Changes in the prevalence of residual pockets and tooth loss in treated periodontal patients during a supportive maintenance care program

Bleeding on probing and the presence of deep periodontal pockets are considered to be the best site-specific indicators for periodontal disease progression during the maintenance phase of periodontal therapy. A major emphasis of supportive periodontal care (SPC) programs, therefore, has been the control of bleeding pockets. This investigation retrospectively evaluated the changes in the prevalence of bleeding on probing, periodontal pockets, bleeding periodontal pockets and the prevalence of tooth loss in a random sample of 273 periodontal patients participating in a supportive maintenance care program at a University Clinic. During an observation period of 67+/-46 months (range 5 months to 23 years), the overall incidence of all causes of tooth mortality was 0.23+/-0.49 teeth per patient per year of observation. 56% of subjects, however, did not experience any tooth loss, while less than 10% of patients lost more than 3 teeth. Thus, participation in the SPC program was effective in preventing tooth loss in the majority of patients. During the SPC period, however, a significant increase in the prevalence of periodontal pockets, and of bleeding on probing positive periodontal pockets, in particular, was observed. At completion of active periodontal therapy, 56.4% of patients were free from bleeding pockets. This decreased to a mere 13.6% at the latest SPC evaluation. The observed increases in the number of bleeding pockets was significantly associated with: longer times since completion of active periodontal therapy, more advanced periodontal diagnosis, higher %s of bleeding sites in the dentition, cigarette smoking, lack of inclusion of periodontal surgery in the active treatment phase, tooth loss, and the response to the active phase of periodontal treatment. The data presented in the paper indicate that the observed increase in the prevalence of bleeding pockets and tooth loss was not homogeneously distributed in the studied SPC population. Rather, high risk groups of individuals could be identified. It is suggested that better knowledge of risk indicators may lead to improved and more efficient risk management efforts during periodontal maintenance care.     

Evaluation of Guamanian dental caries preventive programs after 13 years

The authors followed the collection of 77 eyes with glaucoma (54 eyes with POAG, 16 eyes with PACG and 7 eyes with CG) after ECCE or phacoemulsification with implantation of IOL. The patients were operated in 1990-1991 at the Ophthalmological Clinic FNKV and 3rd Medical Faculty in Prague. The authors evaluated IOP, therapy and visual acuity 6 weeks and 6 months after operation. After 6 months period IOP was decreased in average about 3 mmHg; in POAG the reduction was 1.9 mmHg and in PACG the reduction was 4.7 mmHg. In this time the authors also registered decreasing antiglaucomatous therapy at 38 eyes (i.e. 49.3% operated eyes). The reducing therapy represents 50% eyes with POAG and 69% eyes with PACG. The visual acuity is in 70% 6/6-6/12. Patients with PACG have more expressive postoperative effect. The authors draw the attention to late diagnosis CG, after successful operation the visual acuity is reduced on account of advanced changes of the optic disc.     

Pulp remains viable following vital amputation of the mesio-buccal root of the maxillary fourth premolar in dogs

Vital amputation of the mesio-buccal root of the maxillary fourth premolar (P4) was performed bilaterally in 8 dogs. Histopathologic evaluation of the tooth structure revealed normal pulp in the remaining mesio-buccal, mesio-palatal, and distal roots and crown during a mean follow-up period of 3.5 +/- 1.9 months. Amputation site healing was characterized by a reparative dentin bridge produced by odontoid cells. Tunnel defects were observed in 13 of 16 (81%) dentin bridges. It is concluded that the pulp of a tri-rooted, periodontal disease-free tooth remains viable during a 6-month period following vital root amputation. These results point to the intriguing possibility that this may also occur in humans, however, this needs to be directly tested in man.     

