Pilot study of correlation of pulp stones with cardiovascular disease.

We propose that calcification of dental pulp may have a similar pathogenesis as calcified atheromas and could lead to use of routine dental radiographs as a rapid screening method for early identification of potential cardiovascular disease (CVD). Fifty-five dental patients ages 20 to 55 were chosen because pulp stones in pulpally noninflamed teeth were not expected in this age group. They completed a questionnaire regarding their CVD status and that of their parents and siblings. Entry criteria included at least one asymptomatic, minimally restored, noncarious molar and no history of gout, renal disease, or renal lithiasis. Patients' periapical radiographs of record were viewed to determine the presence of pulp stones. There was a significant relationship between pre-existing CVD and pulp stones (odds ratio of 4.4 with a 95% confidence interval of 1.1, 18.7), but no relationship was found for family history of CVD and pulp stones (odds ratio of 1.7 with a 95% confidence interval of 0.5, 5.5). Seventy-four percent (14/19) of patients with reported CVD had detectable pulp stones while only 39% (14/36) of patients without a history of CVD had pulp stones. This pilot study demonstrates that patients with CVD have an increased incidence of pulp stones in teeth with noninflamed pulps compared to patients with no history of CVD. No relationship was found between presence of pulp stones and family history of CVD. The findings suggest that dental radiographic determination of the presence or absence of pulp stones may have possibilities for use in CVD screening.

Nonspecific human IgG reduces survival in neonatal rats infected with Escherichia coli.

BACKGROUND: Human intravenous IgG (IVIG) containing specific antibodies protects neonatal rats from septic death. However, IVIG has immunosuppressive properties and clinical trials of IVIG in neonates at risk for sepsis have yielded conflicting results. HYPOTHESIS: This study was designed to test the hypothesis that nonspecific antibodies in IVIG reduce survival in neonatal rats infected with Escherichia coli. METHODS: Specific antibodies were adsorbed from IVIG with E. coli to produce IVIG/anti-E. coli-. After transthoracic administration of E. coli, survival was determined in neonatal rats injected intraperitoneally with phosphate-buffered saline, IVIG/anti-E. coli- (500 mg/kg) or IVIG containing anti-E. coli antibodies (IVIG/anti-E. coli+). Complement-mediated hemolytic activity of neonatal rat serum was quantified using sensitized sheep erythrocytes. RESULTS: Compared with placebo, intraperitoneal IVIG/anti-E. coli- reduced neonatal survival after E. coli infection. In contrast, IVIG/anti-E. coli+ protected infected animals. Both IVIG/anti-E. coli- and IVIG/anti-E. coli+ impaired the complement-mediated hemolytic activity of neonatal rat serum. CONCLUSIONS: IVIG contained (1) nonspecific antibodies that reduced survival in neonatal rats infected with E. coli and (2) protective anti-E. coli antibodies that enhanced survival in neonatal rats infected with E. coli. We speculate that in clinical trials of IVIG to treat or prevent neonatal sepsis, inconsistent results may be caused, in part, by lot-to-lot variations in the ratio of immunosuppressive, nonspecific antibodies to protective, specific antibodies.

Effects of providing and withholding postfitting fine-tuning adjustments on outcome measures in novice hearing aid users: a pilot study.

This pilot study was designed to examine the effects of either providing or withholding subject-driven, postfitting electroacoustic changes (fine tuning) on hearing aid performance as measured by tests of speech recognition in noise, sound quality, and benefit. A group of adult first-time hearing aid users with moderate, high-frequency sensorineural hearing loss was studied over a 5-month postfitting period. Half of the group served as a control group; half constituted the treatment group. Treatment consisted of making as many postfitting electroacoustic manipulations as the participants' complaints/observations required. These adjustments were withheld from the control group individuals. Group performance differences were assessed using the COSI, two versions of the APHAB, a Satisfaction scale, a Sound Quality tool, and the SIN test. Analysis revealed no statistically significant differences in the control and treatment groups' performances or perceived benefit at any of the five postfitting test sessions. These data suggested that there was no measurable advantage to be derived from making postfitting frequency-gain adjustments of 10 dB or less to hearing aids with wide dynamic range compression fitted in the manner described in this article. Definitive studies of the effects of postfitting electroacoustic fine tuning must be undertaken.

