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Biomedical subjects

M Maurer

Publications and source records attributed to M Maurer.

At least 73 records · Page 4Linked to original sources
PubMed1997

A simple immunofluorescence technique for simultaneous visualization of mast cells and nerve fibers reveals selectivity and hair cycle--dependent changes in mast cell--nerve fiber contacts in murine skin.

Close contacts between mast cells (MC) and nerve fibers have previously been demonstrated in normal and inflamed skin by light and electron microscopy. A key step for any study in MC-nerve interactions in situ is to simultaneously visualize both communication partners, preferably with the option of double labelling the nerve fibers. For this purpose, we developed the following triple-staining technique. After paraformaldehyde-picric acid perfusion fixation, cryostat sections of back skin from C57BL/6 mice were incubated with a primary rat monoclonal antibody to substance P (SP), followed by incubation with a secondary goat-anti-rat TRITC-conjugated IgG. A rabbit antiserum to CGRP was then applied, followed by a secondary goat-anti-rabbit FITC-conjugated IgG. MCs were visualized by incubation with AMCA-labelled avidin, or (for a more convenient quantification of close MC-nerve fiber contacts) with a mixture of TRITC- and FITC-labelled avidins. Using this simple, novel covisualization method, we were able to show that MC-nerve associations in mouse skin are, contrary to previous suggestions, highly selective for nerve fiber types, and that these interactions are regulated in a hair cycle-dependent manner: in telogen and early anagen skin, MCs preferentially contacted CGRP-immunoreactive (IR) or SP/CGRP-IR double-labelled nerve fibers. Compared with telogen values, there was a significant increase in the number of close contacts between MCs and tyrosine hydroxylase-IR fibers during late anagen, and between MCs and peptide histidine-methionine-IR and choline acetyl transferase-IR fibers during catagen.

Adult↗
PubMed1997

The mast cell products histamine and serotonin stimulate and TNF-alpha inhibits the proliferation of murine epidermal keratinocytes in situ.

To better characterize the proposed growth modulatory functions of mast cells and their products in the regulation of epidermal homeostasis, we have assessed keratinocyte proliferation by incorporation of [3H]thymidine in murine skin organ cultures after incubation with different concentrations of histamine, serotonin or TNF-alpha. Both histamine and serotonin significantly stimulate the proliferation of keratinocytes as compared to controls (P < 0.001), reaching maxima within a range from micro- to nanomolar concentrations. Even at subnanomolar concentration, TNF-alpha significantly inhibits the incorporation of labelled thymidine by epidermal keratinocytes in murine skin organ culture (P < 0.001). These observations support the concept of mast cell products as modulators of keratinocyte proliferation, and suggest a role for mast cells in the regulation of epidermal tissue turnover under physiological conditions.

Animals↗
PubMed1997

Pharmacokinetics of the angiotensin-converting-enzyme inhibitor, benazepril, and its active metabolite, benazeprilat, in dog.

1. The pharmacokinetics of the angiotensin-converting-enzyme (ACE) inhibitor benazepril were evaluated in eight healthy Beagle dogs. Benazepril was administered orally at a dosage of 7.5 mg (about 0.5 mg/kg) both as a single dose and then once daily for 14 consecutive days. The prodrug, benazepril, and its active metabolite, benazeprilat, were measured in plasma using a gas chromatography mass-spectrometry method with mass-selective detection. 2. Benazepril appeared quickly in the plasma (tmax 0.5 h) and was rapidly eliminated by metabolism to benazeprilat. Peak benazeprilat concentrations were attained later (tmax 1.25 h) and declined biphasically with a rapid elimination phase (t1/2 lambda 1 1.1 and 1.7 h after single and the last repeated dose respectively) followed by a terminal elimination phase (t1/2 lambda z 11.7 and 19.0 h after single and repeated dose respectively). The mean residence time for benazeprilat was 15.2 h after the single dose and 17.4 h after the 14th dose. 3. Repeated administration of benazepril produced moderate bioaccumulation of benazeprilat; the ratio of AUC[0-->24 h]'s after the 14th dose as compared with the single dose was 1.47, equivalent to a half-life for accumulation (t1/2acc) of 14.6 h. Steady-state benazeprilat concentrations at peak (Cmax) and trough (Cmin) were reached within three doses. 4. The pharmacodynamics of benazepril were assessed by measurement of plasma ACE activity. After both single doses and at steady-state, benazepril produced inhibition of ACE activity in all dogs that was maximal at peak effect (Emax = 100%) and long-lasting (> 85% inhibition was present at 24 h). The long duration of action of benazepril on plasma ACE is due to the presence of the terminal elimination phase of benazeprilat, even though most of the metabolite is rapidly eliminated from the plasma.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1997

Hair growth modulation by topical immunophilin ligands: induction of anagen, inhibition of massive catagen development, and relative protection from chemotherapy-induced alopecia.

