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Biomedical subjects

M Schultz

Publications and source records attributed to M Schultz.

At least 73 records · Page 4Linked to original sources
PubMed1996

Pharmacokinetics and safety of multiple-dose valaciclovir in geriatric volunteers with and without concomitant diuretic therapy.

A randomized, double-blind study was conducted to evaluate the safety and pharmacokinetics of acyclovir following multiple-dose oral administration of valaciclovir (three times a day for 8 days) in geriatric volunteers (65 to 83 years of age). Pharmacokinetic evaluation was performed for three groups: normotensive subjects given 500-mg doses of valaciclovir (n = 11), normotensive subjects given, 1,000-mg doses of valaciclovir (n = 9), and thiazide diuretic-treated hypertensive subjects given 500-mg doses of valaciclovir (n = 9). Valaciclovir, the l-valyl ester of acylclovir, was rapidly absorbed and converted to acyclovir, with plasma valaciclovir concentrations generally undetectable or < or = 0.4 microgram/ml. The peak concentration of drug in plasma (Cmax) for acyclovir occurred at 1 to 2 h, and the half-life of acyclovir was 3 to 4 h in all three elderly groups. The Cmax and area under the concentration-time curve from 0 h to infinity (AUC0-infinity) values of acyclovir obtained on days 1 and 8 indicated no unexpected accumulation at steady state. The steady-state acyclovir Cmax (4.30 and 5.98 micrograms/ml) and daily AUC0-infinity (44 and 74 h.micrograms/ml) following dosing of valaciclovir (500 and 1,000 mg) three times a day were two to three times greater than those expected after high-dose oral acyclovir treatment (800 mg, five times daily). There were no valaciclovir-related changes or abnormalities in safety parameters and no reports of serious adverse experiences in these elderly volunteers. The plasma acyclovir concentration-time curves for the hypertensive and normotensive (500-mg valaciclovir treatment) elderly groups were almost superimposable, and acyclovir pharmacokinetic parameters for the two groups were not significantly different, indicating that concomitant thiazide diuretics do not alter acyclovir pharmacokinetics following valaciclovir dosing in the elderly. Compared with historical data for younger volunteers (creatinine clearance [CLCR] > 75 ml/min/1.73 m2), the elderly subjects (CLCR = 40 to 65 ml/min/1.73 m2) showed higher (approximately 15 to 20%) mean Cmaxs and higher (approximately 30 to 50%) mean AUC(0-infinity)s of acyclovir (P < 0.01), which were consistent with age-related decreases in CLCR. The increased acyclovir exposure from valaciclovir dosing will permit reduced dosing frequency and may result in improved efficacy in the management of herpesvirus diseases.

Acyclovir↗
PubMed1996

Spontaneous regression of lymphoproliferative disorders in patients treated with methotrexate for rheumatoid arthritis and other rheumatic diseases.

PURPOSE: To determine the clinicopathologic features of lymphoproliferative disorders (LPD) that occur in the setting of methotrexate (MTX) therapy for rheumatic diseases (RD) and to define the relationship between the presence of Epstein-Barr virus (EBV) in tumor cells and the response of LPD to MTX withdrawal. PATIENTS AND METHODS: In addition to nine new cases, we analyzed 28 cases previously reported in the literature of LPD in patients receiving MTX for RD. In addition to MTX, immunosuppressive therapy included corticosteroids in 19 patients, azathioprine in three, and cyclosporine in one. Extranodal disease was identified in 16 patients, but none had CNS involvement. Pathologic findings included five cases of Hodgkin's disease and seven low-grade lymphomas. The remaining patients had intermediate or aggressive lymphomas. In situ hybridization studies (ISHS) for EBV-RNA transcripts were positive in 12 of 27 patients (44%). RESULTS: Among 37 patients, 16 were initially observed after MTX withdrawal without additional antitumor therapy. Six achieved a spontaneous complete remission (CR), three had a partial response (PR), one had a minimal response, and six had no response to MTX withdrawal. Of 10 responding patients, EBV was detected by ISHS (n = 6) or polymerase chain reaction (PCR) (n = 2); one patient had a CR despite the absence of EBV by PCR and one had a CR but did not have viral assays performed. Only one of six patients with negative EBV by ISHS or PCR responded to MTX withdrawal. CONCLUSION: MTX withdrawal and observation for a short period should be considered in the initial management of patients who develop LPD while on MTX therapy. Responses were consistently observed, but not limited to patients in whom EBV was detected by ISHS or PCR. Further studies are required to confirm these findings and to evaluate the role for EBV in LPD that occur in patients receiving MTX.

Adult↗
PubMed1996

[Not Available].

