Assessing Spectrum of Fractures in Elderly; Perspective on Tertiary Care Hospital of Nepal.

Background There is an increasing life expectancy and a surging elderly population in the last few decades, leading to a higher incidence of fractures in the elderly. The health care of the elderly in Nepal is below par and there are no studies done to evaluate the spectrum of fractures in the elderly. Objective To evaluate the demographical and epidemiological aspects of fractures in the elderly (≥ 65 years) presenting to a tertiary care hospital in Nepal in a 15 years' timeline. Method This study was a retrospective epidemiological study conducted in the Department of Orthopedics, Dhulikhel Hospital, Kathmandu University Hospital (DH, KUH), Nepal. The patients of age ≥ 65 years having traumatic injuries, admitted in the orthopedics ward from 2006 January to 2020 December were included. Patient demographics, site of injury, fracture incidence, mechanism of injury, hospital stay duration, and mode of treatment (surgical/ conservative) were evaluated. Result Of the 787 patients with an average age of 73.65 ± 7.5 years, 54% were females. Peritrochanteric fracture was the most common fracture (29.4%) followed by spine (18.3%). The most common mechanism of injury was fall on the labeled ground (38.6%). The incidence of fragility fractures (peri-trochanteric, proximal humerus, spine, and distal radius) was increasing with age. Conclusion Females, peritrochantric fractures, and trivial trauma are the most common occurrences for fractures in elderly. The incidence of fragility fractures is increasing with age but the overall incidence of fractures compared to other studies is low. Higher incidences of road traffic accidents (RTA) and compound fractures among the elderly are serious public health concerns that highlight the importance of primary preventive measures.

Histological Examination of Tissue Obtained in Early Pregnancy Loss.

Background It is a routine practice to send histological sample after surgical evacuation of early pregnancy loss. Objective This study was carried out to see the justification of regular histological study by carrying out the histological study of early pregnancy loss and to find the prevalence of gestational trophoblastic disease in early pregnancy loss. Method It was a descriptive prospective study, conducted in Nepal medical college teaching hospital from February to October 2020 in Obstetrics and Gynaecology department. Clinical data such as age, parity, gestational age and diagnosis were collected of 130 patient of early pregnancy loss. Then histological study were sent after surgical evacuation. Result Among the age group, 21-30 age group was maximum. (64.61%), more than half of the patient was primigravida (53.07%) and most of the cases were between 6 to 9 weeks of gestation. Incomplete abortions were maximum (43.07%), missed abortions 38.46%, blighted abortions 16.15%, enevitable abortions 1.53% and septic abortion was 0.76%. Among histological finding, 72.30% were product of conception, 15.38% of the cases had no product of conception, decidual tissue only in 6.92%, partial mole in one case (0.76%), complete mole in one case (0.76%) and hydrophic changes in one case (0.76%). The total cases of Gestational trophoblastic diseases (GTD) were 3(2.30%). Conclusion In our study we found 2.3% of cases of GTD, which was quite high in compare to Western word. So it is a good practice to do histological study of all cases of EPL in our country to detect GTD, determining cause for recurrent pregnancy loss and detecting unexpected fetal pathology.

Osteosynthesis of Neck of Femur Fracture below 65 years of Age: does timing of surgery influence osteonecrosis, nonunion and functional outcome?

