Effects of daily ingestion of cranberry juice on the pharmacokinetics of warfarin, tizanidine, and midazolam--probes of CYP2C9, CYP1A2, and CYP3A4.

Case reports suggest that cranberry juice can increase the anticoagulant effect of warfarin. We investigated the effects of cranberry juice on R-S-warfarin, tizanidine, and midazolam; probes of CYP2C9, CYP1A2, and CYP3A4. Ten healthy volunteers took 200 ml cranberry juice or water t.i.d. for 10 days. On day 5, they ingested 10 mg racemic R-S-warfarin, 1 mg tizanidine, and 0.5 mg midazolam, with juice or water, followed by monitoring of drug concentrations and thromboplastin time. Cranberry juice did not increase the peak plasma concentration or area under concentration-time curve (AUC) of the probe drugs or their metabolites, but slightly decreased (7%; P=0.051) the AUC of S-warfarin. Cranberry juice did not change the anticoagulant effect of warfarin. Daily ingestion of cranberry juice does not inhibit the activities of CYP2C9, CYP1A2, or CYP3A4. A pharmacokinetic mechanism for the cranberry juice-warfarin interaction seems unlikely.

Grapefruit juice-simvastatin interaction: effect on serum concentrations of simvastatin, simvastatin acid, and HMG-CoA reductase inhibitors.

BACKGROUND: Simvastatin is a cholesterol-lowering agent that is metabolized through CYP3A4. We studied the effect of grapefruit juice on the pharmacokinetics of orally administered simvastatin. METHODS: In a randomized, 2-phase crossover study, 10 healthy volunteers took either 200 mL double-strength grapefruit juice or water 3 times a day for 2 days. On day 3, each subject ingested 60 mg simvastatin with either 200 mL grapefruit juice or water, and an additional 200 mL was ingested 1/2 and 1 1/2 hours after simvastatin administration. Serum concentrations of simvastatin and simvastatin acid were measured by liquid chromatography-tandem mass spectrometry (LC-MS-MS) and those of active (naive) and total (after hydrolysis) 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors by a radioenzyme inhibition assay. RESULTS: Grapefruit juice increased the mean peak serum concentration (Cmax) of unchanged simvastatin about 9-fold (range, 5.1-fold to 31.4-fold; P < .01) and the mean area under the serum simvastatin concentration-time curve [AUC(0-infinity)] 16-fold (range, 9.0-fold to 37.7-fold; P < .05). The mean Cmax and AUC(0-infinity) of simvastatin acid were both increased about 7-fold (P < .01). Grapefruit juice increased the mean AUC(0-infinity) of active and total HMG-CoA reductase inhibitors 2.4-fold (P < .01) and 3.6-fold (P < .01), respectively. The time of the peak concentration of active and total HMG-CoA reductase inhibitors was increased by grapefruit juice (P < .05). CONCLUSION: Grapefruit juice greatly increased serum concentrations of simvastatin and simvastatin acid and, to a lesser extent, those of active and total HMG-CoA reductase inhibitors. The probable mechanism of this interaction was inhibition of CYP3A4-mediated first-pass metabolism of simvastatin by grapefruit juice in the small intestine. Concomitant use of grapefruit juice and simvastatin, at least in large amounts, should be avoided, or the dose of simvastatin should be greatly reduced.

Grapefruit juice increases serum concentrations of atorvastatin and has no effect on pravastatin.