Dental innervation and CGRP in adult p75-deficient mice

Adult dental tissues have unusual neurotrophin biology. Pulpal fibroblasts express nerve growth factor (NGF) and the low-affinity p75 neurotrophin receptor, their sensory nerve fibers express p75 and trk A, and pulpal sympathetic fibers lack p75. Following tooth injury, there is increased pulpal NGF, sprouting of sensory nerve endings, and increased immunoreactivity for the sensory neuropeptide calcitonin gene-related peptide (CGRP). In the present study, we have analyzed tooth structure and innervation of pulp and periodontal ligament in young (6-8 weeks, 3 months) and older (5-12 months) adult mice carrying a null mutation in the p75 gene and compared the results with those of age-matched wild-type controls. Our hypotheses were that tooth structure would be abnormal and that pulpal innervation would be greatly reduced because it consists primarily of nociceptive fibers that have been found to be severely depleted in skin of p75(-/-) mice. Tissues were fixed, X-rayed for gross dental morphology, decalcified, and analyzed for immunoreactivity for CGRP and for a general nerve marker, protein gene product 9.5. Radiographs showed worn-down molar crowns in p75-deficient mice. Light microscopy confirmed the accelerated molar wear and showed intense CGRP immunoreactivity in pulp nerve endings of mutant mice, compared with a gradual decrease in CGRP intensity in controls during normal aging. The CGRP intensity in 5-12-month-old pairs of mice was threefold greater in the mutants (P < 0.03), and in younger mice the mutant always had more CGRP than its matched control. The innervation of molar ligament in all p75-deficient mice was similar to that of controls except there was nerve sprouting near bone loss in mutants. The incisors of mutant mice did not have unusual wear and their pulpal CGRP immunoreactivity remained normal, but their periodontal ligament had fewer thin branched nerve endings at all ages. Thus, most innervation of teeth and their supporting tissues developed normally, and the only neural changes in p75(-/-) mutant mice were the reduction of incisor ligament sensory receptors and increased molar CGRP. Sensory nerves in teeth gradually lose neuropeptide intensity during aging, but that did not happen in the mutant mice, suggesting that the accelerated molar wear stimulated persistent high levels of CGRP.     

The prevalence of Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, and Bacteroides forsythus in humans 1 year after 4 randomized treatment modalities

The relationship between probing attachment changes in treated periodontal pockets and the prevalence of selected periodontal pathogens was assessed in 10 patients with adult periodontitis 1 year following randomized therapy. All patients had at least 1 tooth in each quadrant with an inflamed pocket of probing depth > or =5 mm and clinical attachment loss and harbored at least one of the following 3 major periodontal pathogens: Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, or Bacteroides forsythus. The number of target organisms per site was determined preoperatively; at 1 week; and at 1, 3, 6, and 12 months postoperatively utilizing DNA probes. The following clinical parameters were measured and recorded preoperatively and at 1, 3, 6, and 12 months post-treatment: gingival fluid flow, gingival index, plaque index, probing depth, probing attachment level, gingival recession, and bleeding on probing. One quadrant in each patient was randomly assigned to 1 of the following 4 treatments: 1) scaling and root planing; 2) pocket reduction through osseous surgery and apically-positioned flap; 3) modified Widman flap; and 4) modified Widman flap and topical application of saturated citric acid at pH 1 for 3 minutes. All 4 treatments were rendered in one appointment using local anesthesia. No postoperative antibiotics were used, but patients rinsed with 0.12% chlorhexidine for the first 3 months postoperatively and received a prophylaxis every 3 months. This investigation revealed: 1) 30.0% of the sites were infected by at least 1 species at 3, 6, and 12 months postoperatively. 2) Failing sites were infected by a high number of both Pg and Bf These sites had a mean of 24.2+/-9.0 x 10(3) Pg and 93.1+/-42.0 X 10(3) Bf while stable sites had a mean of 6.8+/-0.5 x 10(3) Pg and 7.2+/-1.2 x 10(3) Bf (P = 0.06 and P = 0.05, respectively). 3) The infected sites lost significantly more mean clinical attachment at 12 months (1.5+/-0.5 mm compared to a loss of 0.2+/-0.3 mm for uninfected sites, P = 0.017). 4) The infected sites had a significantly greater BOP (67+/-14% versus 25+/-8% for uninfected sites at 12 months, P = 0.012). 5) The choice of treatment modality did not affect the prevalence of the target species at 1 year post-treatment. These results suggest that prevalence of microbial pathogens negatively affects the 1 year outcome of periodontal surgical and nonsurgical therapy.     

