A new hyaluronic acid polymer in the augmentation and restoration of labia majora.

Aesthetic surgery of female external genitalia has gained increasing popularity over the past decade, with reduction of the labia minora (labiaplasty) being the procedure most commonly requested and performed. Female external genitalia lose elasticity and volume with age, but few studies describe the techniques for labia majora augmentation. Currently, very few studies have investigated the effectiveness and safety of labia majora augmentation with hyaluronic acid (HA) injection. This study aims to evaluate the effectiveness and safety of labia majora augmentation with hyaluronic acid filler injection. We retrospectively analyzed 37 patients affected by hypotrophy of the labia majora, treated with HA dermal filler 28mg/ml PEG crosslinked (Neauvia® Intense Rose, Matex Lab, Switzerland) between May 2015 and July 2016. Global evaluation of the aesthetics of the intimate area and clinical data were investigated with VAS (Visual Analogic Scale) ad hoc. Adverse events and complications were recorded. A total of 37 women affected by labia majora hypotrophy were treated with 28mg/ml HA dermal filler. A significant clinical improvement was observed in the score provided by both patients and doctor. Only mild adverse events and complications were recorded. HA hydrogel with a novel crosslinking agent is able to provide a considerable rejuvenation with a simple outpatient procedure and to bring a significant clinical improvement. HA-based filler infiltration treatment in labia majora is repeatable, has virtually no complications, and is reversible.

VATS in complicated COVID-19 patients: case series.

Common complications of coronavirus disease 2019 (COVID-19) related ARDS and ventilation are barotrauma-induced pneumothorax, pneumatocele and/or empyema. We analysed indications and results of video-assisted thoracoscopic surgery (VATS) in complicated COVID-19 patients. This is a retrospective single-institution study analysing a case series of patients treated by VATS for secondary spontaneous pneumothorax (SSP), pneumatocele and empyema complicating COVID-19, not responding to drainage in Lodi Maggiore Hospital between February 2020 and May 2021. Out of 2076 patients hospitalized in Lodi Maggiore Hospital with COVID-19, nine Males (0,43%; mean age 58,1-33-81) were treated by VATS for complications of pneumonia (6 SSP and 3 empyema; 1 case complicated by haemothorax). 7 patients (77%) had CPAP before surgery for 21.3 days mean (4-38). Mean Operative time was 80.9 min (38-154). Conversion rate was 0%. 3 (33%) patients were admitted to ICU before VATS. Treatments were: bullectomy in six patients (66%), drainage of the pleural space in all patients, pleural decortication and fluid aspiration in five cases (55%). two patients (22%) needed surgery interruption and bilateral ventilation to restore adequate oxygenation. Mortality was 1/9 (11%) due to respiratory failure for persistent pneumonia. In one patient (11%) redo surgery was performed for bleeding. Mean postop Length of Stay (LOS) was 37.9 days (10-77). Our report shows that VATS can be considered an extreme, but effective treatment for COVID-19 patients with SSP, pneumatocele or empyema, for patients who can tolerate general anaesthesia. Attention must be paid to the aerosol-generation of infected droplets.

Paranasal sinuses anatomic variants: 64-slice CT evaluation.

AIM: The aim of the paper was to perform a 64-slice CT evaluation of the main anatomic variants of paranasal sinuses. METHODS: From April 2005 to January 2006, 100 patients were chosen among all those that had undergone a paranasal sinuses CT examination. They were 45 women and 55 men, all aged between 18 and 70 years, mean age 46 years; they were all caucasian. This research has been conducted using a 64-slice Siemens Somatom Volume-Zoom multidetector Spiral CT. Para-nasal sinuses CT examination has been performed through a thin axial acquisition; the patient was lying on his back and the images were processed with multiplanar reconstruction (MPR). The anatomic variants considered in this study are: concha bullosa, Haller cells, uncinate process abnormalities, agger nasi cells, ethmoidal bulla, Onodi cell, middle turbinate curvature abnormalities. RESULTS: In this research it has been noticed that 29% of patients are affected by concha bullosa, 5% by Haller cells and again 5% by uncinate process abnormalities; 52% are affected by agger nasi cells, 15% by ethmoidal bulla, 9% by Onodi cell and 11% by middle turbinate curvature abnormalities. CONCLUSION: By using a 64-slice CT you can get a better quality of images in terms of spatial and temporal resolution. Osteomeatal complex structures are often featured by many anatomic variants. The most of the time, percentages are the same as recent researches have shown.

