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Previous studies have demonstrated that botulinum toxin type A (BoNT-A) attenuates orofacial nociception. However, there has been no evidence of the participation of the voltage-gated sodium channels (Navs) in the antinociceptive mechanisms of BoNT-A. This study investigated the cellular mechanisms underlying the antinociceptive effects of BoNT-A in a male Sprague-Dawley rat model of trigeminal neuropathic pain produced by malpositioned dental implants. The left mandibular second molar was extracted under anesthesia, followed by a miniature dental implant placement to induce injury to the inferior alveolar nerve. Mechanical allodynia was monitored after subcutaneous injection of BoNT-A at 3, 7, or 12 d after malpositioned dental implant surgery. Subcutaneous injections of 1 or 3 U/kg of BoNT-A on postoperative day 3 significantly attenuated mechanical allodynia, although 0.3 U/kg of BoNT-A did not affect the air-puff threshold. A single injection of 3 U/kg of BoNT-A produced prolonged antiallodynic effects over the entire experimental period. Treatment with BoNT-A on postoperative days 7 and 12, when pain had already been established, also produced prolonged antiallodynic effects. Double treatments with 1 U/kg of BoNT-A produced prolonged, more antiallodynic effects as compared with single treatments. Subcutaneous administration of 3 U/kg of BoNT-A significantly inhibited the upregulation of Nav isoform 1.7 (Nav1.7) expression in the trigeminal ganglion in the nerve-injured animals. These results suggest that antinociceptive effects of BoNT-A are mediated by an inhibition of upregulated Nav1.7 expression in the trigeminal ganglion. BoNT-A is therefore a potential new therapeutic agent for chronic pain control, including neuropathic pain. [ABSTRACT FROM AUTHOR]

Curcumin has diverse therapeutic effects, such as antiinflammatory, anti-oxidant, anti-cancer, and antimicrobial activities. The vanilloid moiety of curcumin is considered important for activation of the transient receptor potential vanilloid 1 (TRPV1), which plays an important role in nociception. However, very little is known about the effects of curcumin on nociception. In the present study, we investigated whether the antinociceptive effects of curcumin are mediated via TRPV1 by using nociceptive behavioral studies and in vitro whole-cell patch-clamp recordings in the trigeminal system. Subcutaneous injection of capsaicin in the vibrissa pad area of rats induced thermal hyperalgesia. Intraperitoneally administered curcumin blocked capsaicin-induced thermal hyperalgesia in a dose-dependent manner. Whereas curcumin reduced capsaicin-induced currents in a dose-dependent manner in both trigeminal ganglion neurons and TRPV1- expressing HEK 293 cells, curcumin did not affect heat-induced TRPV1 currents. Taken together, our results indicate that curcumin blocks capsaicin-induced TRPV1 activation and thereby inhibits TRPV1- mediated pain hypersensitivity. Abbreviations: capsaicin-induced inward currents, ICAP; HEK 293 cells, human embryonic kidney 293 cells; intraperitoneal(ly), i.p.; IRTX, 5'-iodoresiniferatoxin; s.c., subcutaneous(ly); TRPV1, transient receptor potential vanilloid 1. [ABSTRACT FROM AUTHOR]

To investigate chemotherapeutic dose intensity in advanced non-small-cell lung cancer (NSCLC), we evaluated a pharmacokinetically designed schedule of high-dose cisplatin (200 mg/m2 per 28-day cycle) plus mitomycin C. Between March 1987 and March 1989, 62 patients were registered for a phase II study of the Northern California Oncology Group (NCOG). The treatment schedule consisted of cisplatin in hypertonic saline given on a divided days 1 and 8 schedule (100 mg/m2 on each day) plus mitomycin C given at a dose of 8 mg/m2 on day 1 of each cycle. In 61 patients evaluable for response analysis, the overall response rate was 39% (24/61), with a complete response being achieved in 6% (4/61) of cases and a partial response, in 33% (20/61). The response according to reviewed histologic subtype included squamous, 53% of patients (10/19); large cell, 31% (4/13); and adenocarcinoma, 34% (10/29). The median survival for all patients was 29.3 weeks. The mean cisplatin and mitomycin C delivered dose intensities in this study were 45 mg/m2 per week (90% of the projected dose) and 1.5 mg/m2 per week (75%). The toxicity of this combination regimen in the 62 enrolled patients was significant but manageable. Leukopenia (WBC, less than 1,000/mm3) and thrombocytopenia (platelets, less than 25,000/mm3) occurred in 3% and 8% of patients treated, respectively. Dose-limiting renal toxicity and clinically significant ototoxicity developed in 8 patients each (13%), and a peripheral sensory neuropathy was observed in 17 cases (27%). Whether this type of dose-intensive therapy results in an improved therapeutic index in NSCLC is currently being evaluated in a randomized comparative trial versus standard-dose cisplatin therapy. [ABSTRACT FROM AUTHOR]

