Patient-to-patient transmission of hepatitis C virus.
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Biomedical subjects
Publications and source records attributed to W Roth.
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The clinical effects of three lidocaine-containing solutions with and without frigen (freon-113) as a propellant, after different waiting periods, and with different dosages applied were investigated in 130 outpatients who were undergoing dental treatment in the maxilla under local anesthesia. They were divided randomly into five groups (A through E): (A) Xylocaine spray with frigen, two applications (20 mg lidocaine); (B) Xylestesin spray with frigen, two applications (14 mg lidocaine); (C) Xylestesin spray with frigen, three applications (21 mg lidocaine); (D) Xylestesin pump spray without frigen, two applications (14 mg lidocaine); and (E) no topical anesthesia. They were further divided into 12 subgroups to evaluate waiting periods between the application of the topical anesthesia and the injection (1, 2, or 3 minutes). Patients assessed the pain of the injection, intensity of numbness, and intensity of the taste on a visual analog scale; they also assessed the pain of the injection compared to former injections. Pain during injection was reduced by topical application of lidocaine. A waiting period of 2 minutes proved to be sufficient and can be justified to avoid impatience and increased numbness in patients. However, a 3-minute waiting period may be appropriate for sensitive patients. An increase in the dosage failed to show better analgesia. The pump spray without frigen proved to be effective.
The effects of three lidocaine-containing solutions with and without frigen (freon-113) as a propellant on cardiovascular parameters and oxygen saturation, after different waiting periods and with different dosages applied, were investigated in 130 outpatients undergoing dental treatment in the maxilla under local anesthesia. They were divided randomly into five groups: (A) Xylocaine spray with frigen, two applications (20 mg lidocaine); (B) Xylestesin spray with frigen, two applications (14 mg lidocaine); (C) Xylestesin spray with frigen, three applications (21 mg lidocaine); (D) Xylestesin pump spray without frigen, two applications (14 mg lidocaine); and (E) no topical anesthesia. They were further divided into 12 subgroups to evaluate the influence of waiting periods between the application of the local anesthetic and the injection (1, 2, or 3 minutes). Without topical anesthesia and after the 1-minute waiting period, cardiovascular parameters increased immediately after the injection; after 2- and 3-minute waiting periods the increases were far less pronounced. The mean oxygen saturations did not change during the observed period. The higher lidocaine dosage administered (21 mg) did not intensify the positive impact on the cardiovascular parameters compared to the lower dosage (14 mg). The new pump spray without frigen proved to be as effective as the traditional, ecologically harmful aerosol sprays.
A sensitive and selective high-performance liquid chromatographic assay has been developed for a new hypoglycaemic agent AG-EE 388 ZW (I) in human plasma. Plasma samples containing I were acidified with 0.2 M hydrochloric acid, directly injected into C2 reversed-phase pre-columns, and cleaned up on-line. After pre-column switching, the substance was separated isocratically in 15 min on a C18 reversed-phase column. Quantitation was performed after amperometric detection by external standard calibration curves. The linearity of the assay was demonstrated over the therapeutic concentration range 5-200 ng/ml. between-day coefficient of variation was 9.2% at 30 ng/ml. The limit of detection was 5 ng/ml in plasma. Determination of human plasma samples after intravenous and oral administration of 1 mg of 14C-labelled I demonstrated the applicability of the assay for pharmacokinetic studies in humans.
The pharmacokinetics of an i.v. bolus of pimobendan (P) 2.5 mg and 5.0 mg, its tolerability and the effect on heart rate and blood pressure have been studied in 12 subjects (42-70 y) suffering from severe terminal renal impairment. Plasma level data were compared with those obtained in a previous investigation in healthy volunteers. Pharmacokinetics were dose linear and were comparable to those in healthy subjects. No adjustment of the dose of P is necessary in patients with severe renal impairment. Tolerability of P, observed by means of blood pressure monitoring, clinical chemistry tests, electrocardiography and subjective judgement resulted in 4 complaints out of 12 patients: three suffered from orthostatic problems and vomiting, and one patient had nausea. Mean heart rate was elevated by 19% (2.5 mg) and 16% (5.0 mg). Blood pressure was significantly reduced after 2.5 mg P (23% systolic and 26% diastolic pressure), and after 5.0 mg P by 25% systolic and 23% diastolic pressure.
Combined haemoperfusion, haemofiltration and haemodialysis (HPFD) was examined for its systemic effect on 5-fluorouracil (5-FU) kinetics after locoregional application to one female patient with liver metastases of a colon carcinoma. During each HPFD treatment, which lasted 4 h, 5-FU was given via a port-a-cath system into the hepatic artery on 4 separate days. The HPFD extraction rate was 99%. Extracorporal 5-FU clearance (89 ml/min) was 9% of total body clearance (1094 ml/min). The fraction eliminated within 4 h was only 6% of the applied dose (3500-4000 mg 5-FU). Sufficient extracorporal detoxification during combined HPFD can thus not be guaranteed in locoregional chemotherapy with a high dose of 5-FU.
