Course of relapsing-remitting multiple sclerosis before, during and after natalizumab.

The consequences of interruption of natalizumab treatment are incompletely known. The objective was to assess the confirmed annualized relapse rates for patients preceding initiation, during and following suspension of natalizumab therapy. A chart review was conducted and data were analyzed using the Generalized Estimating Equations. During natalizumab therapy the confirmed annualized relapse rate was 0.08, compared to 0.52 (p = 0.0003) during the prior 12 months and to 0.35 (p = 0.0032) during the following 3 to 24 months. Similar results were found when confirmed and unconfirmed were analyzed. To conclude, following cessation of natalizumab therapy disease activity rapidly returned to pre-natalizumab levels.

Comparison of coronary artery calcification scores and National Cholesterol Education program guidelines for coronary heart disease risk assessment and treatment paradigms in individuals with chronic traumatic spinal cord injury.

OBJECTIVE: To investigate the risk of coronary heart disease (CHD) in individuals with spinal cord injury (SCI) according to the National Cholesterol Educational Program (NCEP) guidelines and CT coronary artery calcium scores (CCS). RESEARCH: Cross-sectional study of consecutive sample of males with SCI presenting to a single site for CHD risk assessment. PARTICIPANTS/METHODS: Males age 45-70 with traumatic SCI (American Spinal Injury Association (ASIA) A, B, and C) injured for at least 10 years with no prior history of clinical CHD. Medical history, blood-pressure, and fasting lipid panel were used to calculate risk for CHD with the use of the Framingham risk score (FRS). Risk and treatment eligibility status was assessed based on NCEP/FRS recommendations and by presence and amount of CCS. Percent agreement (PA) and kappa were calculated between the two algorithms. Spearman correlations were calculated between CCS and FRS and individual risk factors. RESULTS: A total of 38 men were assessed; 18 (47.4%) had CCS > 0. The PA between NCEP/FRS assessment and CCS was 18% with a kappa of -0.03. 11 (28.9%) had CCS > 100 or >75th percentile for their age, sex, and race, which might qualify them for lipid-lowering treatment. Only 26 were placed into the same treatment category by NCEP/FRS and CCS, for a PA of 68% with a kappa of 0.35. In all, 20 (52.6%) were eligible for lipid-lowering treatment by either NCEP/FRS (n=9) or CCS (n = 11). Seven subjects were above the treatment threshold based on CCS, but not NCEP/FRS and five subjects were above the NCEP/FRS threshold, but not CCS. Just four subjects were eligible by both algorithms. CCS only correlated with FRS (r = 0.508, P = 0.001) and age (r = 0.679, P < 0.001).

Pushing the envelope in biomaterial research: initial results of prosthetic coating with stem cells in a rat model.

BACKGROUND: Coating prosthetic for hernia repair with a patient's own cells could improve biocompatibility by decreasing inflammation and adhesion formation and by increasing tissue ingrowth and resistance to infection. The objective of this study was to prove the feasibility of prosthetic coating with stem cells and to assess its resistance to adhesion formation when implanted in an animal model. METHODS: Adult Lewis rat bone marrow stem cells were harvested and cultured. Stem cells were then implanted on three different prosthetics. The prosthetic with the best stem cell adherence was implanted intraperitoneally into six adult rats. Untreated prosthetic was implanted in control animals (n = 12). After 2 weeks, intra-abdominal adhesions were graded using an adhesion scoring scale by two surgeons who were blinded to the animal group. Data were analyzed using the Wilcoxon rank-sum test. RESULTS: Stem cells demonstrated the best adherence and growth on polyglactin prosthetics. After implantation, the stem cell-coated polyglactin prosthetic had <25% of its surface area covered with adhesions in five (83%) samples, whereas the control polyglactin group had only one sample (8.3%) with <25% adhesions, and seven of its samples (58.3%) had >50% surface area adhesions (p < 0.05). CONCLUSIONS: The feasibility of hernia prosthetic coating with stem cells was demonstrated. Furthermore, stem-cell coated polyglactin prosthetic exhibited improved biocompatibility by decreasing adhesion formation in an animal model. Further study is needed to determine the factors that promote stem cell adherence to prosthetics and the in vivo prosthetic biomechanics after stem cell coating. This work is underway in our laboratory.