Intracavitary chemotherapy with thiotepa in malignant pericardial effusions: an active and well-tolerated regimen.

PURPOSE: Malignant pericardial effusion, although highly variable, is an uncommon complication of cancer. It is often associated with symptoms like dyspnea, chest pain, and cough, which may be severe and disabling. We analyzed the results of our current treatment policy to evaluate the effectiveness and tolerance of a new approach for this disorder. PATIENTS AND METHODS: Patients with malignant pericardial effusions were treated with intracavitary thiotepa (15 mg on days 1, 3, and 5) through an indwelling pericardial cannula after extraction of as much pericardial fluid as possible on day 0. Responses were assessed by clinical examination, computed tomographic (CT) scan, and echocardiography before treatment, 1 month after treatment, and every 2 months thereafter. Twenty-three patients with malignant symptomatic pericardial effusion were treated and all were assessable for effectiveness and tolerance of the procedure. RESULTS: Nine patients with breast cancer, 11 with lung cancer, two with an unknown primary tumor, and one with metastatic melanoma were treated. In all but three patients, systemic medical treatment was started after completion of intracavitary therapy. Nineteen patients responded to treatment (83%; 95% confidence interval, 61% to 95%) with a rapid improvement of symptoms. The median time to pericardial effusion progression was 8.9 months (range, 1 to 26). No significant side effects were registered, except one patient who had transient grade III thrombocytopenia and leukopenia and one patient who had grade I leukopenia. CONCLUSION: A short course of intracavitary treatment with thiotepa is highly effective and well tolerated in the treatment of malignant pericardial effusion.

Inhibition of diazepam metabolism by fluvoxamine: a pharmacokinetic study in normal volunteers.

The effect of fluvoxamine on the pharmacokinetics of diazepam and metabolically derived N-desmethyl-diazepam was investigated in eight healthy volunteers. Each subject received a single oral dose of diazepam (10 mg) in a control session and on the fourth day of a 16-day treatment with fluvoxamine maleate (100 to 150 mg daily). Compared with the control session, concurrent fluvoxamine intake was associated with increased mean peak plasma diazepam concentrations (from 108 to 143 ng/ml, geometric means, difference not significant), with a marked reduction in apparent oral diazepam clearance (from 0.40 to 0.14 ml/min/kg; p < 0.01) and with a prolongation in diazepam half-life (from 51 to 118 hours; p < 0.01). Although peak plasma N-desmethyldiazepam levels were similar in the two sessions, the time required for the metabolite to reach a peak was longer during fluvoxamine intake than in the control session (206 versus 62 hours; p < 0.01). N-Desmethyldiazepam area under the plasma concentration-time curve values were also significantly increased during fluvoxamine treatment. These data suggest that fluvoxamine inhibits the biotransformation of diazepam and its active N-demethylated metabolite. The magnitude of this interaction is likely to have considerable clinical significance.

Fibrocellular tissue responses to endovascular and external beam irradiation in the porcine model of restenosis.

PURPOSE: Endovascular radiation has reduced postangioplasty restenosis in preclinical and early clinical studies. External radiation treatment may have advantages over endovascular therapy. We examined vascular and perivascular tissue responses to endovascular and external irradiation in pig coronary arteries. METHODS AND MATERIALS: Ninety-one animals received endovascular or external radiation following balloon injury and were sacrificed at 14, 30, or 180 days. Injured segments of coronary vessels including perivascular and myocardial tissues were evaluated with histochemistry. RESULTS: Endovascular radiation was associated with delayed arterial wound healing as late as 6 months, evidenced by paucity of smooth muscle alpha-actin in neointimal cells compared to control. External treatment was associated with increased collagen in neointima and adventitia, and focal interstitial necrosis in adjacent myocardium. CONCLUSIONS: These investigations showed whole-heart 14 Gy external radiation treatment following coronary injury exacerbated certain aspects of arterial healing. In addition focal myocardial necrosis and fibrosis was observed following external but not endovascular irradiation. Endovascular radiation has some advantages over external irradiation; however the persistence of a synthetic smooth muscle cell phenotype in the neointima at 6 months suggests ionizing radiation in general may have profound effects on vessel architecture over the long term.

Intracoronary radiation decreases the second phase of intimal hyperplasia in a repeat balloon angioplasty model of restenosis.

