Epidemiological and diagnostic aspects of feline leishmaniasis with emphasis on Brazil: a narrative review.

The leishmaniases are a group of diseases caused by the protozoan parasite belonging to the genus Leishmania. In the New World, although dogs are considered the main parasite reservoir, in the last two decades, several studies have confirmed the role of cats (Felis catus) in the epidemiology of the disease and feline leishmaniasis (FeL) is now considered to be an emerging disease. The present review summarizes the current knowledge about FeL, focusing on important immunopathological aspects, epidemiology, and diagnostic methods applied for felines in Brazil. Cats are infected with the same species of Leishmania found in dogs (i.e., Leishmania infantum). Like dogs, skin lesions are the most common in cats with clinical FeL, mainly affecting the cephalic region and less frequently the legs which may be accompanied by generalized signs or visceral involvement. Information on the immune response of cats to Leishmania infection is scarce; however, efficient infection control is seen in most cases. For diagnosis, generally, the same methods as those in dogs are used, mainly serological tools. But there is a lack of studies focusing the performance of these methods for diagnosing FeL. The estimated overall prevalence of FeL in Brazil is 8%, with L. infantum being the most prevalent species. However, infections with Leishmania braziliensis and Leishmania amazonensis have also been reported. In conclusion, although there has been an increase in the publication related to FeL in Brazil in recent years, there is a lack of research relating immune response and diagnosis of these animals. Cats have been shown to be competent hosts for Leishmania parasites, and their role in the epidemiology of the disease cannot be underestimated, especially in areas of Brazil where the disease is historically endemic.

Pilot study to evaluate a plasma device for the treatment of onychomycosis.

Onychomycosis is a fungal infection of the nail unit, and is the most common of the nail disorders. Current therapies for onychomycosis have less than ideal efficacy and have the potential for adverse effects. As previous studies have shown that nonthermal plasma inhibits the in vitro growth of Trichophyton rubrum, we conducted a pilot study on 19 participants with toenail onychomycosis. The primary endpoint was safety of the device, and secondary outcome measures were clinical efficacy and mycological cure. Patient satisfaction was measured using questionnaires at the completion of the study. All but one patient met the primary endpoint of safety and there were no long-term sequelae. The overall clinical cure was 53.8% and the mycological cure was 15.4%. The majority of patients were satisfied with the treatment. Our conclusions are that nonthermal plasma is a safe treatment and may have a beneficial effect on toenail onychomycosis.

Clinical comparison and complete cure rates of Terbinafine efficacy in affected onychomycotic toenails.

BACKGROUND: Clinical studies regarding complete cure rate of onychomycosis using oral Terbinafine have a very broad range (14-90%) based solely on response to treatment on the big toenail. OBJECTIVE: To evaluate the efficacy of Terbinafine in all affected onychomycotic toenails and, furthermore, to evaluate differences in mycological, clinical and complete cure rate between affected onychomycotic toenails. PATIENTS AND METHODS: Inclusion criteria are as follows: distolateralsubungual onychomycotic involvement of the hallux and additional involvement of at least two more toenails of the same foot. Exclusion criteria are as follows: patients with nail traumata and hypersensitivity to Terbinafine. Patients were treated with oral Terbinafine 250 mg/day for 16 weeks. Mycological analysis was performed using direct microscopy and culture. Clinical improvement was assessed using digital photography. RESULTS: Statistically significant difference was found in clinical improvement between the great toenail and all other involved toenails. The rate of complete cure (100% clinical cure and mycological cure) of the big toenail was lower (23%) as compared to the second (65%), third (51%) and the fourth toenail (67%). LIMITATIONS: This is a case series study that was based on a single-centre cohort. CONCLUSIONS: Our results support findings that efficacy of Terbinafine should be based on all involved onychomycotic toenails; the big toenail is not superior in response compared to other affected toenails.

Expression of glyceraldehyde 3-phosphate dehydrogenase is enhanced in Leishmania spp naturally resistant to nitric oxide.

