widely.(ABSTRACT TRUNCATED AT 250 WORDS)
Modifications to the chemical structure of antibiotics can modify nearly all pharmacokinetic parameters: digestive absorption, half-life, protein binding, tissue distribution, metabolic biotransformation, biliary and renal elimination. Examples of increased oral bioavailability are given for beta-lactams, macrolides, tetracyclines, fosfomycin, quinolones and acyclovir. The structural modifications responsible for prolonged or shortened half-life, increased or decreased biliary excretion, increased or decreased renal clearance for the different families of antibiotics are reviewed.