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Biomedical subjects

R L Galeazzi

Publications and source records attributed to R L Galeazzi.

At least 37 records · Page 2Linked to original sources

[Pseudopancreatitis in entero-invasive salmonellosis].

The incidence of pancreatitis in bacterial enterocolitis is disputed. Two cases of young patients with S. enteritidis-induced enterocolitis and markedly elevated amylase and lipase blood levels are described. In both patients there were neither clinical nor ultrasonographic signs of pancreatitis. Furthermore, both had increased intestinal permeability for oral 51Cr-EDTA, a condition discussed as "leaky gut" in other publications. In one patient enzyme levels and 51Cr-EDTA resorption became rapidly normal, while in the other the values remained elevated after a 7-month interval with stool culture negative. Enhanced intestinal absorption of 51Cr-EDTA (mw 391) suggests--but does not definitely prove--an inflammatory response of the mucosa leading to increased intestinal permeability, which in turn may allow resorption of amylase (mw 62,000), lipase (43,000) or other macromolecules. Performance of a 51Cr-EDTA resorption test may be helpful in cases of clinical uncertainty.

Adult↗

[Incidence of drug side effects by symptoms and syndromes. From the experiences of the Comprehensive Hospital Drug Monitoring and the Swiss Drug Side Effect Center. As an example: allergic and pseudo-allergic reactions with mild analgesics and NSAID].

From 1974 to 1989, 37,392 patients were admitted to the divisions of general internal medicine of the CHDM hospitals. 19,082 of them were treated with a minor analgesic or an NSAID. In 95 of the exposed patients, an allergic or a pseudoallergic reaction to one or two of these drugs was observed. From 1981 to 1990, general practitioners, hospitals and the pharmaceutical industry reported to SANZ 158 individual cases with comparable reactions to 175 exposures of the same kind. Of the 15 different syndromes and symptoms registered in both institutions, most were reactions of the skin, mainly the usual maculopapular exanthemas (rash), urticaria and angioedema. In the CHDM, allergic or pseudoallergic reactions were observed in 0.23% of patients exposed to minor analgesics (including ASA preparations on a daily dose up to 1.0 g and pyrazolones, mainly metamizole, propyphenazone) and in 0.81% of patients exposed to NSAIDs (including the pyrazolone oxyphenbutazone). In the experience of the Comprehensive Hospital Drug Monitoring in Berne and St. Gallen (CHDM) and the Spontaneous Adverse Drug Reactions Center of Switzerland (SANZ).

Adverse Drug Reaction Reporting Systems↗

[Adverse reactions to natural remedies].

There are only a few systematic epidemiological studies concerning the frequency of adverse reactions (AR) to natural remedies. However, there are numerous case reports which sometimes also include some detailed pathophysiological investigations. In general, four different categories of side effects to natural remedies can be distinguished: 1--at normal use; 2--at excessive use; in this regard many publications exist, since natural products are generally assumed to be safe and, therefore, are frequently taken in overdose; 3--induced by falsified products, e.g. through addition of steroids to for example "natural" antiasthmatics; 4--induced through omission of an efficient and proven therapy because of unshakable believe in "nature". Since conclusive studies in this matter are methodologically cumbersome and very difficult to perform, two newer studies that address these problems in special situations (oncologic patients) are the more interesting.

Drug Contamination↗

[Rhodococcus erythropolis infection in HIV-associated immunodeficiency].

We report the first case in the literature of human infection with Rhodococcus erythropolis in an HIV-positive patient. A 24-year-old bisexual flight attendant had severe HIV-associated immunodeficiency with a CD4 cell count of 0.02 G/l. He complained of multiple subcutaneous nodules at different sites on the extremities. Biopsy of one node at his left knee revealed granulomatous inflammation filled with acid-fast rods. These bacteria were identified as Rhodococcus erythropolis. The disseminated infection was restricted to the skin and showed a slow response to long-term therapy with amoxicillin/clavulanic acid. No relapse has been observed more than 6 months after discontinuation of antibiotic therapy. The etiology of a concomitant polyarthritis remains unknown; a relationship with the rhodococcus infection is possible as the arthritis responded well to the antibiotic therapy and did not reactivate after discontinuation of antibiotics. Due to the difficult isolation technic, this pathogen may be overlooked in routine diagnostic procedures. The implications in clinical practice are discussed.