Leishmania spp are the causative agents of a spectrum of diseases termed leishmaniasis that affect mammals, including humans and dogs. Although reactive nitrogen species are employed in the control of parasitism by the immune system, it is known that Leishmania can withstand this oxidative stress. As the mechanism by which these species are resistant to nitric oxide (NO) is poorly understood, the main objective of this study was to evaluate the expression of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) in Leishmania amazonensis and Leishmania chagasi promastigotes showing natural resistance to NO. GAPDH transcript levels were quantified by real-time polymerase chain reaction amplification, and GAPDH activity (assessed by levels of NADH oxidation) was measured by spectrophotometry. The level of nitration in total protein was assessed by immunoblotting. The results demonstrated an increase in GAPDH expression in resistant isolates of both species compared to susceptible isolates. The increase in GAPDH expression led to an increase in the activity of GAPDH in L. amazonensis human isolates resistant to NO. The pattern of protein nitration did not differ between sensitive and resistant isolates. Our results suggest that changes in expression of GAPDH may be responsible, at least in part, to natural resistance to NO found in human and canine Leishmania spp.

Repellency and Larvicidal Activity of Essential oils from Xylopia laevigata, Xylopia frutescens, Lippia pedunculosa, and Their Individual Compounds against Aedes aegypti Linnaeus.

In order to find new alternatives for vector control and personal protection, we evaluated the larvicidal and repellent activity of essentials oils from plants found in the Northeast of Brazil against Aedes aegypti Linnaeus mosquitoes. The plants tested include Xylopia laevigata, Xylopia frutescens, and Lippia pedunculosa and their major compounds, piperitenone oxide, and (R)-limonene. The essential oil of L. pedunculosa and its major volatile compounds were shown to be toxic for Ae. aegypti larvae with a LC50 lower than 60 ppm. The essential oil of plants from the Xylopia genus, on the other hand, showed no activity against Ae. aegypti, proving to be toxic to mosquito larvae only when concentrations were higher than 1000 ppm. All plants tested provided some degree of protection against mosquitoes landing, but only the essential oil of L. pedunculosa and the volatile compound piperitenone oxide suppressed 100% of mosquitoes landing on human skin, in concentrations lower than 1%. Among the plants studied, the essential oil of L. pedunculosa and its volatiles compounds have shown the potential for the development of safe alternative for mosquito larvae control and protection against Ae. aegypti mosquito bites.

Phase II study of estramustine and vinblastine, two microtubule inhibitors, in hormone-refractory prostate cancer.

PURPOSE: Estramustine phosphate (EMP) and vinblastine are two microtubule inhibitors with distinct molecular targets and at least additive antimicrotubule effects in vitro. Their modest single-agent activities in hormone-refractory prostate cancer, nonoverlapping toxicities, and lack of cross-resistance prompted a phase II trial in hormone-refractory prostate cancer. PATIENTS AND METHODS: Thirty-six assessable patients at the Fox Chase Cancer Center and seven Fox Chase Cancer Center Network institutions were treated with oral EMP 600 mg/m2 on days 1 to 42 and vinblastine 4 mg/m2 intravenously (IV) once a week for 6 weeks. Courses were repeated every 8 weeks. Response assessment was based on a change in serum prostate-specific antigen (PSA) levels and was correlated with change in pain scores. RESULTS: PSA decreased from baseline by at least 50% in 22 patients (61.1%) and by > or = 75% in eight patients (22.2%). A 50% or more decrease in PSA on three successive 2-week measurements together with an improved or stable pain score, performance status, and measurable soft tissue disease (if present) was required for a partial response (PR), which occurred in 11 patients for an overall response rate of 30.5% (95% confidence interval, 15.6% to 45.6%). In seven patients with measurable nonosseous disease, there was one PR (14%) and one minor response (MR). In 28 patients with assessable pain, major pain responses occurred in 12 (42.9%). PSA response (> or = 50% decrease times three measurements) was predictive of major pain response with a 93.7% specificity, a 50% sensitivity, and a positive predictive value of 85.7%. CONCLUSION: We conclude that EMP and vinblastine is an active combination in hormone-refractory prostate cancer.

Phase II trial of topotecan as a 21-day continuous infusion in patients with advanced or metastatic adenocarcinoma of the pancreas.

