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Background: Particularly in clinical studies, it has been found that rapid swelling of tissue expanders leads to high-pressure peaks that can cause hypoxia in the tissue and thus also skin damage. For this reason, the present study in animals investigated whether an osmotic expander with silicone shell is capable of expanding in tissue and bringing about useful tissue expansion without complications. It was also examined whether and what quantitative and qualitative differences there are between conventional osmotic expanders and the new expanders with silicone shell., Methods: The expansion of osmotic expanders with silicone shell was compared with that of osmotic expanders without silicone shell in four mini pigs. The expander type used was an M1 rectangle with an initial volume of 6 ml. Five expanders were implanted in each pig, meaning that 20 expanders were measured. The volume of the expanders was measured directly after explantation. Indirect volume determination was performed by producing plaster casts for subsequent laser optical measurement., Results: Comparison of the two curve profiles showed a much flatter profile for the expanders with silicone shell. The absolute values for the volumes of the expanders with silicone shell were likewise substantially lower., Conclusions: Controlled skin expansion is a technique of providing localized donor tissue for reconstructive surgery. The new expanders could be in a position to lower the rate of complications in tissue expansion.

Purpose: The combination of paclitaxel with carboplatin is effective in advanced-stage non-small cell lung cancer (NSCLC). This phase III study was designed to compare the efficacy and tolerability of a weekly versus an every-3-week schedule in the first-line treatment of advanced-stage NSCLC., Patients and Methods: Chemotherapy-naive patients were randomized to receive paclitaxel 100 mg/m2 and carboplatin at an area under the curve of 2 once weekly for 6-8 weeks (arm A) or paclitaxel 200 mg/m2 and carboplatin at an area under the curve of 6 on day 1 every 21 days (arm B)., Results: A total of 883 patients received >or= 1 chemotherapy cycle and were included in the results. The objective response rates observed (complete response plus partial response) were 38% for arm A and 33% for arm B. Median times to progression and median survival times were 6.1 months and 8.9 months in arm A and 7.2 months and 9.5 months in arm B, respectively. There were no significant differences between treatment arms. The chemotherapy was well tolerated in both schedules. However, grade 3/4 sensory neuropathy occurred more frequently with the every-3-week schedule (9.1% vs. 4.4%), whereas grade 3/4 diarrhea occurred more frequently with the weekly schedule (4.2% vs. 1.1%)., Conclusion: In terms of response and survival, paclitaxel/carboplatin administered once weekly is comparable with the every-3-week schedule. Toxicity differences should be considered when choosing the appropriate schedule for the individual.

Apolipoprotein E (apoE) 4 and aging are risk factors for Alzheimer's disease (AD). Mice expressing human apoE4 and aged wild-type mice show a similarity in the transbilayer distribution of cholesterol in synaptic plasma membranes (SPMs) but differ markedly compared with apoE3 mice and young mice. The largest changes in cholesterol distribution were observed in the SPM exofacial leaflet where there was a doubling of cholesterol. Lipid rafts are thought to be associated with the exofacial leaflet, and we proposed that lipid raft protein and lipid composition would be associated with apoE genotype and age. Lipid rafts were isolated from synaptosomes of different age groups (2, 12, 24 months) of mice expressing human apoE3 and apoE4. Lipid raft markers, alkaline phosphatase (ALP), flotillin-1, cholesterol and sphingomyelin (SM) were examined. Lipid rafts of young apoE4 mice were more similar to older mice as compared with young apoE3 mice in reductions in alkaline phosphatase activity and flotillin-1 abundance. Lipid raft cholesterol and sphingomyelin levels were not significantly different between the young apoE3 and apoE4 mice but cholesterol levels of lipid rafts did increase with age in both genotypes. Results of the present study demonstrate that the two risk factors for Alzheimer's disease, apoE4 genotype and increasing age have similar effects on brain lipid raft protein markers and these findings support the notion that the transbilayer distribution of cholesterol is associated with lipid raft function.