Selected immunophilin ligands (IPLs) are not only potent immunosuppressants but also modulate hair growth. Their considerable side effects, however, justify at best topical applications of these drugs for the management of clinical hair growth disorders. Therefore, we have explored hair growth manipulation by topical cyclosporin A (CsA) and FK 506 in previously established murine models that mimic premature hair follicle regression (catagen) or chemotherapy-induced alopecia, two major pathomechanisms underlying human hair loss. We confirm that topical CsA and FK 506 induce active hair growth (anagen) in the back skin of C57BL/6 mice with all follicles in the resting stage (telogen) and show that both IPLs also inhibit massive, dexamethasone-induced, premature catagen development in these mice. Furthermore, we demonstrate that CsA and FK 506 provide relative protection from alopecia and follicle dystrophy induced by cyclophosphamide, possibly by favoring the dystrophic anagen pathway of follicle response to chemical damage. Although it remains to be established whether these IPLs exert the same effects on human hair follicles, our study provides proof of the principle that topical IPLs can act as potent manipulators of clinically relevant hair-cycling pathomechanisms. This strongly encourages one to explore the use of topical IPLs in the management of human hair growth disorders.

Administration, Topical↗
PubMed1997

Activated skin mast cells are involved in murine hair follicle regression (catagen).

Increasing evidence supports a role for mast cells (MC) in the control of tissue remodeling. Using the cyclic growth and regression activity of the murine hair follicle (HF) as a model, we have previously demonstrated that MC are involved in regulating the HF transformation from resting (telogen) to active hair growth (anagen). In the present study, we investigated the potential role of skin MC in spontaneous HF regression (catagen), a rapid and highly controlled process of organ involution characterized by massive epithelial cell apoptosis. By histochemistry, immunohistochemistry, and electron microscopy, we first assessed the number, location, and granulation status of perifollicular MC during the anagen-catagen-telogen transformation of back skin HF. Spontaneous catagen induction was associated with a dramatic reduction of dermal MC numbers, preceded by an increase in the percentage of degranulated MC. In vivo, the MC-secretagogues substance P and adrenocorticotropic hormone induced premature and dystrophic catagen development in anagen HF, whereas inhibitors of MC degranulation retarded normal catagen development. Comparing HF cycling in MC-deficient WBB6F1-KitW/KitWv and congenic normal (+/+) mice, catagen development was retarded in the virtual absence of MC. These data support the notion that MC function as hair cycle regulators and are involved in the control of HF regression. The mouse model employed here offers an excellent tool for dissecting the physiologic role of MC as "central switchboards of tissue remodeling" in developmentally regulated systems, specifically in organ involution processes.

Adrenocorticotropic Hormone↗
PubMed1996

Home versus hospital deliveries: follow up study of matched pairs for procedures and outcome. Zurich Study Team.

OBJECTIVE: To assess procedures and outcomes in deliveries planned at home versus those planned in hospital among women choosing the place of delivery. DESIGN: Follow up study of matched pairs. SETTING: Antenatal clinics and reference hospitals in Zurich between 1989 and 1992. SUBJECTS: 489 women opting for home delivery and 385 opting for hospital delivery; the women comprised all those attending members of the study team for antenatal care and those attending the reference hospital for antenatal care who could be matched with the women planning home confinement. MAIN OUTCOME MEASURES: Need for medication and incidence of interventions during delivery (caesarean section, forceps, vacuum extraction, episiotomy), duration of labour, occurrence of severe perineal lesions, maternal blood loss, and perinatal morbidity and death. RESULTS: All women were followed up from their first antenatal visit till three months after delivery. Referrals during pregnancy (n = 37) and labour (70), changes of mind (15 home to hospital, eight hospital to home), and 17 miscarriages resulted in 369 births occurring at home and 486 in hospital. During delivery the home birth group needed significantly less medication and fewer interventions whereas no differences were found in durations of labour, occurrence of severe perineal lesions, and maternal blood loss. Perinatal death was recorded in one planned hospital delivery and one planned home delivery (overall perinatal mortality 2.3/1000). There was no difference between home and hospital delivered babies in birth weight, gestational age, or clinical condition. Apgar scores were slightly higher and umbilical cord pH lower in home births, but these differences may have been due to differences in clamping and the time of transportation. CONCLUSION: Healthy low risk women who wish to deliver at home have no increased risk either to themselves or to their babies.

Abortion, Spontaneous↗
PubMed1996

Follow-up assessment of medication-treated dysthymia.