The aim of this study was to determine the efficacy and toxicity of topotecan administered as a 21-day continuous intravenous infusion in patients with advanced or metastatic adenocarcinoma of the pancreas. 26 previously untreated patients with advanced or metastatic pancreatic adenocarcinoma received topotecan at a dose of 0.5 mg/m2/day or 0.6 mg/m2/day as a continuous intravenous infusion for 21 days. Courses were repeated every 28 days. 26 patients were assessable for response and toxicity on an intent-to-treat basis. The initial 8 patients at a starting dose of 0.6 mg/m2/day experienced unacceptable myelosuppression and dose delays. The subsequent 18 patients, therefore began therapy at a dose of 0.5 mg/m2/day. The major toxicity of topotecan at this dose and schedule was myelosuppression, which was reversible and non-cumulative. There were no complete responses and two partial responses for a total response rate of 8% (95% confidence interval, 1-25%). Response durations were 17 and 45 weeks. Stable disease was seen in 3 patients. The median time to progression for all patients was 8 weeks and the median survival was 20 weeks. Topotecan given as a 21-day continuous intravenous infusion has a similar response rate and median survival to our previously reported study of the 5-day short infusion regimen in pancreatic carcinoma.

Tumor hypoxia adversely affects the prognosis of carcinoma of the head and neck.

PURPOSE: Tumor hypoxia adversely affects short term clinical radiation response of head and neck cancer lymph node metastases and long term disease-free survival (DFS) in cervix carcinoma. This study was performed to evaluate the relationship between tumor hypoxia and DFS in patients with squamous carcinoma of the head and neck (SCCHN). METHODS AND MATERIALS: Pretreatment tumor pO2 was assessed polarographically in SCCHN patients. All patients were AJCC Stage IV and had pretreatment oxygen measurements taken from locally advanced primaries (T3 or T4) or neck nodes > or = 1.5 cm diameter. Treatment consisted of once daily (2 Gy/day to 66-70 Gy) or twice daily irradiation (1.25 Gy B.I.D. to 70-75 Gy) +/- planned neck dissection (for > or = N2A disease) according to institutional treatment protocols. RESULTS: Twenty-eight patients underwent tumor pO2 measurement. The average pre-treatment median pO2 was 11.2 mm Hg (range 0.4-60 mm Hg). The DFS at 12 months was 42%. The DFS was 78% for patients with median tumor pO2 > 10 mm Hg but only 22% for median pO2 < 10 mm Hg (p = 0.009). The average tumor median pO2 for relapsing patients was 4.1 mm Hg and 17.1 mm Hg in non-relapsing (NED) patients (p = 0.007). CONCLUSION: Tumor hypoxia adversely affected the prognosis of patients in this study. Understanding of the mechanistic relationship between hypoxia and treatment outcome will allow for the development of new and rational treatment programs in the future.

Preoperative chemoradiation for adenocarcinoma of the pancreas and duodenum.

PURPOSE: This study was designed to evaluate the effects of preoperative chemoradiation on resectability, response, local control, and survival in patients with local or local-regional involvement from carcinoma of the pancreas or cancer of the duodenum and to assess the associated toxicity of such treatment. METHODS AND MATERIALS: This prospective pilot study of preoperative chemoradiation was initiated in 1986 for patients with clinical evidence of adenocarcinoma of the pancreas or duodenum without evidence of distant metastases. Radiation was given at 1.8 Gy per day to a total dose of 50.4 Gy. Two cycles of chemotherapy were given concurrent with radiation. On days 2-5 and 29-32, 5-fluorouracil (1 gm/m2/24 h x 4 days) was given, while mitomycin-C (10 mg/m2) was given on day 2 only. Surgical resection was 4-6 weeks following completion of chemoradiation. Thirty-one patients (17 male and 14 female) were entered on the protocol with a median potential follow-up of 4.5 years (range 6 months to 7.5 years). The median age was 64 years (range 32-73 years). Twenty-seven patients had pancreatic cancer (25 head, two body), while four patients had carcinoma arising from the duodenum. Twenty-one patients were initially judged to be unresectable and ten potentially resectable prior to chemoradiation. RESULTS: Twenty-nine of 31 patients completed the entire course of radiation and both cycles of chemotherapy. Acute toxicity from chemoradiation consisted of nausea, vomiting, diarrhea, stomatitis, or hematologic suppression which was moderate to severe (Grade 3 or 4) in seven patients (23%). One patient died of sepsis following the first week of therapy. Seventeen patients (55%) underwent curative resection with subtotal or total pancreatectomy or Whipple resection (four duodenum, 13 pancreas) and two (2/17) had pathologic nodal involvement, while (0/17) none had involved margins. A complete pathologic response was seen in all four (4/4) patients with duodenal cancer and in none (0/13) with pancreatic cancer who underwent resection. The median postoperative hospitalization stay was 22 days (range 4-144 days). Of 17 patients who underwent curative resection, there were two postoperative mortalities (12%). Late complications have included abscess, one; and nonmalignant ascites, five. Ten of the 31 patients are alive. For patients with pancreatic cancer the median survival is 9 months, while survival at 1 year and 3 years are 36% and 19% overall and 60% and 43% at 1 and 3 years for those undergoing resection. Six of the 27 patients (22%) with pancreatic cancer are alive without recurrence. All four patients with duodenal cancer are alive without recurrence (12 months, 23 months, 35 months, 90 months). CONCLUSION: Preoperative chemoradiation for cancer of the pancreas and duodenal region was relatively well-tolerated and enhanced resectability and downstaging of nodal metastases were suggested. The 3-year survival, particularly in patients who underwent resection, was high. For these reasons the applicability of this treatment regimen for pancreatic cancer is presently being studied in a group-wide multi-institutional Phase II trial. Chemoradiation for duodenal cancer has produced a complete pathologic response in all patients and survival has been excellent, suggesting efficacy of this regimen for duodenal cancer.