Long-term assessment of unipolar and bipolar stimulation and sensing thresholds using a lead configuration programmable pacemaker.

Acute and long-term pacing thresholds were measured prospectively in 74 patients with a unipolar/bipolar multiprogrammable pacemaker. At implantation, mean current threshold was 0.48 +/- 0.16 mA with unipolar mode and 0.55 +/- 0.16 mA bipolar mode (p less than 0.01). R wave amplitude at implantation was 7.78 +/- 2.4 mV with unipolar and 7.67 +/- 2.1 mV in bipolar mode (p = NS). During long-term follow-up (mean 9.3 months; range 3 to 24), no clinically significant differences in pacing or sensing thresholds were observed between bipolar and unipolar configurations. Lead configuration was changed 23 times in 11 patients. Symptomatic myopotential inhibition was corrected in two patients by reprogramming to the bipolar pacing mode. High thresholds and loss of capture were corrected in two patients by reprogramming to the unipolar pacing mode. The remaining configurational changes were made for improved sensing or pacing thresholds. This study documents, in a large group of patients, the equivalence of long-term unipolar and bipolar pacing and sensing thresholds and, in addition, demonstrates that lead configuration programmability offered some advantage in a subgroup of patients and may have prevented reoperation in five patients.

Aminophylline fails to improve the outcome of cardiopulmonary resuscitation from prolonged ventricular fibrillation: a placebo-controlled, randomized, blinded experimental study.

OBJECTIVES: The purpose of this study was to evaluate systematically the effects of the adenosine antagonist aminophylline on resuscitation outcome in a canine model of postcardioversion nonperfusing rhythm. BACKGROUND: Theoretic considerations and experimental studies indicate that myocardial adenosine accumulation during prolonged ventricular fibrillation might play a significant role in postcardioversion asystole and electromechanical dissociation. A recent uncontrolled clinical trial has suggested that the adenosine antagonist aminophylline might improve the outcome of cardiopulmonary resuscitation from refractory bradyasystolic cardiac arrest. METHODS: Two placebo-controlled, randomized, blinded experimental studies were performed. In protocol 1 (20 dogs), ventricular fibrillation was induced and maintained for 7.5 min. Sixty seconds before cardioversion, dogs received 1 mg of epinephrine followed by 250 mg of aminophylline or placebo. In protocol 2 (20 dogs), dogs were cardioverted to electromechanical dissociation after 5 min of unsupported ventricular fibrillation. Sixty seconds later, all dogs received 1 mg of epinephrine followed by 250 mg of aminophylline or placebo. In both experiments, resuscitation efforts were continued until return of spontaneous circulation, or up to 30 min. The primary end point was survival to 1 h. RESULTS: In protocol 1, 4 of 10 dogs survived in the aminophylline group, whereas 7 of 10 dogs survived in the placebo group, a nonsignificant trend toward unfavorable outcome from aminophylline. Pretreatment with aminophylline increased the number of cardioversion applications required to terminate ventricular fibrillation. In protocol 2, 5 of 10 and 6 of 10 dogs survived in the aminophylline and placebo groups, respectively. CONCLUSIONS: The results of this study suggest that aminophylline fails to improve the outcome of resuscitation from prolonged ventricular fibrillation. It does not reverse established electromechanical dissociation and may in fact increase the number of cardioversion applications required to terminate ventricular fibrillation. The rationale for conducting clinical trials with aminophylline during cardiopulmonary resuscitation is questionable.

Randomized controlled trial of pilocarpine hydrochloride for the moderation of oral mucositis during autologous blood stem cell transplantation.

Pilocarpine hydrochloride has been reported to increase salivation and decrease oral mucositis in patients receiving head and neck radiotherapy, but there is only one report of its use in a cancer chemotherapy patient population. This prospective, double-blinded, randomized, placebo-controlled trial was undertaken to determine the efficacy of pilocarpine for the moderation of oral mucositis during autologous blood stem cell transplantation. Subjects were randomized to receive a 5 mg tablet of pilocarpine, or a placebo, during and following chemotherapy. Subjects were seen every other day and evaluated for gingival, oral, and oropharyngeal mucositis; nutrition; oral hygiene; eating; speaking; sleeping; pain at rest and/or with swallowing; and mouth dryness. We recorded the mean and highest scores and duration of problems, along with white blood cell counts and differentials, and the use of systemic narcotics for oral mucosal pain. We enrolled and randomized 36 subjects, and there were no statistically or clinically significant differences for the primary outcome of severity of mucositis and no clinically significant differences in any of the other outcome measures. Pilocarpine has no benefit for the moderation of the incidence, severity, or duration of mucositis in patients receiving autologous blood stem cell transplantation.