Falipamil (2-[3-[3-(3,4-dimethoxyphenetylmethylamino]propyl]-5,6- dimethoxyphthalamidine; 1) is a new specific bradycardic agent for the treatment of sinus tachycardia. Pharmacokinetics of falipamil in humans (n = 6) was determined in plasma and urine after iv administration of 100 mg (1.85 MBq) per person of 14C-labeled drug by liquid scintillation counting and by a specific, sensitive reversed-phase totally automated HPLC system with fluorimetric detection. Recovery of total radioactivity was 91.8 +/- 3.7%, with 68.2 +/- 4.3% in urine and 23.6 +/- 2.5% in the feces. The majority of radioactivity was excreted within 24 to 48 h. The parent drug, falipamil (1), and its N-desmethyl-metabolite (2), which is approximately 100 times less active than 1, contributed 14.1 +/- 1.6 and 4.5 +/- 0.7%, respectively, of the dose to urinary excretion. Plasma protein binding of 1 and 2 was 87.9 +/- 1.2 (concentration range: 2000-8000 ng/mL) and 89.7 +/- 0.5% (concentration range: 62.5-1000 ng/mL), respectively. Plasma concentrations of 1 peaked at 2 min at 724 +/- 173 ng/mL, declined biphasically, and were fitted to a two-compartment open model. Plasma concentrations of 2 were very low, in all cases ranging from 0 to 35 ng/mL. The dominant terminal half-life (beta-phase) of 1 from plasma was 1.8 +/- 0.6 h (range 1.4-2.9 h), mean residence time was 2.4 +/- 0.4 h, total body clearance was 1108.5 +/- 119 mL/min, and renal clearance was 117 +/- 20 mL/min. All parameters demonstrated very low intersubject variability.
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Pimobendan (10 mg on day 1, then 5 mg twice daily for 28 days) was administered orally to nine patients in class III-IV stable congestive heart failure. On day 1, pimobendan appeared in plasma within 30 min, its plasma concentration peaked at 39 +/- 23 ng/ml after 1.5 h, and then decreased with a half-life of 1.44 +/- 0.94 h. Concentrations of its major metabolite UD-CG 212 peaked 3 h after drug intake, at 24 +/- 7 ng/ml. The time course of plasma concentrations was similar on days 1, 2, and 28. Cardiac index increased from 2.2 +/- 0.5 to 2.8 +/- 0.4 L.min-1.m-2 (p = 0.0001) on day 1, from 2.8 +/- 0.5 to 3.4 +/- 0.4 L.min-1.m-2 (p = 0.0032) on day 2, and stayed at 2.7 +/- 0.6 and 2.7 +/- 0.9 L.min-1.m-2 (p = 0.7895) on day 28. On day 1, pulmonary capillary wedge pressure decreased from 16 +/- 7 to 6 +/- 5 mm Hg (p = 0.0001), from 10 +/- 7 to 7 +/- 8 mm Hg (p = 0.0001) on day 2, and from 9 +/- 7 to 5 +/- 3 mm Hg (p = 0.0275) on day 28. Cardiovascular effects of pimobendan were independent of plasma concentrations. All patients improved by at least one NYHA functional class; exercise tolerance increased. No side effect was observed, but two patients died suddenly: Arrhythmogenicity should be ruled out before pimobendan is recommended for treatment of heart failure.
Pimobendan was administered orally (10 mg single dose on day 1, then 5 mg twice daily for 4 weeks) to nine patients with chronic heart failure undergoing hemodynamic monitoring. The time course of changes in plasma concentrations of pimobendan and of its major active metabolite. UD-CG 212 CL, was similar on days 1, 2, and 28. Pimobendan plasma levels peaked 1.5-2.0 h after drug intake: plasma concentrations of UD-CG 212 CL reached a maximum 1 h later; the terminal half-life of pimobendan in plasma varied between 1.44 +/- 0.94 h on day 1 and 1.19 +/- 0.36 h on day 2. Initially, cardiovascular variables changed with increasing plasma drug levels and reached a maximum 4 h after pimobendan intake; later, we found no correlation between plasma concentrations and hemodynamic effects. A steady state of hemodynamic improvement was achieved after 4 weeks of maintenance therapy with pimobendan. Baseline pulmonary capillary wedge pressure dropped from 16 +/- 7 mm Hg on day 1 to 5 +/- 3 mm Hg at noon on day 28 (-69%; p less than 0.001), and baseline cardiac index increased from 2.2 +/- 0.5 L/min/m2 on day 1 to 2.7 +/- 0.9 L/min/m2 on day 28 (+23%; p less than 0.01). Pimobendan is a long-acting drug that effectively improves cardiac performance in patients with chronic congestive heart failure.