Aim: To minimize the perioperative risk of transfusion-associated complications, preoperative autologous blood donation is routinely performed in orthognathic surgery. This study critically analyzed the necessity of this procedure with respect to clinical, economic, and juridical issues., Material and Methods: In the Department of Oral and Maxillofacial Surgery, Bonn Medical School, 178 orthognathic surgical procedures were performed from 1994 to 2002. All patients (women, n=101; men, n=77) were informed about the possibility of autologous blood donation. This procedure was carried out in 83%, for single jaw surgery two and for bimaxillary osteotomies three to four units of packed red blood cells were predeposited. Of the patients, 99 underwent monognathic surgery in the lower jaw, 27 patients in the upper jaw, and bimaxillary osteotomy was performed in 52 patients., Results: The average blood loss for the monognathic procedure in the lower jaw was 756 ml, in the upper jaw 858 ml, and in double jaw surgery 1391 ml. In 13 patients the hemoglobin concentration fell below 7.5 g/dl and 12 patients received their predeposited autologous blood units. A total of 57.7% of all donated autologous blood units were discarded., Conclusion: Autologous blood donation should be performed from the medical point of view for double jaw surgery and considered in single cases with special risks in monomaxillary osteotomies.

Background: Advanced glycation end (AGE)-products are a complex group of compounds that have been implicated in diabetes related long-term complications. Up to the present only few data exist about serum levels of the AGE-proteins N-epsilon-Carboxymethyllysine (CML) and pentosidine in patients with diabetes mellitus., Patients and Methods: In the present 10-year, population-based trial of a selection-free cohort of patients with insulin-treated diabetes mellitus, serum CML and pentosidine levels were examined in correlation to the patients' quality of diabetes control and the prevalence of diabetes related long-term complications., Results: Following the reunification of Germany in 1989 the health care system was decentralised. Up to 1994/95 the relative HbA1c (HbA1c/mean normal) of patients with type 1 diabetes increased (1.65 +/- 0.35 versus 1.52 +/- 0.31, p = 0.002). For patients with type 2 diabetes it remained constant (1.75 +/- 0.4 versus 1.78 +/- 0.31, p = 0.669). During the following period (from 1994/95 to 1999/2000) specialised diabetes care, structured treatment and teaching programmes (TTP), intensified insulin therapy and blood glucose self-monitoring for all patients were broadly implemented. This was accompanied by a substantial improvement in the relative HbA1c of both, patients with type 1 (1.48 +/- 0.3, p<0.0001), and insulin-treated type 2 diabetes mellitus (1.47 +/- 0.25, p<0.0001). During the same period the mean concentration of the AGE-product CML in the sera of patients with type 1 and insulin-treated type 2 diabetes decreased (type 1: 1994/95: 1158.1 +/- 410.0 ng/ml versus 1999/2000: 938.5 +/- 422.4 ng/ml, p<0.0001, type 2: 1994/94: 1244.7 +/- 1231.3 ng/ml versus 1999/2000: 970.9 +/- 458.6 ng/ml, p = 0.007). For pentosidine the same tendency was found for patients with type 1 diabetes (1994/95: 253.6 +/- 280.7 pmol/ml versus 1999/2000: 148.2 +/- 91.4 pmol/ml, p<0.0001). For patients with type 1 diabetes there was a positive correlation between the relative HbA1c-value calculated over the total follow-up period of 10 years and the CML-concentration in 1999/2000 (r = 0.405, p = 0.017). In 1999/2000 a reduced creatinine clearance (

Background: The oral mucosa represents a unique immunologic unit with a high frequency of native allergen contact within the gastrointestinal tract in which immune tolerance is the natural outcome of allergen contact. Although Langerhans' cells (LC), known to play a crucial role in initiating allergen-dependent immune responses in the skin, have also been detected in the oral mucosa, little is known about their phenotype and exact physiologic role., Objective: To elucidate whether LC from oral mucosa (oLC) differ from skin LC (sLC), these cells were subjected to detailed comparative analysis., Methods: Crude epidermal and oral mucosa cell suspensions were prepared by trypsinization. oLC and sLC were compared phenotypically by flow cytometry techniques and functionally in T-cell proliferation assays., Results: In contrast to sLC, freshly isolated oLC expressed significantly higher amounts of MHC class I and II, as well as costimulatory molecules CD40, CD80/B7.1, and CD86/B7.2. oLC displayed FcgammaRIII/CD16 and FcgammaRI/CD64. Most surprisingly, oLC constitutively expressed the high affinity receptor for IgE (FcepsilonRI) even in nonatopic donors. FcepsilonRI expression on oLC was further increased and correlated with the serum IgE levels in atopic individuals. oLC showed a higher allogeneic stimulatory activity than sLC, whereas the activation of autologous T cells correlated to the FcepsilonRI expression., Conclusion: Taken together, our results strongly indicate that oLC profoundly differ from their skin counterparts. The constitutive high expression of FcepsilonRI on oLC could point to particular skills of these cells within the regional immune system of the oral mucosa.