Effect of carbon dioxide pneumoperitoneum and wound closure technique on port site tumor implantation in a rat model.

BACKGROUND: The purpose of this study was to evaluate the effects of carbon dioxide (CO2) pneumoperitoneum and wound closure technique on port site tumor implantation. METHODS: A standard quantity of rat mammary adenocarcinoma (SMT2A)was allowed to grow in a flank incision in Wistar-Furth rats (n = 90) for 14 days. Thereafter, 1-cm incisions were made in each animal in three quadrants. There were six control animals. The experimental animals were divided into a 60-min CO2 pneumoperitoneum group (n = 42) and a no pneumoperitoneum (n = 42) group. The flank tumor was lacerated transabdominally in the experimental groups. The three wound sites were randomized to closure of (a) skin; (b) skin and fascia; and (c) skin, fascia, and peritoneum. The abdominal wounds were harvested en bloc on postoperative day 7. RESULTS: Histologic comparison of the port sites in the pneumoperitoneum and no-pneumoperitoneum groups did not demonstrate a statistically significant difference in tumor implantation for any of the closure methods. Evaluation of the closure techniques showed no statistical difference between the pneumoperitoneum group and the no-pneumoperitoneum group in the incidence of port site tumor implantation. Within the no-pneumoperitoneum group, there was a significant increase (p = 0.03) in tumor implantation with skin closure alone vs all three layers. Additionally, when we compared all groups by closure technique, the rate of tumor implantation was found to be significantly higher (p = 0.01) for skin closure alone vs closure of all three layers. CONCLUSIONS: This study suggests that closure technique may influence the rate of port site tumor implantation. The use of a CO2 pneumoperitoneum did not alter the incidence of port site tumor implantation at 7 days postoperatively.

Evaluation of adhesion formation, mesh fixation strength, and hydroxyproline content after intraabdominal placement of polytetrafluoroethylene mesh secured using titanium spiral tacks, nitinol anchors, and polypropylene suture or polyglactin 910 suture.

BACKGROUND: The purpose of this study is to evaluate fixation methods for polytetrafluoroethylene (ePTFE) mesh with an in vivo model of laparoscopic ventral hernia repair. METHODS: In 40 New Zealand white rabbits, a 4 x 4-cm ePTFE mesh (n = 80, two per animal) was attached to an intact peritoneum with polyglactin 910 (PG 910) (n = 20) or polypropylene (PP) (n = 20) suture, titanium spiral tacks (TS) (n = 20), or nitinol anchors (NA) (n = 20). Mesh was harvested at 8 and 16 weeks for fixation strength testing, adhesion assessment, and collagen (hydroxyproline) content. Fixation strength on day 0 was determined with mesh attached to harvested abdominal wall. Statistical significance was determined as p < 0.05. RESULTS: There was no difference in fixation strength between PP (39.1 N) and PG 910 (40.0 N) sutures at time zero. At week 8, PP (25.7 N) was significantly stronger (p < 0.05) than PG 910 (11.4 N) suture, but not at week 16. The fixation strength of TS and NA (day 0, 15.4 vs 7.4 N; week 8, 17.5 vs 15.3 N; week 16, 19.1 vs 13.8 N) was not significantly different. Fixation with PP suture was significantly (p < 0.05) stronger than that with TS and NA at day 0 (39.1, 15.4, and 7.4 N, respectively) but not at weeks 8 or 16. The fixation strength of suture decreased significantly (p < 0.05) from day 0 to week 16 (PP: day 0 = 39.1 N, week 8 = 25.7 N, week 16 = 21.4 N; PG 910: day 0 = 40.0 N, week 8 = 11.4 N, week 16 = 12.8 N). The fixation strength of NA and TS did not change significantly (NA: day 0 = 7.4 N, week 8 = 15.3 N, week 16 = 13.8 N; TS: week 0 = 15.4 N, week 8 = 17.5 N, week 16 = 19.1 N). There were no differences in adhesion area based on fixation device used; however, there were more (p < 0.05) mesh samples using NA with adhesions compared to TS and adhesion tenacity was greater (p < 0.05) compared to that of TS, PP, and PG. Hydroxyproline content at weeks 8 and 16 was similar for all fixation devices. CONCLUSIONS: The initial fixation strength for nonabsorbable suture is significantly greater than that of the metallic fixation devices, but after 8 weeks there is no difference. Laparoscopic ventral hernia repair without transabdominal suture fixation may be predisposed to acute failure. The metallic devices have similar fixation strength, although the incidence of adhesions and tenacity of adhesions appear to be greater with the nitinol anchors. Since these devices have similar fixation strengths and most likely provide adequate supplementation to transabdominal sutures for mesh fixation after laparoscopic ventral hernia repair, their use should be based on other factors, such as their propensity for adhesions, ease of application, and cost.