BACKGROUND: Grapefruit juice greatly increases the bioavailability of lovastatin and simvastatin. We studied the effect of grapefruit juice on the pharmacokinetics of atorvastatin and pravastatin. METHODS: Two randomized, two-phase crossover studies were performed--study I with atorvastatin in 12 healthy volunteers and study II with pravastatin in 11 healthy volunteers. In both studies, volunteers took 200 mL double-strength grapefruit juice or water three times a day for 2 days. On day 3, each subject ingested a single 40 mg dose of atorvastatin (study I) or pravastatin (study II) with either 200 mL grapefruit juice or water, and an additional 200 mL was ingested 1/2 hour and 1 1/2 hours later. In addition, subjects took 200 mL grapefruit juice or water three times a day on days 4 and 5 in study I. In study I, serum concentrations of atorvastatin acid, atorvastatin lactone, 2-hydroxyatorvastatin acid, 2-hydroxyatorvastatin lactone, and active and total 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors were measured up to 72 hours. In study II, pravastatin, pravastatin lactone, and active and total HMG-CoA reductase inhibitors were measured up to 24 hours. RESULTS: Grapefruit juice increased the area under the serum concentration-time curve of atorvastatin acid from time zero to 72 hours [AUC(0-72)] 2.5-fold (P < .01), whereas the peak serum concentration (Cmax) was not significantly changed. The time of the peak concentration (tmax) and the elimination half-life (t1/2) of atorvastatin acid were increased (P < .01). The AUC(0-72) of atorvastatin lactone was increased 3.3-fold (P < .01) and the Cmax 2.6-fold (P < .01) by grapefruit juice, and the tmax and t1/2 were also increased (P < .05). Grapefruit juice decreased the Cmax (P < .001) and AUC(0-72) (P < .001) of 2-hydroxyatorvastatin acid and increased its tmax and t1/2 (P < .01). Grapefruit juice also decreased the Cmax (P < .001) and AUC(O-72) (P < .05) of 2-hydroxyatorvastatin lactone. The AUC(0-72) values of active and total HMG-CoA reductase inhibitors were increased 1.3-fold (P < .05) and 1.5-fold (P < .01), respectively, by grapefruit juice. In study II, the only significant change observed in the pharmacokinetics of pravastatin was prolongation of the tmax of active HMG-CoA reductase inhibitors by grapefruit juice (P < .05). CONCLUSIONS: Grapefruit juice significantly increased serum concentrations of atorvastatin acid, atorvastatin lactone, and active and total HMG-CoA reductase inhibitors, probably by decreasing CYP3A4-mediated first-pass metabolism of atorvastatin in the small intestine. On the other hand, grapefruit juice had no effect on the pharmacokinetics of pravastatin. Concomitant use of atorvastatin and at least large amounts of grapefruit juice should be avoided, or the dose of atorvastatin should be reduced accordingly.

Duration of effect of grapefruit juice on the pharmacokinetics of the CYP3A4 substrate simvastatin.

BACKGROUND: Grapefruit juice is a potent inhibitor of CYP3A4-mediated drug metabolism. We wanted to investigate how long the inhibitory effect of grapefruit juice lasts, with the CYP3A4 substrate simvastatin used as a model drug. METHODS: This crossover study consisted of 5 study days, during which 10 healthy volunteers ingested 40 mg simvastatin with water (control), with "high-dose" grapefruit juice (200 mL double-strength grapefruit juice three times a day for 3 days), or 1, 3, and 7 days after ingestion of "high-dose" grapefruit juice. For safety reasons, the study was performed in three parts to allow simvastatin-free days between the study days. Serum concentrations of simvastatin and simvastatin acid were measured by liquid chromatography-tandem mass spectrometry up to 12 hours. RESULTS: When simvastatin was taken with grapefruit juice, the mean peak serum concentration (Cmax) and the mean area under the serum concentration-time curve [AUC(0-infinity)] of simvastatin were increased 12.0-fold (P < .001) and 13.5-fold (P < .001), respectively, compared with control. When simvastatin was administered 24 hours after ingestion of the last dose of grapefruit juice, the Cmax and AUC(0-infinity) were increased 2.4-fold (P < .01) and 2.1-fold (P < .001), respectively, compared with control. When simvastatin was given 3 days after ingestion of grapefruit juice, the Cmax and AUC(0-infinity) were increased 1.5-fold (P = .12) and 1.4-fold (P = .09), respectively, compared with control. Seven days after ingestion of grapefruit juice, no differences in the Cmax or AUC(0-infinity) of simvastatin were seen. The mean Cmax and AUC(0-infinity) of simvastatin acid were increased 5.0-fold and 4.5-fold, respectively (P < .001), compared with control when simvastatin was taken with grapefruit juice and 1.7-fold (P < .01) when it was taken 24 hours after ingestion of grapefruit juice. After an interval of 3 or 7 days between ingestion of grapefruit juice and simvastatin, the pharmacokinetic variables of simvastatin acid did not differ significantly from those in the control phase. CONCLUSIONS: When simvastatin is taken 24 hours after ingestion of "high-dose" grapefruit juice, the effect of grapefruit juice on the AUC of simvastatin is only about 10% of the effect observed during concomitant intake of grapefruit juice and simvastatin. The interaction potential of even high amounts of grapefruit juice with CYP3A4 substrates dissipates within 3 to 7 days after ingestion of the last dose of grapefruit juice.