Objective: To determine the hemopoietic effects of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients having autologous hemopoietic stem cell transplantation for Hodgkin or non-Hodgkin lymphoma.Design: Placebo or GM-CSF was administered after bone marrow or peripheral blood stem cell transplantation or both in a randomized, double-blind phase III trial by daily intravenous infusion (10 micrograms/kg body weight) until absolute neutrophil counts reached greater than or equal to 1000/mm3 on 3 consecutive days.Setting: Bone marrow transplantation unit in a university hospital.Patients: Sixty-nine consecutive patients with Hodgkin or non-Hodgkin lymphoma received GM-CSF (36 patients) or placebo (33 patients).Measurements and Main Results: Patients who received GM-CSF achieved absolute neutrophil counts greater than or equal to 500/mm3 (median, 12 compared with 16 days, P = 0.02) and absolute neutrophil counts greater than or equal to 1000/mm3 (median, 15 compared with 24 days, P less than 0.001) more quickly than patients who received placebo. Multivariate analysis indicated that use of GM-CSF, peripheral blood stem cells, and unpurged bone marrow were the strongest predictors for early neutrophil recovery greater than 500/mm3. Bacterial infections were significantly reduced in the GM-CSF group (P = 0.04). Delayed engraftment (neutrophils less than 500/mm3 at day 30) occurred in 26% and 17% of the placebo and GM-CSF groups, respectively, and correlated with the absence of detectable myeloid progenitor cells (colony-forming units-granulocyte macrophage, CFU-GM) (P less than 0.001) in marrow aspirate specimens obtained on day 15. Time to platelet independence, duration of hospital stay, severe adverse reactions, relapse, and disease-free survival rates did not differ significantly between the two groups.Conclusions: Administration of GM-CSF after autologous hemopoietic stem cell transplantation in patients with lymphoma resulted in accelerated myeloid recovery, particularly in patients who received peripheral blood stem cells and nonpurged bone marrow, and was associated with a decreased incidence of bacterial infections. [ABSTRACT FROM AUTHOR]

Ninety-seven male homosexuals with the acquired immunodeficiency syndrome or other group IV human immunodeficiency virus disease were studied for anal human papillomavirus infection and intra-anal cytological abnormalities. Human papillomavirus DNA was detected in 52 subjects (54%), and 38 subjects (39%) were found to have abnormal anal cytological findings; anal intraepithelial neoplasia was detected in 15 specimens (15%). Abnormalities on anal cytological smear were significantly associated with the presence of human papillomavirus DNA, with a risk ratio of 4.6. Infection with multiple human papillomavirus types was common (12%) and was associated with a risk ratio for cytological abnormalities of 39.0. Median T4 counts of subjects with abnormal cytological findings were significantly lower than those with normal findings. These studies indicate that immunosuppressed male homosexuals have a high prevalence of anal human papillomavirus infection and anal intraepithelial neoplasia, and this population may be at significant risk for the development of anal cancer. [ABSTRACT FROM AUTHOR]

Context: Cardiovascular disease (CVD) risk factors are higher among ethnic minority women than among white women in the United States. However, because ethnic minority women are disproportionately poor, socioeconomic status (SES) may substantially explain these risk factor differences.Objective: To determine whether differences in CVD risk factors by ethnicity could be attributed to differences in SES.Design: Third National Health and Nutrition Examination Survey conducted between 1988 and 1994.Setting: Eighty-nine mobile examination centers.Participants: A total of 1762 black, 1481 Mexican American, and 2023 white women, aged 25 to 64 years, who completed both the home questionnaire and medical examination.Main Outcome Measures: Ethnicity and years of education (SES) in relation to systolic blood pressure, cigarette smoking, body mass index (BMI, a measure of weight in kilograms divided by the square of height in meters), physical inactivity, non-high-density lipoprotein cholesterol (non-HDL-C [the difference between total cholesterol and HDL-C]), and non-insulin-dependent diabetes mellitus.Results: As expected, most CVD risk factors were higher among ethnic minority women than among white women. After adjusting for years of education, highly significant differences in blood pressure, BMI, physical inactivity, and diabetes remained for both black and Mexican American women compared with white women (P<.001). In addition, women of lower SES from each of the 3 ethnic groups had significantly higher prevalences of smoking and physical inactivity and higher levels of BMI and non-HDL-C than women of higher SES (P<.001).Conclusions: These findings provide the greatest evidence to date of higher CVD risk factors among black and Mexican American women than among white women of comparable SES. The striking differences by both ethnicity and SES underscore the critical need to improve screening, early detection, and treatment of CVD-related conditions for black and Mexican American women, as well as for women of lower SES in all ethnic groups. [ABSTRACT FROM AUTHOR]