PURPOSE: Repeat balloon angioplasty is likely to induce intimal proliferation, which is associated with a higher restenosis rate. This study examined the effect of intracoronary ionizing radiation on restenotic lesions using repeat balloon injury in a normolipemic swine. METHODS AND MATERIALS: Eight domestic normolipemic pigs underwent overstretch balloon angioplasty with a 3.5 mm balloon in the LAD and LCX, followed by repeat balloon injury at the same sites 4 weeks after the initial injury. At that time a high activity 192Iridium source was introduced immediately after the angioplasty by random assignment to deliver 14 Gy at 2 mm in eight of the injured coronary arteries (LAD and LCX). One month later the animals were killed and the coronary arteries pressure perfusion fixed. Serial sections were stained with H&E and VVG, then evaluated by histopathologic and morphometric techniques. Maximal intimal thickness (MIT), intimal area (IA), and intimal area corrected for the extent of injury (IA/FL) were measured in the irradiated and control arteries and were compared to control arteries with single injuries from previous studies. RESULTS: Repeat balloon injury induced significant additional medial damage, which was associated with marked intimal hyperplasia in a concentric pattern. Intracoronary irradiation significantly decreased the total of neointima area formation (IA 93 + 0.35 mm2 compared to control 1.38 + 0.33 mm2 p < 0.01) and the MIT was also significantly reduced in the irradiated vessels (0.57 + 0.18 mm vs. 0.71 + 0.08 mm, p = 0.05). CONCLUSIONS: Intracoronary irradiation immediately after the second balloon dilatation inhibits the intimal hyperplasia due to that injury. However, there was no effect on the existing neointima from the initial injury.

Oral sustained-release aminophylline and bronchodilator response to inhaled fenoterol in patients with chronic airflow obstruction.

The bronchodilator response to inhaled fenoterol (400 micrograms) was examined in the morning and in the afternoon before and during oral sustained-release aminophylline treatment in eight patients with chronic reversible airway obstruction. Bronchodilatation was evaluated by measuring serial peak expiratory flow rates (PEFR) for eight hours after inhaled fenoterol and calculating the area under the time-response curves and the percentage increment from the baseline values. The patients showed an enhancement of the bronchodilatation achieved with fenoterol in the morning during aminophylline treatment. In the afternoon, instead, the effect of the fenoterol was not improved by oral aminophylline. This different effect of oral aminophylline might depend on the variable degree of potential reversibility present or diurnal variation in the bronchial response.

Inhibition of platelet deposition with local delivery of heparin using a double balloon catheter.

Heparin is an effective agent in the treatment of unstable angina and myocardial infarction. The clinical utility of heparin is limited by bleeding complications. This study was performed to determine whether static delivery of heparin could effectively inhibit further platelet deposition. Thrombogenic graft segments were incorporated into chronic arteriovenous shunts in pigs. Autologous platelets were labeled with 111Indium. Platelet deposition was quantitated with gamma camera imaging. The grafts were exposed to blood flow for 15 min in order to induce platelet deposition on the thrombogenic surface. Heparin was delivered locally either by direct exposure or with a double balloon catheter. After a 15 minute exposure period, the heparin solution was removed and subsequent platelet deposition was monitored for 90 minutes. Heparin, administered with the double balloon catheter in doses as low as 12.5 U, effectively inhibited further platelet deposition. An intravenous injection of 100 U of heparin, the highest dose use for local delivery, did not perturb bleeding time or the activated partial thromboplastin time. In conclusion, platelet deposition can be inhibited with static local delivery of heparin at doses that are not associated with systemic bleeding.

High-performance liquid chromatography of food colours and its relevance in forensic chemistry.

The forensic interest in the use of food colours is related to health rights and safeguard of the consumer, as established in national legislations. The regulations related to food dyes consider the health of human beings and the adulteration of foodstuffs and economic needs connected with quantitative restrictions on imports. Efficient analytical methods are required for evaluating toxicity and authenticity or adulteration, in order (a) to determine whether there are synthetic dyes present in foods and whether they are permitted, (b) to determine the levels, (c) to confirm the absence of added dyes in foods where they are not declared and (d) to check on the stability of dyes during processing and storage. Recent HPLC methods for the identification and determination of natural and synthetic dyes and of carcinogenic amines contained as impurities in synthetic dyes are reviewed.

Annual dose of noise absorbed by machine drivers in wine and cereal growing.