A prospective study of free bilirubin and other risk factors in the development of kernicterus in premature infants.

To assess the value of free bilirubin (FB) measurements in predicting kernicterus (KI) in sick premature infants, 91 newborns weighing less than 1,500 gm at birth were observed during the first week of like with twice daily FB and total bilirubin determinations. Autopsies were performed on 30 of the 53 infants who died. Seven had KI and 23 did not. There were no differences between infants with and with out KI in the maximum FB level (KI 18.2 +/- 4.5 [SEM] nm/liter, no KI 11.1 +/- 0.9 nm/liter, P not significant) or the total bilirubin level (KI 7.3 +/- 1.3 mg/100 ml, no KI 6.1 +/- 0.5 mg/100 ml, P not significant). In fact, three kernicteric infants had very low maximum FB levels (less than 10 nm/liter). These three infants had prolonged episodes of acidosis, hypoxemia, or hypothermia during the 24 hours preceding their maximum level of FB. Although elevated levels of FB may be predictive of KI in some infants, other factors may make the blood-brain barrier more permeable to low levels of FB. This may limit the clinical applicability of FB measurements.

Ribavirin aerosol treatment of bronchiolitis associated with respiratory syncytial virus infection in infants.

In a double-blind study, bronchiolitis associated with respiratory syncytial virus infection in 12 randomly selected patients treated with ribavirin aerosol improved more rapidly than in 14 control patients given saline aerosol (P = .044, Wilcoxon rank sum test, two-tailed). An estimated 10 mg of ribavirin per kilogram of body weight was administered in daily 12-hour treatments over a five-day period. Respiratory syncytial virus disappeared from secretions at about the same rate in treated and control patients. There was no local or systemic intolerance, and there was no evidence of hematologic or other organ toxicity in the ribavirin-treated patients.

Evaluation of an intravenous immunoglobulin preparation for the prevention of viral infection among hospitalized low birth weight infants.

An intravenous immunoglobulin (IVIG) preparation was evaluated prospectively in hospitalized low birth weight infants for the prevention of respiratory virus infection. Premature neonates were evaluated from October 19, 1987, through July 31, 1988. Nasopharyngeal secretions were cultured weekly for viruses and clinical information was obtained daily on each infant. Ninety-one infants with birth weights between 500 and 1750 g were randomized to receive either IVIG, 500 mg/kg (46 infants), or 5% albumin-normal saline (placebo), 10 ml/kg (45 infants), between Days 3 and 7 of life, 7 days later and every 14 days thereafter for a maximum of 5 doses. Demographic and life event data during pregnancy were similar for IVIG and placebo groups. Birth weight, gestational age, gender, age at entry into the study and incidence of respiratory distress syndrome at birth were also similar in both groups of premature infants. Twenty-six viruses were isolated from 25 infants. There were 13 and 12 infections in the IVIG and placebo groups, respectively. Severity of disease, as measured by clinical factors and outcomes of virus-infected infants were no different in IVIG-treated and placebo groups. Adenoviruses and cytomegalovirus accounted for 57.7 and 23.1%, respectively, of the viral isolates. In this study the use of IVIG did not prevent or modify adenovirus and cytomegalovirus infections in premature infants.