Actinomycetales Infections↗

[Amborum Special F and ASFO--2 glucocorticoid-containing herbal remedies].

Amborum Special F and ASFO are two names of a herbal remedy which is adulterated with the glucocorticoid betamethasone. Patients with asthma, rheumatic and chronic diseases import the drug direct from Burbank, California, USA. Its impressive antiasthmatic effect is reported in two patients. While under therapy the first patient developed Cushing's syndrome and the second showed suppression of adrenal cortisol production. The manufacturer, who claims that the drug contains no "western medicine" and in particular no cortisone, is unscrupulous enough to recommend it for children under two years of age. We have observed that a marked glucocorticoid effect and marked glucocorticoid side effects are achieved with small doses of betamethasone. A review of the literature and the two cases reported here suggest that the equivalence doses given in textbooks and tables of glucocorticoid equipotency are incorrect for betamethasone. Betamethasone is a more potent glucocorticoid than hitherto reported.

Adult↗

The development of a German language (Berne) pain questionnaire and its application in a situation causing acute pain.

The adjectives used in the McGill Pain Questionnaire were translated into German. Nine of the 76 adjectives could not be translated satisfactorily. Accordingly, 10 new German adjectives were added by 22 physicians and psychologists, who were also asked to judge the grouping of the words and how adequately they express pain. Concordance of grouping was reached by more than 82% of the raters. The adjectives were assigned to 20 groups. In a next step 80 subjects assessed the words in each group on a visual analogue scale (VAS) with respect to intensity: for 3 of the 20 groups we found no difference in intensity between the adjectives within a group. They were not retained in the final version tested. Additionally each group was reduced to 3 adjectives by dropping the least discriminating words of each group; 17 groups of 3 words each were retained. In a third step a comparably composed group of 82 subjects rated the words in each group on VAS with respect to intensity: for each of the 17 triads there was a significant overall difference between the 3 adjectives on the VAS. In all but 4 of the 17 triads all 3 possible pairwise differences were significant as well. In spite of the significant differences of mean values there was considerable disagreement in individual intensity rankings of the 3 adjectives within the 17 groups. The validity of the German language (Berne) pain questionnaire (BPQ) was tested together with a verbal rating scale (VRS) and a VAS in a double-blind, complete cross-over study. A low osmolar (LO), a high osmolar (conventional) (HO) compound and 0.9% NaCl (placebo) (PL) were injected intra-arterially in patients with arteriovascular disease. We expected the LO compound to cause much less pain than the HO compound. The 3 conditions HO, LO and PL had significantly different effects on all 4 scales: VAS, VRS, RaW (scale of rank of words), and NoW (scale of number of words). The pairwise comparisons of PL with HO and LO resulted in significant differences also. The square of the correlation r for VAS/VRS was 0.64, for RaW/NoW 0.61, all other possible correlations were not significant. Our conclusions are: the translation of the MPQ into German was successful, and its validity could be shown. In our experiment, it differentiated acute, short lasting pain as well as the visual analogue and the verbal rating scales. The BPQ is a tool worth being examined in the laboratory and in studies of clinical pain syndromes.

Evaluation Studies as Topic↗

[Polyneuropathy, organomegaly, endocrinopathy and skin changes in a case of solitary myeloma].

The case is reported of a 32-year-old woman with polyneuropathy, organomegaly, edema, endocrinopathy, dark skin and solitary myeloma with monoclonal gammopathy of IgG/lambda type. More than 100 cases of this rare disorder have been observed up to now, mainly in Japan. In recent reviews the terms POEMS-syndrome or Crow-Fukase-syndrome have been used. Local radiotherapy of the myeloma led to lasting regression of symptoms. Studies with immunocytochemistry and immunoelectroblotting revealed specific antibody activity against hypophysis, suggesting that the pathologic monoclonal myeloma antibodies may damage the neuroendocrinic centers in hypothalamus and hypophysis as the primary target. Most of the multisystemic symptoms would thus be explained as secondary alterations.