Predictable multiple site root coverage using an acellular dermal matrix allograft.

BACKGROUND: The primary aim of this randomized, controlled, blinded clinical investigation was to determine if orientation of an acellular dermal matrix (ADM) allograft, basement membrane side against the tooth or connective tissue side against the tooth, affected the percent root coverage. Additional aims were to: 1) compare results of this study with results obtained from other root coverage studies; 2) determine if multiple additional sites could be successfully covered with the same surgery; 3) determine the effect of the procedure on keratinized tissue; and 4) evaluate the amount of creeping attachment obtained. METHODS: Ten patients with 2 Miller Class I or II buccal recession defects > or =3 mm were treated with a coronally positioned flap plus ADM and followed for 12 months. Test sites received ADM with the basement membrane side against the root (AB), while the control sites received the connective tissue side against the root (AC). Multiple additional recession sites were treated with the same flap procedure. RESULTS: Mean baseline recession for the AB sites was 4.2 mm and for the AC sites, 3.7 mm. Mean root coverage of 95% was obtained for both AB and AC sites. Sixty-eight additional Class I or II AB and AC sites obtained about 93% root coverage. The mean increase in keratinized tissue for both treatments was 0.80 mm. No additional root coverage was gained due to creeping attachment between 2 and 12 months. CONCLUSIONS: Treatment with ADM was an effective and predictable procedure for root coverage. The orientation of the material did not affect the treatment outcome for any of the parameters tested.

Effect of adhesive retention of maxillofacial prostheses. Part 2: Time and reapplication effects.

STATEMENT OF PROBLEM: The success of most non-implant-retained extraoral prostheses depends on retention derived from skin adhesives. Part 1 of this study found that Skin-Prep Protective Dressing improved the retentive properties of adhesives and that Secure(2) Medical Adhesive was stronger than Epithane-3. Part 2 investigates the application of a second layer of adhesive to the prosthesis, which was earlier noted to improve retention at later time periods. PURPOSE: This study measured the force needed to remove silicone elastomer strips with Secure(2) Medical Adhesive from the skin of human subjects. Testing was performed before and after the removal of the strips and reapplication of the adhesive. MATERIAL AND METHODS: Secure(2) Medical Adhesive was painted on silicone rubber strips and placed in a nonsequential random order of the 3 variables to 3 sites on the ventral forearms of 21 human subjects and tested over an 8-hour period. The bond strength was measured at 0, 4, and 8 hours. After a reapplication of adhesive over the existing adhesive, additional bond strength measurements were made at 4 and 8 hours. Testing was at 10 cm/min in an Instron. All subjects had Skin-Prep coating applied before adhesive application. RESULTS: Bond strengths for both single applications and reapplications of the adhesive were greater at 0 hours and became significantly weaker after the 4- and 8-hour periods. The second application of the adhesive produced the strongest bonds when measured at 4 hours (110 N/m). Bonding was significantly higher at 8 hours if a second application of adhesive was applied at 0 or 4 hours. CONCLUSION: The results of this study indicate that the bond strength of silicone elastomer to skin decreased over an 8-hour interval. After removal of the silicone rubber strip and reapplication of Secure(2) Medical Adhesive over the existing adhesive, bond strengths increased.

Clinical relevance of urokinase-type plasminogen activator, its receptor, and its inhibitor type 1 in endometrial cancer.