Description of an adenovirus type 8 outbreak in hospitalized neonates born prematurely.

An adenovirus (Ad) type 8 outbreak was prospectively studied in a neonatal intensive care unit. Nasopharyngeal secretions were cultured weekly for viruses and clinical information was obtained daily in each infant. Eleven of 112 neonates were infected with Ad; 8 of 9 available isolates represented one variant of Ad 8. The median age at infection was 54 days and the median duration of virus shedding was 2 days. Seven of 11 infants had onset of new symptoms and/or required acute respiratory support; only 2 infants had eye disease. Maternal characteristics, race, gender, age at entry into study and respiratory distress syndrome at birth were similar for both groups. Ad-infected infants tended to have earlier gestations and lower birth weights. Ad-infected neonates stayed longer in the neonatal intensive care unit, required more days of respiratory support and were more likely to develop bronchopulmonary dysplasia. Thus an association was established between lung disease in premature neonates and Ad infection.

Identification of elementary school children at risk for disruptive behavioral disturbance: validation of a combined screening method.

OBJECTIVES: To examine the validity of the teacher-rated Inattention/Overactivity With Aggression (IOWA Conners) questionnaire followed by the Conners Abbreviated Symptom Questionnaire (CASQ) as a feasible, combined screening method to identify children at high risk for externalizing behavioral disturbance in a school setting. METHOD: The IOWA Conners and CASQ were administered to the entire population of children, grades K through 6, in a single elementary school. Using a whole-number IOWA Conners threshold score of 18 (1.5 SD), coupled with a CASQ score of 18 (1.0 SD), a high-risk group and an age-, sex-, and classroom-matched low-risk control group were selected for comparison on the Child Behavior Checklist (CBCL), Teacher's Report Form (TRF), Child and Adolescent Functional Assessment Scale (CAFAS), and Diagnostic Interview for Children and Adolescents-Revised diagnoses. RESULTS: The data showed significant intergroup differences in CBCL (p < .0002), TRF (p < .0006), and CAFAS (p < .0002) scores and higher numbers of DSM diagnoses (1.7 +/- 0.3 versus 0.1 +/- 0.3, p < .0007) between the high- and low-risk group. The positive predictive value for externalizing diagnoses for the IOWA Conners plus CASQ was 100% and negative predictive value was 70%. CONCLUSIONS: The IOWA Conners combined with the CASQ is a useful initial screening strategy in the school setting for identification of children with disruptive behavioral difficulties.

Impact of compliance and side effects on the clinical outcome of patients treated with oral erythromycin.

STUDY OBJECTIVE: To determine the relationship among compliance, side effects, and self-reported outcome for patients in an erythromycin trial. DESIGN: A retrospective analysis of data from a multicenter, prospective, single-blind, randomized trial. SETTING: Five metropolitan ambulatory care offices. PATIENTS: The 252 adults (> 18 yrs) were prescribed oral erythromycin 1.0 g/day (base equivalent) for infectious disorders. INTERVENTION: Subjects received erythromycin for 10 days and reported compliance, drug efficacy, and side effects in a daily diary. Compliance was measured by tablet count. RESULTS: A negative correlation was found between gastrointestinal symptom severity score and percentage of tablets taken (p < 0.001). A significant positive correlation was seen between compliance and outcome (p < 0.001). Subjects who took greater than 80% of the drug achieved the treatment goal more frequently than those taking 80% or less (94% vs 59%, p < 0.001). CONCLUSIONS: Side effects of erythromycin adversely affected compliance. Compliance had a positive effect on self-reported outcome.

Is surgical excision necessary for atypical ductal hyperplasia of the breast diagnosed by Mammotome?

BACKGROUND: Core biopsy findings of atypical ductal hyperplasia (ADH) underestimates the diagnosis of malignancy by 18% to 88%. Using the Mammotome biopsy technique, more accurate assessment of the lesion is possible, making selective excision of these lesions a consideration. METHODS: The records of 62 patients who were found to have ADH at Mammotome biopsy and subsequently underwent excision of the lesion were reviewed. Patient data were statistically analyzed for predictors of malignancy at the time of surgical excision. RESULTS: Of the 62 patients, 9 (15%) had malignancy at excision. Variables predicting for malignancy included markedly atypical hyperplasia and incomplete removal of calcifications at Mammotome biopsy, a previous contralateral breast cancer, and a family history of breast cancer, with a combined sensitivity of 100% and specificity of 80%. CONCLUSIONS: Mild ADH found on Mammotome, not associated with a personal or family history of breast cancer, may not need excision if all calcifications have been removed.