Purpose: Chronic hyperactivity of the masticatory muscles is a common functional disorder associated with chronic facial pain and headache. The positive therapeutic effect of botulinum toxin type A on functional disorders and pain symptoms has been known in connection with the treatment of cervical dystonia. The purpose of this report is to assess whether the targeted reduction of masticatory muscular hyperactivity by local injection treatment with botulinum toxin type A can improve facial pain headache symptoms in the event that other treatment methods prove ineffective., Materials and Methods: In an randomized blinded placebo-controlled study, 90 patients (60 verum and 30 placebo) with chronic facial pain were treated with botulinum toxin type A (Botox; Allergan, Ettlingen, Germany) injections into masticatory muscles., Results: Ninety-one percent of patients who received botulinum toxin improved by a significant mean reduction of approximately 3.2 on a visual analog pain scale. By comparison with t test and chi(2) test, there was a significant difference compared with the placebo group (P <.01)., Conclusions: The local injection of botulinum toxin type A constitutes an innovative and adequately efficient treatment method for chronic facial pain associated with hyperactivity of the masticatory muscles. An improvement in the painful symptoms can be expected in up to 90% of patients who do not respond to conservative treatment methods.

Background: Basal cell carcinomas (BCCs) are the most common cutaneous tumors, accounting for approximately 70% of all malignant skin tumors. A morphometric analysis was performed to evaluate whether morphometric parameters of the nuclei of BCC tumor cells may serve as predictors for biological behavior like recurrence rate or are able to differentiate morphological subtypes (multifocal superficial, nodular, sclerosing and miscellaneous forms of BCC)., Materials and Methods: N = 130 histological sections from n = 126 patients with BCC of the head and neck were analyzed. Morphometry included: maximum and minimum diameter, perimeter, nuclear area (direct parameters). According to the direct parameters, so called form factors were evaluated: axis ratio, shape factor, nuclear contour index, nuclear roundness and circumference/contour ratio., Results: Morphometric parameters were not able to differentiate significantly between primary and recurrent BCC. Concerning the histological subtypes, multifocal superficial BCC differed significantly (< 0.05) from all other subtypes by direct parameters., Conclusion: Morphometry can help to distinguish between histological subtypes of BCC. Morphometry alone is not able to predict recurrence rate.

The literature describes various treatment concepts for the pre-operative sanitation of septic foci in the oromaxillofacial area prior to liver transplantation. There are no uniform guidelines, and so far, a connection between dental foci and postoperative infection after transplantation has not yet been proven. Taking into account the complications occurring during focus sanitation, the appropriate extent of, and the most suitable point of time for, focus sanitation have to be ascertained. The clinical and radiological findings from 80 patients were analyzed, with particular attention being paid to dental foci prior to liver transplantation. The complications performed in 39 sanitations and the oral hygiene status of 37 patients were included in the analysis. All the obtained findings were correlated to the etiology of the liver disease and the Child-Pugh stage. Former alcoholics had significantly poorer oral hygiene and more foci than non-alcoholics. After sanitation, complications occurred more frequently in alcoholics (43.8%) and patients in Child-Pugh stage C (41.2%) than in the other groups. Secondary bleeding, severe in some cases, occurred in a total of 15.4% of all patients, despite coagulatory preparations. We can conclude that, given the high rate of complications found in this study after sanitation prior to transplantation, the demand for radical prophylactic dental sanitation should be reconsidered. Rather, it would appear more appropriate for only absolutely necessary sanitation to be carried out prior to transplantation and for the definitive measures to be postponed until after transplantation when liver function has stabilized.