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Amputation, Surgical↗
PubMed1996

[Frequency and histopathologic features of chronic gastritis in 300 patients without endoscopic lesions].

Three gastric mucosal biopsies were obtained from 300 patients showing a normal upper digestive tract endoscopy. Histologically, in 9% of the patients the biopsies were normal: in 87%, showed a common-type chronic gastritis, and in 4% showed a reactive (chemical or reflux-type) gastritis. Helicobacter pylori was present in 25.9% of the patients without gastritis, in 33.3% of the patients with reactive gastritis, and in 87.7% of those with common-type gastritis. In 19.9% of the patients with common-type chronic gastritis there was intestinal metaplasia, consisting of type I metaplasia in 14.1%, type II in 3.1% and type III metaplasia in 2.3%. The association of type III intestinal metaplasia with the other forms of metaplasia, its lower frequency and its tendency to be present in older patients supports the hypothesis that type III incomplete colonic metaplasia represents a more advanced stage than complete and incomplete small bowed metaplasia of the gastric mucosa.

Adolescent↗
PubMed1996

[Semiquantitative histopathologic analysis of chronic gastritis: extension and grading score].

Three endoscopic systematic biopsies were obtained from 261 patients showing chronic gastritis. Histopathologic features of chronic gastritis were graded from 0 to 3 points according to the Sydney System. In addition, an extension and grading histopathologic score was applied. This score was obtained from the sum of qualified grades for each feature in all three samples. Inflammation, activity, atrophy, and intestinal metaplasia were predominantly grade 1 and H pylori density was predominantly grade 2. Only 2.6% of the sections without atrophy showed intestinal metaplasia, while 79.3% of the sections depicting grade 2-3 intestinal metaplasia showed moderate to severe atrophy. Inflammation was more severe in the antral lesser curvature and the more severe atrophy was present in the antrum than in the corpus mucosa. Sydney System and extension and grading histopathologic score showed more extensive activity in patients older than 45 years. A lower histopathologic score of H pylori was seen in these patients. The presence of H pylori was directly correlated with inflammation severity and inversely with atrophy. These results, in accordance with data shown in the literature, suggest that the Sydney System and the extension and grading histopathologic score can be applied to compare chronic gastritis features in different groups of patients.

Chronic Disease↗
PubMed1995

Duchenne muscular dystrophy and myotonic dystrophy in the same patient.

We report on the first patient identified with myotonic dystrophy and Duchenne muscular dystrophy (DMD). The family of the propositus had a strong history of myotonic dystrophy, and there was an intrafamilial pathological expansion of the responsible CTG repeat between the mildly affected mother (160 repeats; normal 27 repeats) and her more severely affected son (650 repeats), and his sister (650 repeats). The propositus was an isolated case of Duchenne muscular dystrophy with marked dystrophin deficiency in muscle biopsy. The patient was still ambulatory post age 16. Myotonic dystrophy could interfere to some extent with the progression of Duchenne dystrophy. However, other interpretations are possible. Twelve percent of dystrophin revertant fibers as observed by immunohistochemistry could be sufficient to ameliorate typical DMD clinical severity, or the patient may present a somatic mosaic. The pathophysiological interactions of these two unlinked disorders are discussed at the clinical and histopathological levels.

Child↗
PubMed1995

Chemical and enzymatic synthesis of glycopeptides.

Progress recently made in the synthesis of biologically relevant N- and O-glycopeptides is illustrated by examples. In this context, developments in the preparation of complex saccharide side chains and in the subsequent coupling to peptide portions is described. Special emphasis is given to the synthesis of Lewis antigen-type structures. Furthermore, modern methods in solid phase peptide syntheses utilizing glycosylated building blocks are presented. Recent advances in glycopeptide syntheses employing enzymatic methods in deprotection steps as well as in peptide/saccharide chain elongation are reported.

Amino Acid Sequence↗
PubMed1995

Simulated exposure of hospital emergency personnel to solvent vapors and respirable dust during decontamination of chemically exposed patients.

STUDY OBJECTIVE: To ascertain the breathing-zone level of organic solvents and respirable particulates in a simulated hospital patient decontamination. DESIGN: An adult-sized, clothed plastic mannequin was contaminated with a solvent or particulate, then decontaminated. Rescuers were exposed to acetone, p-xylene, iron oxide, or zinc oxide during decontamination. We performed breathing-zone air sampling on the two rescuers. Five trials were run with each chemical. PARTICIPANTS: Two physicians performed the decontamination. RESULTS: Measured breathing-zone concentrations for the chemicals tested were significantly lower than their respective short-term breathing-zone limits (P = .042, .043, .001, and .001 for acetone, p-xylene, iron, and zinc oxide, respectively). CONCLUSION: The chemicals tested during simulated hospital decontamination did not pose a respiratory health risk to rescuers. This model may be useful in the extrapolation of breathing-zone exposure to more toxic chemicals. Because ours are preliminary data, the use of respiratory protective equipment during decontamination must be recommended.

