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Biomedical subjects

B Schmidt

Publications and source records attributed to B Schmidt.

At least 253 records · Page 14Linked to original sources

Precision and accuracy of clinical and radiological signs in premature infants at risk of patent ductus arteriosus.

OBJECTIVE: To determine the precision (interobserver agreement) and accuracy (agreement with criterion standard) of clinical and radiological signs in premature infants at risk of patent ductus arteriosus (PDA) with left-to-right shunting. DESIGN: Masked comparison of clinical and radiological examination with Doppler flow echocardiography (criterion standard). SETTING: Neonatal intensive care unit. PATIENTS: One hundred infants with birth weights less than 1750 g were studied once between days 3 and 7 of life. A third of the cohort was intubated at the time of study. INTERVENTION: Five independent observers noted the presence or absence of an increased pulse volume, an active precordium, a heart murmur, a cardiothoracic ratio greater than 60%, increased pulmonary vascular markings on a concurrent chest x-ray film, and a relative increase of the cardiothoracic ratio compared with that from the previous chest x-ray film. Pulsed and color flow Doppler echocardiography was performed within 4 hours. All 100 tapes were reviewed by a second pediatric cardiologist. RESULTS: Twenty-three infants had a PDA with left-to-right shunting. The precision of clinical signs was modest, with average kappa values of 0.15 for pulse volume, 0.32 for precordium, and 0.41 for murmur. Pulse quality (43%) and murmur (42%) had the highest mean sensitivities. Corresponding specificities were 74% for pulse volume and 87% for murmur. The combination of a cardiac murmur with an abnormal pulse volume had the highest positive predictive value (77%). The radiological examination did not improve the observers' ability to distinguish between patients with and without PDA. CONCLUSIONS: The precision and accuracy of clinical and radiological signs of a PDA with left-to-right shunting are unsatisfactory. Therefore, Doppler flow echocardiography is required to diagnose PDA confidently in preterm infants between days 3 and 7 of life.

Ductus Arteriosus, Patent↗

Seasonal and daily rhythms of body temperature in the European hamster (Cricetus cricetus) under semi-natural conditions.

Body temperature of five European hamsters exposed to semi-natural environmental conditions at 47 degrees N in Southern Germany was recorded over a 1.5-year period using intraperitoneal temperature-sensitive radio transmitters. The animals showed pronounced seasonal changes in body weight and reproductive status. Euthermic body temperature changed significantly throughout the year reaching its maximum of 37.9 +/- 0.2 degrees C in April and its minimum of 36.1 +/- 0.4 degrees C in December. Between November and March the hamsters showed regular bouts of hibernation and a few bouts of shallow torpor. During hibernation body temperature correlated with ambient temperature. Monthly means of body temperature during hibernation were highest in November (7.9 +/- 0.8 degrees C) and March (8.2 +/- 0.5 degrees C) and lowest in January (4.4 +/- 0.7 degrees C). Using periodogram analysis methods, a clear diurnal rhythm of euthermic body temperature could be detected between March and August, whereas no such rhythm could be found during fall and winter. During hibernation bouts, no circadian rhythmicity was evident for body temperature apart from body temperature following ambient temperature with a time lag of 3-5 h. On average, hibernation bouts lasted 104.2 +/- 23.8 h with body temperature falling to 6.0 +/- 1.7 degrees C. When entering hibernation the animals cooled at a rate of -0.8 +/- 0.2 degrees C.h-1; when arousing from hibernation they warmed at a rate of 9.9 +/- 2.4 degrees C.h-1. Warming rates were significantly lower in November and December than in January and February, and correlated with ambient temperature (r = -0.46, P < 0.01) and hibernating body temperature (r = -0.47, P < 0.01). Entry into hibernation occurred mostly in the middle of the night (mean time of day 0148 hours +/- 3.4 h), while spontaneous arousals were widely scattered across day and night. For all animals regression analysis revealed free-running circadian rhythms for the timing of arousal. These results suggest that entry into hibernation is either induced by environmental effects or by a circadian clock with a period of 24 h, whereas arousal from hibernation is controlled by an endogenous rhythm with a period different from 24 h.

Animals↗

Acute glaucoma and intracranial hypertension in a child on long-term peritoneal dialysis treated with growth hormone.