Background: Distinguishing osteomyelitis from soft-tissue infection of the foot is important because osteomyelitis is associated with more operations, amputation, and prolonged antibiotic exposure. Both erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are routinely ordered inflammatory biomarkers for evaluating foot infection. When initial evaluation is inconclusive, advanced imaging is indicated, and high clinical or radiographic suspicion of osteomyelitis may indicate bone biopsy to identify organisms and antibiotic sensitivity. Although ESR and CRP levels are helpful for distinguishing osteomyelitis from soft-tissue infections in patients with diabetes-related foot infections, parameters regarding optimal cutoff values for those tests have not, to our knowledge, been defined., Questions/purposes: (1) What are the optimal cutoff values for ESR and CRP to differentiate osteomyelitis from soft-tissue infection in patients with diabetes-related foot infection? (2) Can a diagnostic algorithm be derived to guide interpretation of ESR and CRP to improve recognition of osteomyelitis in the setting of diabetic foot infection?, Methods: The medical records of 1842 patients between 18 and 89 years of age treated at our institution between January 1, 2010 and February 6, 2017 for foot infection were reviewed. For inclusion, patients must have had a diagnosis of diabetes mellitus, moderate or severe infection, ESR and CRP values within 72 hours of admission, either advanced imaging (MRI or single-positron emission computed tomography/computed tomography [SPECT/CT]) or bone biopsy during admission and must not have had comorbidities that could affect ESR and CRP, such as autoimmune disorders. As such, 1489 patients were excluded, and 353 patients were included in the study. Osteomyelitis was diagnosed by positive bone culture or histopathology. Osteomyelitis was considered to be absent if there was a negative MRI or SPECT/CT result, or negative bone culture and histology findings if imaging was inconclusive. We identified 176 patients with osteomyelitis and 177 with soft-tissue infection. A blinded investigator performed the statistics. Optimal cutoffs of ESR and CRP were determined using receiver operative characteristic (ROC) analysis. A diagnostic algorithm was determined using epidemiologic principles of screening evaluations., Results: An ESR of 60 mm/h and a CRP level of 7.9 mg/dL were determined to be the optimal cutoff points for predicting osteomyelitis based on results of the ROC analysis. The ESR threshold of 60 mm/h demonstrated a sensitivity of 74% (95% confidence interval [CI], 67-80) and specificity of 56% (95% CI, 48-63) for osteomyelitis, whereas the CRP threshold of 7.9 mg/dL had a sensitivity of 49% (95% CI, 41-57) and specificity of 80% (95% CI, 74-86). If the ESR is < 30 mm/h, the likelihood of osteomyelitis is low. However, if ESR is > 60 mm/h and CRP level is > 7.9 mg/dL, the likelihood of osteomyelitis is high, and treatment of suspected osteomyelitis should be strongly considered., Conclusions: While ESR is better for ruling out osteomyelitis initially, CRP helps distinguish osteomyelitis from soft-tissue infection in patients with high ESR values. Further prospective studies addressing the prognostic value of ESR and CRP are needed, and a more comprehensive diagnostic algorithm should be developed to include other diagnostic tests such as probe-to-bone and imaging., Level of Evidence: Level III, diagnostic study.