Background Influence of timing of injury surgery interval in outcome of osteosynthesis of neck of femur has always been a matter of debate. Patients in our set up have been surgically treated for neck of femur fracture with wide range of injury surgery interval which could have resulted in varied functional outcome and radiological outcome. Objective To evaluate the difference in functional outcome, femoral head osteonecrosis and non-union in fracture neck of femur fixed within and after twenty-four hours. Method All patients, who had undergone osteosynthesis for the neck of femur fractures via open or closed technique from 2010 to 2018 were analyzed retrospectively. The cases were examined and evaluated in terms of injury surgery interval, fracture union, functional status using Modified Harris Hip Score, complications like femoral head osteonecrosis and non-union. Result Fifty patients with an average injury surgery interval of 34±28 hours were evaluated. Twenty three (46%) cases were included in early surgery group (< 24 hours) and 27 (54%) patients were included in delayed (> 24 hours) surgery group. Incidence of femoral head osteonecrosis was reported in two (4%) cases, both being in delayed fixation group (p=0.49). Non-union was reported in four (8%) patients, one in early fixation group and three in delayed fixation group (p=0.61). The average Modified Harris Hip Score in early fixation group was 87 and in delayed fixation group was 84 (p=0.1). Forty two (84%) cases had a good quality of reduction and eight (16%) had a poor reduction. Non-union and functional outcome significantly differed between the good and poor reduction group (p=0.001 and 0.004 respectively). Conclusion There is no significant difference in the functional and radiological outcome of cases operated before and after 24 hours for osteosynthesis of neck of femur fractures in patients 16 to 65 years age group. However, poor reduction is significantly associated with the increased rate of non-union and poor functional outcome.

Orthopaedic Services during Nationwide COVID-19 Lockdown: Dhulikhel Hospital, Kathmandu University Hospital Experience and Review of Literature.

Background The Nepal government issued a nationwide lockdown due to COVID-19 from 24 March to 21 July 2020. This halted elective medical services in our hospital. A number of modifications in the orthopaedic practices at our department were made. Objective This article discusses the impact on orthopaedic load at the Department of Orthopaedics and Trauma, Dhulikhel Hospital, Kathmandu University Hospital during the lockdown. Method This is a longitudinal observational study done during the nation-wide lockdown including all the patients who presented to the hospital requiring orthopaedic consultation. For comparison purposes, the patient numbers from the same date in previous year (2019) were retrieved. Result We received no COVID-19 cases requiring orthopaedics consultation. A total of 1828 patients were seen in the Orthopaedic Outpatient Department, 1077 trauma patients in the Emergency Department, 216 patients were admitted and 210 orthopaedics procedures were performed at the operation theatre. There was 82.21% decrease in OPD patients and 56% less surgeries in OT compared to the same duration of last year. Conclusion There was a great reduction in the patient numbers visiting the hospital, which reflected in decreased number of admission and surgery. A greater part of our work during the lockdown was trauma.

Displaced Intra-Articular Calcaneal Fractures: Evaluation of Clinical and Radiological Outcome Following Open Reduction and Internal Fixation with Locking Branched Calcaneal Plate.

Background Calcaneal fractures are common, but are difficult to manage. Immediate concern is soft tissue problems, while long term concern is pain as a sequelae of subtalar arthritis. A consensus has not been reached in the management of calcaneal fractures. Objective This study aims to evaluate clinical and radiological outcomes of the patients managed with open reduction and internal fixation with Calcaneal Locking Plates for the displaced intra-articular calcaneal fractures presenting in Dhulikhel Hospital, Kathmandu University Hospital. Method This was a prospective study, conducted on displaced intra articular calcaneal fractures from January 2014 through December 2016. The patients underwent open reduction and internal fixation with Locking Branched Calcaneal Plates through the extensile lateral approach. Post-operatively, ankle was mobilized after two weeks. Weight bearing was started after 12 weeks. Patients were evaluated clinically with Maryland foot score and radiologically with measurements of Boehler's and Gissane angle. Result Twenty-two cases of calcaneal fractures managed with open reduction and internal fixation with Locking Branched Calcaneal Plates were available for final evaluation. Seventeen of the enrolled patients were males in their third decade of life. On average, calcaneal fractures were operated on seven days after the injury. Sanders Type II were seen in 68.2% of the cases and Sanders Type III were in 31.8%. Mean follow-up duration was 21.5 months. The average Maryland foot score was 77.27. Seventeen cases (77.13%) had good, four cases (18.2%) had fair, and one case (5.5%) had poor outcome score. There was statistically significant improvement in Boehler's and Gissane angle across all enrolled patients. Conclusion Displaced intra-articular calcaneal fractures treated operatively with open reduction and internal fixation with Locking Branched Calcaneal Plates through the extended lateral approach, with proper planning of operation and surgical techniques in soft tissue handling, results in good clinical as well as radiological outcomes.