120烧结单辊破碎机齿冠抗磨研究

烧结机尾部的单辊破碎机齿冠使用寿命过短是制约烧结工艺的技术难题之一。由于工作环境恶劣破碎机齿冠平均使用寿命不到5个月。通过分析齿冠受力情况、失效特征及影响高铬铸铁抗磨性能的各方面原因,提出了优化辊齿结构和改进齿形的方法,实施后提高了破碎机齿辊使用寿命。     

Dental caries, restoration and tooth conditions in U.S. adults, 1988-1991. Selected findings from the Third National Health and Nutrition Examination Survey

This article provides estimates of dental caries experience and selected restorative and tooth conditions among U.S. adults, obtained from Phase 1 (1988-1991) of the Third National Health and Nutrition Examination Survey. Between 1988 and 1991, 94 percent of adults in the United States showed evidence of past or present coronal caries. Based on the data collected, the authors estimate that about 40.5 percent, or 61.6 million, dentate adults had at least one tooth or tooth space that could potentially benefit from professional treatment. Minimally, it is estimated that 135.6 million tooth or tooth spaces among U.S. adults may benefit from professional treatment. These estimates supplement information available from the DMF index to provide a broader profile of the impact of dental caries on permanent tooth of U.S. adults.     

Expression patterns of bone morphogenetic proteins (Bmps) in the developing mouse tooth suggest roles in morphogenesis and cell differentiation

Bone morphogenetic proteins (BMP) are secretory signal molecules which have a variety of regulatory functions during morphogenesis and cell differentiation. Teeth are typical examples of vertebrate organs in which development is controlled by sequential and reciprocal signaling between the epithelium and mesenchyme. In addition, tooth development is characterized by formation of mineralized tissues: the bone-like dentin and cementum as well as epithelially derived enamel. We have performed a comparative in situ hybridization analysis of the expression of six different Bmps (Bmp-2 to Bmp-7) starting from initiation of tooth development to completion of crown morphogenesis when dentine and enamel matrices are being deposited. Bmps-2, -4, and -7 were frequently codistributed and showed marked associations with epithelial-mesenchymal interactions. Their expression shifted between the epithelium and mesenchyme starting from the stage of tooth initiation. They were subsequently expressed in the enamel knot, the putative signaling center regulating tooth shape. Their expression domains prior to and during the differentiation of the dentine-forming odontoblasts and enamel-forming ameloblasts was in line with functions in regulation of cell differentiation and/or secretory activities of the cells. The expression of Bmp-3 was confined to mesenchymal cells, in particular to the dental follicle cells which give rise to the cementoblasts, forming the hard tissue covering the roots of teeth. Bmp-5 was expressed only in the epithelial ameloblasts. It was upregulated as the cells started to polarize and intense expression continued in the secretory ameloblasts. Bmp-6 was expressed only weakly in the dental mesenchyme during bud and cap stages. Our results are in line with regulatory functions of Bmps at all stages of tooth morphogenesis. Bmps-2, -4, and -7 are conceivably parts of signaling networks regulating tooth initiation and shape development. They as well as Bmp-5 may be involved in the induction and formation of dentine and enamel, and Bmp-3 in the development of cementum. The remarkable overlaps in the expression domains of different Bmp genes may implicate functional redundancy and/or formation of active heterodimers between different BMPs.     

Surveillance of nosocomial infections in geriatric patients

The authors report 18 cases of transfer of several ulnar nerve fascicles onto the biceps muscle nerve, performed between 1990 and 1997. The patients were between the ages of 17 and 41 years, and presented C5-C6 paralysis in 8 cases and C5-C6-C7 paralysis in 10 cases. The operation was tempted between 4 months and 6 years (m = 17 months) after the initial accident. In the 8 cases of C5-C6 paralysis reviewed, 7 patients recovered elbow flexion and only one required an additional Steindler transfer. In the 9 cases of C5-C6-C7 paralysis reviewed, 4 patients recovered elbow flexion after nerve surgery alone, while 4 patients only obtained elbow flexion after a complementary Steindler transfer. Two of these 4 patients were operated very late (27 and 75 months). Finally, a single 40-year-old patient, operated 28 months after the accident, was considered to be a complete failure. Overall, ulnar biceps nerve transfer appears to be indicated in C5-C6 avulsion, during the months following the initial accident. Flexion against gravity is then regularly obtained in less than 6 months, without any objective or subjective sequelae of the hand.     