A 7-year-old boy with end-stage renal disease on long-term peritoneal dialysis is described. The child developed intracranial hypertension and acute glaucoma during therapy with recombinant human growth hormone (rhGH), 18 months after the onset of treatment. Symptoms developed within 1.5 days and required neurosurgical treatment to reduce the intracranial hypertension because of imminent impaction of the cerebellum and brain stem. After ventricular cerebrospinal fluid drainage and cessation of growth hormone, all symptoms of intracranial hypertension and increased intraocular pressure disappeared. To our knowledge this is the first report of intracranial hypertension or hydrocephalus and acute glaucoma during rhGH therapy. Continuous and long-term control of the ophthalmological and neurological status of patients treated with rhGh is indicated.

Acute Disease↗

Ascent of the testis in children.

Among 460 children who had an orchiopexy (ORP), we identified 72 children who had attended our institution 1-12 years earlier and in whom the testicular position had been specified. Of the 72 boys 19 were had ascended testes (26%). The age at ORP of the children with ascent of the testes was 7.0 years (1.8-14.0 years). Light and electron microscopy of 13 testicular biopsies taken at ORP, showed alterations of germ cells and Sertoli cells, similar but less pronounced than alterations seen in congenital undescended testes. Conclusion. A normally positioned testis may ascend into the inguinal region or upper scrotum and remain there fixed. This secondary cryptorchidism does not usually respond to human chorionic gonadotropin treatment and must be corrected by orchiopexy.

Adolescent↗

Atypical and anaplastic meningiomas--does the new WHO-classification of brain tumours affect the indication for postoperative irradiation?

We retrospectively analysed 13 patients (pts.) treated at the University of Tübingen from 1985 to 1993 to evaluate the results of radiation therapy (XRT) given as an adjuvant to totally or subtotally resected meningiomas. The overall survival was 38% at five years with a probability of relapse of 50% at this time. Reclassification of the tumours according to the new WHO-classification of brain tumours [14] revealed 10 grade-II-tumours (atypical meningioma) and 3 grade-III-tumours (anaplastic meningioma). Radiotherapy failed in all 3 pts. with macroscopically incomplete resection (Simpson's grade IV), who died with relapse between 4 and 51 months after radiotherapy. 5 out of 10 pts. with grade-II-tumours relapsed. All 3 pts. with grade-III-tumours died with relapse between 6 and 21 months after XRT. Morbidity was seen in 2 pts. after irradiation with 60 GY (ICRU dose specification). Complete surgical exstirpation offers the best possibility of tumour control. Grade-III-tumours should be irradiated whatever the extent of the primary surgery was. Our results might indicate a possible indication for XRT in pts. with atypical grade-II-tumours especially when radical surgery must be in doubt. Prospective multicentre trials are warranted to prove the prognostic value of the new WHO-classification for atypical and anaplastic meningiomas and to define the ultimate role of radiotherapy in this setting.

Adult↗

The effect of WSEWS pentapeptide and WSEWS-specific monoclonal antibodies on constitutive and IL-6 induced acute-phase protein production by a human hepatoma cell line, HEPG-2.

Interleukin-6 receptor (IL-6R) is a member of the cytokine receptor superfamily characterised by the obligatory presence of WSXWS (Trp-Ser-X-Trp-Ser) sequence motif near the transmembrane domain. To more clearly understand the role of this motif, we treated the HepG2 hepatoma cell line with synthetic WSEWS peptide (E is glutamic acid) and checked the spontaneous and IL-6-induced production of acute-phase protein fibrinogen and C1-inhibitor (C1-INH). The peptide revealed a definitely stimulatory effect both on the constitutive synthesis of C1-INH and on the IL-6-induced fibrinogen synthesis of HepG2 cells. Monoclonal antibody specific for WSEWS pentapeptide was stimulatory for the spontaneous secretion of both fibrinogen and C1-INH. However, the IL-6-induced elevations of these acute-phase proteins were oppositely regulated, since the anti-WSEWS monoclonal antibody was inhibitory on the production of fibrinogen induced by IL-6 but strongly augmented the IL-6 induced production of C1-INH. Our study indicates that the WSEWS motif is critical in the effect of IL-6 on the acute-phase protein production influencing either the ligand binding by the WSEWS-containing receptor molecule or the signal transduction.

Acute-Phase Proteins↗

In vitro complement activation by ragweed allergen extract in the sera of ragweed allergic and non-allergic persons.

Ragweed allergen (RWA)-induced complement activation in sera of 40 RW allergic patients and of 40 non-allergic controls was investigated. After treatment of the sera with RWA, levels of C3a, C5a, C3bBbP, C1rC1sClinh, SC5b-9 and granulocyte-aggregating activity were determined. Concentration of RW-specific IgG was also measured. After RWA treatment dose-dependent complement activation was detected in sera of RW allergic and non-allergic persons. C3a generation was observed mostly in the sera of RW allergic individuals, while levels of C3bBbP and of RW-specific IgG were significantly higher in sera of allergics, and a strong correlation was found between these two parameters. In a prospective clinical study, a significant positive correlation was observed between the extent of RWA-induced alternative pathway (AP) activation and the severity of symptoms of allergic rhinoconjunctivitis that were developed in a 4-week period subsequent to blood sampling. These observations suggest that complement activation has a role in the development of the symptoms of RW allergy.