Study of Clinical Variables Affecting Long Term Outcome after Microdisectomy for Lumbar Disc Herniation.

Background Outcome of lumbar disc herniation are influenced by various clinical, socioeconomic and psychological factors. In the absence of provision of medical insurances, worker's compensation and sick leave, predictors for outcome after lumbar disc herniation surgery will be different in Nepalese population. Objective To evaluate different clinical variables that can affect outcome after lumbar disc herniation surgery. Method Among 88 patients who underwent microdisectomy for lumbar disc herniation, 63 patients (43 male, 20 female) with follow up at least six months were retrospectively evaluated for clinical variables which can affect Oswestry disability index (ODI) score, its interpretation and Mcnab classification of post operative outcome. Result Average age of patients was 42.54±8.60 years. Mean follow up period was 34.89±23.80 months (range 6 -111 months). Thirty four patients had follow up period > 24 months. Mean ODI score before surgery and at final follow up was 37.87±8.76 vs 7.78±7.7; (p=0.00). Success rate was 90.47% (change in ODI score at least by 10), 93.65% (ODI score interpretation <40%), and 85.71%. (Mcnab outcome excellent and good). Significant correlation was found between age and ODI at final follow up but not with duration of symptoms. Male, non alcoholic, low level of education, numbness as a predominant symptom, disc at L4-L5 were significantly associated with better ODI at final follow up. For ODI score interpretation, gender, smoking habit, presence of leg pain as a predominant symptom were statistically significant factors whereas smoking and drinking habit, level of education, occupation, back pain and numbness as predominant pre-operative symptom, types of disc in MRI were significantly related to Mcnab outcome. There was 9.5% peri- or post-operative complications and recurrence in seven patients. Conclusion Age, gender, smoking and drinking habit, level of education, occupation, types of disc in MRI are important variables for ODI score, ODI score interpretation and Mcnab outcome.

Epidemiological and outcome analysis of orthopedic implants removal in Kathmandu University Hospital.

BACKGROUND: Orthopedic Implant removal is one of the commonly performed elective orthopedic surgeries. Implants are generally removed after the purpose of keeping implant is solved by healing of the fracture, but there is no consensus whether routine implant removal should be a policy for all fractures that were fixed. OBJECTIVE: This study aims to analyze the epidemiology and outcome of implant removal surgery carried out in the past three years in Kathmandu University Hospital. METHODS: Patients who underwent implant removal between 2010 January to 2012 December constituted the study cohort. Demographic data, indications, types of hardware and location of fractures were recorded. Similarly, duration of surgery, type of anesthesia and duration of hospital stay were recorded. All the patients who had undergone implant removal in this three years period were called for follow up examination but those who were not able to come were interviewed on telephone. RESULTS: There were 275 implant removals constituting 7.8% of total orthopedic operations and 26.3% of fracture fixations. Male to Female ratio was 189: 86. Pediatric age group (34.5%) had the highest incidence of implant removal. Moderate sized implants were the commonest hardwares removed (63.2%). Femur (27.3%) followed by radius (26.9%) were the commonest bone for implant removal. Average operative time was 47.3 minutes with average hospital inpatient stay of 2.6 days. Commonest indication for the implant removal procedure was pain (45%). CONCLUSION: Implant removal procedures are one of the most commonly performed elective orthopedic surgeries. Though, after orthopedic implants removal, pain relief can be expected but it is not so predictive and hence patient should be well counseled before and the indications for implant removal has to be evaluated for better patient satisfaction and safety.

A comparative study on epidemiology, spectrum and outcome analysis of physical trauma cases presenting to emergency department of Dhulikhel Hospital, Kathmandu University Hospital and its outreach centers in rural area.