Clinical and demographic prognostic indicators for human disc cell proliferation in vitro: pilot study.

STUDY DESIGN: Human anulus cells were cultured under control and experimental conditions to study associations between proliferation and clinical-demographic features of subjects from which cells were obtained. Statistical multiple regression analyses were applied to develop mathematic models relating proliferation to age, gender, Thompson score (denoting stage of disc degeneration), and status (control donor [postmortem]; surgical patient). OBJECTIVES: To identify the effect of donor characteristics on proliferative capacities of human disc cells. SUMMARY OF BACKGROUND DATA: As therapeutic options for disc degeneration increase, novel biologic options are important future considerations. Little is known about the influence of clinical-demographic features on cell proliferation. METHODS: Anulus cells were studied in two designs: 1) Cells from 12 individuals were grown in monolayer with 50 ng/mL interleukin growth factor-1 (IGF-I), 100 ng/mL insulin, or control conditions. 2) Cells from nine individuals were grown in three-dimensional culture with 10 ng/mL IGF-I or control conditions. Cell proliferation data and data on age, gender, Thompson score, and status were collected. Standard statistical analyses were used to develop correlation models. RESULTS: Data from monolayer experiments produced significant models fitting proliferation in the presence of low serum, 50 ng/mL IGF-I, or insulin, with age, gender, Thompson score, and status (respective R2: 0.827, 0.680, 0.850). Three-dimensional cultures exposed to 10 ng/mL IGF-I resulted in proliferation that correlated in a significant negative manner with Thompson score (r = -0.798). CONCLUSIONS: Clinical-demographic prognostic indicators may help predict levels of proliferation. Greater age, greater disc degeneration, female gender, and surgical derivation had deleterious effects on proliferation potential in this model.

Anti-apoptotic effects of IGF-1 and PDGF on human intervertebral disc cells in vitro.

STUDY DESIGN: Human cells from the anulus were grown in tissue culture in an experimental design to study the anti-apoptotic effect of two selected cytokines. OBJECTIVES: To determine whether two selected cytokines, insulin-like growth factor-1 and platelet-derived growth factor, were effective in decreasing apoptosis in human cells from the anulus grown in culture for 10 days. SUMMARY OF THE BACKGROUND DATA: Previous studies have shown that there is a small cell population in the aging human intervertebral disc. Earlier work from the authors' laboratory suggested that apoptosis (programmed cell death) may be a major contributing factor to the decrease in cell number. A wide variety of inhibitors of apoptosis have now been identified; the present report presents findings on the actions of insulin-like growth factor-1 and platelet-derived growth factor in retarding or preventing apoptosis. METHODS: Using previously published culture methods, cells from the anulus of 25 subjects (mean age, 41.7 years) were grown in monolayer culture for 10 days and tested under the following conditions: 1) control growth in the presence of 20% fetal bovine serum; 2) positive control conditions promoting the development of apoptosis in the absence of serum; or 3) in dose-response regimes where insulin-like growth factor-1 or platelet-derived growth factor were added in the presence of only 1% fetal bovine serum (necessary for basal cell maintenance). Specimens were derived from 18 lumbar, 9 cervical, and 1 thoracic sites; the average Thompson score was III. Cells were grown on chambered slides and evaluated in situ using the TdT in situ apoptosis detection reaction to identify apoptotic cells. An average of 300 cells were counted in replicate cultures at each dose to determine the incidence of apoptosis; results were analyzed with standard statistical techniques. Cultured cells also were examined with transmission electron microscopy. RESULTS: Serum withdrawal to a 1% level was used as a positive apoptosis control in vitro and resulted in a significantly greater percentage of apoptosis compared with the 20% serum negative control (1.02% +/- 0.34 (28) versus 0.14% +/- 0. 04 (27; mean +/- SEM (n)), P < 0.0001). Exposure to 50 ng/mL insulin-like growth factor-1 significantly reduced the percentage of apoptosis (vs.- 1% serum) to 0.49% +/- 0.26 (P = 0.005); 500 ng/mL was also significantly effective (% apoptosis = 0.09% +/- 0.04 (P = 0.0001). Platelet-derived growth factor at a dose of 100 ng/mL also significantly reduced apoptosis (0.18 +/- 0.11, P = 0.0001). CONCLUSIONS: Data demonstrate a significant reduction in the percentage of apoptotic disc cells after exposure to 50-500 ng/mL insulin-like growth factor-1 or exposure to 100 ng/mL platelet-derived growth factor. These findings expand the understanding of the cell biology of the disc cell and show that selected cytokines can retard or prevent programmed cell death in vitro. The administration of these cytokines may have future therapeutic potential in the treatment of disc degeneration.