We calculated the annual noise dose absorbed by machine drivers engaged in wine and cereal growing. In order to do that it has been measured the average daily noise dose in the various mechanized operations and then calculated in respect of its duration in a working year. The days spent in manual works were also taken in account. The annual dose of noise became somewhat higher than 90 dB(A) in wine growing, while in cereal growing it was a bit higher than 95 dB(A). The reliability of these data was confirmed by an epidemiological study of hearing damage. In 106 tractor-drivers, employed in farms where wine and cereal growings are done, it was found that the hearing threshold shift due to noise (average 1000-2000-4000 Hz) in relation to the years of employment, had a similar course to that forecasted by the Normative ISO-DIS 1999 in those exposed to a noise dose of 95 dB(A).

Omeprazole does not enhance the metabolism of phenacetin, a marker of CYP1A2 activity, in healthy volunteers.

Omeprazole has been reported to increase cytochrome P450IA2 (CYP1A2) activity in vitro, but whether this effect also occurs in vivo is controversial. To clarify this issue, the effect of omeprazole (20 mg/day for 8 days) on the kinetics and metabolism of phenacetin, an in vivo marker of CYP1A2 activity, was examined in 10 healthy volunteers. The pharmacokinetic parameters of phenacetin and metabolically derived paracetamol on the 8th day of omeprazole administration were very similar to those observed in a control session in the absence of omeprazole administration, the only significant difference being a higher peak plasma phenacetin concentration during omeprazole treatment. It is concluded that at the dosage used omeprazole does not increase the rate of oxidative and conjugative reactions involved in the metabolism of phenacetin and paracetamol respectively. These data are consistent with the hypothesis that omeprazole is generally devoid of inducing effects on CYP1A2 activity in vivo, at least in a Caucasian population with a low prevalence of the omeprazole-mephenytoin poor metabolizer phenotype.

Gastric motor effects of triptans: open questions and future perspectives.

Sumatriptan is a 5-HT1B/D receptor agonist of documented efficacy in relieving migraine and associated symptoms such as nausea and vomiting. In the past decade, several studies reported an important delay of gastric emptying induced by sumatriptan in healthy humans. The impact of this gastric motor effect of sumatriptan in migraineurs is difficult to predict: a further delay in gastric emptying could be detrimental (i.e. increased nausea and epigastric symptoms) in patients already having delayed gastric emptying. However, in patients with functional dyspepsia, sumatriptan is also reported to improve gastric accommodation to a meal and reduce perception of gastric distention, hence relieving epigastric symptoms. Thus, reduced visceral perception could be a mechanism involved in reducing nausea during a migraine attack. Paradoxically, sumatriptan is reported both to relieve the nausea of a migraine attack and to have nausea as a side effect. Although careful analysis of the time of onset of nausea may offer a clue as to the origin of this symptom, available data do not support definite conclusions, all the more so because the gastric motor effect of second-generation triptans are still unexplored. Taken together, the available evidence warrants further studies to clarify the following issues: first, the mechanism responsible for the gastric motor effect of sumatriptan [receptor subtype(s) involved; central vs peripheral mechanism]; secondly, the effects on gastric motility/visceral sensitivity of second-generation triptans (which are 5-HT1B/D receptor agonists) and more recent selective 5-HT1D receptor agonists (proposed as investigational antimigraine agents with less potential to induce coronary vasoconstriction through 5-HT1B receptors); finally, the possible use of drugs improving gastric accommodation to a meal in the management of those dyspeptic patients with impaired fundic relaxation/altered visceral sensitivity.

The influence of ethnic factors and gender on CYP1A2-mediated drug disposition: a comparative study in Caucasian and Chinese subjects using phenacetin as a marker substrate.

To assess potential ethnic and gender-related differences in the expression of cytochrome CYP1A2-mediated activity, the pharmacokinetics of phenacetin (a CYP1A2 substrate) and its metabolite paracetamol were compared in 20 Caucasian and 20 Chinese subjects after administration of a single oral 900 mg phenacetin dose. Peak plasma concentrations and apparent oral clearance values for phenacetin did not differ between the two groups (geometric means: 3.4 micrograms/ml and 1.56 ml h-1 kg-1, respectively, for Caucasians vs. 4.7 micrograms/ml and 1.25 ml h-1 kg-1, respectively, for Chinese, after excluding one Caucasian with aberrantly low plasma phenacetin values). Pharmacokinetic parameters for metabolically derived paracetamol were also similar in the two groups. When subjects were divided into subgroups according to gender, phenacetin apparent oral clearance values were found to be lower in Chinese women compared with both Chinese men and Caucasian subjects of either sex. It is concluded that there are no major interethnic differences in the expression of CYP1A2-related activity between Caucasians and Chinese, although Chinese women as a subgroup may exhibit comparatively lower enzyme activity.

