Estrogen synthesis by osteoblast cell lines.

Estrogens play a central role in modulating bone turnover and in the postmenopausal female are formed almost exclusively by peripheral conversion of sex steroid precursors derived from the adrenals. In this study we have demonstrated that three human osteoblastic cell lines [HOS, U20S (HTB96) and MG63] possess the enzymes necessary for estrogen synthesis and metabolism. Aromatase, estradiol 17 beta-hydroxysteroid dehydrogenase (reductive and oxidative) and estrone sulfatase activities were measured in whole cell monolayers over a 20 h period by isotopic assay techniques. Significant aromatase activity was detected in all three cell lines ranging from 1.8 +/- 0.2 fmol/20 h/10(6) cells (mean +/- S.D., n = 3) for MG63 cells to 51 +/- 1.5 fmol/20 h/10(6) cells for HOS cells. The specific aromatase inhibitor, 4-hydroxyandrostenedione (1 mumol/L) completely inhibited aromatase activity in these cells. Two of the cell lines, HOS and MG63, had significant estradiol 17 beta-hydroxysteroid dehydrogenase activity with oxidative (32.7 +/- 1.9 and 1068.4 +/- 40.2 fmol/20 h/10(6) cells respectively) predominant over reductive activity (1.6 +/- 0.4 and 38.7 +/- 1.8 fmol/20 h/10(6) cells). All three cell lines were able to hydrolyse estrone sulfate to estrone with activities ranging from 13.3 +/- 1.5 fmol/20 h/10(6) cells for U20S cells to 482.2 +/- 3.7 fmol/20 h/10(6) cells for MG63 cells. Since estrogen has been implicated as a critical factor in the modulation of bone resorption and formation, the regulation of skeletal estrogen production, particularly at the time of the menopause, is likely to be an important mechanism by which bone volume is determined in physiological and pathological states.     

Facial Volumetric Correction with Injectable Poly-l-Lactic Acid

Background. Polymers of lactic acid have been widely used for many years in different types of medical devices, such as resorbable sutures, intrabone implants, and soft tissue implants. Injectable poly-l-lactic acid (PLLA; Sculptra), a synthetic, biodegradable polymer, has gained widespread popularity in Europe for the treatment of facial changes associated with aging.
Objective. To provide background information on injectable PLLA and to describe clinical experience with its use in Europe for facial volume enhancement.
Methods. Technique varies with site of injection. Generally, the product is implanted subcutaneously or intradermally in a series of treatments. No allergy testing is required.
Results. Based on experience in more than 2,500 patients, injectable PLLA has been used successfully for the correction of nasolabial folds, mid- and lower facial volume loss, jawline laxity, and other signs of facial aging. Correction lasts for 18 to 24 months in most patients.
Conclusions. Injectable PLLA treatment provides an excellent and prolonged correction of a variety of facial wrinkles, depressions, and laxity with a minimally invasive procedure that does not require allergy testing or a recovery period.     

Mechanisms of opioid-induced tolerance and hyperalgesia.

Opioid tolerance and opioid-induced hyperalgesia are conditions that negatively affect pain management. Tolerance is defined as a state of adaptation in which exposure to a drug induces changes that result in a decrease of the drug's effects over time. Opioid-induced hyperalgesia occurs when prolonged administration of opioids results in a paradoxic increase in atypical pain that appears to be unrelated to the original nociceptive stimulus. Complex intracellular neural mechanisms, including opioid receptor desensitization and down-regulation, are believed to be major mechanisms underlying opioid tolerance. Pain facilitatory mechanisms in the central nervous system are known to contribute to opioid-induced hyperalgesia. Recent research indicates that there may be overlap in the two conditions. This article reviews known and hypothesized pathophysiologic mechanisms surrounding these phenomena and the clinical implications for pain management nurses.     

Epidermal growth factor receptor inhibition modulates the nuclear localization and cytotoxicity of the Auger electron emitting radiopharmaceutical 111In-DTPA human epidermal growth factor.