OBJECTIVE: Tumor invasion involves degradation of extracellular matrix. The urokinase plasminogen activation system participates in this process. Urokinase-type plasminogen activator (uPA), its receptor (uPAR), and its inhibitor, plasminogen activator inhibitor type 1 (PAI-1), are proposed to be prognostic factors in some cancers. There are conflicting data regarding the prognostic role of this system in endometrial cancer. METHODS: To determine the prognostic value of the urokinase plasminogen activation system, contents of uPA, uPAR, and PAI-1 were measured in extracts of endometrial cancer tissue using ELISAs. uPA, uPAR, and PAI-1 levels were determined in 91, 54, and 92 extracts, respectively, and correlated with tumor histology, stage, grade, lymph node involvement, prevalence of metastasis, and recurrence as well as with estrogen (ER), progesterone (PR), epidermal growth factor (EGFR) receptor and HER-2/neu contents. RESULTS: Patients with cancers exhibiting advanced stage, high grade, unfavorable tumor histology, nodal involvement, recurrence, and lower PR levels determined by ligand binding had significantly higher uPA content than others. PAI-1 was significantly elevated in patients with advanced stage, high-grade tumor, recurrence, decreased ER content, and lower PR levels determined by ligand binding. uPAR did not show any relation to any of clinical and laboratory parameters. Elevated expression of PAI-1 was associated with significantly shorter disease-free (P = 0.005) and overall (P = 0.0003) survival. Multivariate analysis revealed that PAI-1 was a predictor of survival although stage was the strongest independent factor. CONCLUSION: Elevated uPA and PAI-1 levels appear to correlate with unfavorable prognosis in endometrial cancer.

Thyroid function in neonates with severe respiratory failure on extracorporeal membrane oxygenation.

The object was to study thyroid function in neonates with severe respiratory failure on extracorporeal membrane oxygenation (ECMO) and determine whether abnormal thyroid function correlates with prognosis. Total and free thyroxine (T4, FT4), total and free triiodothyronine (T3, FT3), reverse triiodothyronine (rT3), thyroid-stimulating hormone, and thyroxine binding globulin were measured in 14 newborn infants with severe respiratory failure (age 1-30 days) from samples collected before anesthesia for cannula placement, at 30, 60, and 360 min after initiation of ECMO, and on days 2, 4, 6, and 8. The patients were divided into survivors and non-survivors for statistical analyses. No differences were noted between survivors and non-survivors in the pre-ECMO mean serum concentrations of the thyroid function tests analyzed. In nine survivors, mean serum T4, FT4, T3, FT3, and rT3 all declined significantly within 30-60 min after initiation of ECMO, compared to baseline values. The values for all mean serum concentrations recovered completely and exceeded baseline between days 2 and 8. In five non-survivors, the decline of all mean serum values was not statistically significant and recovery to baseline was not achieved. The ratios of mean serum concentration of rT3/FT3 were significantly different between survivors and non-survivors across all times during the ECMO course (p < 0.0005). These findings indicate that abnormalities in thyroid function occur in neonates with severe respiratory failure on ECMO and that the rT3/FT3 ratio correlates with prognosis over the ECMO course. Survival was associated with a significant reduction of serum thyroid hormone concentrations followed by recovery. We speculate that, in neonates with respiratory failure on ECMO, adaptive mechanisms which enhance survival include the capacity to down-regulate the pituitary-thyroid axis.

Effect of adhesive retention on maxillofacial prostheses. Part I: skin dressings and solvent removers.

STATEMENT OF PROBLEM: The success of most maxillofacial prostheses depends on retention by medical adhesives. Products such as Smith-Nephew's Skin-Prep (SP) are available that can be used on the skin that could improve prosthesis adhesion protective dressing. The removal of adhesive from the skin is also problematic, so solvents, such as Uni-Solve adhesive remover (US), are often used. PURPOSE: This study measured the removal force of silicone elastomer strips with 2 adhesives from the skin of human subjects during the day, as affected by the use of SP and US, and determined the site of adhesive failure. MATERIAL AND METHODS: Silicone rubber strips were applied in a predetermined random order to the ventral arm surfaces of 20 human subjects. US was applied to half the sites 1 day before testing. SP was also applied to half the sites just before Epithane-3 (E3) or Secure(2) Medical Adhesive (SMA) were used to adhere the strips. They were peeled from the skin 6 hours later in an Instron at a rate of 10 cm/min. RESULTS: A 3-way within-group MANOVA revealed significant differences without interactions between adhesives (SMA=96.3 N.m, E3=24.1 N.m; P<.0005) and between use or nonuse of SP (SP=65.8 N.m, no SP=54.6 N.m; P<.0005). The use of US was not significant (no US=61.8 N.m, with US=58.6 N.m; P=.197). SMA adhered to the prostheses, whereas E3 adhered to the skin, leaving a residue (Fisher exact test; P<.0003). CONCLUSION: The combination of SMA and SP showed the highest adhesive bond strength. Overall, SMA was 3 to 5 times more retentive than E3. SP improved adhesion of both SMA (15%) and E3 (27%). SMA was still far more retentive. US had no effect on retention. SMA remained on the prostheses, whereas E3 left a difficult-to-remove residue on the skin.

