Head and neck squamous cell carcinoma: evaluation of iodine overlay maps and low-energy virtual mono-energetic images acquired with spectral detector CT.

AIM: To evaluate the diagnostic value of spectral detector computed tomography (SDCT)-derived iodine overlay maps and low-energy virtual mono-energetic images (VMI) for the initial locoregional assessment of primary, therapy-naive head and neck cancer. MATERIALS AND METHODS: Fifty-six patients with histologically confirmed untreated squamous cell carcinoma of the head and neck who underwent SDCT of the neck for staging purposes were included in this retrospective study. Attenuation, image noise as well as signal- and contrast-to-noise ratios (S-/CNR) in VMI40-70keV were obtained from region of interest (ROI)-based measurements in the tumour and important anatomical landmarks (sternocleidomastoid muscle, subcutaneous fat, thyroid gland, submandibular gland, carotid artery, and jugular vein). Tumour conspicuity and delineation, as well as subjective image quality, were rated for conventional images, VMI40-70keV, and iodine overlay maps using five-point Likert scales. RESULTS: The CNR of the tumour versus the floor of the mouth and the CNR of the tumour versus the sternocleidomastoid muscle was significantly higher in VMI40keV in comparison to conventional images (10.0 ± 7.3 versus 3.8 ± 3.3 and 11.3 ± 7.6 versus 3.6 ± 2.8; p<0.05 each). This was supported by qualitative results, as tumour conspicuity and delineation received superior ratings in iodine overlay maps and VMI40keV compared to conventional images (5 [3-5] and 5 [4-5] versus 3 [2-5]; 5 [2-5] and 5 [3-5] versus 3 [2-4], respectively, all p<0.05). VMI40keV yielded the highest score among all included image reconstructions for overall image quality (p<0.05 all). CONCLUSION: Iodine overlay maps and low-energy VMI derived from SDCT improve initial assessment of primary squamous cell carcinoma of the head and neck compared to conventional images.

[Intraosseous foreign body or osteoma : Challenging differential diagnosis after open radius fracture]. / Intraossärer Fremdkörper oder Osteom : Anspruchsvolle Differenzialdiagnose nach offener Radiusfraktur.

Presentation of a 16-year-old male patient due to a cycling accident while mountain biking 14 days after primary treatment after open epiphyseal injury. Metaphyseal intraosseous stones within the anatomically reduced distal radius fracture were misinterpreted as an incidental osteoma.

Prevalence of an inflammation and necrosis syndrome in suckling piglets.

The current study describes the results obtained from clinical examination of over 4700 suckling piglets from 19 individual herds in Germany. In this cohort the prevalence of inflammation and necrosis in the tails, ears, claw coronary bands, heels and teats was determined using a pre-defined scoring system. Results show that already in the 1st days of life, piglets were affected by inflammation and necrosis of the heels (80%), claw coronary bands (50%) and tail base (20%). The praevalences of these alterations in piglets were influenced by genetics (P <0.001) and age, decreasing gradually in the 2nd week of life (P <0.001). Moreover, a correlation between tail length after tail docking and the prevalence of tail necrosis (P⩽0.04) was found. Tail and ear biting as a behavioural trait was not detected during this study. The early onset, appearance and multiple locations of clinical signs of inflammation and the positive correlation with the genetic background of the piglets may suggest an impairment of the innate immune system by infectious and non-infectious agents. This is in contrast to previously described behavioural abnormalities seen in fattening pigs. Considering the obvious reduction of animal welfare due to the described lesions, there is a need to create awareness among pig farmers and to understand the multifactorial causality involved in this inflammation and necrosis syndrome in piglets.

Population Pharmacokinetics of Liposomal Irinotecan in Patients With Cancer.