Complement Activation↗

Infection following treatment of mandibular fractures in human immunodeficiency virus seropositive patients.

PURPOSE: There are little data available on the prevalence of human immunodeficiency virus (HIV) disease and its relationship to postoperative infection in patients presenting with mandibular fractures. This retrospective study assesses these parameters. PATIENTS: The study population consisted of 251 patients treated for mandibular fractures at San Francisco General Hospital (SFGH) between January 1990 and December 1993. Group 1 (n = 20) was composed of patients with documented HIV infection and group 2 (n = 231) served as controls. The groups were comparable with regard to age, sex, etiology, and number and types of fractures. RESULTS: HIV prevalence for this population was 7.9%, and was consistent with previously documented prevalence studies in SFGH surgical patients. In the HIV-positive group, 6 of 20 patients (30%) developed postoperative infection: 2 soft tissue (10%) and 4 bone-related (20%). In the control group, 22 of 231 patients (9.5%) developed postoperative infections: 16 soft tissue (6.9%) and 6 bone-related (2.6%). Statistical analysis showed a significant difference between the two groups with regard to overall (P = .016) and to bone-related (P = .001) infection rates. There was no statistically significant difference in soft tissue infections between the two groups (P = .953). The rate of postoperative infection was significantly higher in those patients (both HIV-positive and controls) who had open reduction and internal fixation (ORIF; 25/155; 16%) versus those who had closed reduction and maxillomandibular fixation (3/96; 3.1%; P = .003). The postoperative infection rate after ORIF was significantly higher in the HIV-positive (5/11; 45%) compared with the control group (20/144; 13.9%; P = .02). CONCLUSIONS: The results of this study indicate that the overall rate of postoperative infection after treatment of mandibular fractures is significantly higher in HIV-positive than in HIV-negative patients. Specifically, the use of ORIF in HIV-positive patients represents a significant risk.

Acquired Immunodeficiency Syndrome↗

The relationship of the lingual nerve to the mandibular third molar region: an anatomic study.

PURPOSE: This study evaluated the relationship of the mandibular third molar to the lingual nerve. MATERIALS AND METHODS: An anatomic dissection of the lingual nerve in the third molar region was done on 20 cadavers (40 sides). RESULTS: The position of the nerve on one side bore no statistical relationship to the position of the nerve on the opposite side. The position of the lingual nerve was variable in both the sagittal and coronal planes. In two specimens the nerve lay superior to the lingual plate and in another the superior surface of the nerve was level with the crest of the lingual plate. CONCLUSION: These findings have implications for the avoidance of lingual nerve damage during surgery in the third molar and retromolar region of the mandible.

Cadaver↗

Proteolysis of IGFBPs by cathepsin D in vitro and in cathepsin D-deficient mice.

Affinity-purified lysosomal protease cathepsin D cleaved recombinant human IGFBP-1 to -5 in fragments of defined sizes, while IGFBP-6 was not degraded. To assess the role of cathepsin D for proteolytic processing of IGFBP in vivo, serum from cathepsin D-deficient mice and conditioned media from cathepsin D-deficient fibroblasts and organ explants were analyzed. No differences for the pattern and level of IGFBPs were detected. When conditioned media from fibroblasts were incubated at acid pH, proteolysis of IGFBP-1 and -4 was observed only in media derived from cathepsin D-expressing cells. Additional experiments showed that the proteolysis of IGFBP-4 is mediated by cathepsin D and not by a protease activated by cathepsin D. The IGFBP-4 degrading activities in media from organ explants from cathepsin D-deficient mice were found to be sensitive to inhibitors of aspartyl and cysteine proteases. The data indicate that different classes of acid pH-dependent proteases can contribute to the regulation of IGFBP-4 abundance.

Animals↗

Biomechanics of the human flexor tendon sheath investigated by tenography.

Tenography has been performed on eight detached fingers and two intact hands of cadavers. Bulging and overlapping of synovial pockets between the ligamentous structures during flexion, their flattening during extension and the continuous change in expansion of the proximal cul de sac suggests a possible mixing mechanism for the synovial fluid. During flexion and extension a physiological joint-type bowstringing of the flexor tendons was observed at the PIP and DIP joints. This finding supports the theory that the flexor tendon moment arm is increased at these joints.