Decontamination↗
PubMed1995

Novel urinary metabolite of alpha-tocopherol, 2,5,7,8-tetramethyl-2(2'-carboxyethyl)-6-hydroxychroman, as an indicator of an adequate vitamin E supply?

Previously, the metabolism of alpha-tocopherol was considered to involve the opening of the chroman structure because of its oxidation to tocopherylquinone. In contrast, we describe here 2,5,7,8-tetramethyl-2(2'-carboxyethyl)-6-hydroxychroman (alpha-CEHC) as the major urinary metabolite of alpha-tocopherol that appears in human urine after vitamin E supplementation. It is formed directly from alpha-tocopherol without previous oxidative splitting of the chroman ring. The correlation of alpha-tocopherol intake, plasma alpha-tocopherol concentrations, and urinary excretion of alpha-CEHC in human volunteers supplemented with RRR-alpha-tocopherol dosages ranging from 0 to 800 mg/d was examined. HPLC and gas chromatography-mass spectroscopy analysis revealed that alpha-CEHC was only excreted when a plasma threshold of 7-9 mumol alpha-tocopherol/g total lipid was exceeded. This concentration was obtained by a daily intake of approximately 50-150 mg alpha-tocopherol. We suggest that alpha-CEHC excretion indicates a saturated binding capacity of vitamin E in the plasma and thus may be considered to be a marker of optimum vitamin E intake.

Biomarkers↗
PubMed1995

Microscopic haematuria as a relative contraindication for tranexamic acid.

Tranexamic acid has been advocated for patients with severe bleeding tendency due to thrombocytopenia not responding to platelet transfusions. Macroscopic haematuria is a well-known contraindication for its use in such patients. We present three clinical cases with microscopic haematuria, in whom tranexamic acid caused problems of clot formation in the urinary tract, indicating that microscopic haematuria should also be considered as a contraindication for tranexamic acid.

Adult↗
PubMed1995

Venous transcranial Doppler ultrasound monitoring in acute dural sinus thrombosis. Report of two cases.

BACKGROUND AND PURPOSE: We sought to establish the efficacy of the Doppler technique in the evaluation of the intracranial venous system and to assess its usefulness in the monitoring of venous collateral pathways in superior sagittal sinus thrombosis. METHODS: Venous Doppler ultrasound was performed with a range-gated 2-MHz transducer in 10 healthy volunteers and in two patients with superior sagittal sinus thrombosis confirmed by cerebral angiography. RESULTS: In normal control subjects, a venous signal was found at a depth ranging from 40 to 72 mm, which was considered to correspond to the deep middle cerebral vein and the basal vein of Rosenthal. Mean blood flow velocities ranged from 9 to 20 cm/s. In both patients with superior sagittal sinus thrombosis, Doppler studies detected elevated mean blood flow velocities (146 and 33 cm/s), which normalized after 16 weeks and 1 week, respectively. CONCLUSIONS: Venous transcranial Doppler ultrasonography provides a reliable, noninvasive, and rapid technique for intracranial venous examination. It was performed without difficulty in young health volunteers, and it can be applied as a monitoring tool in the evaluation of collateral venous flow in superior sagittal sinus thrombosis.

Acute Disease↗
PubMed1995

Targeted mutation of the murine goosecoid gene results in craniofacial defects and neonatal death.

The goosecoid gene encodes a homeodomain-containing protein that has been identified in a number of species and has been implicated in a variety of key developmental processes. Initially suggested to be involved in organizing the embryo during early development, goosecoid has since been demonstrated to be expressed during organogenesis-most notably in the head, the limbs and the ventrolateral body wall. To investigate the role of goosecoid in embryonic development, we have inactivated the gene by gene targeting to generate mice mutant for the goosecoid gene. Mice that are homozygous for the goosecoid mutation do not display a gastrulation phenotype and are born; however, they do not survive more than 24 hours. Analysis of the homozygotes revealed numerous developmental defects affecting those structures in which goosecoid is expressed during its second (late) phase of embryonic expression. Predominantly, these defects involve the lower mandible and its associated musculature including the tongue, the nasal cavity and the nasal pits, as well as the components of the inner ear (malleus, tympanic ring) and the external auditory meatus. Although the observed phenotype is in accordance with the late expression domains of goosecoid in wild-type embryos, we suggest that the lack of an earlier phenotype is the result of functional compensation by other genes.