Analysis of pulmonary fat embolism in blunt force fatalities.

OBJECTIVE: To investigate the incidence, severity, and origin of pulmonary fat embolism (PFE) in persons dying from blunt force trauma within 24 hours of injury. METHODS: The study population consisted of blunt force fatalities. Controls were subjects dying from natural causes or nonblunt force injury. Tissue was removed from lung lobes and prepared for histologic examination using osmium tetroxide to stain for fat. Lung sections were graded for PFE on a scale of 0 (no emboli) to 4 (five or more emboli in a majority of fields). RESULTS: The blunt force group consisted of 56 decedents. Mortality was 93% within 4 hours. Fractures were present in 54 (96%) of decedents, and soft tissue injury was universal. Thirty eight (68%) of decedents were positive for PFE vs. 3 of 20 (15%) in controls. Mean score for PFE was 2.94 +/- 1.15 and 1.01 +/- 0.94, respectively (p < 0.005). Bone marrow emboli were not observed in any of the sections. Severity of PFE was positively associated with survival time. Analysis of PFE against sex, age, height, weight, number of injuries, and number of fractures showed no significant correlations. CONCLUSIONS: A significant degree of PFE develops rapidly in a majority of persons dying of blunt force trauma. Although the source of fat for embolization has been suggested to be bone marrow, no evidence of myeloid tissue was found in any of the lung sections. Nor was there a correlation of PFE and number of fractures. Soft tissue injury is considered the primary cause of PFE.

Postpartum contraceptive use among adolescent mothers.

OBJECTIVE: To compare the incidence of repeat pregnancy and method continuation rate at 12 months postpartum in young women who chose either depot medroxyprogesterone acetate or oral contraceptives (OCs) as contraception. METHODS: We conducted a prospective cohort study of 122 postpartum women younger than 18 years of age who delivered between January 8, 1997 and December 31, 1997. Patients choosing depot medroxyprogesterone acetate (n = 76) and OCs (n = 46) were accrued for 12 months and were followed-up for a minimum of 12 months. Main outcome measures were median contraceptive method continuation and the incidence of repeat pregnancy at 12 months postpartum. RESULTS: There was no difference in mean age at delivery (P =.47), parity (P =.84), or gravidity (P =.78) between depot medroxyprogesterone acetate and OC users. At 12 months postpartum, 27.4% of OC users and 55.3% of depot medroxyprogesterone acetate users were still using contraception. Median time to contraceptive discontinuation was longer for those choosing depot medroxyprogesterone acetate compared with OCs (17.8 vs 7.4 months, respectively, P =.002). The overall incidence of repeat pregnancy at 12 months postpartum was 10.6%. Among OC and depot medroxyprogesterone acetate users, respectively, 24% and 2.6% became pregnant again, producing a relative risk (RR) of 9.09 (95% confidence interval [CI] 2.1, 39.2) for repeat pregnancy among OC users. The mean time to repeat pregnancy (this was reported instead of the median time whenever the pregnancy rate had not reached 50% at the end of the follow-up period) was longer for depot medroxyprogesterone acetate compared with OC users (17.1 months vs 13.2 months, respectively, P <.001). CONCLUSION: Adolescent mothers using depot medroxyprogesterone acetate injection for contraception have a higher method continuation rate and a lower incidence of repeat pregnancy at 12 months postpartum than those selecting OCs during the same period.

Comparison of a two-finger versus two-thumb method for chest compressions by healthcare providers in an infant mechanical model.