Biomechanical Phenomena↗

Intrathecal baclofen therapy for adults with spinal spasticity: therapeutic efficacy and effect on hospital admissions.

A prospective trial to demonstrate the efficacy of intrathecal baclofen therapy by implanted pump for adults with spasticity due to spinal cord injury or multiple sclerosis was initiated in our hospital. Of the 140 patients assessed, 7 met the following criteria for inclusion in the study: a modified Ashworth score > 3, a spasm frequency score > 2, and an inadequate response to oral anti-spasticity drugs, (i.e., baclofen, clonidine and cyproheptadine). All patients responded to intrathecal bolus injection of baclofen in the double blind, placebo-controlled screening phase (mean bolus dose = 42.8 micrograms). Programmable Medtronic pumps were implanted in 4 patients while 3 patients received non-programmable Infusaid pumps. Post-implantation, a marked decrease in spasticity occurred with a significant reduction of the Ashworth score (mean = 1.8, p < .005), a reduced spasm score (mean = 0.8, p < .005), and an improved leg swing in the pendulum test. These effects were maintained during a follow-up of 24-41 months (average infusion dose = 218.7 micrograms/day). The gross cost-savings due to reduced hospitalizations related to spasticity was calculated by comparing the cost for the two year period before pump implantation to the same period after treatment for 6 of the 7 patients. The cost of in-hospital implantation as well as the cost of the pumps were deducted from the gross savings. There was a net cost-saving of $153,120. Our findings agree with the reported efficacy and safety of intrathecal baclofen treatment, and illustrate the cost-effectiveness of this treatment.

Adult↗

Neonatal thrombosis: are we doing the right studies?

Although neonatal thrombosis may be fatal or cause serious morbidity in survivors, strong clinical recommendations on the management of affected infants could not be made in the 1980s because of the lack of sound data from high-quality studies. To determine whether the "right" studies are now being done, a Medline search (exp infant, newborn, and exp thrombosis) for English language articles 1991-1994, was done and 135 citations were found. After exclusion of 59 nonrelevant articles (such as thrombosis in pregnant women or in vitro studies), plus nine letters to the editor, two reviews, and one consensus report, 64 original articles remained. Eighty-four percent of those (54 citations) were case reports and small case series. Experimental designs (prospective or retrospective cohort and case-control studies) were used in only 10 reports. The recently published literature on neonatal thrombosis continues to show an overabundance of anecdotal reports and a shortage of well-designed collaborative studies. The latter are sorely needed to improve the management of affected infants.

Female↗

Synthetic modification of PAN membrane: biocompatibility and functional characterization.

A disturbing interaction of PAN membranes and the bradykinin generation system particularly in the presence of angiotensin converting enzyme inhibitors has been described. A modified new membrane, SPAN (special PAN), was produced by varying the polymer components in type and composition, in particular by a reduction in Na-Methallylsulfonate. Although the SPAN membrane successfully averted the bradykinin generating ability of PAN, it was important to determine whether such a modification did not lead to a loss of the satisfactory biocompatibility profile characteristic of the parent membrane. For this purpose, we conducted the present clinical study in nine patients comparing 3 membranes; (i) a polysulphone membrane (F60S); (ii) PAN; and (iii) SPAN, to examine the clinical biocompatibility profile and performance of the new membrane. A small increase in C5a with F60S and SPAN was found which is in the range expected for highly biocompatible synthetic membranes. The three dialysers had a similar inert profile for terminal complement complex arterial values, and had similar venous values. A minimal nonsignificant decline in white cell count was observed at 15 min for all dialysers, but otherwise WBC counts were unchanged. Platelet counts were unchanged throughout treatment for the three dialysers. Arterial and venous thrombin-anti-thrombin complex values were similar for all three dialysers. F60S and SPAN dialysers had similar urea clearances.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Immunophenotypic and functional characteristics of haemopoietic cells from human cord blood.

Cord blood (CB) as a new source for bone marrow transplantation represents advantageous features concerning stem cell and leucocyte compartments and function. We attempted to get more information about the phenotypes and function of CB cells by investigating their cell surface markers and also the production of IL-2, IFN-gamma and IL-6 by mitogen and alloantigen stimulation. The CB cells were characterized by a low proportion of CD3+ T cells, CD4+ T subpopulation, activated T cells and CD3+CD16/CD56+ cytotoxic cells, suggesting reduced graft versus host potential. The significant increase of CD19/CD3 double positive cells and decrease of CD19/HLA-DR double positive mature B cells reflect that immature B cells exist in CB. In the functional studies, a 27- and 5-fold reduction was observed in the production of IFN-gamma by CB cells stimulated with PHA and allogeneic cells, respectively. The production of IL-2 in PHA-stimulated CB cells also showed a 50% determination. Decrease in the production of these cytokines by CB cells is supported by the decline of the proportion of CD3+ T cells. However, an increase was observed in the production of IL-6 by CB cells stimulated with allogeneic cells as compared with the controls. These results suggest a difference in the functional activity of the T helper cell subsets between the CB and peripheral blood and/or differences in the functional maturity of T helper cell subsets and B cells in these compartments.

