Line-field confocal optical coherence tomography for the in vivo real-time diagnosis of different stages of keratinocyte skin cancer: a preliminary study.

BACKGROUND: The treatment of keratinocyte cancers (KC) strictly depends on their differentiation and invasiveness. Non-invasive diagnostic techniques can support the diagnosis in real time, avoiding unnecessary biopsies. This study aimed to preliminarily define main imaging criteria and histological correlations of actinic keratosis (AK), Bowen's disease (BD) and squamous cell carcinoma (SCC) using the novel device line-field confocal optical coherence tomography (LC-OCT). METHODS: Dermoscopy and LC-OCT images of 73 histopathologically confirmed lesions (46 AKs, 11 BD and 16 SCCs) were included in the study. Exemplary lesions (10 AKs, 5 BD and 5 SCCs) were additionally investigated with optical coherence tomography and reflectance confocal microscopy. RESULTS: Most common LC-OCT findings of KC in the descriptive statistics were hyperkeratosis/parakeratosis, disruption of stratum corneum, broadened epidermis, basal and suprabasal keratinocyte atypia, dilated vessels/neoangiogenesis and elastosis/collagen alterations. In the univariate multinomial logistic regression, a preserved DEJ was less common in SCC compared with AK and BD, BD displayed marked keratinocyte atypia involving all epidermal layers (bowenoid pattern), while SCC showed ulceration, increased epidermal thickness, keratin plugs, acantholysis, not visible/interrupted DEJ and epidermal bright particles. LC-OCT increased the diagnostic confidence by 24.7% compared with dermoscopy alone. CONCLUSIONS: Our study describes for the first time specific LC-OCT features of different stages of KC and their histopathological correlates, focusing on keratinocyte morphology and architecture of the epidermis and DEJ. LC-OCT may open new scenarios in the bedside diagnosis, treatment planning and follow-up of KC.

Line-field optical coherence tomography: in vivo diagnosis of basal cell carcinoma subtypes compared with histopathology.

BACKGROUND: Basal cell carcinoma (BCC) is the most common skin cancer in the general population. Treatments vary from Mohs surgery to topical therapy, depending on the subtype. Dermoscopy, reflectance confocal microscopy (RCM) and optical coherence tomography (OCT) have gained a foothold in daily clinical practice to optimize diagnosis and subtype-oriented treatment. The new technique of line-field confocal OCT (LC-OCT) allows imaging at high resolution and depth, but its use has not yet been investigated in larger studies. AIM: To evaluate the main LC-OCT criteria for the diagnosis and subtyping of BCC compared with histopathology, OCT and RCM. METHODS: In total, 52 histopathologically confirmed BCCs were evaluated for imaging criteria. Their frequency, predictive values and ROC curves were calculated. A multinominal regression with stepwise variables selection to distinguish BCC subtypes was performed. RESULTS: Nodular BCCs were mainly characterized by atypical keratinocytes, altered dermoepidermal junction (DEJ), tumour nests in the dermis, dark clefting, prominent vascularization and white hyper-reflective stroma. Superficial BCCs showed a thickening of the epidermis due to a series of tumour lobules with clear connection to the DEJ (string of pearls pattern). Infiltrative BCCs were characterized by elongated hyporeflective tumour strands, surrounded by bright collagen (shoal of fish pattern). The overall BCC subtype agreement between LC-OCT and conventional histology was 90.4% (95% CI 79.0-96.8). CONCLUSION: LC-OCT allows noninvasive, real-time identification of BCCs and their subtypes in vertical, horizontal and three-dimension mode compared with histology, RCM and OCT. Further larger studies are needed to better explore the clinical applications of this promising device.

Daily mortality and air pollution in Atlanta: two years of data from ARIES.