Distribution of a newly described species, Kingella oralis, in the human oral cavity

The oral distribution of Kingella oralis was investigated in 10 periodontally healthy subjects. 11 untreated adult periodontitis patients and 6 untreated localized juvenile periodontitis patients. From each subject, 6-8 each of supra- and subgingival tooth samples, 4 mucosa samples and a saliva sample were examined by culture for the presence of K. oralis. K. oralis was found in at least one oral site in 26 of the 27 study subjects, and in at least one tooth site in each of these 26 positive subjects. Its prevalence in dental plaque ranged from 23% to 59% in different subject groups. The mean percentage of K. oralis in total microbiota in the dental plaque ranged from 0.40% in the periodontally healthy group to 4.60% in localized juvenile periodontitis subjects. The organism was a significant species in a few periodontitis sites, constituting > 5% of the total microbiota.     

Contrast medium assisted dynamic MR-mammography after diagnostic and therapeutic interventions on the breast

In a retrospective study, the authors evaluated the signal behavior of 150 patients after intervention in the breast (40 fine-needle biopsies, 10 core biopsies, 50 open biopsies, 50 tumor-ectomies with additional irradiation therapy). The MR imaging was performed on 1.5-Tesla whole-body scanners using T1-WI GRE sequences in 2D FLASH technique before and 5 times after i.v. application of 0.1 mmol gadopentetate-dimeglumine per kg body weight. There was no signal enhancement after fine-needle biopsy. Hematoma due to core biopsy caused signal increase in every 5th patient. Enhancement after open biopsy was no more visible 6 months postoperatively. 12 months after tumorectomy and radiation therapy, most patients showed no more signal enhancement. In conclusion, MR mammography can be performed after fine-needle biopsy without problems. In case of core biopsy, hematoma should be excluded by sonography before. MR mammography should not be performed within 6 months after open biopsy, or within 12 months after tumorectomy and radiation therapy.     

Interventional methods in breast diagnosis. Histological vs. cytological evaluation of core cut biopsies of the breast

The features of enamel hypoplasia in a small group of patients with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) are described. Using a recently developed method, the authors evaluated quantitatively the amount of defect in each tooth by measuring the width of the hypoplastic lesions and dividing the value by the crown height. They then assessed the degree of damage in each tooth type (from central incisors to second premolars) and patient. Canines were the most severely affected among maxillary and mandibular teeth, but all tooth types were involved. Analysing both the differences between patients and their age at the beginning of the defect, the authors observe that hypoparathyroidism is not responsible for the onset of enamel hypoplasia in APECED, although it may contribute to the damage.     

Dynamics of tissue changes found after mechanical loading of the rat incisor. II. A three-dimensional longitudinal study of the histopathologic aspects

The study comprised 60 lower left rat incisors subjected to 2 weeks of loading (19.7 +/- 1.6 gm) and 5 control teeth. After the loading period, 10 rats were killed with the springs in situ, and the remainder were killed in groups of 5 at intervals of 1 through 10 weeks after the springs were removed. The teeth were cross-sectioned serially (2 microns). The distance of each section from the apex and the time of its tissue formation in relation to load removal were calculated. Bone remodeling and dental and periodontal trauma were plotted according to their location on the tooth axis and circumference. Vigorous bone remodeling continued throughout the observation period, apposition and resorption sites intermingling around the tooth. Directionality, as expressed by the resorption/apposition ratio, for the formerly tensed and stressed areas was 0.61 +/- 0.07 and 1.79 +/- 0.52, respectively. However, in some of the groups directionality was negligible or reversed. New lesions of dentin (folding and resorption) were formed for 6 weeks after loading, whereas new damage to the enamel organ and enamel matrix appeared until week 9. The integrity of the PDL deteriorated for the first 8 weeks, as evidenced by edema, cell loss, scarring, and collagen fiber disorientation. Necrosis occurred throughout the recovery period. Fiber to bone attachment was disrupted by formation of big sinusoids adjacent to the bone. The frequency of most lesions decreased toward the end of the observation period. It is suggested that tissue recovery proceeds in subsiding cycles of tissue injury/tissue repair, a process that is much more prolonged than is generally believed.     