Cells, Cultured↗

Influence of site specifically altered Mip proteins on intracellular survival of Legionella pneumophila in eukaryotic cells.

Legionella pneumophila, the causative agent of Legionnaires' disease, is able to survive intracellularly in eukaryotic cells such as monocytes, macrophages, and protozoan organisms. The Mip (macrophage infectivity potentiator) protein represents a factor of L. pneumophila necessary for optimal intracellular survival. Interestingly, Mip belongs to the substance class of FK 506-binding proteins and exhibits peptidyl-prolyl cis/trans isomerase (PPIase) activity that can be inhibited by the immunosuppressant FK506. In order to identify amino acids most likely to be involved in the enzymatic activity of Mip, site-directed mutagenized Mip proteins were constructed and characterized. It was shown that an Asp-142 to Leu-142 mutation and a Tyr-185 to Ala-185 substitution resulted in strongly reduced PPIase activity of the recombinant Mip proteins (5.3 and 0.6% of the activity of the wild-type Mip, respectively). Genes coding for the wild-type and for site-directed-mutagenized Mip proteins were used to complement three different Mip-negative mutants of the L. pneumophila Corby, Philadelphia I, and Wadsworth. While Mip protein expression could be restored in the corresponding complementants, significant Mip-specific PPIase activity could be detected only in Mip mutants complemented with wild-type mip genes. To investigate the influence of the PPIase activity of Mip on intracellular survival of L. pneumophila, invasion assays were performed using the macrophage-like cell line U937, human blood monocytes, and Acanthamoeba castellanii. The Mip-negative mutants were approximately 50- to 100-fold less infective for A. castellanii and for human mononuclear phagocytes in vitro compared with their isogenic Mip-positive parental strains. The wild-type invasion rate could be restored by introducing an intact copy of the mip gene into Mip-negative strains. In addition, no differences in intracellular survival were observed between the wild-type isolates and the Legionella strains exhibiting strongly reduced PPIase activity. These data indicated that the enzymatic activity of Mip does not contribute to intracellular survival of L. pneumophila.

Amino Acid Isomerases↗

Differential sites of action of 8OHDPAT, a 5HT1A agonist, on ACTH and PRL secretion in the rat.

We recently obtained evidence that activation of the 5HT1A subtype receptor enhances both plasma ACTH and prolactin (PRL) concentrations in rats. In order to explore the possible neuroanatomical structures involved in this interaction, we examined ACTH and PRL responses to intracerebral infusions of the 5HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8OHDPAT). In addition we also tested in vitro effects of 8OHDPAT added to the perifusion medium of pituitary cells or of hypothalamic slices on hormone or neurotransmitter release, respectively. The ACTH response to 8OHDPAT (0.1 mg/kg) was decreased after depletion of endogenous 5HT stores by p-chlorophenylalanine (PCPA) treatment. In contrast, the PRL response was markedly increased under that condition. Infusion of 8OHDPAT (1 microgram/microliter/15 min) into the dorsal raphe nucleus induced a slow elevation of ACTH release but was ineffective on PRL secretion while infusion of 8OHDPAT into the PVN induced a moderate elevation of both ACTH and PRL. After bilateral destruction of the PVN, PRL response to 8OHDPAT (0.1 and 0.25 mg/kg) was markedly potentiated. In contrast, PVN-lesioned animals showed a blunted ACTH response to 8OHdPAT. Basal or CRF-stimulated ACTH secretion rates from perifused dispersed adenohypophyseal cells were not affected by 8OHDPAT but the 5HT1A agonist induced a very slight and transient inhibition of PRL release. 8OHDPAT antagonized, in a dose-dependent manner, the K(+)-induced release of 3H-DA previously taken up in neurons of mediobasal hypothalamic slices. This data suggests that major sites of 5HT1A interaction in PRL and ACTH regulation are located within the CNS and not in the pituitary.(ABSTRACT TRUNCATED AT 250 WORDS)

8-Hydroxy-2-(di-n-propylamino)tetralin↗