Associations between daily mortality and air pollution were investigated in Fulton and DeKalb Counties, Georgia, for the 2-yr period beginning in August 1998, as part of the Aerosol Research and Inhalation Epidemiological Study (ARIES). Mortality data were obtained directly from county offices of vital records. Air quality data were obtained from a dedicated research site in central Atlanta; 15 separate air quality indicators (AQIs) were selected from the 70 particulate and gaseous air quality parameters archived in the ARIES ambient air quality database. Daily meteorological parameters, comprising 24-h average temperatures and dewpoints, were obtained from Atlanta's Hartsfield International Airport. Effects were estimated using Poisson regression with daily deaths as the response variable and time, meteorology, AQI, and days of the week as predictor variables. AQI variables entered the model in a linear fashion, while all other continuous predictor variables were smoothed via natural cubic splines using the generalized linear model (GLM) framework in S-PLUS. Knots were spaced either quarterly, monthly, or biweekly for temporal smoothing. A default model using monthly knots and AQIs averaged for lags 0 and 1 was postulated, with other models considered in sensitivity analyses. Lags up to 5 days were considered, and multipollutant models were evaluated, taking care to avoid overlapping (and thus collinear) AQIs. For this reason, PM(2.5) was partitioned into its three major constituents: SO(2-)(4), carbon (EC + 1.4 OC), and the remainder; sulfate was assumed to be (NH(4))(2)SO(4) for this purpose. Initial AQI screening was based on all-cause (ICD-9 codes <800) mortality for those aged 65 and over. For the (apparently) most important pollutants--PM(2.5) and its 3 major constituents, coarse PM mass [CM], 1-h maximum CO, 8-h maximum O(3)--we investigated 15 mortality categories in detail. (The 15 categories result from three age groups [all ages, <65, 65+] and five cause-of-death groups [all disease causes, cardiovascular, respiratory, cancer, and other "remainder" disease causes]). The GLM model outputs that were considered included mean AQI effects and their standard errors, and two indicators of relative model performance (deviance and deviance adjusted for the number of observations and model parameters). The latter indicator was considered to account for variations in the number of observations created by varying amounts of missing AQI data, which were not imputed. The single-AQI screening regressions on all-cause 65+ mortality show that CO, NO(2), PM(2.5), CM, SO(2), and O(3), followed by EC and OC, consistently have the best model fits, after adjusting for the number of observations. Their relative rankings, however, vary according to the smoothing knots used, and there is no correspondence between mean AQI effect and overall model fit.(Other regression runs often show that the best model fits are obtained with no AQI in the model.) There is no correspondence between mean AQI effect and statistical significance or between mean effect and serial correlation. There is a highly significant (.001 level) relationship between overall model fit and serial correlation; the best fitting models have the most frequent knot spacing and the most negative serial correlation. The regression analyses by cause of death find elderly circulatory deaths to be consistently associated with CO for all models.

Patient-administered tampon-collected genital cells in the assessment of Chlamydia trachomatis infection using polymerase chain reaction.

BACKGROUND: Diagnosis of genital Chlamydia trachomatis infection in women traditionally requires a speculum examination to collect endocervical cells, followed by cell culture. This method is time consuming, requires stringent transport conditions, and is technically demanding. GOALS: To compare tampons as a patient-administered collection method followed by detection with polymerase chain reaction (PCR) with the traditional endocervical swab culture followed by cell culture detection. STUDY DESIGN: At the emergency department of a hospital for obstetrics and gynecology, 1,000 consecutive women with symptoms suggestive of infection with C. trachomatis were tested for C. trachomatis infection by PCR on both tampon (PCR-T) and swab (PCR-S) specimen and by culture of the swab specimen. RESULTS: Seventeen PCR-T and 16 PCR-S specimens were positive; 16 endocervical specimens were positive by culture, and 14 of the endocervical samples were positive by the three methods. Sixty-one PCR-S samples were inadequate as shown by the lack of amplification of the beta-globin gene segment, indicating poor collection of specimens by endocervical swab for chlamydial testing. CONCLUSIONS: Tampon specimens collected for PCR detection provided an easy and sensitive method of detection of C. trachomatis and overcame the obstacle of endocervical sampling and subsequent stringent transport requirements of culture.

Increased detection of hepatitis C virus infection in commercial plasma donors by a third-generation screening assay.

BACKGROUND: Routine screening of blood donations with second-generation hepatitis hepatitis C virus (HCV) assays has substantially reduced the occurrence of posttransfusion hepatitis. However, following the development of third-generation assays, several studies indicated that these assays may identify HCV-infected individuals who are not identified by second-generation assays. STUDY DESIGN AND METHODS: The sensitivity of a third-generation HCV enzyme-linked immunosorbent assay (ELISA-3) was compared with a second-generation ELISA (ELISA-2) in a side-by-side study of 9936 commercial blood donors. ELISA-reactive specimens were subjected to supplemental analysis by third-generation recombinant immunoblot assay and polymerase chain reaction. RESULTS: ELISA-3 demonstrated greater sensitivity than ELISA-2, detecting 1 additional recombinant immunoblot assay-positive specimen per 2000 tested. ELISA-3 also detected 1 additional HCV-infectious polymerase chain reaction-positive unit among approximately 10,000 units screened. CONCLUSION: The incremental sensitivity achieved with ELISA-3 can be expected to eliminate approximately 20 infectious donations per week among those made by commercial donors in the United States. In accordance with previous studies, most of the improved sensitivity of ELISA-3 derives from its increased detection of anti-c33c (NS3), rather than from the inclusion of HCV antigen NS5.