Nanoliposomal irinotecan (nal-IRI) is a liposomal formulation of irinotecan with a longer half-life (t1/2 ), higher plasma total irinotecan (tIRI), and lower SN-38 maximum concentration (Cmax ) compared with nonliposomal irinotecan. Population pharmacokinetic (PK) analysis of nal-IRI was performed for tIRI and total SN-38 (tSN38) using patient samples from six studies. PK-safety association was evaluated for neutropenia and diarrhea in 353 patients. PK-efficacy association was evaluated from a phase III study in pancreatic cancer NAPOLI1. Efficacy was associated with longer duration of unencapsulated SN-38 (uSN38) above a threshold and higher Cavg of tIRI, tSN38, and uSN38. Neutropenia was associated with uSN38 Cmax and diarrhea with tIRI Cmax . Baseline predictive factors were race, body surface area, and bilirubin. Analysis identified PK factors associated with efficacy, safety, and predictive baseline factors. The results support the benefit of nal-IRI dose of 70 mg/m2 (free-base; equivalent to 80 mg/m2 salt base) Q2W over 100 mg/m2 Q3W.

A KRAS mutation status-stratified randomized phase II trial of gemcitabine and oxaliplatin alone or in combination with cetuximab in advanced biliary tract cancer.

BACKGROUND: Previous clinical trials have not proved that adding epidermal growth factor receptor inhibitors to chemotherapy confers a survival benefit for patients with advanced biliary tract cancer (ABTC). Whether the KRAS mutation status of tumor cells confounded the results of past studies is unknown. PATIENTS AND METHODS: ABTC patients stratified by KRAS status, Eastern Cooperative Oncology Group performance status, and primary tumor location were randomized 1 : 1 to receive GEMOX (800 mg/m(2) gemcitabine and 85 mg/m(2) oxaliplatin) or C-GEMOX (500 mg/m(2) cetuximab plus GEMOX) every 2 weeks. The primary end point was objective response rate (ORR). RESULTS: The study enrolled 122 patients between December 2010 and May 2012 (62 treated with C-GEMOX and 60 with GEMOX). Compared with GEMOX alone, C-GEMOX was associated with trend to better ORR (27% versus 15%; P = 0.12) and progression-free survival (PFS, 6.7 versus 4.1 months; P = 0.05), but not overall survival (OS, 10.6 versus 9.8 months; P = 0.91). KRAS mutations, which were detected in 36% of tumor samples, did not affect the trends of difference in ORR and PFS between C-GEMOX and GEMOX. The two treatment arms had similar adverse events, except that more patients had skin rashes, allergic reactions, and neutropenia in the C-GEMOX arm. Of patients with C-GEMOX, the presence of a grade 2 or 3 skin rash was associated with significantly better ORR, PFS, and OS. CONCLUSIONS: Addition of cetuximab did not significantly improve the ORR of GEMOX chemotherapy in ABTC, although a trend of PFS improvement was observed. The trend of improvement did not correlate with KRAS mutation status. CLINICAL TRIALS NUMBER: This study is registered at ClinicalTrials.gov (NCT01267344). All patients gave written informed consent.

Comparison of clinical outcome of single-incision laparoscopic surgery using a simplified access system with conventional laparoscopic surgery for malignant colorectal disease.

AIM: Instrument crowding is encountered in single-incision laparoscopic surgery (SILS). Our aim was to compare the results of SILS with those of conventional laparoscopic surgery (CLS) for malignant colorectal disease. METHODS: The records of 27 patients who received SILS for the treatment of malignant disease using a home-made multiple-port system were compared with those of 68 patients who received CLS performed in a standard manner using four to five trocar sites. RESULTS: There were no significant differences in age, gender, disease stage, tumour location or tumour size between the SILS and CLS groups. The most common surgery was high anterior resection in both groups (SILS, 63.0%vs CLS, 58.8%). There were no significant differences between the groups in types of surgery performed, length of bowel resected, resection margin, blood loss, duration of surgery or postoperative complications. Postoperative pain scores were significantly higher in the SILS group than in the CLS group (3.07 ± 1.14 vs 2.41 ± 0.63, respectively, P < 0.001). CONCLUSIONS: SILS is as effective as CLS, and is not associated with increased duration of surgery, blood loss or complications.

Cost-effectiveness of biological therapy in remission induction of moderate to severe plaque psoriasis.