Endovascular low-dose irradiation inhibits neointima formation after coronary artery balloon injury in swine. A possible role for radiation therapy in restenosis prevention.

BACKGROUND: Restenosis after percutaneous transluminal coronary angioplasty remains a major limitation of the long-term success of this procedure. Restenosis is a form of wound healing. Low-dose ionizing radiation has been effective in inhibiting exuberant wound healing responses in a variety of clinical situations. METHODS AND RESULTS: Vascular neointimal lesions resembling human restenosis were created in the coronary arteries of normal pigs by overstretch balloon angioplasty injury. To test the effect of low-dose endovascular gamma radiation on lesion formation, a high-activity 192Ir source was introduced into one of the injured arteries in each animal and left in place for a period sufficient to deliver one of three doses: 350, 700, or 1400 cGy. To test potential benefits of delayed irradiation, 700 cGy was given in another group 2 days after injury. Animals were killed 14 days after balloon injury and the coronary vasculature was pressure-perfusion fixed. To test the late effect and safety of endovascular low-dose irradiation, 700 or 1400 cGy was given in miniswine coronary arteries after injury as well as in noninjured carotid arteries; this group was followed up for 6 months. Tissue sections were measured by computer-assisted planimetry. All arteries treated with radiation demonstrated significantly decreased neointima formation compared with control arteries. The ratio of intimal area-to-medial fracture length (IA/FL) was inversely correlated with the different radiation doses: control, 0.59; 350 cGy, 0.38; 700 cGy, 0.42; and 1400 cGy, 0.17 (r = -0.75, P < .0001). Delay of 700-cGy irradiation for 2 days after injury significantly decreased neointima formation compared with the same dose given immediately after injury. Analysis of long-term specimens showed reduction of IA/FL in the arteries irradiated with 700 cGy (0.3, P = .009) and 1400 cGy (0.31, P = .001) compared with control arteries (0.50). There was no excess fibrosis in the media, adventitia, or perivascular space of the coronary arteries or adjacent myocardium in pigs that received radiation compared with control animals. CONCLUSIONS: Low-dose intracoronary irradiation delivered to the site of coronary arterial overstretch balloon injury in pigs inhibited subsequent intimal thickening (hyperplasia). A dose-response relationship was demonstrated, and delay of treatment for 48 hours appeared to augment the inhibitory effect. Six months of follow-up without fibrosis or arteriosclerosis demonstrated the durability of the beneficial effect in the treated group. These data suggest that intracoronary irradiation therapy may aid in preventing clinical restenosis.

Induction of ethinylestradiol and levonorgestrel metabolism by oxcarbazepine in healthy women.

PURPOSE: To evaluate the effect of oxcarbazepine (OCBZ) on the pharmacokinetic profile of steroid oral contraceptives. METHODS: Twenty-two healthy women aged 18-44 years were recruited, and 16 of them completed the study. By using a randomized double-blind crossover design, each woman was studied in two different menstrual cycles, during which placebo or OCBZ (maintenance dosage, 1,200 mg/day) was given in randomized sequence for 26 consecutive days with a washout of at least one cycle in between. A steroid oral contraceptive containing 50 microg ethinylestradiol (EE) and 250 microg levonorgestrel (LN) was taken for the first 21 days of each cycle. Plasma concentrations of EE and LN were measured by gas chromatography-mass spectrometry in samples collected at regular intervals on days 21-23 of each cycle. RESULTS: Compared with placebo, areas under the plasma concentration curves (AUC(0-24h, geometric means) decreased by 47% for both EE (from 1,677 to 886 pg.h/ml; p < 0.01) and LN (from 137 to 73 ng.h/ml; p < 0.01), during OCBZ treatment. Peak plasma EE concentrations decreased from 180 pg/ml during the placebo cycle to 117 pg/ml during the OCBZ cycle (p < 0.01), whereas peak plasma LN concentrations decreased from 10.2 to 7.7 ng/ml (p < 0.01). The half-lives of EE and LN also decreased from 13.6 to 7.9 h (p < 0.01) and from 28.8 to 15.8 h, respectively (p < 0.01). CONCLUSIONS: OCBZ reduces plasma concentrations of the estrogen and progestagen components of steroid oral contraceptives, presumably by stimulating their CYP3A-mediated metabolism in the liver or gastrointestinal tract or both. Because this may lead to a decreased efficacy of the contraceptive pill, women treated with OCBZ should receive preferentially a high-dosage contraceptive and should be monitored for signs of reduced hormonal cover.