Quantitative analysis of inputs to somatostatin-immunoreactive descending interneurons in the myenteric plexus of the guinea-pig small intestine

An unusual case of bilateral inflammatory external/internal root resorption developed in the maxillae of a 28 year-old female approximately 4 years following routine segmental orthognathic surgery. The patient experienced dental pain in a tooth adjacent to a segmental osteotomy cut 8 months postsurgery, however, the tooth later became asymptomatic. A definitive diagnosis of inflammatory cervical root resorption was not established until nearly 4 years later on routine dental examination. The external/internal resorptive lesions were located 4 to 6 mm apical to the connective tissue attachment on 3 of the 4 tooth roots adjacent to osteotomy cuts. Two of the affected teeth required non-surgical root canal therapy due to pulpal communication with the resorptive defects. The lesions were accessed by flap surgery, thoroughly debrided, and obturated with an intermediate restorative material until definitive restorative therapy could be completed. All sites healed uneventfully and the patient has been closely observed for approximately 2 years without symptoms or recurrence of the resorptive lesions. Dental health care providers should be alert to the possible occurrence of inflammatory root resorption in sites adjacent to osteotomy cuts over extended periods of time. Routine radiographic examination may be beneficial in the postoperative management of the segmental orthognathic surgery patient.     

Comparison of the effects of growth hormone, insulin-like growth factor-I and fetal calf serum on mouse molar odontogenesis in vitro

The effects of growth hormone, its mediator insulin-like growth factor-I (IGF-I), and fetal calf serum on odontogenesis were compared to those of serum-free medium. Explanted, 16-day, fetal mouse first molar tooth germs in early bell stage were grown on semisolid, serum-free medium supplemented with ascorbic and retinoic acids. Recombinant human growth hormone at 50 or 100 ng/ml, IGF-I at 100 or 200 ng/ml, or fatal calf serum at 20% concentration were added to the media. Volumetric changes in serial sections of six tooth germs per treatment over 3 days of treatment (4, 5, 6 days in vitro) were compared by digitized morphometry. Mitotic indices were also compared and the cell densities of the dental papillae recorded. Qualitative ratings of differentiation were ascribed to each tooth germ by light microscopy. Differences in volume, mitotic activity and cell densities were found. The growth hormone-treated tooth germs were not larger than the serum-free ones but had increased mitotic indices and higher cell densities in the dental papillae. IGF-I-treated tooth germs had larger volumes than with all other treatments, e.g. germs treated with 200 ng/ml of IGF-I, after 6 days in culture, were significantly larger than with all other treatments (p<0.01-<0.001). Whilst IGF-I-treated germs displayed the greatest extent of differentiation, growth hormone-treated germs also showed advanced differentiation compared to those on serum-free medium. These results suggest that growth hormone and IGF-I are involved in odontogenesis of murine teeth in vitro by affecting mitotic activity, tissue volume and cell differentiation. In conjunction with previous immunohistochemical studies that show expression of growth hormone receptor and IGF-I in developing teeth, these results provide evidence that both growth hormones and its mediator play a part in odontogenesis.     

Insulin effects on ouabain binding in A6 renal cells

OBJECTIVES: This study sought to identify risk markers associated with the provision of new restorations in children and to investigate whether the carious status of a tooth surface is associated with the restorative decisions of dentists. METHODS: A total of 911 schoolchildren in grades one, two, and three were randomly selected from the island of Montreal, Quebec, Canada. Dental examinations were carried out in 1990, 1991, and 1992. Tooth surfaces of first permanent molars were classified as sound, noncavitated, and cavitated. The carious status of a tooth was matched with restorative decisions reported to the insurance board. RESULTS: The presence of a carious cavity was a strong risk marker for placement of new restorations (odds rations > or = 4.11). After one year, less than 2 percent of sound tooth surfaces of first permanent molars were restored and about 21 percent of noncavitated tooth surfaces were restored. When new class I restorations placed in maxillary first permanent molars within 3-6 months after the baseline examination were evaluated, we found that between 73 percent and 86 percent of these new restorations were placed in sound or noncavitated tooth surfaces. A similar trend also was observed in mandibular first permanent molars. Poor agreement between epidemiologic diagnosis and restorative decisions was found. The restorative profile of dentists was a significant risk marker for placement of new restorations. CONCLUSION: The majority of new restorations in first permanent molars were placed in sound and noncavitated tooth surfaces because of the ubiquitous prevalence of these tooth surfaces and the validity problems of current caries diagnosis methods.     