BACKGROUND: The introduction of biological agents has considerably changed the treatment of moderate to severe psoriasis. So far only limited data on their cost-effectiveness exist. OBJECTIVE: Determination of the cost-effectiveness of biologicals from a German third payer's perspective, assessed over a 12-week period. METHODS: Efficacies of the biologicals were determined by a literature review. Treatment modalities were taken from the European S3 psoriasis guideline. Costs were calculated on the basis of the German physicians' fee schedule. Cost-effectiveness was determined and a sensitivity analysis performed. RESULTS: Infliximab at a dose of 3 mg/kg was the most cost-effective agent, directly followed by adalimumab, infliximab 5 mg/kg and ustekinumab. The least cost-effective agent was etanercept 2 × 50 mg/week. Sensitivity analysis showed considerable overlap of the cost-effectiveness ratios. CONCLUSION: Under the conditions of the German health care system, biological agents for psoriasis differ in their cost-effectiveness ratios. Differences are small, however. A major limitation of the study is the short time horizon of 12 weeks.

Heat sensitization in skin and muscle nociceptors expressing distinct combinations of TRPV1 and TRPV2 protein.

Recordings were made from small and medium diameter dorsal root ganglia (DRG) neurons that expressed transient receptor potential (TRP) proteins. Physiologically characterized skin nociceptors expressed either TRPV1 (type 2) or TRPV2 (type 4) in isolation. Other nociceptors co-expressed both TRP proteins and innervated deep tissue sites (gastrocnemius muscle, distal colon; type 5, type 8) and skin (type 8). Subpopulations of myelinated (type 8) and unmyelinated (type 5) nociceptors co-expressed both TRPs. Cells that expressed TRPV1 were excellent transducers of intense heat. Proportional inward currents were obtained from a threshold of approximately 46.5 to approximately 56 degrees C. In contrast, cells expressing TRPV2 alone (52 degrees C threshold) did not reliably transduce the intensity of thermal events. Studies were undertaken to assess the capacity of skin and deep nociceptors to exhibit sensitization to repeated intense thermal stimuli [heat-heat sensitization (HHS)]. Only nociceptors that expressed TRPV2, alone or in combination with TRPV1, exhibited HHS. HHS was shown to be Ca(2+) dependent in either case. Intracellular Ca(2+) dependent pathways to HHS varied with the pattern of TRP protein expression. Cells co-expressing both TRPs modulated heat reactivity through serine/threonine phosphorylation or PLA(2)-dependent pathways. Cells expressing only TRPV2 may have relied on tyrosine kinases for HHS. We conclude that heat sensitization in deep and superficial capsaicin and capsaicin-insensitive C and Adelta nociceptors varies with the distribution of TRPV1 and TRPV2 proteins. The expression pattern of these proteins are specific to subclasses of physiologically identified C and A fiber nociceptors with highly restricted tissue targets.

Expression of TWIK-related acid sensitive K+ channels in capsaicin sensitive and insensitive cells of rat dorsal root ganglia.

Previous reports have demonstrated that small- to medium-diameter dorsal root ganglia (DRG) cells in rats can be subgrouped into individual cell types by patterns of voltage-activated currents. These cell types have consistent responses to algesic compounds and maintain characteristic histochemical phenotypes. Using immunocytochemical methods, we have now examined expression of TWIK (tandem of P domains in a weak inwardly rectifying K+ channel)-related acid sensitive K+ (TASK) channels, TASK-1, TASK-2 and TASK-3, in nine electrophysiologically identified small- to medium-diameter DRG cell types. The immunoreactivity in DRG cells was diverse, with all nine cell types expressing one to all three TASK channels. Some cells expressed TASK-1 (types 1, 4, 6 and 9), some TASK-2 (types 2, 4, 5, 6, 7 and 9), and some TASK-3 (types 1, 2, 3, 4, 5, 6 and 8). The co-expression of TASK-1 and TASK-3 in cell types 1, 4 and 6 suggests that these sensory afferents might contain functional heterodimeric channels. In peripheral sensory afferents, TASK channels have been implicated in the pain sensory transduction pathway, and can be modulated by anesthetics and neuroprotective agents. This study seeks to identify TASK channel populations in electrophysiologically characterized populations of putative nociceptive afferents.

