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Biomedical subjects

W Kern

Publications and source records attributed to W Kern.

At least 145 records · Page 8Linked to original sources

Resin versus standard blood culture media used with the new BACTEC automated infrared system: an evaluation in febrile granulocytopenic patients.

Resin-containing aerobic and anaerobic blood culture media (NR 16A and NR 17A) for use with the new BACTEC infrared blood cultures system were compared with standard BACTEC media (NR 6A and NR 7A) in their efficacy to detect bacteremia in febrile granulocytopenic patients receiving antimicrobial treatment. A total of 1185 sets of blood cultures obtained from 341 patients during a 12-month period were evaluated. There were 109 positive cultures (9.2%) with 128 pathogenic organisms isolated from 52 patients (15.2%). Statistically significant differences were found between aerobic media, but not between anaerobic media. Aerobic resin bottles (NR 16A) were more often positive (90 versus 78, p less than 0.05) than standard aerobic bottles (NR 6A). They yielded a higher number of microorganismS (98 versus 80, p less than 0.05) per culture and per culture-positive patient (53 versus 42, p less than 0.01). NR 16A cultures also were more often positive after 1-day incubation (44% versus 21%, p less than 0.01) than NR 6A cultures and allowed earlier subcultivation. The use of NR 16A medium instead of resin-free aerobic NR 6A medium may enhance the detection of bacteremia in selected groups of patients receiving antimicrobial treatment, and can shorten the time until detection of bacteremia.

Agranulocytosis↗

Evaluation of piperacillin-tazobactam in experimental meningitis caused by a beta-lactamase-producing strain of K1-positive Escherichia coli.

We evaluated the pharmacokinetics and therapeutic efficacy of piperacillin combined with tazobactam, a novel beta-lactamase inhibitor, in experimental meningitis due to a beta-lactamase-producing strain of K1-positive Escherichia coli. Different doses of piperacillin and tazobactam, as single agents and combined (8:1 ratio; dosage range, 40/5 to 200/25 mg/kg per h), and of ceftriaxone were given to experimentally infected rabbits by intravenous bolus injection followed by a 5-h constant infusion. The mean (+/- standard deviation) rates for penetration into the cerebrospinal fluid of infected animals after coadministration of both drugs were 16.6 +/- 8.4% for piperacillin and 32.5 +/- 12.6% for tazobactam. Compared with either agent alone, combination treatment resulted in significantly better bactericidal activity in the cerebrospinal fluid. The bactericidal activity of piperacillin-tazobactam was dose dependent: cerebrospinal fluid bacterial titers were reduced by 0.37 +/- 0.19 log10 CFU/ml per h with the lowest dose versus 0.96 +/- 0.25 log10 CFU/ml per h with the highest dose (P less than 0.001). At the relatively high doses of 160/20 and 200/25 mg of piperacillin-tazobactam per kg per h, the bactericidal activity of the combination was comparable to that of 10 and 25 mg of ceftriaxone per kg per h, respectively.

Animals↗

Differential effects of human and pork insulin-induced hypoglycemia on neuronal functions in humans.

Insulin has been found to cross the blood-brain barrier, and insulin receptors have been detected in different structures of the brain. However, the biological significance of insulin acting in the brain remains unclear. Reports of differential awareness of hypoglycemic symptoms during human insulin (HI)- and pork insulin (PI)-induced hypoglycemia hint at a modulatory influence of insulin on sensory processing. In a double-blind study, we recorded auditory-evoked potentials (AEPs), indexing neuronal transmission along sensory pathways, in 30 healthy male subjects during a baseline condition and HI- and PI-induced mild hypoglycemia of 2.65 mM. Fifteen subjects were tested after 20 min and another 15 after 50 min of constant hypoglycemia. During hypoglycemia, subjects had to indicate the severity of hypoglycemic symptoms and their current mood. Hypoglycemia increased latencies of the P3 component and reduced amplitudes of the N1, P2, and P3 components. Despite identical blood glucose and serum insulin levels in both sessions, effects of PI-induced hypoglycemia on AEP components were significantly stronger than those of HI-induced hypoglycemia (P less than 0.05). Differences between the effects of the insulins were consistently apparent after 20 min of hypoglycemia, indicating a short-term action of these hormones on central nervous system functions. Also, after 20 min, but not after 50 min, of steady-state hypoglycemia, subjects felt more excited during PI than HI infusion (P less than 0.05). The results indicate different influences of HI and PI on sensory function during hypoglycemia. These differences, occurring during early hypoglycemia, could contribute to the differential awareness of hypoglycemic warning symptoms during HI- and PI-induced hypoglycemia in diabetic patients.