Elevated tumor lactate concentrations predict for an increased risk of metastases in head-and-neck cancer.

PURPOSE: Hypoxia shifts the balance of cellular energy production toward glycolysis with lactate generation as a by-product. Quantitative bioluminescence imaging allows for the quantitation of lactate concentrations in individual tumors. We assessed the relationship between pretreatment tumor lactate concentrations and subsequent development of metastatic disease in patients with newly diagnosed head-and-neck cancer. METHODS AND MATERIALS: At the time of biopsy of the primary site, a separate specimen was taken and flash-frozen for subsequent quantitation of lactate concentration using a luciferase bioluminescence technique. The two-dimensional spatial distribution of the bioluminescence intensity within the tissue section was registered directly using a microscope and an imaging photon counting system. Photon intensity was converted to distributions of volume-related tissue concentrations (micromol per gram wet weight). Treatment consisted of either surgery and postoperative radiotherapy or primary radiotherapy, based on presenting disease stage and institutional treatment policies. The subsequent development of metastatic disease constituted the primary clinical endpoint. RESULTS: Biopsies obtained from 40 patients were evaluable in 34. The larynx was the most frequent primary site (n = 25). Other sites included oropharynx (n = 5), hypopharynx (n = 3), and oral cavity (n = 1). Most patients (74%) presented with an advanced stage T3 or T4 primary tumor. Nodal involvement was present in 19 (54%) patients. The median tumor lactate concentration was 7.1 micromol/g. Tumors were classified as having either low or high lactate concentrations according to whether these values were below or above the median. The median follow-up time for surviving patients is 27 months. Two-year actuarial survival was 90% for patients with low-lactate-concentration tumor vs. 35% for patients with high-lactate-concentration primaries (<0.0001). Two-year metastasis-free survival was adversely influenced by high tumor lactate concentrations (90% vs. 25%, p < 0.0001). The median lactate concentration for tumors that subsequently metastasized was 12.9 micromol/g vs. 4.8 micromol/g for patients who remained continuously free of disease (p < 0.005). Lactate concentration was not correlated with presenting T stage or N stage. DISCUSSION: Elevated tumor lactate concentrations are associated with the subsequent development of nodal or distant metastases in head-and-neck cancer patients. This more aggressive malignant phenotype is probably associated with hypoxia-mediated radioresistance and the upregulation of metastasis-associated genes.

Phase I dose escalating trial of hyperfractionated pre-operative chemoradiation for locally advanced rectal cancer.