Mutant Bik expression mediated by the enhanced minimal topoisomerase IIalpha promoter selectively suppressed breast tumors in an animal model.

To ensure the success of systemic gene therapy, it is critical to enhance the tumor specificity and activity of the promoter. In the current study, we determined that topoisomerase IIalpha promoter is selectively activated in breast cancer cells. An element containing an inverted CCAAT box (ICB) was shown to be responsible for the breast cancer specificity. When the ICB-harboring topoisomerase IIalpha minimal promoter was linked with an enhancer sequence from the cytomegalovirus immediate early gene promoter (CMV promoter), this composite promoter, CT90, exhibited activity comparable to or higher than the CMV promoter in breast cancer cells in vitro and in vivo, yet expresses much lower activity in normal cell lines and normal organs than the CMV promoter. A CT90-driven construct expressing BikDD, a potent proapoptotic gene, was shown to selectively kill breast cancer cells in vitro, and to suppress mammary tumor development in an animal model of intravenously administrated, liposome-delivered gene therapy. Expression of BikDD was readily detectable in the tumors but not in the normal organs (such as heart) of CT90-BikDD-treated animals. The results indicate that liposomal CT90-BikDD is an effective systemic breast cancer-targeting gene therapy.

Proton sensitivity Ca2+ permeability and molecular basis of acid-sensing ion channels expressed in glabrous and hairy skin afferents.

We contrasted the physiology and peripheral targets of subclassified nociceptive and nonnociceptive afferents that express acid-sensing ion channel (ASIC)-like currents. The threshold for current activation was similar in eight distinct cell subclasses regardless of functional modality (pH 6.8). When potency was determined from concentration-response curves, nonnociceptors exhibited currents with significantly greater potency than that of all but one class of nociceptors (pH50 = 6.54 and 6.75 vs. 6.20-6.34). In nonnociceptive cells, acid transduction was also confined to a very narrow range (0.1-0.3 vs. 0.8-1.4 pH units for nociceptors). Simultaneous whole cell recording and ratiometric imaging of three peptidergic nociceptive classes were consistent with the expression of Ca2+ -permeable ASICs. Sensitivity to psalmotoxin and flurbiprofen indicated the presence of Ca2+ -permeable ASIC1a. Immunocytochemistry on these subclassified populations revealed a differential distribution of five ASIC proteins consistent with Ca2+ permeability and differential kinetics of proton-gated currents (type 5: ASIC1a, 1b, 2a, 2b, 3; type 8a: ASIC1a, 1b, 3; type 8b: ASIC1a, 1b, 2a, 2b, 3). Using DiI tracing, we found that nociceptive classes had discrete peripheral targets. ASIC-expressing types 8a and 9 projected to hairy skin, but only types 8a and 13 projected to glabrous skin. Non-ASIC-expressing types 2 and 4 were present only in hairy skin. We conclude that ASIC-expressing nociceptors differ from ASIC-expressing nonnociceptors mainly by range of proton reactivity. ASIC- as well as non-ASIC-expressing nociceptors have highly distinct cutaneous targets, and only one class was consistent with the existence of a generic C polymodal nociceptor (type 8a).

The mechanisms and managements of hormone-therapy resistance in breast and prostate cancers.

Breast and prostate cancer are the most well-characterized cancers of the type that have their development and growth controlled by the endocrine system. These cancers are the leading causes of cancer death in women and men, respectively, in the United States. Being hormone-dependent tumors, antihormone therapies usually are effective in prevention and treatment. However, the emergence of resistance is common, especially for locally advanced tumors and metastatic tumors, in which case resistance is predictable. The phenotypes of these resistant tumors include receptor-positive, ligand-dependent; receptor-positive, ligand-independent; and receptor-negative, ligand-independent. The underlying mechanisms of these phenotypes are complicated, involving not only sex hormones and sex hormone receptors, but also several growth factors and growth factor receptors, with different signaling pathways existing alone or together, and with each pathway possibly linking to one another. In this review, we will discuss the potential mechanisms of antihormone-therapy resistance in breast and prostate cancers, especially focusing on the similarities and differences of these two cancers. We will also discuss novel agents that have been applied in clinical practice or with clinical potential in the future.