BACKGROUND: Physical trauma is one of the major cause of mortality and morbidity among young and active age group and its increasing trend is of main concern. There are only few studies concerning the spectrum of physical trauma in Nepal. OBJECTIVE: This study aims to evaluate the epidemiological spectrum, the extent, severity of the physical trauma and the outcome evaluation of patients with physical trauma over a period of one year in the emergency department of the Kathmandu University Hospital and compare the same parameters with those patients presenting to the various outreach centers of the hospital in the community. METHODS: Patient treatment files from the emergency department and the reports from various outreach centers were retrieved for a period of one year (May 2011 to April 2012). Epidemiological information, mode, type and anatomic location of injuries were recorded. Outcome evaluation was assessed by number of patients discharged from emergency department of the hospital or the outreach centers after the treatment, patients admitted for inpatient management and referred to other centers for further specialty management. RESULT: In a period of one year, total 2205 (20%) of physical trauma cases presented to the emergency department and 1994 (6.12%) in the outreach centres. Most commonly involved age group in physical trauma both in Hospital set up and in Community set up were the young adults (15 to 49 years). Fall from height was the commonest mode of injury followed by road traffic accidents among the patients coming to the hospital while significant number of trauma patients coming to outreach centers were due to fall from height. In the hospital set up, 1525 (69.2%) of the cases were discharged while 537 (24.4%) needed inpatient management and 85 (3.8%) needed referral to other centers for the specialty management. In case of outreaches, half of the patients were discharged after the primary treatment and almost another half were referred to the hospital, mainly for need of further investigations. CONCLUSION: Fall related injuries and road traffic accidents are the most common mode of trauma in the hospital set up and fall related injuries are the single most important mode of trauma seen in the outreaches. Mostly young adults in their active period of life are involved in physical trauma so appropriate preventive measures through public health approach should be included in comprehensive trauma management for reducing mortality and morbidity rates related to physical trauma.

Study of endometrial tissue in dysfunctional uterine bleeding.

Dysfunctional uterine bleeding (DUB) is defined as heavy and or irregular menstruation in the absence of recognizable pelvic pathology, pregnancy or general bleeding disorder. Hyperplastic endometrium is abnormal histology finding found in DUB. Out of three type of hyperplasia, atypical type is associated with co-existent ca endometrium and the chance of progression to ca endometrium is very high. Thus this study was conducted to see the incidence of hyperplasia of endometrium in cases of DUB and to see the risk factors for endometrial hyperplasia. It was a prospective study carried out in span of two years (2010 JULY- 2013 Jan) in Nepal Medical College and Teaching Hospital. Hundred cases DUB who under went D&C or hysterectomy were included to study the age range, the relation of parity, patient symptom, contraceptive method and medical disease with the type of endometrial histology. It was found that DUB was common in perimenopusal age (49%) and the incidence increase with the increase of parity. Abnormal endometrial finding (hyperplasia) was found in 31% of the cases. Atypical and complex hyperplasia were associated with irregular menstruation and one third of the hyperplastic patient had hypertension (32.26%). Thus perimenopausal age, irregular menstruation and hypertension are risk factors for hyperplasia. So it is mandatory to do endometrial sampling in cases of perimenopausal age with irregular menstruation withor without hypertension.

Short-term versus long-term catheterization after vaginal prolapse surgery.

Utero-vaginal prolapse is one of the commonest cause for vaginal operations in our country. The expense of this operation can be reduced by reducing duration of catheterization and thereby reducing hospital stay. A prospective, comparative hospital based study was used to assess whether removal of an in-dwelling catheter after 24 hours of vaginal operations with anterior colporrhaphy affects the rate of recatheterization, asymptomatic urinary tract infections, and hospital stay in comparison to 72 hours catheterization. We assigned 100 women who underwent vaginal operations. In-dwelling catheter was removed after 24 hours in group A and after 72 hours in group B. The association between Post-operative urinary retention, pus cells count > 5 per High Power Field, bacterial culture positivity and the length of catheterization were assessed by Chi square test. Recatheterization occurred in three patients (6%) of group A and none in group B (P value 0.241). Mean hospital stay after operation was 3.42 days in group A and 4.48 days in group B. Asymptomatic urinary tract infections (pus cells > 5 per High Power Field) occured in nine (18%) in group A and fifteen (30%) in group B (P value 0.16). Bacterial culture positivity occured in seven (14%) in group A and twenty-two (44%) in group B (P value 0.001). Despite increased recatheterization rate, early removal of in-dwelling catheters after uncomplicated vaginal hysterectomy pelvic floor repair and anterior colporrhaphy decreased mean catheterization time, mean hospital stay and asymtomatic urinary tract infection.