Animals↗
PubMed1994

Cytologic atypia associated with microglandular hyperplasia.

Although it has long been known that microglandular hyperplasia (MGH) may be associated with cytologic atypia in cervical smears, the cytomorphology of MGH has not been described in great detail. To clarify its cytomorphology, Pap smears obtained from biopsy proven cases of MGH over a 3-yr period were reviewed. Of 122 smears containing endocervical cells, 34 (28%) showed striking glandular abnormalities. In two cases, adenocarcinoma and adenocarcinoma in situ were falsely suggested and a high grade squamous intraepithelial lesion (HGSIL-CIN III) was not confirmed in a conization specimen which showed only low grade SIL and MGH. Review of six cytologic diagnoses of HGSIL (CIN III) unconfirmed on biopsy suggested overcalls related to MGH related atypia in five. Cytologic features of MGH, therefore, may occasionally result in erroneous interpretations of HGSIL as well as glandular neoplasia. Although these changes may be striking, comparison with glandular atypia not associated with MGH shows that they are not entirely specific.

Adolescent↗
PubMed1994

The macroscopic and microscopic structure of double-head antlers and pedicle bone of cervidae (Mammalia, Artiodactyla).

Ortho- and heterotopically formed double-head antlers were studied in red, fallow and roe deer. The malformation was the result of new antler growth without previous casting of the old antlers. Thus, two antler structures belonging to successive antler generations originated from one pedicle. These two structures were always separated by a horizontal groove. Histologically, signs of osteoclastic resorption were observed in the interior and at the outer circumference of the distal parts of the pedicles of the double heads. The resorptive process had, however, not been of an intensity necessary for subsequent antler casting. We also observed that the double-head's second antler generation had developed as a periosteal exostosis of the distal pedicle bone. Thus, we assume that in normogenesis formation of the bony component of subsequent antlers is also probably dependent on cells derived from pedicle periosteum. Finally, the process of antler regrowth in deer is compared with epimorphic regeneration occurring in other vertebrates.

Animals↗
PubMed1993

Effects of an antiandrogen treatment on the antler cycle of male fallow deer (Dama dama L.).

Weekly application of the antiandrogen cyproteron acetate (CA) to 3 adult (group 1, treatment starting 3 weeks prior to the rut) and 4 subadult (group 2, treatment starting after the rut) fallow bucks led to premature antler casting after about 9 weeks (group 1) or 16 to 17 days (group 2). Variation in time span between onset of CA administration and induced casting (in late November/early December) is attributed to age- and season-dependent differences in androgen levels before and during the treatment period. Casting surfaces of the antlers were flat. In all bucks, casting was followed by a complete though shortened antler cycle, occurring under short day conditions. In February/March velvet was shed from the antlers, indicating a rise in plasma androgen levels at that time. At time of fraying, antlers exhibited signs of immaturity and were shorter than normal. In the most pronounced case of immaturity, the antlers consisted mainly of cancellous woven bone, revealing that bone remodeling and antler mineralization had not occurred to a larger extent. These observations prove that onset of fraying behaviour does not depend on prior maturation of antler bone or necrosis of velvet. Occurrence of the additional antler cycle in late autumn and winter had no negative effect on subsequent antler formation starting in the following spring.

Animals↗
PubMed1993

Bacterial ventriculitis and duration of ventriculostomy catheter insertion.

Invasive monitoring of intracranial pressure (ICP) plays an important role in managing many neurosurgical patients. While there are several techniques available to monitor ICP, the ventricular catheter is most commonly used and the most accurate. ICP monitoring poses potential risks to the patient. The most common and one of the most devastating complications is infection. This research study examined the rate of bacterial ventriculitis in relation to duration of ventricular catheter insertion as well as other factors which may contribute to ventriculitis. Data were collected prospectively on 78 patients with a ventriculostomy who were 14 years of age or older and admitted to the neuroscience intensive care unit. Patients were followed from the time of ventricular catheter placement to two weeks after the catheter was removed or until the patient was discharged from the hospital. A significantly higher ventriculitis rate was found in patients with a mean catheter duration of 11 days or longer (p = .004). In the group that developed ventriculitis there was a significant rise (means = 6.03592, p = .014) in the cerebrospinal fluid (CSF) lactate prior to the onset of ventriculitis. Neuroscience nurses should be aware of the factors which may increase the rate of ventriculitis, such as duration of catheter placement and factors which may indicate impending infection such as a rise in the CSF lactate. Future studies should compare various methods of ventriculostomy site care for efficacy of infection prevention, cost and caregiver time.

Adolescent↗