The response properties of tooth pulp neurons that respond to noxious thermal stimulation of the dental pulp have been not well-studied. The present study was designed to characterize the response properties of tooth pulp neurons to noxious thermal stimulation of the dental pulp. Experiments were conducted on 25 male ferrets, and heat stimulation was applied by a computer-controlled thermode. Only 15% of tooth pulp neurons (n = 39) responded to noxious thermal stimulation of the teeth. Tooth pulp neurons were found in both the superficial and deep nuclear regions of the subnucleus caudalis (Vc) and in the interface between the nucleus caudalis and interpolaris (Vc/Vi). Thirty-seven neurons had cutaneous receptive fields and were classified as either NS (16) or WDR (21) neurons. Repeated heat stimulation of the dental pulp sensitized and increased the number of electrically evoked potentials of tooth pulp neurons. These results provide evidence that both the Vc and Vc/Vi regions contain neurons that respond to noxious thermal stimulation of the dental pulp, and that these cells may contribute to the sensitization process associated with symptomatic pulpitis.

The analgesic effects of dexamethasone on neuropathic pain have been controversial. The present study investigated the effects of dexamethasone on mechanical allodynia in rats with mal-positioned dental implants. Under anesthesia, the left mandibular second molar was extracted and replaced by a miniature dental implant to injure the inferior alveolar nerve. Nociceptive behavior was examined on each designated day after surgery. Mal-positioned dental implants significantly decreased air-puff thresholds both ipsilateral and contralateral to the injury site. Distinct mechanical hyperalgesia and cold and thermal hypersensitivity were also observed bilaterally. Daily administration of dexamethasone produced prolonged anti-allodynic effects (25 or 50 mg/kg, i.p.), but failed to reduce mechanical allodynia when it had already been established. Therefore, our findings provide that early treatment with dexamethasone is important in the treatment of nociceptive behavior suggestive of trigeminal neuropathic pain.

The morphology of intradental nerve fibers of permanent teeth and of continuously growing rodent incisors has been studied in detail but little information is available on the parent axons that give rise to these fibers. Here we examined the axons and somata of trigeminal neurons that innervate the rat upper molar and lower incisor pulp using tracing with horseradish peroxidase and light and electron microscopic analysis. The majority (approximately 80%) of the parent axons in the proximal root of the trigeminal ganglion that innervated either molar or incisor pulp were small myelinated fibers (<20 microm(2) cross-sectional area). The remaining approximately 20% of the fibers were almost exclusively large myelinated for the molar pulp and unmyelinated for the incisor pulp. The majority of neuronal somata in the trigeminal ganglion that innervated either molar (48%) or incisor pulp (62%) were medium in size (300-600 microm(2) cross-sectional area). Large somata (>600 microm(2)) constituted 34% and 20% of the trigeminal neurons innervating molar and incisor pulp, respectively, while small somata (<300 microm(2)) constituted 17% of the molar and 18% of the incisor neurons. The present study revealed that the morphology of parent axons of dental primary sensory neurons may differ from that of their intradental branches, and also suggests that the nerve fiber function may be carried out differently in the molar and incisor pulp in the rat.

The present study investigated the effects of intracisternal administration of MCP-1, Rantes or IL-8 on pain transmission in the orofacial area. We also investigated mechanisms of hyperalgesic responses produced by intracisternal administration of IL-8. An orofacial formalin test was employed to assess the effects of chemokines on nociceptive processing. For each animal, the number of behavioral responses and the time spent grooming, rubbing and/or scratching the facial region proximal to the formalin injection site was recorded for nine successive 5-min intervals. Intracisternal administration of MCP-1, Rantes or IL-8 significantly increased formalin-induced scratching behavioral responses in the orofacial area. Intracisternal pretreatment with indomethacin, a non-selective cyclooxygenase inhibitor, did not block IL-8-induced hyperalgesia. Pretreatment with 100 microg propranolol, a non-selective beta-adrenergic receptor antagonist and 50 microg atenolol, a selective beta(1)-adrenergic receptor antagonist, inhibited the number of scratches and the duration of scratching produced by 1 ng of IL-8 injected intracisternally. These results indicate that intracisternal administration of chemokines produce a hyperalgesic response with an orofacial inflammatory pain model and that the IL-8-induced hyperalgesia is mediated by central beta(1)-adrenergic receptor.