Understanding of tobacco and lung cancer among medical students in Kathmandu University School of Medical Sciences (KUSMS).

BACKGROUND: Often, lung cancer is diagnosed at terminal stages. Poor awareness about the symptoms or risk factors of lung cancer among medics may be one of the factors for delayed diagnosis. OBJECTIVE: We explored the knowledge of medical students and their behavior with the patients of lung cancer. METHOD: Qualitative and quantitative approaches were used for data collection from 153 medical student of Kathmandu University School of Medical Sciences from December 2011 to May 2012. RESULTS: Among the results, eighty-nine students had over 80% knowledge of the 14 cancer warning signs, among them 83% knew the nine risk factors for lung cancer. Twenty-three students told lung cancer can be hereditary. Sixty five percent of all participants believed that lung cancer can be detected at early stage; of them 81% told that it can be treated. About 24% of the total students were current or exsmokers and about half of them believed that lung cancer does not occur in light smokers. Only 10% have heard of Framework Convention on Tobacco Control in Nepal. CONCLUSION: Study finds that all medical students who know about any cancers may not necessarily have knowledge about lung cancers. Their perception about the cause of lung cancer may be influenced by their smoking behavior and there was little knowledge of public health measures for smoking control. Awareness about national policies needs to be increased.

A fatal presentation of dermatomyositis.

Dermatomyositis (DM) is an autoimmune disease that mainly affects the skin, muscle, and lung. The pathogenesis of skin inflammation in DM is not well understood. We present a 40-year-old male who presented with four months history of generalized skin lesion, pain and weakness. He had elevated transaminases with detectable muscle weakness. This case highlights the need to consider dermatomyositis with skin lesion and weakness; and the use of aggressive immunosuppressive therapies due to its associated vasculopathies.

Problem based learning in medical education.

Problem based learning, originally introduced in the Medical School at Mc-Master University in Canada in the late 1960s, and is now being used as a learning method in many medical schools in the United Kingdom and worldwide. Problem based learning have been adapted in many medical colleges of Nepal be used either as the mainstay of an entire curriculum or for the delivery of individual courses. Institution of Medicine, Tribhuvan University in 1980, BP Koirala Institute of Health Sciences at Dharan in 1999, KUSMS with the great support of faculties from Harvard University in 2001, Patan Academy of Health Sciences (PAHS), and lately all the affiliated medical colleges of Kathmandu University have adapted Problem based learning.

Complications of home delivery: our experience at Nepal Medical College Teaching Hospital.

A prospective study was conducted at Nepal Medical College Teaching Hospital to find out the complications of home delivery, maternal and fetal outcome and the main factors leading to home delivery. Among the 114 women who were brought to the hospital after home delivery, one was brought dead and one more died shortly after arrival. Sixty point five percent were housewives with no formal occupation, 68.4% were illiterate, 64.0% were multipara, Maximum no. of women belonged to the age group 20-24 years, 15.8% were adolescents, Lasheta (Lama, Sherpa , Tamang) was the most common ethnic group, Most of the women delivered at full term, whereas preterm delivery occurred in 4 (3.6%). Majority (73.7%) of the women had attended antenatal care at least once and half of the women had attended 4 and more visits. More than half had been fully immunized with tetanus toxoid and taken iron supplementation. As the reasons to deliver at home: 32.5% stated to be due to financial limitations, 30.7% due to ignorance and 16.7% due to transport limitations, and rest due to 'other reasons' which were most commonly stated as to be lack of attendant at home, long distance to hospital or delivery occurring too quickly or too late at night to attend the facility of choice. Ninety four point seven percent delivered at home with no trained assistance. Majority of the women (72.8%) were brought with retained placenta or excessive bleeding per vaginum. Twenty one point nine percent of the women were brought in shock needing active resuscitation. Twenty seven point two percent had postpartum hemorrhage. It was found that antenatal services were well utilized, but mothers were less likely to access good quality delivery/postnatal care. Despite the availability of services however, women still went on to deliver at home without any trained assistance, and this effect was greatest for the t less educated, poorer women. Financial and transport limitations appear to be some of the most important factors in women's inability to access skilled care. This important barrier to care will need to be addressed if we intend to improve delivery service to the most vulnerable of women.