Advanced glycation end (AGE)-products, a complex and heterogeneous group of compounds, have been implicated in diabetes-related long-term complications. Up to the present, only few data exist about serum levels of the AGE-proteins N- epsilon -carboxymethyllysine (CML) and pentosidine in selection-free populations of patients with type 1 and insulin-treated type 2 diabetes mellitus. In the present 10-year, population-based trial of patients with insulin-treated diabetes mellitus, serum CML and pentosidine levels were examined in correlation to the patients' quality of diabetes control and the prevalence of diabetes-related long-term complications. Jena's St. Vincent Trial (JEVIN) was started in 1989/1990. At this time, a centralised diabetes care system existed. After the baseline examination of 190 patients (83% of the target population) with insulin-treated diabetes mellitus, follow-up examinations were performed in 1994/1995 and 1999/2000. In 1994/1995, the CML concentration in patients with type 1/type 2 diabetes mellitus was 1096.47+/-405.50/1136.43+/-405.24 ng/ml. In 1999/2000, it was significantly lower (727.49+/-342.91 ng/ml, P=.033/743.76+/-312.47 ng/ml, P<.0001). The same tendency showed the AGE-protein pentosidine (type 1: 1994/1995 203.18+/-118.88 vs. 1999/2000 156.59+/-104.84 pmol/ml [P=.029], type 2: 1994/1995 189.72+/-67.66 vs. 1999/2000 151.54+/-127.73 pmol/ml [P=.020]). Parallel to the decrease in the mean concentration of the AGE-products CML and pentosidine mean HbA1c improved and the prevalence of diabetic long-term complications (retino-, neuro-, and nephropathy) remained comparable 1999/2000-1989/1990. Comparing the data of 1999/2000 with those from 1994/1995, there was not only a substantial improvement in patients' quality of diabetes control but also a decrease in the concentration of AGE-products. In patients with diabetes mellitus, the AGE-products seem to be mainly influenced by the quality of diabetes control. However, the most important parameter reflecting the risk for development and progression of diabetes-related long-term complications seems not to be the AGE-products, but patients' HbA1c.

Purpose: In cases of soft tissue defects with exposed bone surfaces in the head and face region, there is the option of treating the defect with free split-thickness skin grafts following appropriate wound granulation. Secondary granulation on free bone surfaces is often a lengthy process, as granulation primarily occurs from the edges of the wound. Hydrocolloid dressings are gaining increasing attention in this context. The question arises as to whether the positive properties of hydrocolloid dressings can bring about rapid and positive conditioning of the base of the wound in soft tissue defects with exposed bone in the head and face region, with a view to subsequent split-thickness skin graft transplantation., Materials and Methods: In the period from 1997 to 2000, a total of 25 patients with soft tissue defects with exposed bone surfaces in the head and face region were treated with hydrocolloid dressings in the framework of a prospective clinical study., Results: The average time taken for complete granulation of the bone surface was 39.44 days (minimum, 10 days; maximum, 72 days). As a rule, this necessitated 12.8 changes of dressing (minimum, 3; maximum, 26). The granulation tissue was of good quality, generously vascularized, and occasionally exuberant at the edges of the wound, Conclusion: On the whole, the combination of hydrocolloid dressing and alginate compress was found to have significant advantages as regards conditioning the exposed bone surface., (Copyright 2002 American Association of Oral and Maxillofacial Surgeons)

Objective: This study is an analysis of neonatal outcome in 70 fetuses diagnosed over a 10-year period as having cleft lip with or without cleft palate (CL-P) by ultrasonographic examination., Methods: We describe the natural history of these 70 fetuses with orofacial clefts and select those who may be candidates for fetal surgery. The sonograms of 70 fetuses with orofacial clefts were evaluated for the nature of the CL-P and for the nature of the associated anomalies. Additionally, karyotyping was performed in 63 of 70 patients (90%)., Results: The frequency of additional anomalies and the mortality rate varied with the type of cleft. Also, the frequency and type of chromosomal abnormalities varied with the type of cleft. The overall mortality rate was 63% (n = 44). 3 of the surviving 26 fetuses had severe associated anomalies. In 13 of the remaining 23 cases, the fetal age at diagnosis (> or =22 weeks) excluded the fetuses from the potential benefits of fetal intervention., Conclusion: Of 70 fetuses with prenatally diagnosed orofacial clefts, only 10 (14%) were candidates for fetal CL-P surgery., (Copyright 2002 S. Karger AG, Basel)

Objective. The primary diagnosis of synovial chondromatosis of the temporomandibular joint is extremely rare. Often many months, or even years pass before the diagnosis is confirmed. Study Design. Eight patients with synovial chondromatosis were treated by arthrotomy. In addition to the definitive diagnosis, histologic classification according to the stages proposed by Milgram was undertaken and confirmed with the literature. Results. The predominant symptoms of synovial chondromatosis, including pain, swelling, restricted movement of the mandible, and crepitation, were evaluated. Nevertheless, more than 80% of the patients were previously primarily treated on the basis of other tentative diagnoses. Conclusion. Synovial chondromatosis of the temporomandibular joint should be included in the differential diagnosis of chronic swelling and pain in the preauricular region, and the patient should be sent for appropriate diagnostics and therapy at an early stage.