Grapefruit juice substantially increases plasma concentrations of buspirone.

BACKGROUND: Buspirone has a low oral bioavailability because of extensive first-pass metabolism. The effect of grapefruit juice on the pharmacokinetics and pharmacodynamics of orally administered buspirone is not known. METHODS: In a randomized, 2-phase crossover study, 10 healthy volunteers took either 200 mL double-strength grapefruit juice or water 3 times a day for 2 days. On day 3, each subject ingested 10 mg buspirone with either 200 mL grapefruit juice or water, and an additional 200 mL was ingested 1/2 hour and 1 1/2 hours after buspirone administration. Timed blood samples were collected up to 12 hours after ingestion, and the effects of buspirone were measured with 6 psychomotor tests up to 8 hours after ingestion. RESULTS: Grapefruit juice increased the mean peak plasma concentration of buspirone 4.3-fold (range, 2-fold to 15.6-fold; P < .01) and the mean area under the plasma buspirone concentration-time curve 9.2-fold (range, 3-fold to 20.4-fold; P < .01). The time of the peak concentration (tmax) of buspirone increased from 0.75 to 3 hours (P < .01), and the elimination half-life (t1/2) was slightly increased (P < .01) by grapefruit juice. A significant increase in the pharmacodynamic effects of buspirone by grapefruit juice was seen only in subjective overall drug effect (P < .01). CONCLUSIONS: Grapefruit juice considerably increased plasma buspirone concentrations. The probable mechanism of this interaction is delayed gastric emptying and inhibition of the cytochrome P450 3A4-mediated first-pass metabolism of buspirone caused by grapefruit juice. Concomitant use of buspirone and at least large amounts of grapefruit juice should be avoided.

Repeated consumption of grapefruit juice considerably increases plasma concentrations of cisapride.

BACKGROUND: Grapefruit juice increases the bioavailability of several drugs that are metabolized during first pass by CYP3A4. In this study, the effect of grapefruit juice on the pharmacokinetics of orally administered cisapride was investigated. METHODS: In a randomized, two-phase crossover study, 10 healthy volunteers took either 200 mL double-strength grapefruit juice or water three times a day for 2 days. On day 3, each subject ingested 10 mg cisapride with either 200 mL grapefruit juice or water, and an additional 200 mL was ingested 1/2 hour and 1 1/2 hours after cisapride administration. Timed blood samples were collected for 32 hours after cisapride intake, and a standard 12-lead ECG was recorded before the administration of cisapride and 2, 5, 8, and 12 hours later. RESULTS: The mean peak plasma concentration of cisapride was increased by 81% (range, 38% to 138%; P < .01) and the total area under the plasma cisapride concentration-time curve by 144% (range, 65% to 244%; P < .01) by grapefruit juice. The time of the peak concentration of cisapride was prolonged from 1.5 to 2.5 hours (P < .05) and the elimination half-life from 6.8 to 8.4 hours (P < .05) by grapefruit juice. ECG tracings did not show any significant differences in the QTc interval between the grapefruit juice and control phases. CONCLUSIONS: Grapefruit juice significantly increases plasma concentrations of cisapride, probably by inhibition of the CYP3A4-mediated first-pass metabolism of cisapride in the small intestine. Concomitant use of high amounts of grapefruit juice and cisapride should be avoided, at least in patients with risk factors for cardiac arrhythmia.

Elevated phosphorylation of AKT and Stat3 in prostate, breast, and cervical cancer cells.

We examined whether the persistent activation of AKT or Stat3 oncogene product is present in prostate, breast, and cervical cancer cells. We found that some prostate and breast cancer cell lines express high levels of phosphorylated AKT. Interestingly, the cancer cells, which only express low levels of phosphorylated AKT express high levels of phosphorylated Stat3. AKT or Stat3 is also highly phosphorylated in human papilloma virus-negative cervical cancer cells. Therefore, these results indicate that AKT and Stat3 are highly phosphorylated in some breast, prostate and cervical cancer cells, which may play a role in tumorigenesis of these cancers.

Incidence of perihepatic adhesions in ectopic gestation.