Adult↗

The antiemetic activity of high-dose alizapride and high-dose metoclopramide in patients receiving cancer chemotherapy: a prospective, randomized, double-blind trial.

Alizapride is a new substituted benzamide with suggested superior antiemetic efficacy to and fewer side effects than metoclopramide. High-dose alizapride (4 mg/kg X five doses) was compared with high-dose metoclopramide (2 mg/kg X five doses) in a prospective, randomized, double-blind trial in 62 evaluable patients undergoing strongly emetic cancer chemotherapy. Patients receiving metoclopramide experienced significantly fewer vomiting episodes than patients receiving alizapride (median of three episodes vs. eight episodes; P less than 0.001). Metoclopramide was more effective in decreasing the volume of emesis than was alizapride (median of 100 ml vs. 360 ml; P less than 0.02). Seventy-two percent of the patients receiving alizapride and 57% of those receiving metoclopramide experienced side effects. High-dose metoclopramide is an effective antiemetic in patients receiving cancer chemotherapy. Alizapride is less effective and has more side effects than metoclopramide. We do not recommend the further use of alizapride.

Adult↗

[Hemodynamic effects of a new long-acting isosorbide dinitrate].

The following hemodynamic parameters were measured at rest and 1, 2, 4, 6, 8, 12 and 24 hours after 100 mg of ISDNSR p.o. in 10 patients with dilated cardiomyopathy (NYHA class III-IV): mean pulmonary artery, pulmonary capillary wedge (PCW) and arterial pressures (AP), and cardiac output (thermodilution). Plasma levels of ISDN were determined by capillary gas chromatography at the same intervals and correlated with the hemodynamic changes. PCW fell from 24 +/- 1.5 (SE) to 18 +/- 1.8 mm Hg after 1 hour (p less than 0.05) and after 2 hours to 16.9 +/- 1.6 mm Hg. This change was sustained for 8 hours. At 12 hours PCW had increased again to 21 +/- 1.5 mm Hg and at 24 hours to 22 mm Hg. AP dropped from 89 +/- 5 to 81 +/- 4 mm Hg at 1 hour (p less than 0.2) and remained 80-84 mm Hg for 8 hours. It returned to baseline levels at 12 hours. Heart rate, cardiac index, systemic vascular resistance, stroke index and left ventricular work index did not change significantly during the observation period. Plasma levels of ISDN remained between 3 and 12 ng/ml for 16 hours. Thus, ISDNSR is an effective long-acting nitrate preparation which reduces preload for 8-12 hours. After this interval, nitrate tolerance starts to develop.

Blood Pressure↗

Steady-state concentration of cotinine as a measure of nicotine-intake by smokers.

Measurement of plasma cotinine, the major metabolite of nicotine, is usually done to determine nicotine-intake in smokers. Cotinine is used instead of nicotine because it has a much longer half-life than the mother substance and its plasma concentrations are therefore less dependent on the exact times of blood sampling. However, the linearity of the relationship between nicotine-intake and cotinine level in plasma has never been proven. Therefore cotinine was measured in 6 healthy volunteers infused over 4 days with several doses of nicotine i.v. up to 480 micrograms/kg/day. Cotinine concentrations in plasma were shown to be linearly and directly related to nicotine intake. The concentration of cotinine showed little variation during and for up to 2 h after the last dose of nicotine. Therefore, cotinine can be used as an epidemiological marker of nicotine intake if it is measured around the time of the last cigarette of the day.

Adult↗

Alizapride, a new substituted benzamide, as an antiemetic during cancer chemotherapy.