A double-blind, placebo-controlled study on the effect of vigabatrin on in vivo parameters of hepatic microsomal enzyme induction and on the kinetics of steroid oral contraceptives in healthy female volunteers.

PURPOSE: This study was conducted to determine whether vigabatrin affects in vivo indices of hepatic microsomal enzyme activity and the pharmacokinetics of steroid oral contraceptives in healthy subjects. METHODS: Under double-blind conditions, 13 female healthy volunteers received, in random order and with a washout interval of > or = 4 weeks, two oral 4-week treatments with vigabatrin (VGB) (maintenance dosage, 3,000 mg daily) and placebo, respectively. The clearance and half-life of antipyrine (a broad marker of drug oxidation capacity), the urinary excretion of 6-beta-hydroxycortisol (a selective marker of cytochrome CYP3A-mediated oxidation), and the activity of serum gamma-glutamyltransferase (a nonspecific index of microsomal enzyme activity) were determined after 3 weeks of each treatment. The single-dose kinetics of a combined oral contraceptive containing 30 micrograms ethinyl estradiol and 150 micrograms levonorgestrel were also determined after 3 weeks of treatment by specific radioimmunologic assays. RESULTS: VGB treatment had no influence on antipyrine clearance (28 +/- 5.6 vs. 30 +/- 4.5 ml/h/kg on placebo), antipyrine half-life (15.5 +/- 3.5 vs. 14.1 +/- 2.1 h), urinary 6-beta-hydroxycortisol excretion (488 +/- 164 vs. 470 +/- 228 nmol/ day), 6-beta-hydroxycortisol-to-cortisol concentration ratio (6.8 +/- 3.1 vs. 6.1 +/- 3.1) and serum gamma-glutamyltransferase activity (12 +/- 3 vs. 11 +/- 3 IU/L). No difference in pharmacokinetic parameters between VGB and placebo sessions were found for ethinyl estradiol (half-life, 12.5 +/- 3.2 vs. 13.9 +/- 3.2 h; AUC, 874 +/- 301 vs. 939 +/- 272 ng/ L/h) and levonorgestrel (half-life, 17.7 +/- 5.2 vs. 23.1 +/- 9.8 h; AUC, 27.5 +/- 9.6 vs. 30.0 +/- 12.0 micrograms/L/h). Two subjects, however, showed a 50 and a 39% reduction in ethinyl estradiol AUC during VGB treatment. CONCLUSIONS: At therapeutic dosages, VGB did not modify in vivo indices of hepatic microsomal enzyme activity and did not interfere significantly with the CYP3A-mediated metabolism of ethinyl estradiol and levonorgestrel. Based on these data, VGB is unlikely to affect consistently the efficacy of steroid oral contraceptives or interact pharmacokinetically with drugs that are eliminated mainly by oxidative pathways, particularly those involving cytochrome CYP3A.

Reduced plasma nisoldipine concentrations in phenytoin-treated patients with epilepsy.

PURPOSE: To assess whether phenytoin affects the pharmacokinetics of the dihydropyridine calcium antagonist nisoldipine. METHODS: Twelve patients with epilepsy receiving chronic phenytoin therapy and 12 healthy control subjects matched for age and gender received a single oral dose of nisoldipine (40 and 20 mg, respectively). Blood samples were collected for up to 48 h for estimation of plasma nisoldipine levels by capillary gas chromatography. RESULTS: Mean plasma nisoldipine concentrations were much lower in the patients. Geometric means for areas under the concentration-time curve (AUC0-tn) normalized to a 20-mg dose were 1.6 micrograms/L/h (95% confidence intervals, 0.6-3.8 micrograms/L/h) in the patients compared with 15.2 (10.7-21.6) micrograms/L/h in control subjects (p < 0.002). CONCLUSIONS: These results suggest that phenytoin increases the first-pass metabolism of nisoldipine to a clinically important extent. In view of the magnitude and variability of interaction, use of nisoldipine in patients receiving chronic phenytoin therapy is contraindicated.