The present study was performed to examine peripheral cytokine-induced mechanical allodynia in the orofacial area and to investigate whether peripheral excitatory amino acids participate in the cytokine-induced mechanical allodynia. Experiments were carried out on male Sprague-Dawley rats. After interleukin-1beta (IL-1beta) was applied subcutaneously to the orofacial area, we examined withdrawal responses produced by air puffs applied to the IL-1beta injection site. The threshold of air puffs that produced withdrawal behavioral responses decreased significantly in a dose-dependent manner after injection of IL-1beta. Pretreatment with an IL-1 receptor antagonist abolished the decrease in the threshold of air puffs. Pretreatment with dl-2-amino-5-phosphonvaleric acid, an N-methyl-d-aspartic acid (NMDA) receptor antagonist, did not affect IL-1beta-induced mechanical allodynia. However, pretreatment with 6,7-dinitroquinoxaline-2,3-dione, a non-NMDA receptor antagonist, abolished the decrease in the threshold of air puffs. These results suggest that peripheral cytokine can produce mechanical allodynia in the orofacial area and that excitatory amino acids can modulate IL-1beta-induced mechanical allodynia via non-NMDA receptors.

The present study was performed to investigate effects of central cyclooxygenase (COX) on interleukin (IL)-1beta-induced hyperalgesia in the orofacial area. Experiments were carried out on 72 male Sprague-Dawley rats weighing 220-280 g. Surgical procedures were performed under pentobarbital sodium. We examined noxious behavioral scratching responses induced by 50 microl of 5% formalin injected subcutaneously into the vibrissa pad without any restraints. The orofacial formalin responses exhibited two distinct phases with early responses (0-10 min) and continuous prolonged responses (11-45 min). Intracisternal injection of 100 pg IL-1beta significantly increased noxious behavioral responses. Pretreatment with indomethacin, a non-selective COX inhibitor, or NS-398, a selective COX-2 inhibitor, blocked IL-1beta-induced hyperalgesic responses. However, pretreatment with SC-560, a selective COX-1 inhibitor, did not change hyperalgesic response to IL-1beta. These data suggest that central IL-1beta modulates the transmission of nociceptive information in the orofacial area and that central COX-2 plays an important role in IL-1beta-induced hyperalgesia.

SV40 large T antigen, a viral oncoprotein, is known to immortalize human diploid fibroblast by soaking up cellular RB and p53, but its frequency is extremely low. Additional genetic alteration is necessary for single-step immortalization. We attempted to find out what this alteration is by overexpressing cellular signal mediator genes; c-myc and cyclin D frequently amplified in many cancer cells. Overexpression of cyclin D did not affect the immortalization, but, overexpression of c-myc along with T antigen could immortalize normal human diploid fibroblast. Several cellular markers tested during immortalization process showed that p21, a cyclin-dependent kinase inhibitor and a marker of cellular senescence, disappeared in the life span-extended cells by T antigen and in the immortalized cells by c-myc. p21 was, however, elevated in the senescent cells and in the cells of crisis. Interestingly, p16 was upregulated whenever T antigen is overexpressed. Telomerase activity was also activated only in the immortalized cells. These results suggest that overexpression of c-myc contributes to immortalization of human diploid fibroblast by activating telomerase activity and suppressing p21 activity.

Bronchogenic cyst is noted shortly after birth or in early childhood and usually presents as a swelling or draining sinus in the presternal area. Its origin and pathogenesis can be explained as a developmental anomaly of the tracheobronchial buds from the primitive foregut. The patient was a 4-year-old boy with a child-fist-sized soft mass over his left scapula, which had been detected at birth and had been gradually growing. Grossly, it appeared to be a simple cyst with clear mucoid fluid. Histopathological study demonstrated a unilocular cyst composed of ciliated pseudostratified columnar epithelia, interspersed goblet cells, smooth muscles, and mucous glands on the cyst wall, which are features compatible with cutaneous bronchogenic cyst.

1. Experiments were carried out in rats with stimulating electrodes implanted in the dental pulp, recording electrodes inserted into the anterior digastric muscle, and indwelling cannula implanted in the central amygdaloid nucleus and the cisterna magna area. 2. Injection of 4.4 nM and 8.8 nM carbachol into the central amygdaloid nucleus suppressed digastric electromyogram (dEMG) to 81 +/- 8% and 47 +/- 9% of the control, respectively. 3. Atropine, a muscarinic receptor antagonist, blocked the suppression of dEMG in response to the administration of 8.8 nM carbachol into the amygdala. However, a mecamylamine, a nicotinic receptor antagonist, did not affect changes in dEMG. 4. Intracisternal naloxone, an opioid receptor antagonist, reduced the suppression of dEMG from 47 +/- 10 to 72 +/- 12% of the control. 5. Intracisternal methysergide, a serotonin receptor antagonist, also reduced the suppression of dEMG from 50 +/- 9 to 78 +/- 9% of the control. 6. The carbachol-induced antinociception from the central amygdaloid nucleus was attributed to opioid and serotonergic descending inhibitory influences on nociceptive pathways.