PURPOSE: To determine the acute toxicity, post-operative complications, pathologic response and extent of downstaging to high dose pre-operative radiation using a hyperfractionated radiation boost and concurrent chemotherapy in a prospective Phase I trial. MATERIALS & METHODS: To be eligible for this study, patients had to have adenocarcinoma of the rectum less than 12 cm from the anal verge with either Stage T4 or T3 but greater than 4 cm or greater than 40% of the bowel circumference. All patients received 45 Gy pelvic radiation (1.8 Gy per fraction). Subsequent radiation was given to the region of the gross tumor with a 2 cm margin. This "boost" treatment was given at 1.2 Gy twice daily to a total dose of 54.6 Gy for Level I, 57 Gy for Level II, and 61.8 Gy for Level III. 5-FU was given at 1g/m2 over 24 hours for a four day infusion during the first and sixth weeks of radiation, with the second course concurrent with the hyperfractionated radiation. Surgical resection was carried out 4-6 weeks following completion of chemoradiation (in curative cases) and additional adjuvant chemotherapy consisting of 5-FU and Leucovorin was given for an additional 4 monthly cycles Days 1 through 5 beginning four weeks post surgery. RESULTS: Twenty-seven patients, age 40-82 (median 61), completed the initial course of chemoradiation and are included in the analysis of toxicity. The median follow-up is 27 months (range 8-68). Eleven patients were treated to a dose of 54.6 Gy, nine patients to 57 Gy, and seven patients to 61.8 Gy. Twenty-one patients had T3 tumors, and six patients T4 tumors. Grade III acute toxicity from chemoradiation included proctitis (5 patients), dermatitis (9), diarrhea (five), leukopenia (1), cardiac (1). Grade IV toxicities included one patient with diarrhea (on dose Level I) and one patient (on dose Level III) with cardiac toxicity (unrelated to radiation). Surgical resection consisted of abdominal perineal resection in 16 and low anterior resection in 7. Four patients did not undergo a curative resection; three initially presented with metastases and one developed metastasis during the pre-operative regimen. Post-operative complications included pelvic or perineal abscess in two (on dose Levels I & II), and delayed wound healing in two (one of whom, on dose Level III, developed perineal wound dehiscence requiring surgical reconstruction). Of the 23 patients who had a curative resection, four manifested pathologic complete responses (17.4%). Thirteen of 23 patients (57%) had evidence of pathologic downstaging and only 1/23 patients (on dose Level I) had a positive resection margin. Of these 23 patients (with a minimum follow-up of 8 months), the patient with positive margins was the only one who developed a local failure (Fisher's Exact p=.04). The 3-year actuarial OS, DFS and LC rates are 82%, 72% and 96%, respectively. Twelve of 13 patients (92% at 3 years) > or = 61 years vs. 5/10 patients (45% at 3 years) < 61 years remained disease-free (log-rank p=0.017). CONCLUSION: This regimen of high dose pre-operative chemoradiation employing a hyperfractionated radiation boost is feasible and tolerable and results in significant downstaging in locally advanced rectal cancer. The vast majority of patients (96%) achieved negative margins, which appears to be a prerequisite for local control (p= 0.04). Older age (> or =61 years) was a significant predictor for improved DFS. This regimen (at dose Level III, 61.8 Gy) is currently being tested in a Phase II setting.

Effects of abstinence and smoking on information processing in adolescent smokers.

RATIONALE: Although adolescent smokers appear to display some of the hallmark features of dependence, the biological and behavioral effects of smoking in this population are poorly understood. OBJECTIVES: This study aimed to define empirically the effects of abstinence and smoking in adolescent smokers, using indices validated in adult smokers. METHODS: Subjects were 16 young novice smokers (five male, 11 female), ages 14-18 years. A modified Stroop task measured the ability to inhibit attention to smoking-related cues; the classic Stroop task measured the ability to inhibit a pre-potent response (i.e. reading a word); a rapid information processing (RIP) task measured vigilance. RESULTS: Abstinence increased and smoking decreased the intrusiveness of smoking cues. Parallel effects were seen in commission errors on the RIP task. These effects were restricted to heavier smokers (>11 cigarettes/day). Subjective withdrawal effects predicted the intrusiveness of smoking words during abstinence. The number of cigarettes smoked per day predicted the beneficial effect of smoking on the classic as well as modified Stroop tasks. The physiological effects of abstinence and smoking predicted RIP performance. CONCLUSIONS: Abstinence impairs and smoking improves inhibitory information processing in young novice smokers in a manner similar to adult smokers. Daily frequency of smoking is a critical moderator of these effects.

Response of psoriatic nails to oral photochemotherapy.

Ten patients with generalized psoriasis, which included nail involvement, were treated with total-body oral photochemotherapy. A combination of methoxsalen and high-intensity ultraviolet A radiation was employed and its therapeutic efficacy in nail psoriasis ascertained. Among the ten patients, there were 26 instances of the following nail signs: pitting, onycholysis, "oil drop" change, subungual hyperkeratosis, nail-plate crumbling, proximal nail-fold psoriasis, and onychorrhexis. Of the 26, eighteen improved by 50% or more. Only pitting failed to respond to therapy in all of the eight patients who had this change.

Pachyonychia congenita tarda. A late-onset form of pachyonychia congenita.