Complications: Arthroscopy of the temporomandibular joint is an invasive procedure that can entail potential complications. Based on many years of personal experience and taking data from the literature into account, this article discusses functional, surgical, and anesthesiological complications of arthroscopy of the temporomandibular joint. The majority of these complications can be avoided by heeding specific knowledge of topography, careful manipulation, and corresponding surgical experience., Informing the Patient: The information given to the patient prior to the intervention should cover not only hemorrhaging, swelling, and wound infection, but also damage to (branches of) the facial nerve, the risk of perforation of the auditory canal as well as the possibility of temporary occlusal disturbances.

The treatment of hypertrophy of the masseter and temporal muscles has to date been dominated by conservative and surgical measures. Local therapy with type A botulinum toxin permits an alternative method of treatment. After targeted, sometimes electromyographically controlled, intramuscular injection of the affected muscles, marked inactivity atrophy occurred in the muscles of seven patients over the course of 3 to 8 weeks. This atrophy remained constant over a follow-up period of up to 25 months, and no side effects were observed. Because of its minimal invasiveness, this technique seems to have an advantage over conventional surgical therapy. Consequently, treatment with type A botulinum toxin can be regarded as a sensible alternative to surgery in cases of hypertrophy of the masseter and/or temporal muscles.

The temporomandibular joint is rarely affected by crystal deposition disease (gout and pseudogout). Only the temporomandibular joint was affected in a 69-year-old patient with calcium pyrophosphate dihydrate deposition disease (pseudogout). This case is described here. Clinically presenting as painless swelling, computed tomography and magnetic resonance imaging showed signs of a chronic destructive arthritis. The evidence for calcium pyrophosphate dihydrate crystals was provided by histological examination. Diagnostic criteria, differential diagnosis and possibilities for treatment are discussed on the basis of our own experience and the literature.

In order to restore function and esthetics in mandibular hypoplasia, transplantation of osteochondral grafts and the distraction osteogenesis technique are used alternatively. In a retrospective study the indication, growth and complication rate of osteochondral graft and distraction osteogenesis cases in mandibular hypoplasia were compared. In total, 12 patients (4-14 years old; 7 female, 5 male) with different grades of mandibular hypoplasia received osteochondral grafts (7 costochondral, 5 iliac crest; observation period 4-9 years). In 5 patients (10-12 years old; 1 female, 4 male), distraction osteogenesis was performed (observation period 10 months to 3 1/2 years). In the results, according to the literature, the range of growth after osteochondral grafting varied considerably, approximate normal growth was noticed in only two cases. On the other hand, all patients treated by distraction osteogenesis showed a stable increase of bone length as expected. After osteochondral grafts, adequate growth is to be expected in the minority of cases and it does not seem predictable in individual cases. Therefore, the indication for osteochondral grafts should be restricted to severe hypoplasia, where the local amount of bone does not allow the use of a distraction device, and to cases where support of the mandibula at the skull base is necessary. In all other cases of mandibular hypoplasia in children, distraction osteogenesis should be discussed as the primary option, even if in the long term a second surgical procedure should be necessary.

Problem: There is a lack of clear criteria for the use of MR and CT in the diagnosis of head and neck cancer--some of it is even contradictory. The results of this study should lead to the establishment of more clear criteria., Patients: 165 patients suffering from head and neck tumors were subjected to a total of 463 CT and 197 MRI examinations., Results: The CT and MRI staging corresponded in 67% and 60% of the oropharynx tumors, respectively, with the clinical findings. In the case of oral cavity tumors, the clinical TNM stages were identical with CT and MRI results in 50% and 43% of cases, respectively. In the case of lymphatic node staging, the frequency of error was slightly higher using MRI, at 27%, compared with the CT rate of 22%. In the evaluation of cervical lymphatic nodes, CT proved to be more sensitive attaining 78% compared to the MRI rate of 69%., Conclusion: The results provide clear indications as to the MRI and CT examinations. Primary preoperative screening and post-therapeutic aftercare should be assessed using CT, as should lymphatic node diagnosis in the neck area. In the case of special problems such as, for example, the relevant bone and periostium infiltration, MR should be considered as a supplementary examination at a second stage.