Diverse immunocytochemical expression of opioid receptors in electrophysiologically defined cells of rat dorsal root ganglia.

The development of opiate analgesics that do not produce adverse side effects is hampered by the difficulty in developing drugs that are tissue/sensory cell-specific. Previously, our laboratory has demonstrated that small- and medium-diameter dorsal root ganglia (DRG) cells can be subclassified into at least nine distinct cell types based upon their patterns of voltage activated currents [Petruska, J.C., Napaporn, J., Johnson, R.D., Gu, J.G., Cooper, B.Y., 2000. Subclassified acutely dissociated cells of rat DRG: histochemistry and patterns of capsaicin-, proton-, and ATP-activated currents. J. Neurophysiol. 84 (5), 2365-2379; Petruska, J.C., Napaporn, J., Johnson, R.D., Cooper, B.Y., 2002. Chemical responsiveness and histochemical phenotype of electrophysiologically classified cells of the adult rat dorsal root ganglion. Neuroscience 115 (1), 15-30.] Based on their responses to algesic compounds and histochemical phenotype, eight of the nine subtypes are likely nociceptors. In the present study, we examined the immunoreactivity (IR) of delta-, kappa- and mu-opioid receptors (DOR, KOR and MOR, respectively), in 164 electrophysiologically subclassified DRG neurons. The expression of opioid receptors in the DRG cell types was diverse. Type 1 (25-30 microm cell diameter) and type 9 (35-45 microm) expressed MOR-IR, but were negative for DOR-IR and KOR-IR. Type 2 (25-30 microm) co-expressed DOR-IR and MOR-IR, but did not express KOR-IR. Type 3 (15-20 microm), the non-nociceptive cell type, was not immunoreactive. Type 4 (35-45 microm), type 6 (35-45 microm), and type 7 (15-20 microm) expressed all three opioid receptors. Type 5 (35-45 microm) and type 8 (35-45 microm), co-expressed KOR-IR and MOR-IR, but did not express DOR-IR. The co-expression of opioid receptors in some of the cell types suggests that these sensory afferents might contain heteromeric opioid receptors. Additionally, the diverse expression patterns of opioid receptors between cell types and the consistency of these patterns maintained within each cell type provides further evidence of distinct functional properties of DRG nociceptors.

Nicotinic AChR in subclassified capsaicin-sensitive and -insensitive nociceptors of the rat DRG.

Nociceptive cells of the dorsal root ganglion (DRG) were subclassified, in vitro, according to patterns of voltage-activated currents. The distribution and form of nicotinic ACh receptors (nAChRs) were determined. nAChRs were present on both capsaicin-sensitive and -insensitive nociceptors but were not universally present in unmyelinated nociceptors. In contrast, all A delta nociceptors (types 4, 6, and 9) expressed slowly decaying nAChR. Three major forms of nicotinic currents were identified. Specific agonists and antagonists were used to demonstrate the presence of alpha7 in two classes of capsaicin-sensitive, unmyelinated nociceptors (types 2 and 8). In type 2 cells, alpha7-mediated currents were found in isolation. Whereas alpha7 was co-expressed with other nAChR in type 8 cells. These were the only classes in which alpha7 was identified. Other nociceptive classes expressed slowly decaying currents with beta4 pharmacology. Based on concentration response curves formed by nicotinic agonists [ACh, nicotine, dimethyl phenyl piperazinium (DMPP), cytisine] evidence emerged of two distinct nAChR differentially expressed in type 4 (alpha3beta4) and types 5 and 8 (alpha3beta4 alpha5). Although identification could not be made with absolute certainty, patterns of potency (type 4: DMPP > cytisine > nicotine = ACh; type 5 and type 8: DMPP = cytisine > nicotine = ACh) and efficacy provided strong support for the presence of two distinct channels based on an alpha3beta4 platform. Studies conducted on one nonnociceptive class (type 3) failed to reveal any nAChR. After multiple injections of Di-I (1,1'-dilinoleyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate) into the hairy skin of the hindlimb, we identified cell types 2, 4, 6, 8, and 9 as skin nociceptors that expressed nicotinic receptors. We conclude that at least three nicotinic AChR are diversely distributed into discrete subclasses of nociceptors that innervate hairy skin.