OBJECTIVE: To compare the two-finger versus the two-thumb method of chest compression on an infant model. STUDY: an unblinded, prospective, cross-over experimental study. SETTING: the metropolitan area of a city with a population of greater than 260,000. PARTICIPANTS: pediatric medical personnel and emergency workers. Anyone unable to complete the study was excluded. INTERVENTIONS: participants performed chest compressions on an infant mannikin for 2 min. PARTICIPANTS were randomized to use the two-finger method or the two-thumb method for the first minute. The investigators recorded the skillguide readings of green (correct), green and orange (too deep), red (wrong placement), or no light (too shallow). Sixty or more correct compressions were judged to be adequate. RESULTS: Two hundred and nine participants completed the study. PARTICIPANTS included: 66 nurses, 45 EMTs, 38 physicians, 27 paramedics, 14 nurse's assistants/emergency department technicians, 10 firefighters, five respiratory therapists, and four students. Seventy-one percent (149/209) of participants failed to give adequate compressions by either method. Only 40 participants performed adequate compressions using the two-thumb method (95% confidence interval. 14-25%). Thirty-eight participants gave adequate compressions using the two-finger method (95% confidence interval, 13-24%). No statistically significant difference existed between the two groups (P = 0.877; the McNemar test). A statistically significant difference was found in the number of shallow compressions for each method. Forty participants (19.1%) had more than 40 compressions that were too shallow versus 15 (7.2%) using the two-thumb method (P < 0.005). CONCLUSIONS: Medical personnel often fail to give adequate compressions. The two-thumb method was as adequate as the two-finger method. Overall, more compressions were measured as shallow with the two-finger method.

Penicillin minimum inhibitory concentration drift in identical sequential Streptococcus pneumoniae isolates from colonized healthy infants.

We monitored the timing of acquisition of nasopharyngeal colonization of Streptococcus pneumoniae in 125 healthy infants during their first 2 years of life. S. pneumoniae was isolated at least once from 59 (47%) of 125 infants aged between 2 and 18 months. Twenty-four infants (19%) were colonized with penicillin-resistant S. pneumoniae at some time during the study. During the course of this investigation, we identified sequential pneumococcal isolates of the same serotype from 5 infants, in which the penicillin minimum inhibitory concentration (MIC) increased over time. For 4 of the 5 infants, sequential isolates were identical, as determined by pulsed-field gel electrophoresis. Sequential S. pneumoniae nasopharyngeal isolates from some healthy infants demonstrated drift in penicillin MIC values over time, from penicillin-susceptible to penicillin-resistant.

Oral ketamine/midazolam is superior to intramuscular meperidine, promethazine, and chlorpromazine for pediatric cardiac catheterization.

UNLABELLED: An IM combination of meperidine, promethazine, and chlorpromazine (DPT) has been given as sedation for pediatric procedures for more than 40 years. We compared this IM combination to oral (PO) ketamine/midazolam in children having cardiac catheterization. A total of 51 children, ages 9 mo to 10 yr, were enrolled and randomized in this double-blinded study. All children received an IM injection at time zero and PO fluid 15 minutes later. We observed acceptance of medication, onset of sedation and sleep, and sedative efficacy. The cardiorespiratory changes were evaluated. Sedation was supplemented with IV propofol as required. Recovery time, parental satisfaction, and patient amnesia were assessed. Ketamine/midazolam given PO was better tolerated (P < 0.0005), had more rapid onset (P < 0.001), and provided superior sedation (P < 0.005). Respiratory rate decreased after IM DPT only. Heart rate and shortening fraction were stable. Oxygen saturation and mean blood pressure decreased minimally in both groups. Supplemental propofol was more frequently required (P < or = 0.02) and in larger doses (P < 0.05) after IM DPT. Parental satisfaction ratings were higher (P < 0.005) and amnesia was more reliably obtained (P = 0.007) with PO ketamine/midazolam. Two patients needed airway support after the PO medication, as did two other patients when PO ketamine/midazolam was supplemented with IV propofol. Although PO ketamine/midazolam provided superior sedation and amnesia compared to IM DPT, this regimen may require the supervision of an anesthesiologist for safe use. IMPLICATIONS: Oral medication can be superior to IM injections for sedating children with congenital heart disease; however, the safety of all medications remains an issue.

Effect of root canal sealers and irrigation agents on retention of preformed posts luted with a resin cement.