OBJECTIVE: To compare the incidence of perihepatic adhesions in patients undergoing surgery for ectopic pregnancy with the incidence in patients undergoing elective laparoscopic sterilization. Fitz-Hugh-Curtis syndrome is a perihepatitis that usually occurs as a complication of pelvic inflammatory disease. Perihepatic adhesions may be an aftereffect of the acute hepatic episode, and because the cause of ectopic gestation is thought to be salpingitis, women with an ectopic gestation may also have a higher prevalence of coexisting perihepatic adhesions. METHODS: We reviewed charts of 97 women who had undergone laparoscopy or laparotomy for ectopic pregnancy (study group) and 116 women who had laparoscopic sterilization (control group). We recorded all perihepatic, pelvic, or abdominal adhesions that were documented at the time of surgery. Medical histories and sites of adhesions in the two groups were compared. RESULTS: The incidence of perihepatic adhesions was 14% in the study group compared with 3% in the control group (P < .01). For the total patient population, a history of pelvic infection correlated positively with the presence of perihepatic adhesions (P < .01), and the study (ectopic) group had a higher incidence of previous pelvic infection. CONCLUSION: Compared with control subjects, significantly more women with ectopic pregnancies had perihepatic adhesions. In women who have history of pelvic infection or ectopic pregnancy, physicians should inquire about long-term right upper quadrant pain. The inclusion of lysis of perihepatic adhesions in the preoperative consent form may be useful.

Vibrio parahaemolyticus gastroenteritis. An outbreak associated with raw oysters in the Pacific northwest.

During a 3-month period in the late summer and fall of 1981, six cases of gastroenteritis and one wound infection due to Vibrio parahaemolyticus were reported to public health agencies in Washington and Oregon. An investigation revealed that all of the gastroenteric illnesses were associated with eating raw oysters; that oysters eaten by five of the six patients were harvested at four divergent sites at Willapa Bay, Washington, a large commercial growing area; and that the V. parahaemolyticus isolates from those five patients were all Kanagawa positive, belonged to serotype 04:K12, and exhibited an atypical biochemical reaction, urea hydrolysis. No further cases linked to Willapa Bay oysters have been reported, and the infecting strain could not be found in sediment samples from the bay in February 1982. Thus, even though the origin of this self-limiting outbreak is obscure, the investigation demonstrated that the geographic distribution of V. parahaemolyticus infection in the United States includes the Pacific seacoast . Furthermore, oysters must be considered, along with crabs, shrimp, and lobster, as a vehicle of transmission of this infection in the United States.

Inhibition of tumour vascularization by tranexamic acid. Experimental studies on possible mechanisms.

The vascularization of an intramuscularly transplanted rat sarcoma was studied by microangiography. Administration of tranexamic acid as well as of indomethacin reduced the vascular connections between tumour and surrounding normal muscle. These drugs also reduced tumour growth rate irrespective of whether they were administered early or late during tumour growth. An electron microscopy study of tumour specimens from animals given tranexamic acid did not reveal any degenerative vascular changes. One explanation of the inhibition of tumour growth and vascularization by tranexamic acid and by indomethacin may be reduction of a local inflammatory reaction induced by tumour transplantation and stimulating tumour vascularization.

Growth suppression activity of the PTEN tumor suppressor gene in human endometrial cancer cells.

The AKT proteins are constitutively activated in several types of human cancers, which may play a role in carcinogenesis. In this study, we examined the activation of AKT in a panel of human endometrial cancer cell lines and tumor samples in this study. Two endometrial cancer cell lines, Ishikawa (ISK) and RL-95 and several tumor samples showed elevated levels of phosphorylated AKT PTEN, which is mutated in 45% of endometrial cancers, is a negative regulator of AKT. We examined the growth suppression activity of PTEN in ISK and KLE endometrial cancer cells. Expression of PTEN significantly suppressed the growth of both cell clines. In primary rat embryo fibroblasts, PTEN also inhibited malignant transformation mediated by ras and c-myc oncogenes. These two oncogenes are commonly mutated or amplified in endometrial cancer. These results suggest that PTEN may be a potent therapeutic agent for endometrial cancer.

The nationalization of the Swedish pharmacies.

The first Swedish parliamentary bill suggesting government-owned pharmacies was introduced in 1907 and was rejected. A number of official proposals were put forward until 1970 when the government decided to nationalize the Swedish pharmacies. The process leading to nationalization was influenced by background and by more specific 'release' factors operating in the 1960s. The opposition in parliament to nationalization was only minor. The new organization formed, Apoteksbolaget AB, was given a drug selling monopoly and was organized as a limited company regulated by an agreement between the government and Apoteksbolaget.