Study of ovarian tumours in Nepal Medical College Teaching Hospital.

This was a retrospective study of all the cases of ovarian tumours operated in Nepal Medical College Teaching Hospital from January 2006 to July 2008. All the cases of ovarian tumour were included, irrespective of whether diagnosed preoperatively or found incidently during operation. The nature of tumour whether benign or malignant, their presenting symptoms, age, parity age of menarche, type of operation and histopathological finding was recorded. The incidence of ovarian tumour was 16.7% among total gynaecological admissions, out of which malignant ovarian tumour was 9.5%. The age range was 18 to 70 years. Benign tumour occurred in all age group 86 (90.5%) while maximum of malignant tumour occurred after 40 years (66.7%). Eleven point six percent were unmarried, 20.0% nulliparous, 7.4% were pregnant and 38.9% were of one to two parity. 10.0% were asymptomatic and commonest symptom was pain in lower abdomen (84.0%). Seventy two point six percent were surface epithelium tumour which is common in older women. Twenty seven percent were germ cell tumour which is common in younger age group. Commonest surface epithelial tumour was serous cyst adenoma (40.0%) and commonest germ cell tumour was Dermoid (25.3%).Commonest complication of ovarian cyst was torsion (12.6%).

Study of low birth weight babies in Nepal Medical College.

This was a retrospective study conducted to study the newborns weigth less than 2500gm delivered in Nepal medical college in the year 2005 and 2006. The cases were studied to find out the incidence and relation of maternal age, parity, gestational age, sex, etiological factors, mode of deliveries with Low Birth Weight (LBW) babies. There were 172 patients with LBW babies out of 1517 patient. Including the 9 twin babies, there were total 181 babies with LBW. Thus the incidence of LBW babies was 11.9%. There were only 26 (15.0%) under 20 years of age. As for parity, 92 (53.0%) were primigravida and 80 (46.0%) were multigravida. There were 6 (3.5%) of the babies less than 28 weeks, 22 (13.0%) between 29 to 32 weeks, 61 (33.7%) between 33 to36 weeks, 78 (43.1%) between 37 to 40 weeks and 14 (7.7%) 41 weeks or above. The babies under 1000gm or 1000 gms were 7 (4.1%),1001-1500 gms were 15 (8.7%), 1501-2000 gms were 40 (23.0%) and 2001-2500 gins were 119 (69.2%). Male babies were 94 (52.0%) and female babies were 87 (48.0%). Caesarian section was 15.7% remaining babies were delivered vaginally. Among the risk factor for LBW babies, spontaeneous preterm labour were 61 (35.5%), intra-uterine growth restriction were 51 (29.0%), antepartum haemorrhage 10 (5.8%), twin 9 (5.2%), pregnancy induced hypertension 12 (7.0%), preterm premature rupture of labour 8 (4.7%), anomalies were 4 (2.3%) and urinary tract infection were 20 (11.6%). Other infection were Typhoid 4 (2.3%) and chest infection 2 (1.2%). Thus the incidence of LBW babies in our hospital is quite high in comparision to the Western world and primigravida has more chance of delivering LBW babies. Spontaeneous preterm labour and intra uterine growth restriction are major risk factor leading to LBW babies. Urinary tract infection also plays important role in spontaeneous preterm labour. So to reduce the prevalence of LBW babies, we should identify in early the high risk pregnancy, taking more care to primigravida, treating clinical and subclinical infection in time to prevent spontaeneous preterm labour, diagonosing and managing the intra uterine growth restricted babies in time.