1. The objective was to assess long-term efficacy of antidepressant medications in dysthymia. 2. In a naturalistic study, patients with DSMIII-R dysthymia who had participated in previous antidepressant trials with fluoxetine and trazodone were evaluated at a mean of 40.0 weeks of follow-up to assess whether medication response persisted over time. A multivariate analysis was performed for patients on vs. off medication. Relapse rates (with relapse defined as HDRS score > 13) were also compared for these two groups. 3. Of 40 patients, the 24 still on medication showed significantly lower scores on most rating scales (HDRS, Cornell Dysthymia Rating Scale, and CGI, but not on the SCL-58) than the heterogeneous group of 16 patients not taking medication. Relapse was low (17.4%) among patients remaining on medication. 4. These preliminary findings suggest that dysthymia patients who remain on medication maintain improvement over time.

Adult↗
PubMed1996

Pharmacological disruption of hair follicle pigmentation by cyclophosphamide as a model for studying the melanocyte response to and recovery from cytotoxic drug damage in situ.

Here we show that cyclophosphamide induces disruption of follicular melanogenesis, which is characterized by abnormal transfer of pigment granules to ectopic hair bulb locations, extrafollicular melanin incontinence, disordered formation of melanosomes, and inhibition of melanosome transfer into precortical keratinocytes. This is in contrast to dexamethasone-induced termination of follicle melanogenesis, which activates premature but predominantly normal catagen development. Cyclophosphamide-induced pigmentation disruption was accompanied by significant alterations of biochemical and biophysical markers of melanogenesis, compared to control mice treated either with vehicle or with topical dexamethasone. Electron paramagnetic resonance spectroscopy shows a decline in the melanin signal and predominant eumelanin production. Tyrosine hydroxylase activity of tyrosinase and dihydroxyphenylalanine oxidation drop rapidly, while DOPAchrome tautomerase activity increases and dihydroxyindole carboxylic acid conversion factor activity remains unchanged in cyclophosphamide-treated mice compared to controls. These observations emphasize the key role of tyrosinase as opposed to postdihydroxyphenylalanine oxidase steps in normal and pathological termination of melanogenesis and shows that tyrosinase is the most sensitive target of the melanogenic apparatus for pharmacological regulation. Follicle pigmentation recovers only during the subsequent hair cycle, i.e., after a new anagen hair bulb has been constructed, which points to the existence of a relatively chemoresistant melanoblast-like cell population residing in the noncycling part of the hair follicle.

Animals↗
PubMed1996

Benign biliary obstruction: is treatment with the Wallstent advisable?

PURPOSE: To evaluate the effectiveness of the self-expanding Wallstent in the treatment of benign biliary strictures. MATERIALS AND METHODS: Twenty patients with benign biliary strictures were included in this retrospective study. Seven patients had chronic pancreatitis, two had fibrous papillary stenosis, one had primary sclerosing cholangitis, and 10 had postsurgical strictures, including four who had a stenosed bilidigestive anastomosis. Primary and secondary patency of the stents and clinical outcome after stent insertion were evaluated. RESULTS: Stent placement was successful in all patients. At the end of the observation period, which lasted 3-78 months (mean, 31.2 months +/- 4.5 [standard error]), 10 patients were alive. Median primary patency was 32 months +/- 8.7. In 10 patients, patency was preserved during the observation period (two with secondary patency). Six patients had a good clinical result. Among the other four patients, one had recurrent cholangitis, one had a biliary abscess, and two had stent revisions. In the other patients, stents became occluded after 3-55 months. The reason for stent occlusion was a stone in one patient; in the others, the causes were not proved. CONCLUSION: Results of stent placement for treatment of benign biliary strictures are not encouraging. However, the patient population is too limited to allow final conclusions.

Cholestasis↗
PubMed1996

Comparison of antegrade with antegrade/retrograde cold blood cardioplegia for myocardial revascularization.

There has been increasing interest in the use of retrograde coronary sinus perfusion for delivery of cardioplegic solution during myocardial revascularization. Despite evidence of improved cardiac protection, it is unclear if a combined antegrade/retrograde approach to myocardial preservation offers significant clinical benefits. One hundred twenty patients undergoing elective 1st-time coronary bypass surgery for 3-or-more-vessel disease received aortic root, antegrade cold blood cardioplegia (Group I, n=52) or combined antegrade/retrograde cardioplegia via coronary sinus cannulation (Group II, n=68). All preoperative variables were similar, including age, severity of coronary artery disease, functional status, and ejection fraction. Intraoperative and postoperative variables, including the degree of hypothermia, temperature of infusion solution, number of bypass grafts, defibrillation attempts and spontaneous return to sinus rhythm, the use of intraaortic balloon pump counterpulsation, and inotropic support during weaning from cardiopulmonary bypass, were not statistically different. Cardioplegia infusion time was longer in Group II than in Group I (2.5 +/- 0.8 vs 1.7 +/- 0.7 min, p < 0.05). The postoperative cardia output, electrocardiographic and cardiac enzyme evidence of ischemia, the need for temporary pacing, and 30-day morbidity were similar for both groups. The data indicate that in this non-risk-stratified group of patients, the route of cardioplegia administration is not a determinant of clinical outcome.