Indigenous and multinational pharmaceutical companies.

There is a set of complex relationships between governments and the pharmaceutical companies. These relationships can be analysed in many different ways. In the following article the drug system of each country will be the unit of analysis. The drug system includes all the decision processes, formal as well as informal, from the production or importation of drugs to the intake of the drug by the patient. The aim of this paper is to discuss how environmental factors, the strategies of the drug companies and the national policies, will effect the drug system of a country. Satisfying solutions to the economical and health goals of the country will be searched for. If we want a more rational discussion in this area, professionally and politically, we need more empirical knowledge about the multinational drug companies and their effects on society. This does not mean that we shall sit waiting for this new knowledge. We have to make decisions using todays knowledge. However, in the long run rational decision strategy must include ways to collect important empirical data about the phenomenom under investigation. The aim of this survey is to indicate areas where we already have quite good knowledge and indicate other areas where this data is missing.

The evaluations of drug information programs.

In spite of the great number of published reports about the effects of drug information programs there are few studies concerning the drug information process. One result of this has been that new studies have frequently been planned without sufficient consideration being given to the results of earlier research. The aim of this paper is to describe alternative ways of measuring the effects of drug information programs. The survey has been limited to information programs intended for the general public including patients.

When topical hydrocortisone became an OTC drug in Sweden--a study of the users and their information sources.

On 1 October 1983 hydrocortisone skin ointments in Sweden were declared OTC drugs and were made available without prescription. These preparations, however, were restricted to pharmacy-only sales. The effect of this reform was studied via telephone interviews with samples of customers who had bought hydrocortisone skin ointments, both with and without prescription. The aim of the study was to analyse the reform from the user's point of view. The interviews were conducted at four points in time: before the reform, during the month after the reform, 9 months and 6 years after the change. The total sales of hydrocortisone ointments have increased in the period from 1983 to 1989, both in terms of number of packages and in weight. Most of the background variables of the OTC users did not change over time. However, the percentage of the OTC group who had university education was high at the time of the reform but decreased later. It was found that journal articles were the most frequently used source of information about preparation availability at the time of the reform. However, their importance decreased over time and pharmacy personnel and nurses had become the most important sources 6 years after the reform. Pharmacy personnel had also become the most important source on brand selection and on how to use the preparation 6 years after the reform. An individual tended to use the same source of information about availability, brand selection and how to use the preparation. Those with university education had seen and used written material more often than those without such a background.

Dietary habits affect the susceptibility of low-density lipoprotein to oxidation.

OBJECTIVE: To study, if there are differences in the fatty acid composition of low-density lipoprotein (LDL) in people eating three different long-standing habitual diets: vegetarian, high fish intake, or high saturated fat (milk fat) diet as a control group, and to study if these differences influence the oxidation susceptibility of LDL. DESIGN: Cross-sectional study using blood samples and a validated dietary frequency questionnaire with illustrations. SETTING: Helsinki University Central Hospital, Finland. SUBJECTS: The effect of three different types of long-standing diets of different fatty acid content (a strict vegetarian diet, n=11; a high fish intake diet, n=9; and a high saturated fat (milk fat) diet, controls, n=7) on the serum and LDL fatty acid content, and on the susceptibility of LDL to oxidation in vitro, was studied in healthy normocholesterolemic volunteers who had been on these diets for years. Oxidation of LDL was carried out by using CuSO4 as a pro-oxidant. RESULTS: There were no statistically significant differences in the serum lipids or lipoproteins, though the vegetarian group exhibited lowest mean values of total, high-density lipoprotein (HDL) and LDL cholesterol levels. Both the serum and LDL eicosapentaenoic, docosapentaenoic and docosahexaenoic acid proportions were highest in the fish and lowest in the vegetarian groups. Linoleic acid was highest among the vegetarians. In the fish group, the vitamin A concentration in serum was higher than in vegetarians and controls and beta-carotene lower than in controls, but in alpha-tocopherol, or lycopene concentrations there were no statistically significant differences. The lag phase of LDL oxidation was shortest (116 min) in the fish group and longest (165 min) in the vegetarian group, and the control group was between them (129 min). The mean oxidation percentage after 2.5 h of copper-induced oxidation was highest (44%) in the fish group and lowest (22%) in the vegetarian group and intermediate (31%) in the control group. CONCLUSION: Long-term dietary habits predict the fatty acid composition of serum and LDL, and influence the susceptibility of LDL to oxidation. In the fish group with the highest content of omega-3 fatty acids in LDL, the oxidation susceptibility of LDL was highest. In the vegetarian group with less omega-3 fatty acids in LDL, the LDL was more resistant to oxidation. SPONSORSHIP: Helsinki University Central Hospital.