Animals↗

Different effects of human and porcine insulin on hypoglycemia-induced abnormalities of brainstem sensory function.

Following a switch from porcine insulin (PI) to human insulin (HI), a subgroup of diabetic patients complained of unawareness of hypoglycemia. In the present study, a glucose clamp technique was used to assess changes in auditory evoked brainstem responses (ABR) during infusion of HI and PI (0.015 IU/kg/min) under conditions of euglycemia (about 5.00 mM) and of hypoglycemia (3.40 and 2.60 mM) in 9 healthy volunteers. Serum insulin and plasma glucose did not differ between HI and PI conditions. ABR components remained unchanged during the euglycemic clamp, but increased in latency during hypoglycemia in all subjects. At mean glucose levels of 2.60 mM, the increase in latency of ABR wave V ranged between 50 and 400 microseconds during PI infusion, and between 100 and 2,460 microseconds during HI infusion. Thus, compared to the PI condition, changes during HI infusion were significantly more variable (p less than 0.01) due to some subjects displaying extremely prolonged ABR latencies. These findings suggest that hypoglycemia induced by HI can be more detrimental to early sensory processing in humans as compared to PI.

Adult↗

[Fish breeder granuloma: infection caused by Mycobacterium marinum and other atypical mycobacteria in the human. Analysis of 8 cases and review of the literature].

Granulomatous lesions of the skin and tendon sheaths after exposure to fish tank or aquarium water are frequently caused by non-tuberculous so-called atypical mycobacteria. Mycobacterium marinum is the species most often isolated from such lesions. Rarely, other non-tuberculous species of mycobacteria may be isolated. In contrast to swimming-pool granuloma as the epidemic form of Mycobacterium marinum infection of man, fish tank granuloma seems to be a rare sporadic human disease that is often misdiagnosed. We report eight cases of fish tank granuloma. Five patients had sporotrichoid lesions, and one patient had a singular lesion. Three patients presented with tenosynovitis. Culture-proven Mycobacterium marinum infection was found in four patients, in one patient the causative organism isolated from the biopsy specimen was identified as Mycobacterium kansasii. In three patients with typical appearance of the lesions and exposure to fish tank water, biopsy specimens for culture were not available, and the diagnosis was histopathologically confirmed. Surgical treatment had an unfavourable outcome in two of three patients. Conservative antimicrobial therapy was evaluated in six patients. Similar to published reports, the treatment with rifampicin in combination with other agents seemed to be a useful therapy. Complete remission was, however, also achieved with doxycycline monotherapy. Microbiological diagnosis should be attempted in suspected cases of fish tank granuloma, and, if therapy is indicated, we strongly suggest primary medical treatment.

Adult↗

Fragments of ACTH affect electrophysiological signs of controlled stimulus processing in humans.

It has been proposed that the systemic administration of the 4-10 fragment of ACTH in humans affects primarily attention. In the present study, influences of ACTH 4-10 on event-related potential (ERP) indicators of attention were evaluated in healthy men. The influences were compared with those of an analog of the ACTH 4-9 sequence (HOE 427) which was expected to have an increased potency. Following an adaptation session, each of 20 healthy men was tested on four occasions in a double-blind study designed according to a latin-square. On each occasion, subjects received (iv) one of the following treatments: placebo, ACTH 4-10 (1 mg), HOE 427 (60 micrograms) and HOE 427 (200 micrograms). Treatments were administered 40 min prior to recordings of ERPs. ERPs were recorded while the subjects performed on a dichotic listening task paradigm. The various tone pips presented in this task elicit ERPs providing measures of controlled stimulus processing (Nd reflecting selectivity of attention, and P3) and automatic processing of stimulus deviance (mismatch negativity). ACTH 4-10 as well as 200 micrograms HOE 427 reduced Nd and also P3 amplitudes following attended stimuli. Smaller (non-significant) changes in the same direction were observed following 60 micrograms HOE 427. The results suggest an impairing influence of ACTH 4-10 and of HOE 427 on signs of controlled stimulus processing, particularly on the Nd. The analog appeared to be more potent than the endogenous 4-10 fragment.

Adrenocorticotropic Hormone↗

Lesion and regeneration of the anterior and posterior lens capsule and cortex in rabbits Nd:YAG laser.