In early clinical trials alizapride showed a better antiemetic activity with fewer side effects than metoclopramide. Alizapride has now been evaluated in an open dose-ranging study in 24 patients receiving strongly emetic chemotherapy. Alizapride 4-8 mg/kg was given as a 15 min infusion 0.5 h before and 1.5, 3.5, 5.5 and 8.5 h after the chemotherapy. At the dose levels of 6 and 8 mg/kg x 5, respectively 6 out-of 9 and 4 of 4 patients experienced side effects (hypotension, dizziness, profuse sweating, general malaise and diarrhoea). At 4 mg/kg x 54 of 15 patients experienced side effects due to alizapride (dyspnoea 1, diarrhoea 2, extrapyramidal syndrome 1 patient). Overall, 9 of 24 patients were partially or completely protected from nausea and vomiting. Based on this experience alizapride has antiemetic activity and few side effects in the dose of 4 mg/kg x 5.

Adult↗

Effects of the calcium antagonist tiapamil on pulmonary gas exchange in patients with chronic obstructive pulmonary disease who receive salbutamol.

Patients with chronic obstructive pulmonary disease (COPD) and cardiovascular diseases are frequently given combination therapy with a beta 2-agonist and a calcium antagonist. Each drug is known to increase ventilation-perfusion inequalities. It was our aim to define the effects of their combination on lung function and on pulmonary gas exchange in eight subjects with COPD but partially reversible airway obstruction. Sixty minutes after placebo or 450 mg tiapamil, subjects inhaled 0.2 mg salbutamol. There was no significant effect of tiapamil on specific airway conductance and the forced expiratory volume in 1 second before or after the inhalation of salbutamol. Blood was drawn 30, 55, 80, and 100 minutes after placebo or tiapamil dosing. After placebo the mean (+/- SD) arterial oxygen tension (Pao2) fell from 67.1 +/- 7.3 to 64.4 +/- 5.5 mm Hg and the mean alveolar-arterial oxygen tension difference (AaDo2) rose from 34.6 +/- 8.4 to 40.5 +/- 6.8 mm Hg. After tiapamil the mean Pao2 fell from 68.7 +/- 7.3 to 66.4 +/- 5.8 mm Hg and the mean AaDo2 rose from 35.1 +/- 6.8 to 38.7 +/- 7.4 mm Hg. The changes in Pao2 were not significant. The increase in AaDo2 after placebo was significant, but that after tiapamil was not. We conclude that the combination of the calcium antagonist tiapamil and the bronchodilator salbutamol is safe with respect to lung function in COPD. There is no evidence that tiapamil increases beta 2-agonist-induced impairment in pulmonary gas exchange.

Adult↗

Isosorbide dinitrate bioavailability, kinetics, and metabolism.

We studied the kinetics of isosorbide dinitrate (ISDN) after a dose of 5 mg iv and the bioavailability of a sublingual and an oral preparation of ISDN. Plasma levels of isosorbide 5-mononitrate (IS-5-MN), isosorbide 2-mononitrate (IS-2-MN), and ISDN were determined by GLC. After intravenous and sublingual dosing, ISDN plasma levels declined biexponentially and could adequately be described by an open two-compartment body model. Distribution was rapid; the t1/2 was 4.7 minutes after intravenous injection and 8.7 minutes after sublingual dosing. The volume of distribution at steady state was 90 L. The terminal disappearance t1/2 was 54.7 minutes after intravenous injection, 48.8 minutes after sublingual dosing, and 47.7 minutes after oral dosing. Total plasma clearance was 136 L/hr, exceeding normal liver plasma flow and indicating extrahepatic metabolism of ISDN. ISDN bioavailability after oral (10 mg) or sublingual dosing (10 mg) was similar (about 29%), indicating that the first-pass effect cannot be avoided by sublingual ISDN dosing. After intravenous ISDN, mononitrate plasma levels could be adequately described by another two-compartment body model. The terminal t1/2 was 4.33 hours for IS-5-MN and 1.83 hours for IS-2-MN. Noncompartmental calculations of the mononitrate levels revealed 100% systemic availability after oral and sublingual ISDN. We assume that ISDN was completely absorbed from the gastrointestinal tract, but 70% was metabolized during the first pass through the liver. After 5 mg iv ISDN, 16 mumol IS-5-MN and 5.3 mumol IS-2-MN reached systemic circulation. The entire dose of ISDN was converted to its two metabolites in a ratio of 3:1 (i.e., 75% IS-5-MN and 25% IS-2-MN).