Characterization and function of TWIK-related acid sensing K+ channels in a rat nociceptive cell.

We examined the properties of a proton sensitive current in acutely dissociated, capsaicin insensitive nociceptive neurons from rat dorsal root ganglion (DRG). The current had features consistent with K(+) leak currents of the KCNK family (TASK-1, TASK-3; TWIK-related acid sensing K(+)). Acidity and alkalinity induced inward and outward shifts in the holding current accompanied by increased and decreased whole cell resistance consistent with a K(+) current. We used alkaline solutions to open the channel and examine its properties. Alkaline evoked currents (AECs; pH 10.0-10.75), reversed near the K(+) equilibrium potential (-74 mV), and were suppressed 85% in 0 mM K(+). AECs were insensitive to Cs(+) (1 mM) and anandamide (1 microM), but blocked by Ba(++) (1 mM), quinidine (100 microM) or Ruthenium Red (10 microM). This pharmacology was identical to that of rat TASK-3 and inconsistent with that of TASK-1 or TASK-2. The TASK-like AEC was not modulated by PKA (forskolin, kappa opioid agonists U69593 and GR8696, somatostatin) but was inhibited by PKC activator phorbol-12-myristate-13 acetate (PMA). When acidic solutions were used, we were able to isolate a Ba(++) and Ruthenium Red insensitive current that was inhibited by Zn(++). This Zn(++) sensitive component of the proton sensitive current was consistent with TASK-1. In current clamp studies, acidic pH produced sensitive changes in resting membrane potential but did not influence excitability (pH 7.2-6.8). In contrast, Zn(++) produced substantial changes in excitability at physiological pH. Alkaline solutions produced hyperpolarization followed by proportional burst discharges (pH 10.75-11.5) and increased excitability (at pH 7.4). In conclusion, multiple TASK currents were present in a DRG nociceptor and differentially contributed to distinct discharge mechanisms.

Treatment of HIV-associated wasting with recombinant human growth hormone: monitoring of body composition changes by bioelectrical impedance analysis (BIA).

INTRODUCTION: Recombinant human growth hormone (r-hGH) has demonstrated efficacy in treating HIV-associated wasting (HAW), however, HAW has become less prominent since the introduction of highly active antiretroviral therapy (HAART). Recent studies suggest that patients receiving HAART may still experience HAW. We investigated the nature of HAW and the efficacy of r-hGH in these patients. METHODS: We treated 27 HIV-positive patients receiving HAART who had either recent loss of >5% body weight or weight <90% lower limit of normal with 12 weeks of r-hGH (6 mg given either daily or every other day). Body composition changes were monitored using bioelectrical impedance analysis (BIA). RESULTS were assessed for all patients and for a subgroup meeting more stringent definitions of wasting (BIA phase angle a<5.6 degrees, n = 14). - RESULTS: Significant increases from baseline in weight and body cell mass (BCM) occurred in the full population (medians: 2.0 kg weight, 1.5 kg BCM). Patients with phase angle alpha<5.6 degrees also showed increases in weight and BCM (medians: 2.5 kg weight, 1.95 kg BCM), and 10 of 14 showed improvements in the ratio of extracellular mass (ECM) to BCM. At follow-up there was a trend towards loss of the weight and BCM gained on treatment. Treatment was well tolerated. CONCLUSION: Patients receiving HAART continue to experience wasting, and respond well to r-hGH therapy as monitored by BIA.

Co-expression of P2X receptor subunits on rat nodose neurons that bind the isolectin GS-I-B4.