Endocrine and neurochemical effects of (+)-PHNO, a dopamine D2 agonist.

The naphthoxazine compound, (+)-PHNO, is a dopamine D2 receptor agonist which acts within the central nervous system. The effects of this drug on serum concentrations of corticosterone and prolactin and on brain concentrations of catecholamines and some of their metabolites were determined in male rats. Administration of (+)-PHNO in doses ranging from 3-300 micrograms/kg i.p. resulted in increased serum corticosterone, decreased serum prolactin and decreased concentrations of the dopamine metabolites, DOPAC and HVA, in the brain. At the higher doses of (+)-PHNO, concentrations of MHPG sulfate in the brain stem were increased and hypothalamic epinephrine concentrations were decreased. Pretreatment with centrally acting dopamine antagonists (spiperone or haloperidol) prevented the (+)-PHNO-induced changes in serum corticosterone, prolactin and brain catecholamines. In contrast, pretreatment with halopemide, a dopamine antagonist which penetrates poorly into the brain, was unable to block the effects of (+)-PHNO on serum corticosterone and brain catecholamines. These data show that (+)-PHNO, a dopamine agonist structurally unrelated to other dopamine agonists, acts centrally to affect serum corticosterone and brain catecholamines.

Further characterization of tolerance to the corticosterone-elevating effect of pergolide in rats.

Four daily injections of pergolide, an ergoline dopamine agonist, made male rats tolerant to the corticosterone-elevating effects of an acute injection of pergolide on the fifth day. This tolerance occurred not only to acute treatment with pergolide, but also to other dopamine agonists differing in structure, potency and receptor subtype selectivity. Plasma corticosterone was elevated following administration of opioid or serotonin agonists in both vehicle- and pergolide-pretreated rats. The current findings strengthen the conclusion that tolerance to the acute elevation of corticosterone by pergolide is not due to impairment of pituitary-adrenocortical function but instead to changes in dopamine receptors that initiate the response.

Concentrations of luteinizing hormone, follicle stimulating hormone and prolactin following transection of the pituitary stalk in ovariectomized ewes.

Two experiments (Spring and Fall) were conducted in ovariectomized ewes to determine changes in pituitary hormone secretion immediately after pituitary stalk-transection. Ewes underwent either pituitary stalk-transection (SS), sham-transection (SH) or administration of anesthesia only (AO). Stalk-transected, but not sham-operated or anesthetized ewes had polyuria and polydipsia for 7 to 14 days after surgery. Concentrations of luteinizing hormone (LH), follicle stimulating hormone (FSH) and prolactin were measured in peripheral blood samples collected every 10 minutes for a six-hour period. Results were comparable for each season. During the six hours following surgery or removal from anesthesia, concentrations of LH declined in all ewes, but more slowly in SS ewes. No differences in patterns or mean concentrations of FSH were observed. Immediately after surgery, concentrations of prolactin were elevated, then declined in SH and SS ewes. The decrease was greater in SH than SS ewes. Data are consonant with the view that hypothalamic inhibition as well as LHRH stimulation regulate gonadotropin release by the pituitary.

Relationships between LH and estradiol-17 beta after removal of luteal progesterone in the ewe.

Three experiments were conducted to examine the relationship between systemic concentrations of luteinizing hormone (LH) and estradiol-17 beta (E2) after withdrawal of progesterone in cycling ewes. In Exp. 1, ewes were assigned randomly to one of three treatments: laparotomy (C), removal of the luteal ovary (ULO), or ULO plus anesthesia with sodium pentobarbital for 6 h beginning 4 h after surgery. Anesthesia was used in an attempt to block the expected increase in tonic secretion of LH. Patterns of LH and E2 in these three groups did not differ during the 24-h experimental period. In Exp. 2, a longer period of anesthesia was utilized. Forty-eight ewes were assigned at random to one of four treatments: C, ULO, lutectomy or an intrafollicular injection of prostaglandin F2 alpha (PGF2 alpha). One-half of the ewes in each group were anesthetized with sodium pentobarbital from initiation of treatment (0 h) until 10 h after surgery. Sodium pentobarbital did not suppress the increases in LH and E2 after progesterone withdrawal. The regression of concentrations of E2 on concentration of LH was not significant. In Exp. 3, ewes were infused with either saline or dopamine after receiving an im injection of PGF2 alpha. Tonic secretion of LH increased after 4 h in ewes infused with saline, but not in ewes infused with dopamine. Despite the suppression of LH, concentrations of E2 increased in dopamine-treated ewes as in control ewes. Therefore, the initial increase in E2 after a decline of progesterone in cycling ewes is independent of increases in LH.