With a mode-locked Nd:YAG laser set at various energy levels, anterior and posterior capsular and cortical lesions were produced in the lens of rabbits. Biomicroscopic and Scheimpflug examinations showed the anterior lesion to be healing in a whitish scar that was restricted to the area of the original lesion. Histology and transmission electron microscopy (TEM) demonstrated the proliferation of epithelial cells that produced a new, continuous, basement membrane-like capsule. In the area of the lesion collagenous material, myofibroblast-like cells and macrophages were found. Laser-induced lesions in the posterior lens capsule and lens protein resulted in damage to the capsule and grey opacity of the lenticular proteins, which remained unchanged for 6 weeks. Neither inflammatory nor epithelial cells appeared within the locally damaged lens. Macrophages migrated from the vitreous into the lesion; they were observed either in intercellular clefts or within a lens fibre, almost completely taking up their cross section.

Animals↗

Fetal pericardial effusion.

Forty-four fetuses with pericardial effusions have been identified by ultrasonographic examinations. The clinical histories and courses of these patients were reviewed. At least eight different clinical features accompanied and were probably responsible for the pericardial effusions. The most common cause of a fetal pericardial effusion was heart failure (13 fetuses). Fetal renal cystic dysplasia with oligohydramnios and other anomalies was present in six fetuses. Four of this group had microscopic evidence of pericarditis on postmortem examination. Fetal pericardial effusions are always a manifestation of another disease process often presenting as fetal hydrops. Some pericardial effusions are transient. The etiologic origin of fetal pericardial effusions differs from that in the child or adult.

Female↗

Influences of corticotropin-releasing hormone, adrenocorticotropin, and cortisol on sleep in normal man.

We studied the effects of the hormones of the hypothalamus-pituitary-adrenocortical axis on sleep processes in normal men. In one experiment, 10 men received placebo, cortisol (6 mg/h), and ACTH (0.55 U/h) as continuous iv infusions from 2200-0700 h on 3 separate nights. In another experiment, placebo and CRH (30 micrograms/h) were administered to another 10 men in the same manner. The mean plasma cortisol levels were comparable during the cortisol and ACTH infusions (552 vs. 668 nmol/L). During both infusions, the time spent in rapid eye movement (REM) sleep was significantly (P less than 0.01) reduced compared to that during the placebo infusion, and the cortisol infusion significantly (P less than 0.05) enhanced the time spent in slow wave sleep (SWS). The CRH dose used only moderately increased plasma ACTH and cortisol levels; the changes in SWS and REM sleep during CRH infusion were in the same direction as occurred during the cortisol infusion, but were not significant. These results suggest that cortisol has a sleep modulatory effect. The decrease in REM sleep during the ACTH infusion may be mediated by the rise in endogenous cortisol. However, ACTH specifically altered sleep, in that it inhibited the cortisol-induced increase in SWS. Peripherally administered CRH had no intrinsic influence on sleep.

Adrenocorticotropic Hormone↗

[Liposomes--drug carriers for retinally active drugs?].

Small lipid droplets, the so-called liposomes, can serve as drug carriers and can in theory be targeted directly at diseased tissue. Thus, comparatively smaller quantities of drugs than usual are necessary. However, liposomes are recognized by the immune system and are absorbed by the reticuloendothelial system and therefore also by the Kupffer cells in the liver. These cells are storage compartments for esterified vitamin A. As about 80% of the liposomes are metabolized in the liver, retinoids form a pool for substances transported with retinoid-binding proteins. Whether retinoids reach the retina via direct liposome contact or through the endocytotic process is still not clear. In rabbits, however, retinoids applied in small unilamellar liposomes (SUV) produce photoreceptor malfunctioning (isotretinoin and etretinate) and photoreceptor outer segment damage with an increase in phagocytotic activity of the retinal pigment epithelium (etretinate).

Drug Carriers↗

In vitro antibacterial activity of imipenem in combination with newer quinolone derivatives.