This study examined the effect of three sealers and four irrigants on retention of Dentatus preformed posts luted with Panavia 21 resin cement. Gutta-percha with one of the following sealers--EWT, AH26, Nogenol, or no sealer (control)--was used to fill the root canals of 160 autoclaved incisor and premolar tooth roots. After 72 hr 8 mm post spaces were created with Dentatus Probos Pathfinders and Dentatus reamers. After irrigating the post spaces with saline, 5.25% NaOCl, 50% citric acid followed by NaOCl, or 40% H3PO4, followed by NaOCl, Panavia 21 TC cement was introduced into the canal on the Dentatus #4 stainless steel post's threads. An up-and-down and counterclockwise motion and then a forward twist seated the posts without engaging dentin. Mesiodistal and faciolingual radiographs visualized the chambers. After 72 hr posts were removed axially with an Instron at 5 mm/min. Surprisingly, using Nogenol sealer reduced post retention whereas EWT and AH26 increased retention compared with no sealer. Post retention improved after acid etchants, especially for AH26.

Clinical relevance of urokinase-type plasminogen activator, its receptor and inhibitor type 1 in ovarian cancer.

Urokinase-type plasminogen activator (uPA), its receptor (uPAR) and inhibitor, plasminogen activator-type 1 (PAI-1) are proposed to be of prognostic significance in some cancers. To determine the prognostic value of the urokinase plasminogen activation system in ovarian cancer, levels of uPA, uPAR, and PAI-1 were measured in extracts of ovarian cancer tissue using ELISA tests. uPA and PAI-1 were determined in 70 tumor extracts and uPAR in 43 extracts. Levels were correlated with age, tumor histology, stage, grade, lymph node and metastatic status, residual disease, risk of recurrence, epidermal growth factor receptor (EGFR) expression, cathepsin D (Cath-D), and c-erbB-2 levels. uPA and uPAR did not exhibit correlation with any of these parameters. However, patients with high grade tumor, recurrence, and lower EGFR and Cath-D had significantly higher PAI-1 levels compared to those of others (P < 0.05). Kaplan-Meier plots of survival were compared. uPA and uPAR were not related to disease-free or overall survival. Although low PAI-1 appeared to predict a longer overall survival, the difference was not statistically significant. Multivariate analysis revealed that PAI-1 was a predictor for overall survival although it was not as strong as stage. These results suggest that elevated PAI-1 seems to be correlated with an unfavorable prognosis in ovarian cancer.

Oral-steroid sparing effect of inhaled fluticasone propionate in children with steroid-dependent asthma.

OBJECTIVE: To evaluate the oral steroid-sparing effect of inhaled fluticasone propionate (FP) in eight children with steroid-dependent asthma. DESIGN AND SETTING: Treatment protocol study at a tertiary pulmonary care centre at a children's hospital. PATIENTS: Eight children with severe persistent steroid dependent asthma (mean age 11.6 years [range 10 to 13 years], mean duration of asthma 8.37 years [range three to 11 years]) were enrolled in the study. MEASUREMENTS: Inhaled FP 880 mug/day (two puffs of 220 mug/puff, two times a day) was added to the children's asthma treatment, and attempts were made to reduce the dose of oral steroids by 20% every two weeks over a six-month period. After this six-month period, in the patients responding to inhaled FP, the dose of inhaled FP was reduced to 440 mug/day (two puffs of 110 mug/puff, two times a day) for the next six months. The mean percentage predicted values for forced expiratory volume in 1 s (FEV(1)) and maximal mid-expiratory flow rate (FEF(25%-75%)) were compared during the first month, at two to six months, and at seven to 12 month intervals before and after starting FP. The number of asthma exacerbations, emergency room visits, hospital admissions and number of school days lost were also compared. RESULTS: Within three months of starting inhaled FP, the mean alternate-day oral steroid dose decreased from 38 mg to 2.5 mg. In addition, six patients (66%) were able to discontinue the use of oral steroids. There was significant improvement in the number of mean emergency room visits per patient (P=0.016), mean asthma exacerbations per patient (P=0.016), mean hospital admissions per patient (P=0.016) and mean number of school days lost per patient (P=0.004) while patients were receiving high dose inhaled FP compared with oral steroids. There was no deterioration of any of the above mentioned parameters during the six month period when the dose of inhaled FP was reduced. The mean FEV(1) and FEF(25%-75%) during the two- to six-month and seven- to 12-month periods showed significant improvement, while the patients were receiving FP compared with oral steroids (P<0.05 for both parameters for both time periods). CONCLUSIONS: High dose inhaled FP 880 mug/day has an important oral steroid-sparing effect. After oral steroids are tapered, patients maintain adequate control of asthma with low dose inhaled FP. These findings suggest that FP may control asthma better than oral steroids.