A polysaccharide consisting of mainly 1,4-linked glucose units was found associated with prion rods, which are composed mainly of insoluble aggregates of the N-terminally truncated prion protein (PrP 27-30) exhibiting the ultrastructural and tinctorial properties of amyloid. The polysaccharide differs in composition from the Asn-linked oligosaccharides and the GPI-anchor of the prion protein. Prion rods were prepared from scrapie-infected hamster brains using two different purification protocols. Prolonged digestion of rods with proteinase K reduced PrP by a factor of at least 500, leaving about 10% (w/w) of the sample as an insoluble remnant. Only glucose was obtained by acid hydrolysis of the remnant and methylation analysis showed 80% 1,4-, 15% 1,6- and 5% 1,4,6-linked glucose units. The physical and chemical properties as well as the absence of terminal glucose units indicate a very high molecular mass of the polysaccharide. No evidence was found for covalent bonds between PrP and the polysaccharide. The polysaccharide certainly contributes to the unusual chemical and physical stability of prion rods, acting like a scaffold. A potential structural and/or functional relevance of the polysaccharide scaffold is discussed.

The N-terminally truncated form of the prion protein, PrP 27-30, and the corresponding recombinant protein, rPrP, were solubilized in 0.2% SDS, and the transitions induced by changing the conditions from 0.2% SDS to physiological conditions, i.e. removing SDS, were characterized with respect to solubility, resistance to proteolysis, secondary structure and multimerization. Circular dichroism, electron microscopy and fluorescence correlation spectroscopy were used to study the structural transitions of PrP. Within one minute the alpha-helical structure of PrP was transformed into one that was enriched in beta-sheets and consisted mainly of dimers. Larger oligomers were found after 20 minutes and larger multimers exhibiting resistance to proteolysis were found after several hours. It was concluded that the monomeric alpha-helical conformation was stable in SDS or when attached to the membrane; however, the state of lowest free energy in aqueous solution at neutral pH seems to be the multimeric, beta-sheet enriched conformation.

With the aim of eliminating pathological growth during the active period of condylar hyperplasia, 17 patients were treated with a high condylectomy with a retroauricular incision. Postoperatively none of the patients showed signs of continuing growth activity neither clinically nor roentgenologically. Thus, the high condylectomy can be recommended as a reliable technique to stop pathological and untimely growth with a low risk of complications, before occlusion and skeletal asymmetry are corrected by orthodontic surgery.

During a period of 8 years (1986-1994) we treated 183 patients with mandibular fractures. Within this period we changed our treatment protocol from the rigid internal fixation (AO/ASIF method) to monocortical noncompression miniplates. The complications of 127 AO/ASIF cases versus 41 miniplate cases were studied. Complications mostly consisted in dehiscences. Comparing the two methods we found more complications (19.5%) when the AO plate is applicated via an intraoral approach. After extraoral AO treatment and after monocortical miniplates there was no significant difference concerning our complications (8.1% versus 7.3%).

Solid-phase radioimmunoassay methods for the uniform analysis in hemolyzed whole blood and urine of opiates, methamphetamine, cocaine, free morphine, and phencyclidine using Coat-A-Count kits available from Diagnostic Products Corporation were tested for cost effectiveness without compromising the reliability of the results. Results indicate these kits are superior in performance in cross-reactivity studies, noted particularly in the methamphetamine assay, labor conservation, and cost-effectiveness to double-antibody radioimmunoassay methods.

Four-hundred-twenty-six women, aged 18 to 36, completed a four-cycle comparative, randomized, single-blind (observer blind), multicenter study of a new graduated estrogen formulation with three constant-dosed combination oral contraceptives containing the same synthetic steroid compounds. The products studied were Loestrin 1/20, Loestrin 1.5/30, Norlestrin 1/50, and a new graduated estrogen product, Estrostep. A total of 1,850 cycles were completed and analyzed for efficacy, side effects, metabolic changes, and cycle control. Four pregnancies occurred during the course of the study. None of the pregnancies occurred in the group receiving Estrostep. The new formulation produced the lowest rate of breakthrough bleeding (BTB) compared with the other three products. All four combination oral contraceptives resulted in an increase in high-density lipoprotein cholesterol (HDL-C). The levels of HDL-C were greatest with Estrostep.