The antibacterial activity of imipenem combined with norfloxacin, ciprofloxacin, or ofloxacin against 43 gram-positive cocci and 53 aerobic gram-negative rods compared to results obtained with the combination of imipenem with amikacin. Synergistic antibacterial action (defined as FIC index less than or equal to 0.5) was found for 28% of strains with imipenem/amikacin and imipenem/norfloxacin, in 23% with imipenem/ofloxacin, and in 18% with imipenem/ciprofloxacin. Antagonistic activity (FIC index greater than 1.0) was found in 21, 21, 32, and 23% respectively. These rates were not statistically different for gram-positive and gram-negative isolates. Antagonistic activity seemed to occur more frequently with Pseudomonas spp. and enterococci than with staphylococci or Enterobacteriaceae. A tendency for increased rates of antagonism was noted in strains with higher MIC values. Clinically significant and meaningful positive interactions (defined as a decrease of imipenem MICs to below 2.0 micrograms/ml) were found with imipenem/amikacin against several Pseudomonas spp., with imipenem/ofloxacin or ciprofloxacin against Streptococcus faecium and with all combinations against Proteus spp. We conclude that continuous treatment with newer quinolone derivatives for selective decontamination in neutropenic patients receiving imipenem antibacterial therapy for treatment of infection should not be regarded as effective combination therapy.

Amikacin↗

Norfloxacin for prevention of bacterial infections during severe granulocytopenia after bone marrow transplantation.

48 patients treated with bone marrow transplantation (BMT) received the quinolone norfloxacin (NOR) in a total decontamination (TD-NOR, n = 36) or selective decontamination (SD-NOR, n = 12) regimen and were compared with a historical control group of 48 BMT patients receiving oral non-absorbable antibiotics (TD-NAA, n = 31 and SD-NAA, n = 17). 17/36 patients (47%) of group TD-NOR and 16/31 patients (52%) of group TD-NAA remained free of febrile episodes and infections. 4/12 patients (33%) of group SD-NOR and only 1/17 patients (6%) of group SD-NAA remained free of fever and infections. The use of norfloxacin in selective decontamination resulted in a statistically significant lower incidence of fever days than in patients receiving SD-NAA (p less than 0.001). These data suggest that norfloxacin may replace non-absorbable antibiotics in total and in selective decontamination regimens used for infection prophylaxis in BMT recipients.

Adolescent↗

Specificity of routine parasite serological tests in autoimmune disorders, neoplastic disease, EBV-induced mononucleosis, and HIV infection.

Sera from 120 patients with rheumatological disorders, neoplastic disease, infectious mononucleosis, and HIV infection, and from 30 healthy blood donors were tested for nonspecific reactivity in 13 routinely used parasite serological tests. Responses were detected in 3/30 healthy blood donors (10%) vs 25/120 patients (21%). Of 40 responses in these 28 responders most were weakly reactive, and 25 out of 40 responses were only at borderline level. Response rates were highest in patients with mononucleosis presumably due to heterophile antibodies. Only four patients had responses in at least two different serodiagnostic tests for the same parasitic infection. Response patterns indicative of a possible underlying, concurring, or superimposed parasitic infection, thus, were rare. Especially susceptible to nonspecific reactivity seemed to be immunofluorescent antibody tests for filariasis, schistosomiasis, and amebiasis. In conclusion, compared to healthy controls, false-positive serological responses seem to be more frequent in certain disease groups dependent on the test methods used. Second, the use of more than one serodiagnostic test for the same parasitic disease will substantially facilitate the identification of nonspecific reactivity. Third, for better defining the specificity of parasitological serodiagnosis, more studies should include control sera from patients with nonparasitic diseases that frequently show immunological abnormalities.

Acquired Immunodeficiency Syndrome↗

High risk of streptococcal septicemia after high dose cytosine arabinoside treatment for acute myelogenous leukemia.

Twenty-nine adult patients with acute myelogenous leukemia AML who received 40 treatment courses with high dose cytosine arabinoside (HD-A), alone or combined with other cytotoxic drugs, for remission induction (RI) or postremission intensive consolidation (IC) were retrospectively analysed for types and severity of infectious complications. In this paper, we report the unusually high rate of streptococcal septicemia in our patients. Of 13 bacteremic infections in a total of 45 infectious episodes, 10 were caused by streptococci (9 viridans streptococci, 1 group B hemolytic streptococcus). Three of them were lethal. After reviewing all documented cases of streptococcal septicemia in the same study period, four additional cases among adult patients with AML were identified. Three of them have had antileukemic chemotherapy without HD-A, while one have had HD-A as a conditioning regimen for bone marrow transplantation. Only three cases were documented to occur in adult patients with AML. Patients treated with HD-A for RI or IC had a significantly lower risk of streptococcal septicemia during previous chemotherapy-associated febrile neutropenic episodes (1/55 vs 10/45; P = 0.01). Neither prophylactic regimens including trimethoprim-sulfamethoxazole nor those without it were effective in preventing streptococcal septicemia. Further studies are needed to confirm these data before the value of additional or alternative prophylactic antibiotics is proven necessary.

Adolescent↗