Effects of CO2 laser in treatment of cervical dentinal hypersensitivity

The effectiveness of CO2 laser therapy in the reduction and elimination of dentinal hypersensitivity in vivo and its thermal effects on tooth surfaces in vitro were investigated. Twenty-three patients with 91 sensitive teeth participated in this study and were followed for 3 months. The parameters used with CO2 laser were 1 W in a continuous wave mode and irradiation time ranging from 5 to 10 s. Hypersensitivity was assessed by thermal stimulus (a blast of air from a dental syringe). Thermal effects were measured by thermography using 10 extracted human teeth. After laser treatment, all patients were immediately free from sensitive pain. Over 3 months, the CO2 laser treatment reduced dentinal hypersensitivity to air stimulus by 50%. All teeth remained vital with no adverse effects. Thermography revealed no temperature increase on irradiated tooth surfaces subjected to water coolant. These results show that the CO2 laser is useful in the treatment of cervical dentinal hypersensitivity without thermal damage to pulp.     

Dynamic variations in the expression of type I collagen and its molecular chaperone Hsp47 in cells of the mouse dental follicle during tooth eruption

Tooth eruption is a precisely timed and sequenced event that brings the tooth from within bone into a functional position in the mouth. Every part of the developing tooth has been theoretically implicated as a primary factor in this process, but it now appears that eruption is multifactorial, with the dental follicle and type I collagen playing an important part. Immunological probes were used here to investigate in vivo and in vitro the temporal and spatial expression of type I collagen and its molecular chaperone Hsp47 in the dental follicle during eruption. Mandibles were dissected from 2-, 5-, 9- and 11-day-old neonatal mice and fixed in 95% ethanol overnight. Sections of 7 microns were obtained and reacted with antibodies directed against type I collagen. Dental follicles were isolated from 2-, 5-, 9- and 11-day-old neonates and cells were grown in culture for 8 days. Slides were then reacted with antibodies directed against type I collagen and Hsp47. The production of type I collagen and Hsp47 in the follicle varied with the stage of dental development and eruption. There was a progressive decrease of type I collagen in the coronal part of the follicle, leading to an arrest of its production in these areas. These findings support the notion that cells of the coronal portion of the dental follicle stop producing type I collagen as a prerequisite to the initiation of tooth eruption and that this phenotype persists in vitro.     

Retinoscopy after excimer laser photorefractive treatments

Photorefractive keratectomy (PRK) is capable of changing the refractive power of the human cornea. Retinoscopy is an objective method of measuring the refractive power of the eye. The authors performed PRK in 28 myopic eyes with the Aesculap Meditec MEL 60 ArF excimer laser. During a prospective study, the subjective and objective refractive power of the eyes were assessed and compared 6 months after PRK. The average preoperative refractive error was: -5.11 +/- 2.51 D and -5.08 +/- 2.20 D on the right side (n = 16) and on the left side (n = 12), respectively. In order to obtain the best corrected visual acuity 6 months after PRK, the right and left eyes needed an average of -0.09 +/- 0.26 D and -0.33 +/- 0.64 D postoperative correction, respectively. The postoperative refractive change could be verified with the retinoscopy at +/-0.5 D accuracy. The authors describe a double refractive corneal ring after PRK, which may disturb retinoscopy. The post-PRK refractive change can be verified by retinoscopy. Postoperative funduscopy, fundus photography and possible future retinal procedures were not disturbed by the double corneal refractive rings in myopic eyes.     

12-hour pattern of the waking state in the normal infant and in the infant who has survived the 'syndrome of sudden infant death' (author's transl)

The authors report the results of 16 sleep EEGs carried out on 5 infants said to have survived the syndrome of sudden infant death (near-miss group) and 5 controls. The recordings were performed at 1.5 months, 3 months and 4.5 months, times when the risk of sudden death is maximum. The EEG appearance and the organization of sleep patterns have been studied in both groups. The various states of wakefulness, and the modalities of sleep and waking were subjected to statistical analysis with respect to age. The study showed no significant difference between the percentages of different states of wakefulness in the control and 'near-miss' group, but there were more sleep onsets in active sleep (REM) in this group compared with the controls and there were fewer waking periods, although when they occurred these were more prolonged.