Blood↗
PubMed1995

Embolization of biologic glue during repair of aortic dissection.

A 72-year-old patient was operated on because of an acute type A aortic dissection with the primary entry located in the aortic arch and with retrograde involvement of the ascending aorta. Complete replacement of the aortic arch and the ascending aorta was performed after the dissected aortic layers had been readapted and sealed with gelatin-resorcin-formaldehyde biologic glue. Postoperative neurologic status was judged to be normal. The patient died 3 weeks postoperatively of septic shock. Postmortem examination of the brain revealed several small lesions, and microscopy showed very small particles of polymerized glue in the afferent vessels of ischemic cerebral and meningeal regions.

Aged↗
PubMed1995

Predictors of stroke after cardiac surgery.

From January 1, 1988 to September 30, 1993, 44 of 2,455 patients undergoing cardiac surgery for acquired heart disease at our institution sustained an intraoperative or postoperative cerebrovascular accident (CVA). Demographic data, atherosclerosis risk factors, past medical history, cardiac catheterization reports, and intraoperative findings were retrospectively reviewed. The highest rate of CVA was in the sub-group of patients undergoing simultaneous myocardial revascularization and carotid endarterectomy (18.2%). The lowest rate was in a group of patients who underwent aortic valve replacement (0.9%). Severe aortic arch atherosclerosis with the presence of atheromatous material or calcinosis at the cannulation site was identified intraoperatively in 43.2% of patients with neurological complications and in 5% of the group without CVA (x2 = 18.1, p = 0.0001). Of 44 patients with CVA, 13.6% had a history of preoperative completed stroke. CPB time was 90.1 +/- 4.9 min vs. 71.6 +/- 3.7 min (p = 0.004), and aortic cross-clamping time was 54.5 +/- 3.2 min compared to 39.8 +/- 2.7 min (p = 0.001) in groups with and without postoperative stroke, respectively. Hypertension was an independent risk factor of postoperative CVA (x2 = 9.5, p = 0.02), but age was not. Neurological complications correlated with high operative mortality (38.6%) and prolonged postoperative hospital stays (35.1 +/- 5.3). These data describe predictors for the development of post-cardiopulmonary bypass CVA and identify a high-risk subgroup for neurological events. The preoperative recognition of risk factors is an essential step toward the reduction of morbidity and mortality.

Aged↗
PubMed1995

Mast cells as modulators of hair follicle cycling.

While the central role of mast cells (MC) in allergy and inflammation is well-appreciated, much less is known about their physiological functions. The impressive battery of potent growth modulatory MC products, and increasing evidence of MC involvement in hyperproliferative and fibrotic disorders suggest that tissue remodelling may be one of those, namely in the skin. Here, we delineate why this may best be studied by analysing the potential role of MC in hair growth regulation. On the background of numerous, yet widely under-appreciated hints from the older literature, we summarize and discuss our recent observations from the C57BL/6 mouse model for hair research which support the concept that MC are functionally important modulators of hair follicle cycling, specifically during anagen development. This invites to exploit the murine hair cycle as a model for dissecting the physiological growth modulatory functions of MC and encourages the exploration of MC-targeting pharmaceutical strategies for the treatment of hair growth disorders.

Animals↗
PubMed1994

Mast cell involvement in murine hair growth.

We have examined the possibility that an involvement in hair growth regulation is one of the still obscure physiological roles of mast cells (MC) in normal skin. Using the murine hair cycle as a model, we first studied the number, localization and granulation status of skin MC during the hair cycle of C57 BL-6 mice. Shortly after the induction of hair growth (anagen) in the back skin of mice with resting (telogen) follicles, a sharp decline in the number of Giemsa-stainable MC was detected by morphometry. This was evident in depilation-induced, pharmacologically induced, and spontaneous anagen. By light and electron microscopy, the anagen-associated decline was correlated with the occurrence of substantial MC degranulation. In vivo, the IgE-independent MC secretagogues, compound 48/80 and ACTH, induced anagen in mouse telogen follicles after intracutaneous administration, while inhibitors of mast cell degranulation (cromoglycate, tiacrilast) and antagonists of selected MC products (clemastin, ranitidine, ketanserin) significantly retarded the induced development of anagen follicles in these mice. It is suggested that MC act via their secretory products as stimulators of anagen development in mice and that the murine hair cycle is an excellent model for studying growth regulatory functions of MC in developmentally regulated systems.

Animals↗