Airway obstruction and sleep apnea in children with craniofacial anomalies.

Children with severe craniofacial anomalies and breathing problems are rare, and the accumulated experience of their treatment is limited. LeFort III midface advancements have been tried by many craniofacial teams, but no consensus has yet been reached as to the effectiveness of this procedure. In this report of seven patients with craniofacial malformations and severe breathing problems, three had a LeFort II midface advancement, one had release of bilateral temporomandibular joint ankylosis, and two had tonsillectomies. Two patients without a tracheostomy suffocated, four had a long-term tracheostomy, and one was cured by a unilateral tonsillectomy. It was concluded that LeFort III midface advancement is ineffective in these types of cases without a very stable postoperative retention, and it was suggested that all patients with severe craniofacial anomalies and breathing problems, regardless of their planned subsequent treatment, should have a tracheostomy as an initial measure.

Bone grafting at the stage of mixed and permanent dentition in patients with clefts of the lip and primary palate.

Secondary bone grafting of a residual alveolar cleft has become a well established procedure. However, little attention has been paid to the benefits of these bone grafts in patients with clefts of the lip and alveolus only. This retrospective and comparative study includes 21 patients who had received a secondary or a late secondary bone grafting procedure from tibia and whose mean clinical and radiographic follow-up after the bone graft was 5.5 years. Eighteen patients treated without bone grafting served as controls. Length and width of cleft, presence or absence of permanent lateral incisor, size of nasal floor bony defect, and interdental alveolar bony height in the cleft area were investigated. The results showed that bone grafting was indicated particularly in wide clefts with missing lateral incisors. Eruption of a tooth close to the cleft was facilitated and the bony support for teeth neighboring the cleft was improved. In some cases, additional support of the alar base of the nose was achieved and closure of an oronasal fistula facilitated. A further advantage of bone grafting of clefts of the primary palate was that it might make it possible to insert a titanium implant carrying an artificial tooth in the cleft area.

Bone grafting in the mixed and permanent dentition in cleft lip and palatepatients: long-term results and the role of the surgeon's experience.

This long-term study was a follow-up of 46 patients with complete unilateral cleft lip and palate treated with secondary or late secondary bone grafting. Surgeons with different degrees of experience in this procedure had operated on these patients. Morphology of the clefts prior to the grafting was assessed with regard to width of cleft, stage of eruption of permanent canine, presence or absence of permanent lateral incisor and position of permanent lateral incisor and permanent canine in the dental arch. Outcome of surgery was evaluated with regard to the amount of bleeding, flap dehiscence, alveolar bone height, and space closure in the previous cleft area. Dehiscence rate was 23% (11) and total failure rate 4% (2). Alveolar bony height in 38 patients (81%) was more than 75% of the normal alveolar bone height; in 6 cases (13%) between 50-75% bone height and in 3 subjects (6%) surgery had given less than 50% of the normal bone height. Cleft space was closed by orthodontic means in 49% of patients. Best results were obtained when bone grafting was performed prior to canine eruption. Furthermore, significantly better results regarding alveolar bone height were obtained by the more experienced surgeons.

Simultaneous correction of maxillary and mandibular dentofacial deformities without the use of postoperative intermaxillary fixation. A clinical and cephalometric study.

Simultaneous correction of maxillary and mandibular anomalies was performed in 23 patients. The maxillary segment was stabilized by means of steel wires as horizontal mattress sutures, which, in all cases, gave good stability. A modified sagittal split has been applied in all cases. The method makes a safe split osteotomy possible under controlled conditions. The design of the osteotomy and the screw osteosynthesis counteract relapse. Postoperatively, no rigid intermaxillary fixation (IMF) was used. Masticatory function was started from the 1st postoperative day and in most cases was normalized 2-3 weeks after surgery according to the patients own judgement. Cephalometric analysis was performed on 15 patients by a superimposition technique. There was an overall good postoperative stability of the maxilla and mandible in the horizontal and vertical planes. We conclude that omitting IMF has no negative effect on the postoperative stability of the fragments.