Administration, Oral↗

Pharmacokinetics of cefoperazone in patients undergoing chronic ambulatory peritoneal dialysis: clinical and pathophysiological implications.

The pharmacokinetics of cefoperazone after i.p. and/or i.v. administration were studied in 12 CAPD patients. After i.v. injection, the plasma half-life was 2.65 +/- 0.4 h, the total clearance amounting to 70.1 +/- 19.2 ml/min. Peritoneal clearance was calculated to be 6.9 +/- 1 ml/min. After peritoneal instillation, the bioavailability was 63.9 +/- 5%. After repeated i.p. administration, no accumulation of the drug in the body was observed. Thus, cefoperazone can be safely administered for the treatment of peritonitis in CAPD patients.

Cefoperazone↗

Simultaneous modeling of bopindolol kinetics and dynamics.

Bopindolol has beta-blocking effects for 96 hr despite a 4-hr t1/2. To investigate the concentration-effect relationship after single and repeated doses. 2-mg oral doses were given once and then daily for 13 days to six healthy subjects. In plasma, no unchanged drug, only the hydrolysis product of bopindolol (referred to as bopindolol concentration) was detectable or could be measured up to 24 hr. Chemical assay by HPLC and determination of total active beta-adrenoceptor blocking material by radioreceptor assay gave identical results. The t1/2 was 4 to 5 hr. Effects, measured as reduction in exercise-induced tachycardia (REIT) and as the isoproterenol dose ratio (DR - 1), were followed for 96 hr. The concentration of bopindolol in plasma (predicted with a one-compartment body model) could be related to the measured effects by classic effect models for 20 t1/2s. Parameter estimates for kinetic end effect models did not differ after single and repeated doses. With the parameters from the single-dose experiment, the time course of the plasma concentration and the effects after the multiple-dose experiment could be adequately predicted for 24 and 96 hr. A deep compartment, an active metabolite, or irreversible destruction of the receptor (accounting for the persistence of the effect) could be excluded. The "dissociation constant" of 100 pmol/l (from DR -1/concentration) and the minimal effective plasma concentration (from REIT/log concentration) of 1 pmol/l suggest that enough receptors are occupied at chemically unmeasurable levels in plasma to induce an effect. The "dissociation constant" determined in vivo is of the same order as that from in vitro radioligand studies.

Absorption↗

Isosorbide 5-mononitrate and isosorbide 2-mononitrate kinetics after intravenous and oral dosing.

Isosorbide 5-mononitrate (IS-5-MN) and isosorbide 2-mononitrate (IS-2-MN) kinetics were studied in two groups of young healthy subjects after intravenous injection of 5 mg of both and after oral doses of 20 mg of IS-2-MN and 10, 15, and 20 mg of IS-5-MN. Mononitrate plasma levels were measured by GLC with capillary columns. After intravenous injection, IS-5-MN and IS-2-MN plasma levels declined biexponentially and could be described by an open two-compartment body model. Distribution t 1/2 was rapid; 8.6 min for IS-5-MN and 12.5 min for IS-2-MN. Substances were distributed throughout body water; volume of distribution at steady state (Vd ss) was 48 l for IS-5-MN and 55 l for IS-2-MN and elimination t 1/2 was 4.15 hr for IS-5-MN and 1.9 hr for IS-2-MN. Total plasma clearance was 8.5 l/hr for IS-5-MN and 23.2 l/hr for IS-2-MN. After oral doses the mononitrates were rapidly and completely absorbed (absorption t 1/2 ranged from 2.5 to 5 min) from the gastrointestinal tract without first-pass metabolism, i.e., absolute systemic availability was 100%. In the dose range studied, kinetics of the two mononitrates were linear. Compared with isosorbide dinitrate, mononitrate kinetics are different because of greater systemic availability, slower clearance, and smaller Vd ss.

Absorption↗