An analysis of the late effects of radiotherapy in pediatric central nervous system tumors.

PURPOSE: The purpose of this study is to assess the long term results of all pediatric patients diagnosed with central nervous system (CNS) tumors treated with external beam radiotherapy either primarily or postoperatively. MATERIALS: Forty-seven pediatric patients with CNS tumors were treated between 1978 and 1989 with external beam radiotherapy to customized fields using cobalt 60, 4, 6, or 18 MV photons. Daily doses ranged from 1.5 to 2.0 Gray; total doses from 35 to 66 Gray. Ages ranged from one month to 18 years of age, with an average age of 8.2 years. Thirty-nine patients survived more than 12 months (range 36 to 178 months; median 62 months) and were included for analysis. Ten of 39 (25.6%) patients experienced Grade I to II complications and six patients had (15.7%) Grade III to IV complications for an overall incidence of 41%. The influence of field size, radiation dose, chemotherapy, age, and extent of surgical resection upon long-term complications were studied. CONCLUSION: Radiation therapy for pediatric CNS malignancies is associated with long-term complications. Significant long-term complications can be limited to an acceptable level of approximately 15%.

Human chorionic gonadotropin exhibits potent inhibition of preterm delivery in a small animal model.

OBJECTIVE: The purpose of this study was to test the capability of human chorionic gonadotropin to inhibit prostaglandin-induced preterm delivery in a murine model. STUDY DESIGN: A preterm delivery model was developed by using intraperitoneal injection of 20 microgram of prostaglandin F(2)(alpha) to induce preterm labor in C3H/HeN inbred mice. Mice were then pretreated with human chorionic gonadotropin 4 hours before administration of prostaglandin F(2)(alpha), and time to delivery of the first pup was recorded. After initial promising results, mice were then given increasing intraperitoneal doses of human chorionic gonadotropin (100 IU, 250 IU, or 1000 IU or sodium chloride solution vehicle) 4 hours after administration of prostaglandin F(2)(alpha). The specificity of the human chorionic gonadotropin effect was assessed by treating mice with whole human chorionic gonadotropin, an equal mass dose of the beta-subunit or the alpha-subunit of human chorionic gonadotropin, or an equal mass dose of luteinizing hormone 4 hours after administration of prostaglandin F(2)(alpha). Delivery times between groups were compared by using the Mann-Whitney U test and the log-rank test. Survival estimates were computed by using the Kaplan-Meier method. RESULTS: Pilot studies in 52 mice confirmed that a single intraperitoneal injection of 20 microgram of prostaglandin F(2)(alpha) on day 16 (80% gestation) consistently induced preterm delivery compared with the effect of sodium chloride solution on control mice (prostaglandin F(2)(alpha), 19.3 +/- 2.9 hours; sodium chloride solution, 53.5 +/- 13.6 hours; P <.0001). Mice pretreated with human chorionic gonadotropin (1000 IU) demonstrated significant delays in delivery times compared with the prostaglandin-only group (prostaglandin F(2)(alpha) only, 21.9 +/- 2. 0 hours; human chorionic gonadotropin pretreatment plus prostaglandin F(2)(alpha), 48.5 +/- 20 hours; P <.0001; n = 17). Mice treated with human chorionic gonadotropin (100 IU, 250 IU, 1000 IU) 4 hours after administration of prostaglandin F(2)(alpha) demonstrated significant dose-dependent inhibition of preterm delivery compared with the prostaglandin-only group (P <.00005; n = 34). Mice treated with the alpha-subunit or the beta-subunit of human chorionic gonadotropin after prostaglandin administration did not demonstrate delays in delivery times (P =.46; n = 27). Administration of luteinizing hormone delayed delivery compared with the effect of prostaglandin F(2)(alpha) on control animals (P <.05; n = 17); however, the effect was less pronounced than that seen with a mass equivalent of human chorionic gonadotropin. CONCLUSIONS: Human chorionic gonadotropin exhibits potent inhibition of prostaglandin-induced preterm delivery in mice. The effect is dose-dependent, and whole human chorionic gonadotropin is required to elicit inhibition. Further studies are needed to determine the safety and efficacy of human chorionic gonadotropin as a potential therapy for preterm labor inhibition in human pregnancy.