Two paintings from the National Gallery's collection in London were used in an attempt to diagnose dermatologic disease.
Using an oil painting by G.F. Watts displayed in the National Portrait Gallery of London, we made an attempt to diagnose the dermatological alterations recognizable.
IgG and IgM autoantibodies directed against IgE were determined in 95 serum samples from 67 patients with systemic lupus erythematosus, by an enzyme-linked immunosorbent assay. IgM anti-IgE autoantibodies were found in 18 patients (27%) and IgG anti-IgE autoantibodies were detected in 23 patients (34%). The specificity of the immunoassay was confirmed by the ability to inhibit binding with IgE myeloma, but not other immunoglobulin isotypes and the demonstration that the reactivity was directed to the Fc epsilon fragment of IgE. The IgG fraction of certain sera with anti-IgE activity was capable of inducing histamine release from control basophils and cutaneous mast cells. Clinical associations with the presence of anti-IgE activity were sought by retrospective chart analysis of 61 patients. Significant correlation was found with articular involvement, lymphadenopathy, and anti-DNA antibodies (P less than 0.05). Anti-IgE autoantibodies are observed in a significant number of patients with systemic lupus erythematosus and may contribute to the pathogenesis of the vascular and articular lesions characteristic of this disease.
An influence of visual field disorders on sorting performance in the FM 100-hue test is reported. Patients with left-sided field disorders performed worse in the conventional testing direction, i.e. from left to right, compared with patients with right-sided defects. Reversing the direction of sorting led, however, to a similar impairment in patients with right-sided field defects. Observations in normals tested under different conditions of hue sorting support the view that the difference obtained cannot be accounted for by a hemisphere difference in colour processing but by the strategy adopted by subjects.
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) caused a depletion of serum thyroxine, but paradoxically did not change L-3,5,3'-triiodothyronine (T3) levels in serum of rats. The activities of the thyroid-regulated enzymes alpha-glycerol phosphate dehydrogenase (GPD) and malic enzyme (ME) were determined in livers of normal and thyroidectomized (THX) rats treated with 0.1 to 100 nmol TCDD/kg body weight. Mitochondrial GPD activity did not change significantly as a function of TCDD dose in either normal or THX rats. ME activity was induced by TCDD in a dose-dependent fashion, but only in non-THX animals. The absence of ME induction in THX rats treated with TCDD indicates that TCDD is not intrinsically thyromimetic. The dependence of ME induction on thyroid hormones is much like the thyroid-hormone-dependent, multihormonal induction of ME by insulin and glucocorticoids. However, TCDD had no additive or synergistic effects on induction of ME activity in THX rats fed T3. A 30% decrease in steady-state plasma T3 levels of T3-fed animals treated with TCDD relative to T3-fed controls suggested that T3 catabolism was more rapid in TCDD-treated rats than controls. Thus a thyroid-hormone-dependent, multihormonal interaction is suggested as the basis for induction of ME by TCDD, but a strictly T3-dependent process has not been ruled out.
Human lung mast cells have been reported recently to contain small amounts of the elastolytic protease present in the neutrophil and implicated in the pathogenesis of alveolar wall destruction in emphysema. Since mast cells are numerous within alveolar walls, release of inflammatory mediators (and possibly elastase) by cigarette smoking could contribute to alveolar injury in this disease. We therefore examined bronchoalveolar lavage (BAL) fluid for the mast cell granule constituents histamine and tryptase. The results, while not conclusive, supported the possibility that cigarette smoking increases secretion of histamine releasing activity by alveolar macrophages with subsequent degranulation of local mast cells. Mast cell discharge of inflammatory mediators (including neutrophil chemotactic factors and perhaps the elastolytic protease) could then participate in the destruction of alveolar walls.
Osteosynthesis under pressure using two perforating cancellous bone screws in medial and lateral fractures of the neck of the femur and in some cases also in pertrochanteric fractures of the femur has proved successful, in our opinion, in surgery aimed at preserving the head of the femur, as has been confirmed at our hospital by follow-up studies. A striking fact that came to light during follow-up was that there was a higher percentage of incidence of necroses of the femoral head following Pauwels-I-type fractures. However, in our case it was only one necrosis of the head of the femur in a total of five Pauwels-I-type fractures treated by osteosynthesis. A final judgment can surely be passed only by studying a larger number of cases for a longer period of time. We will, therefore, follow up the fractures of the neck of the femur a few years later by re-examination. As a matter of principle, the aim of surgery in osteosynthesis of a medial femoral neck fracture can be attained by means of the cancellous bone screws. A very important aspect which is most essential for successful surgery is the accurate and controlled introduction of the screws via the guide wire. The infection risk is reduced by the small operative approach. In view of the fact that the follow-up examinations revealed more than 72% well-healed fractures of the neck of the femur, we do not think it necessary to effect any changes in our surgical procedure at the present time.