Expression of the hyaluronan receptor, CD44S, in epithelial ovarian cancer is an independent predictor of survival.

Most ovarian carcinomas present at advanced stage, principally as the result of dissemination to peritoneal sites. Standard CD44 (CD44S) is the principal receptor for hyaluronic acid, and in vitro and animal studies have suggested that the attachment of ovarian carcinoma cells to the peritoneal mesothelium involves the interaction between CD44S on ovarian carcinoma cells and hyaluronic acid on mesothelial surfaces. We, therefore, analyzed a series of ovarian carcinomas for the expression of CD44S by immunohistochemistry to see whether expression of this receptor by tumor cells correlated with clinicopathological factors and measures of patient outcome. Fifty-six fixed, paraffin-embedded primary epithelial ovarian tumors were immunostained with antibody to CD44S. Membrane staining was considered positive, and results were correlated with stage, grade, age, histology, and survival. Twenty-two (39%) tumors were positive for CD44S. There was no correlation between CD44 expression and histological type, grade, age, or stage. However, CD44 expression was significantly associated with survival in both univariate (P = 0.003) and multivariate (P = 0.006) analyses. These results support a role for CD44S expression in the spread of ovarian epithelial cancer and suggest that expression of this molecule is a significant independent predictor of survival in women with this disease.

Nicotine and cotinine stimulate secretion of basic fibroblast growth factor and affect expression of matrix metalloproteinases in cultured human smooth muscle cells.

PURPOSE: We have recently shown that nicotine and its metabolite cotinine are mitogenic for smooth muscle cells in vitro. In the present study, we examined the effect of nicotine and cotinine on the production of growth factors and the expression of matrix metallo-proteinases in smooth muscle cells. METHODS: Smooth muscle cells were harvested from human arteries and grown in culture. Subconfluent cultures were incubated for 24 hours in M199 containing 0.1% fetal bovine serum with or without nicotine or cotinine at concentrations ranging from 10(-9) mol/L to 10(-6) mol/L. The supernatants and cell lysates were assayed by enzyme-linked immunosorbent assay for basic fibroblast growth factor (bFGF), tumor necrosis factor alpha (TNF-alpha), platelet-derived growth factor AB (PDGF-AB), and transforming growth factor beta (TGF-beta). Matrix metalloproteinase expression was determined in subconfluent cultures incubated in albumin with or without nicotine or cotinine at 10(-8) mol/L and 10(-7) mol/L for 6, 12, 18, 24 and 36 hours. Northern blot analyses were performed with human cDNA probes for collagenase-1, stromelysin-1, gelatinase A, gelatinase B, and triose phosphate isomerase. Blots were quantified by phosphor-imaging techniques. RESULTS: Both nicotine and cotinine stimulated the production and secretion of bFGF in a dose-dependent manner. PDGF, TNF-alpha, and TGF-beta secretions were not significantly affected by nicotine or cotinine. Collagenase was up-regulated by nicotine at 18 and 24 hours (4.5-fold to 5.8-fold) and by cotinine at 18 hours (from 5.0-fold to 29-fold). Stromelysin-1 was up-regulated by nicotine and cotinine at 12 and 18 hours (1.5-fold to 7.0-fold). Gelatinase A generally peaked at 12 hours and was up-regulated by both agents (2.0-fold to 6.5-fold). CONCLUSION: Nicotine and cotinine enhanced the production of bFGF, a major mitogen for smooth muscle cells, and up-regulated the expression of several matrix metalloproteinases that are critical in cell migration. These data demonstrate mechanisms by which smoking may contribute to the development of intimal hyperplasia, atherosclerosis, and aneurysms.