Triple fluorescent histochemistry was used to describe the types of overlap in visceral sensory neurons (nodose ganglion) for the labeling of the isolectin B4 from Griffonia simplicifolia type one (GS-I-B4) and their immunoreactivity (IR) for two of the ATP receptor subunits (P2X1/3 or P2X2/3). The vast majority of nodose neurons expressed GS-I-B4-binding and most of these displayed P2X receptor IR. Most of the P2X-IR was co-expressed on these individual nodose neurons (P2X1/P2X3 or P2X2/P2X3). A very small subpopulation of neurons that were GS-I-B4 negative but P2X positive displayed a very high relative intensity of P2X3-IR. The functional role that these expression patterns play in visceral sensory processing is currently unclear.

Distribution of P2X1, P2X2, and P2X3 receptor subunits in rat primary afferents: relation to population markers and specific cell types.

We determined the co-expression of immunoreactivity (IR) for ATP-receptor subunits (P2X1, P2X2, and P2X3), neuropeptides, neurofilament (NF), and binding of the isolectin B(4) from Griffonia simplicifolia type one (GS-I-B(4)) in adult dorsal root ganglion neurons. P2X1-IR was expressed primarily in small DRG neurons. Most P2X1-IR neurons expressed neuropeptides and/or GS-I-B(4)-binding, but lacked NF-IR. P2X1-IR overlapped with P2X3-IR, though each was also found alone. P2X2-IR was expressed in many P2X3-IR small neurons, as well as a group of medium to large neurons that lacked either P2X3-IR or GS-I-B(4)-binding. A novel visible four-channel fluorescence technique revealed a unique population of P2X2/3-IR neurons that lacked GS-I-B(4)-binding but expressed NF-IR. Co-expression of P2X1, and P2X3 in individual neurons was also demonstrated. We examined P2X subunit-IR on individual recorded neurons that had been classified by current signature in vitro. Types 1, 2, 4 5, and 7 expressed distinct patterns of P2X-IR that corresponded to patterns identified in DRG sections, and had distinct responses to ATP. Types with rapid ATP currents (types 2, 5, and 7) displayed P2X3-IR and/or P2X1-IR. Types with slow ATP currents (types 1 and 4) displayed P2X2/3-IR. Type 1 neurons also displayed P2X1-IR. This study demonstrates that the correlation between physiological responses to ATP and the expression of particular P2X receptor subunits derived from expression systems is also present in native neurons, and also suggests that novel functional subunit combinations likely exist.

Treatment of upper lip wrinkles: a comparison of the 950 microsec dwell time carbon dioxide laser to manual tumescent dermabrasion.

BACKGROUND: High-energy pulsed or computer-scanned continuous-wave carbon dioxide (CO2) laser resurfacing has gained popularity as a wrinkle treatment because of its minimal thermal injury and precise control of tissue vaporization depth. Manual tumescent dermabrasion has also been effective for treating facial wrinkles. This is, to our knowledge, the first study comparing the use of CO2 laser to manual tumescent dermabrasion for the treatment of wrinkles on the upper lip. OBJECTIVE: To compare prospectively the clinical efficacy of the 950 microsec dwell time CO2 laser to that of manual tumescent dermabrasion in the treatment of upper lip wrinkles. METHODS: Twenty female subjects with moderate to severe upper lip wrinkles were randomly treated with the 950 microsec dwell time CO2 laser on one side of the upper lip and manual tumescent dermabrasion on the other. RESULTS: The average upper lip laser-treated wrinkle score (0 = none to 5 = severe) decreased from 4.3 +/- 0.2 before treatment to 1.8 +/- 0.3 at 6 months after treatment. The average upper lip dermabrasion-treated wrinkle score decreased from 4.4 +/- 0.2 to 1.5 +/- 0.3. The degree to which the wrinkle score improved after laser treatment compared with that after dermabrasion was not statistically significant (P =.216). CONCLUSION: Manual tumescent dermabrasion and 950 microsec dwell time CO2 laser resurfacing are equally effective for the treatment of upper lip wrinkles.