Protracted results of dose-intensive therapy using cyclophosphamide, carmustine, and continuous infusion etoposide with autologous stem cell support in patients with relapse or refractory Hodgkin's disease: a phase II study from the North American Marrow Transplant Group.

To determine the long-term results of high-dose chemotherapy and stem cell support in relapsed or primary refractory Hodgkin disease patients. One hundred and thirty-one patients with relapsed or primary refractory Hodgkin's disease were treated with a dose-intensive therapy protocol consisting of etoposide (2400 mg/m2 continuous intravenous infusion) cyclophosphamide (7200 mg/m2 intravenously), and carmustine (300-600 mg/m2 intravenously) CBVi. All patients had previously failed conventional chemoradiotherapy. Severe toxicities were related to infectious, hepatic, and pulmonary complications. Fatal, regimen-related toxicity was 19%; liver and lung dysfunction, as well as infection, were the most frequent problems. Ninety-one (69%) of the patients achieved a complete response (CR) (95% CI = 59% to 75%) after CBVi and autologous stem cell infusion. With a median follow-up of 5.1 years (range 3.0 to 9.5 years), overall and event-free survival are 44% (95% CI = 33% to 47%) and 38% (95% CI = 28% to 46%) respectively. While univariate analysis did not reveal a statistically significant variable to predict a better response, responsiveness to therapy demonstrated a trend. We conclude that CBVi is an effective therapy for relapsed or refractory Hodgkin's disease, producing long-term, durable remissions.

Comparison of the efficacy of inhaled fluticasone propionate, 880 microg/day, with flunisolide, 1500 microg/day, in moderate-to-severe persistent asthma.

BACKGROUND: Inhaled corticosteroids have become the mainstay of asthma therapy. Few studies however, have compared inhaled steroids in children. We compared the efficacy of inhaled fluticasone propionate (FP), 880 microg/day (2 puffs of 220 microg/puff, BID) with inhaled flunisolide (FLU), 1500 microg/day (3 puffs of 250 microg/puff, BID). METHODS: Thirty children with moderate to severe asthma, mean age 12.7 years (range 10 to 17 years), mean duration of asthma 8.4 years, initially received flunisolide 1500 microg/day for 1 year, and then were switched to fluticasone propionate 880 microg/day and followed for an additional year. Pulmonary function tests (PFTs) were monitored and analyzed before and after the switch for the duration of study. Mean percent predicted for age values for FVC, FEV1, FEF25-75%, and FEFR were compared at 1 month, 2 to 6-month intervals, and 7 to 12-month intervals and during the same season of the year. Pulmonary function tests within 3 weeks of an exacerbation were not included in the study. The number of asthma exacerbations, emergency room visits, hospital admissions, and number of school days lost were also compared. RESULTS: There was significant improvement in mean asthma exacerbations/patient/year (1.7 +/- 1.66 SD) versus (4 +/- 2.6) (P < .0002); mean emergency room visits/patient/year (0.23 +/- 0.62) versus (1.2 +/- 1.74) (P = .004); mean hospital admissions for asthma/patient/year (0.2 +/- 0.61) versus (1.13 +/- 1.45) (P < .0002); and number of school days lost/patient/year (1.4 +/- 2.38) versus (7.93 +/- 6.7) (P < .0002) while patients were receiving fluticasone propionate as compared with flunisolide. Also, the mean percent values predicted for age in all time-periods (at 1 month, 2 to 6 months, and 7 to 12 months) revealed significant improvement in FEV1 and FEF25-75% (P < .05 for both parameters). As PFT can be affected by seasonal changes, PFT parameters were compared during the same season of the year and significant improvement in FVC and FEV1 was observed in all seasons while patients were receiving fluticasone propionate (FP) compared with flunisolide (FLU) (P < .05 for all parameters). Significant improvement in PEFR and FEF25-75% was observed only in spring and summer season. CONCLUSION: Fluticasone propionate 880 microg/day improved lung function and quality of life in adolescents with moderate-to-severe asthma when compared with flunisolide 1500 microg/day.