Little is known about pathways by which socioeconomic status (SES) translates into individual differences in cardiovascular disease (CVD) risk factors. Because the socioeconomic structure is not the same for all ethnic subgroups, the pathways that lead to the development of CVD risk factors may vary by both SES and ethnicity. We used data from a large national survey to examine the independent associations of two indicators of SES (education and income) and ethnicity with six primary CVD risk factors. We then used data on smoking that reflected a temporal sequence to examine the extent to which SES and ethnicity influenced smoking at three different time points, from smoking onset, to a serious quit attempt, to successful quitting. These analyses provide an understanding of the relationships between SES, ethnicity, and CVD risk factors and suggest that if the timing, focus, and content of intervention programs take pathways into account they will result in more successful outcomes.

The potential effects of making a marital transition on subsequent physical activity were evaluated across a ten-year period in a population-based sample of 302 women and 256 men ages 25 to 75 years. Subjects completed a structured interview at five timepoints throughout the ten-year period during which they reported on their physical activity level as well as marital status. The transition from a married to a single state did not affect physical activity relative to remaining married when analyses of either slopes or mean values were used. In contrast, the transition from a single to a married state resulted in significant positive changes in physical activity relative to remaining single throughout the study period when physical activity slopes, though not means, were compared. The results suggest that marriage may potentially set the stage for natural changes in physical activity that could be capitalized on through appropriate intervention, but additional research is needed to verify this in light of the inconsistent pattern of findings.

Purpose: Smoking prevalence in a population is affected by the proportion of adolescents who start to smoke, and the proportion of smokers who quit. Smoking prevalence has declined linearly in the US and in the state of California during the last 2 decades. Due to an increase in female smoking, the Norwegian smoking prevalence has been stable at around 35% since 1980, while other European countries have seen reductions of at least 10 percentage points., Methods: We compared data from two cross-sectional studies; one from Western and Central Norway (n = 5014), and one from Northern California (Stanford Five-City Project) (n = 2189)., Results: Norwegian smoking prevalence figures were significantly higher in all age-sex groups younger than 60 years. The proportion of former smokers was not different, suggesting that the differences between the samples are due to higher smoking initiation in Norway. University education was the most potent covariate of both ever-smoking and current smoking across samples and gender. Amount of physical exercise was associated with never-smoking in Norway, but not in the US. Having smoking parents was related to ever-smoking in women but not in men in both samples. Smoking parents also was related to current smoking in Norway but not in the US., Implications: Norway should increase efforts to prevent smoking initiation among adolescents, and especially among girls.

This study examined the feasibility of fixation of craniofacial bone using Lactosorb biodegradable plates adhered to bone with butyl-2-cyanoacrylate adhesive (Histoacryl) in a pig. The stability and bone-healing characteristics of this rigid fixation method were studied and compared with standard rigid fixation using metal plates and screws on osteotomy sites in the frontal bones and infraorbital rims. Rectangular osteotomies (2.0 x 3.0 cm) were performed on the right and left sides of the frontal bone and wedge-shaped osteotomies (1.5 x 1.7 cm) were made on the left and right infraorbital rims in seven Yorkshire pigs. Metal plates were applied with screws to the osteotomies on one side, and the other side was fixed with a biodegradable plate and butyl-2-cyanoacrylate. The animals were sacrificed at 8 weeks, and both sides were compared biomechanically and histologically. Radiographic, biomechanical, and histologic analyses were performed to evaluate skeletal stability, contour, accurate positioning of bony fragments, bone healing, and maximum torque to failure of the repair sites. Clinical and radiographic observations demonstrated stability of the bone fragments without any evidence of displacement. According to Student's t test for paired data, no statistical difference was found in the maximum torque to failure of fragments fixed with biodegradable plates and glue compared with those fixed with metal plates and screws (p > 0.05), whether or not a gap existed at the osteosynthesis site. Although the sample size was small, no differences were noted between the two types of treatment groups. This study demonstrates that rigid internal fixation of osteotomized cranial bone fragments using biodegradable plates and butyl-2-cyanoacrylate is as effective as metal plate and screw fixation in this animal model.