Breast conservation: trends in a major southern metropolitan area compared with surrounding rural counties.

Despite randomized prospective studies and National Institutes of Health recommendations, surgeons especially in the southern United States have been slow to adopt breast conservation surgery (BCS). Data were analyzed regarding 3,349 cases of stage 0, I, and II breast cancer (1991-1998) from Charlotte-Mecklenburg County, NC; 1057 cases from six surrounding rural counties (1995-1997); and 90,398 cases (1995) from the National Cancer Data Base. During 1995 through 1997 Charlotte-Mecklenburg County had statistically significantly higher rates of BCS compared with six surrounding rural counties for stage I (59% and 42% respectively, P = 0.001) and stage II (37% and 19%, respectively, P = 0.001) breast cancer. The BCS rates in Charlotte-Mecklenburg County (1991-1998) showed the following: Stage 0 rate increased from 17 per cent in 1991 to 78 per cent in 1998 (P = 0.001), stage I rate increased from 31 per cent in 1991 to 65 per cent in 1998 (P = 0.001), and stage II rate increased from 18 per cent in 1991 to 42 per cent in 1998 (P = 0.001). BCS rates for early-stage breast cancer in Charlotte-Mecklenburg County have increased over the last 8 years and now equal national rates; however, patients in surrounding rural counties are not receiving BCS as frequently. There is a need for more widespread education of surgeons, other health care providers, and the general public to increase the use of BCS.

Ritalin for nicotine withdrawal: Nesbitt's paradox revisited.

This was a unblinded clinical trial of the stimulant methylphenidate (Ritalin) for nicotine withdrawal. Nineteen nicotine-dependent smokers received oral methylphenidate (30 mg target daily dosage) for 5 days following abrupt cessation. Tobacco withdrawal, Spielberger state anxiety, blood pressure, and pulse were measured at baseline, then serially for 7 days. Tobacco withdrawal and state anxiety increased significantly, but 12 (71%) of the 17 smokers who completed the study rated withdrawal relief "very define" and 13 (76%) rated this quit attempt "much easier than other times." Methylphenidate neither increased blood pressure nor blocked cessation-related pulse decrease and appears safe for this indication. Twelve (63%) of the enrolled smokers were confirmed abstinent at day 5. Methylphenidate effect on nicotine withdrawal should be studied in a placebo-controlled clinical trial.

Cell shape and gene expression in human intervertebral disc cells: in vitro tissue engineering studies.

The objective of the present study was to examine the relation between gene expression and the shape of human intervertebral disc cells cultured in vitro in three-dimensional (3D) scaffolds. Disc cells from 19 subjects were seeded into either a collagen sponge or collagen gel and cultured for 10 days. In situ hybridization was performed on serial sections of paraffin embedded specimens and assessed for expression of selected genes important for extracellular matrix formation: Types I and II collagen, aggrecan and chondroitin-6 sulfotransferase. Rounded cells grown in collagen gel showed expression of Types I and II collagen, aggrecan and chondroitin-6 sulfotransferase; expression of these genes was absent in spindle shaped cells. Cells in the collagen sponge that lay on the sponge margin were frequently spindle shaped; these cells expressed type I collagen, but not type II collagen, aggrecan or chondroitin-6 sulfotransferase. Results presented here provide novel data concerning disc cell gene expression with collagen 3D constructs. This information is useful for future tissue engineering studies that have the challenging goal of selectively modulating gene expression.