Pachyonychia congenita is an autosomal dominant disorder that usually develops in early infancy. We have observed five patients with the onset of the typical subungual hyperkeratoses of pachyonychia during the teenage years. Leukokeratosis and keratoderma of the palms and soles were associated. The family history of three of the patients suggests that pachyonychia congenita tarda is also inherited in an autosomal dominant manner.

Histologic evaluation of nail clippings for diagnosing onychomycosis.

Nail clippings from patients suspected of having onychomycosis were processed for histologic evaluation in the same manner as routine skin with the addition of a chitin-softening solution prior to processing. The sections were stained by the periodic acid-Schiff method and examined for fungal hyphae. The results were compared with the results of fungal cultures from the same nail. Our findings indicate that routine histopathologic analysis of the nail plate alone is a useful complementary method to fungal culture for diagnosing onychomycosis.

Subungual tumors in incontinentia pigmenti.

A 22-year-old woman presented with intermittently painful subungual keratotic tumors of the hands as a late manifestation of incontinentia pigmenti. Scalloped bony deformities of the distal phalanges of both hands were noted on roentgenograms. The origin of these lytic deformities is uncertain; they may be secondary pressure phenomena or, alternatively, they may be an intrinsic manifestation of incontinentia pigmenti. These subungual tumors clinically resemble verrucae, keratoacanthomas, squamous cell carcinomas, or subungual fibromas. Therefore, it is important to recognize that subungual keratotic tumors may be a late manifestation of incontinentia pigmenti.

The clinical significance of periodic acid-Schiff-positive deposits in cuticle-proximal nail fold biopsy specimens.

In vivo capillary microscopic findings and proximal nail fold biopsy specimens from 19 patients with various connective tissue diseases, idiopathic Raynaud's phenomenon, and non-connective tissue diseases were studied. Periodic acid-Schiff-positive serous cuticular deposits were not specific to the group of patients with connective tissue disease. Generally, the severity of deposits correlated with the severity of the in vivo capillary microscopic pattern but not with disease severity or duration. The finding of these cuticular deposits may help to identify those patients with idiopathic Raynaud's phenomenon who are at risk to develop a connective tissue disease.

Increased aqueous lactate dehydrogenase in Coats' disease.

A 3-year-old boy had glaucoma and a total left retinal detachment that displayed peripheral intraretinal telangiectasis. The most probable clinical diagnosis was Coats' disease. A suspicion of retinoblastoma also existed, and an aqueous aspirate was assayed for lactate dehydrogenase (LDH) and found to contain three times the level present in a matching sample of serum. We enucleated the eye and verified the diagnosis of Coats' disease pathologically. The results of aqueous LDH determinations in eyes with glaucoma, phthisis, or large numbers of histiocytes, erythrocytes, and polymorphonuclear leukocytes should be interpreted with caution.

Acute subjective and physiological responses to smoking in adolescents.

AIMS: To determine the topography of cigarette smoking and the subjective and physiological effects of abstinence and nicotine in adolescents who smoke on a daily versus a non-daily basis. DESIGN: Repeated measures experiment, non-blinded, involving a single test session. SETTING: Human psychopharmacology laboratory. PARTICIPANTS: Twenty-one daily and 21 non-daily adolescent cigarette smokers (21 females; 21 males; age 13-18 years) with life-time use greater than 10 cigarettes, responding to radio and print advertisements. INTERVENTION: Overnight abstinence from cigarettes followed by smoking of a single cigarette furnished by the participant at test. MEASUREMENTS: The Fagerstrom Test for Nicotine Dependence, saliva nicotine and cotinine, expired air carbon monoxide (CO), heart rate (HR), self-report scales and smoking topography. Most measurements were performed before and after smoking. FINDINGS: Saliva nicotine, CO and HR increased, and self-reported intention and desire to smoke decreased, after smoking (p < 0.001). Fagerstrom scores indicated greater dependence and desire to smoke in daily than in non-daily smokers. HR increased substantially over pre-smoking levels in both groups. Puff topography did not differ between the groups, although collectively these participants appeared to take smaller and more puffs than adult smokers tested under similar conditions. CONCLUSION: This study provides initial evidence that adolescent cigarette smokers self-administer physiologically active doses of nicotine very early in their smoking careers. Nicotine dependence in adolescents appears to be a function of the current frequency of cigarette use, and subjective-behavioral consequences of abstinence and smoking are evident even in non-daily smokers.