Data from a large, population-based case-control study were analyzed to investigate the relationship between prenatal exposure to tobacco smoke and childhood brain tumors (CBTs). A total of 540 CBT patients, diagnosed between 1984 and 1991, were identified from population-based tumor registries in 19 West Coast counties that included Seattle, WA (13 counties), San Francisco, CA (5 counties), and Los Angeles, CA (1 county). Random digit dial was used to select 801 control subjects from the three geographical regions to obtain a case:control ratio of 1:2 in San Francisco and Seattle and 1:1 in Los Angeles. The data first were analyzed separately by geographical site and then were combined with adjustments made for gender, age at the time of diagnosis (or reference date of control subjects), birth year of the index child, and maternal race. No association was found between the risk of CBTs and maternal or paternal smoking before pregnancy and there was no association between CBTs and maternal smoking during pregnancy [odds ratio (OR) = 0.98; 95% confidence interval (CI) = 0.72-1.3]. A slightly increased OR for CBTs was found for paternal smoking during pregnancy in the absence of maternal smoking (OR = 1.2; 95% CI = 0.90-1.5) and for maternal exposure to passive smoke from any source (OR = 1.2; 95% CI = 0.95-1.6). The results of this analysis are consistent with results from several prior epidemiological studies that showed no significant association between CBTs and maternal smoking before or during pregnancy or maternal exposure to passive smoke during pregnancy.

An analysis of the relationship between the anatomic site of cutaneous melanoma, sun exposure, and phenotype was conducted in 355 women with histologically confirmed superficial-spreading melanoma and in 935 control subjects. The most frequent site for superficial-spreading melanoma was the leg. However, when major sun-related and phenotype risk factors were examined by site, risk ratios were lowest for melanomas that occurred on the leg. A history of frequent sunburns during elementary or high school, increased number of self-assessed large nevi, and blond hair were more strongly associated with melanoma sites other than the leg. Tumors on the trunk were more likely than tumors at other sites to be associated with histological evidence of a preexisting nevus. Results of this work indicate that associations between melanoma phenotypic factors may differ by anatomic site.

Factors related to menopause and use of exogenous hormones other than p.o. contraceptives were examined in 452 women ages 25-59 who were diagnosed with cutaneous malignant melanoma. Control subjects for this population-based study in the San Francisco Bay Area were 930 women of the same age. An increased risk was observed for superficial spreading melanoma (SSM) in women who reached natural menopause after age 55 [odds ratio (OR), 3.6; 95% confidence interval (CI), 1.1-11.1], and for women who had had a bilateral oophorectomy within 9 years of their diagnosis with SSM (OR, 2.2; CI, 1.1-4.5). A somewhat elevated risk of melanoma after natural menopause or hysterectomy was no longer statistically significant after adjustment for exogenous hormone use. Prolonged use of p.o. exogenous hormones after hysterectomy for women who had retained at least one ovary was associated with an increased risk of SSM (OR, 5.4; CI, 1.5-19.3), and use of these products for fewer than 5 years after bilateral oophorectomy also was associated with an elevated risk of SSM (OR, 2.9; CI, 1.0-7.8). Conjugated estrogen use was associated with somewhat elevated risks for SSM after hysterectomy with one ovary retained (OR, 2.7; CI, 0.97-7.3) and after hysterectomy with bilateral oophorectomy (OR, 2.1; CI, 0.86-5.0). There was a suggestion of a trend for increased risk of SSM with increased dosage of conjugated estrogens after hysterectomy (P for trend = 0.07). Use of vaginal creams that contained estrogen also was associated with an increased risk of SSM (OR, 1.8; CI, 1.0-3.3).

Background: Women smokers were previously reported to be more sexually active but less likely to use contraception than nonsmokers. Differences in contraceptive choices between the two groups were investigated., Methods: Sexually active women, 287 who smoked cigarettes and 263 who did not smoke, were queried about current contraceptive use and demographic, sexual, and reproductive factors., Results: Sexually active smokers were less likely than nonsmokers to use contraceptives, especially oral contraceptives. The deficit of contraceptive use among smokers was most pronounced in women under age 30, black women, single women, women with some college education, nulliparous women, women who reported early age at first intercourse, and women who reported four or more lifetime sexual partners. In contrast, smokers were more than twice as likely as nonsmokers to use sterilization (P = 0.002). Among women over age 30, prevalence of contraceptive use was similar between the two groups. Oral contraceptives were used by fewer smokers than nonsmokers who were under age 24 (P = 0.01), had a high school education or less (P = 0.01), and/or had never been pregnant (P = 0.03)., Conclusions: Young, sexually active women who smoked cigarettes were less likely than nonsmokers to have used contraceptives, especially oral contraceptives, while women smokers over age 30 were more likely than nonsmokers to have used sterilization.

Background: Studies that have investigated the association between exposure to passive smoke and increased risk for disease have had inconclusive results and have raised questions about whether women exposed to passive smoke differ from those not exposed., Methods: The study population included 120 women nonsmokers who reported that they had been exposed to passive smoke in the 24 hr prior to the interview and 213 women who reported no exposure. Women were queried about demographic, lifestyle, sexual, and reproductive factors., Results: Exposed women were younger, less educated, and slightly heavier than nonexposed women. They were more likely to be divorced or separated (OR = 3.3, 95% CI = 1.4-7.6, P = 0.005), to have had first intercourse at or before age 16 (OR = 1.4, 95% CI = 1.0-1.9, P = 0.04), and to have had three or more live births (OR = 2.9, 95% CI = 1.2-6.8, P = 0.02). Women exposed to passive smoke were more likely to have consumed two or more cups of coffee (OR = 2.0, 95% CI = 1.1-3.8, P = 0.03), two or more glasses of beer (OR = 3.7, 95% CI = 1.1-12.5, P = 0.03), or to have smoked marijuana in the past 24 hr (OR = 14.7, 95% CI = 1.8-122.3, P = 0.01) than women who were not exposed. There were no differences noted between exposed and nonexposed women in history of gynecologic diseases or number of cervical microorganisms., Conclusion: Women exposed to passive smoke differed from those not exposed on several factors that should be considered in future studies that seek to investigate smoking-related disease risk.

To clarify the biological and clinical behavior and prognosis of mixed gliomas, 47 patients underwent intraoperative bromodeoxyuridine (BrdU) labeling studies. The mean age was 27.8 years at symptom onset and 31.8 years at labeling (median, 36 years). Forty-five tumors were supratentorial, 30 were frontal, and two were cerebellar; 16 were recurrent at labeling. The median labeling index (LI) was 1% (range, < 1 to 15.1%). Forty-six tumors has oligodendroglial and astrocytic elements, and one had astrocytic and ependymal elements. The median LI was 4.4% in recurrent tumors and < 1% in primary tumors. A higher BrdU LI correlated with an increased risk of recurrence and a shorter time to recurrence. During a median follow-up of 16 months, four patients died; each had a BrdU LI > or = 4.4%. The median time to recurrence was 4.5 months for tumors with BrdU LI's > 5% but was not reached for tumors with LI's < 5% (p < 0.003). The histologic grade of the oligodendroglial component correlated with the median time to recurrence (8 months for Smith Grade C tumors, not reached for Smith Grade B tumors; p < 0.05); there were too few cases to evaluate the median times to recurrence of Smith Grade A and Grade D tumors. The median time to recurrence was not reached for any astrocytic grade, and there were no significant differences in the Kaplan-Meier survival curves. These findings suggest that the BrdU LI and the grade of the oligodendroglial component of mixed gliomas have prognostic significance.

To determine the amount of blood lost, the number of transfusions, and the effectiveness of preoperative autologous blood donation in radical prostatectomy, 163 patients' records from 1987 to 1991 were reviewed at four university hospitals and three community hospitals. Calculated red cell volume lost was 1003 +/- 535 mL (mean +/- SD), which corresponds to 44 +/- 18 percent (mean +/- SD) of total red cell volume. Preoperative donation of blood for autologous use reduced the rate of transfusion of allogeneic blood from 66 to 20 percent (p < 0.001). Of the patients who donated 1 to 2 units, 32 percent received allogeneic blood; 14 percent of those who donated 3 units received allogeneic blood. Donation of 4 units reduced the allogeneic transfusion rate to 11 percent. However, as the number of units donated increased (1-3 units), the units not transfused also increased (0-21%). Ninety-one (56%) of 163 patients donated fewer than 3 units. Autologous blood donation is effective in minimizing the transfusion of allogeneic blood to radical prostatectomy patients, but many patients do not donate enough blood (< 3 units). The donation of 3 units of blood for autologous use is recommended for patients who undergo radical prostatectomy.