(111)In-DTPA-human epidermal growth factor ((111)In-DTPA-hEGF [DTPA is diethylenetriaminepentaacetic acid]) is an Auger electron-emitting radiopharmaceutical that targets EGF receptor (EGFR)-positive cancer. The purpose of this study was to determine the effect of EGFR inhibition by gefitinib on the internalization, nuclear translocation, and cytotoxicity of (111)In-DTPA-hEGF in EGFR-overexpressing MDA-MB-468 human breast cancer cells. METHODS: Western blot analysis was used to determine the optimum concentration of gefitinib to abolish EGFR activation. Internalization and nuclear translocation of fluorescein isothiocyanate-labeled hEGF were evaluated by confocal microscopy in MDA-MB-468 cells (1.3 x 10(6) EGFRs/cell) in the presence or absence of 1 microM gefitinib. The proportion of radioactivity partitioning into the cytoplasm and nucleus of MDA-MB-468 cells after incubation with (111)In-DTPA-hEGF for 24 h at 37 degrees C in the presence or absence of 1 microM gefitinib was measured by cell fractionation. DNA double-strand breaks caused by (111)In were quantified using the gamma-H2AX assay, and radiation-absorbed doses were estimated. Clonogenic survival assays were used to measure the cytotoxicity of (111)In-DTPA-hEGF alone or in combination with gefitinib. RESULTS: Gefitinib (1 microM) completely abolished EGFR phosphorylation in MDA-MB-468 cells. Internalization and nuclear translocation of fluorescein isothiocyanate-labeled EGF were not diminished in gefitinib-treated cells compared with controls. The proportion of internalized (111)In that localized in the nucleus was statistically significantly greater when (111)In-DTPA-hEGF was combined with gefitinib compared with (111)In-DTPA-hEGF alone (mean +/- SD: 26.0% +/- 5.5% vs. 14.6% +/- 4.0%, respectively; P < 0.05). Induction of gamma-H2AX foci was greater in MDA-MB-468 cells that were treated with (111)In-DTPA-hEGF (250 ng/mL, 1.5 MBq/mL) plus gefitinib (1 microM ) compared with those treated with (111)In-DTPA-hEGF alone (mean +/- SD: 35 +/- 4 vs. 24 +/- 5 foci per nucleus, respectively). In clonogenic assays, a significant reduction in the surviving fraction was observed when (111)In-DTPA-hEGF (5 ng/mL, 6 MBq/microg) was combined with gefitinib (1 microM ) compared with (111)In-DTPA-hEGF alone (42.9% +/- 5.7% vs. 22.9% +/- 3.6%, respectively; P < 0.01). CONCLUSION: The efficacy of (111)In-DTPA-hEGF depends on internalization and nuclear uptake of the radionuclide. Nuclear uptake, DNA damage, and cytotoxicity are enhanced when (111)In-DTPA-hEGF is combined with gefitinib. These results suggest a potential therapeutic role for peptide receptor radionuclide therapy in combination with tyrosine kinase inhibitors.     

Interhemispheric and ipsilateral connections in Parkinson's disease: relation to mirror movements.

Mirror movements (MM) occur in early, asymmetric Parkinson's disease (PD). To examine the pathophysiology of MM in PD, we studied 13 PD patients with MM (PD-MM), 7 PD patients without MM (PD-NM), and 14 normal subjects. Cross-correlogram did not detect common synaptic input to motoneuron pools innervating homologous hand muscles in PD-MM patients. Transcranial magnetic stimulation studies showed no significant difference in ipsilateral motor-evoked potentials between PD-MM patients and normal subjects. The MM side of PD-MM patients showed a slower increase in ipsilateral silent period area with higher level of muscle contraction than the non-MM side and normal subjects. There was less interhemispheric inhibition (IHI) at long interstimulus intervals of 20 to 50 ms in PD-MM than PD-NM. IHI reduced short interval intracortical inhibition in normal subjects and PD-NM, but not in PD-MM. IHI significantly increased intracortical facilitation in PD-MM and PD-NM patients, but not in normal subjects. Our results suggest that MM in PD is due to activation of the contralateral motor cortex. PD-MM patients had reduced transcallosal inhibitory effects on cortical output neurons and on intracortical inhibitory circuits compared to PD-NM patients and controls. These deficits in transcallosal inhibition may contribute to MM in PD patients.     

Cognitive behaviour therapy approach to disputing automatic thoughts: a two-stage model

Research shows that clients with automatic thoughts (dysfunctional thinking) often do not think of alternative explanations in relation to negative events. Furthermore, these automatic thoughts are characterized by a broad global, self-evaluative and ambiguous nature that could make disputing (or changing the ways they think) the most difficult part of the therapeutic process. This paper proposes a two-stage practise-based disputing model, guided by research, that aims to 'bring' an automatic thought to a specific, objective, quantifiable and concrete level at which not only is the particular aspect(s) of the automatic thought that causes emotional disturbances finely focused, but the disputing is also likely to be effective and manageable. Furthermore, it will also generate alternative explanations that are helpful in reducing emotional disturbances and in facilitating problem solving approach. In this paper, the authors use a case example to discuss the rationale that underpins the conceptualization of the model and to illustrate the process in which the strategies of the model are effectively used.     

Respiratory failure with diffuse patchy lung infiltrates: an unusual presentation of squamous cell carcinoma

The case history is presented of a patient with squamous cell carcinoma of the lung with diffuse bilateral pulmonary shadowing mimicking bronchioloalveolar cell carcinoma which led to type I respiratory failure.     

Major complications arising from 1265 operative laparoscopic cases: a prospective review from a single center

STUDY OBJECTIVE: To identify the volume and type of laparoscopic surgery being performed. To review the incidence, nature of associated complications, and reasons for conversion to laparotomy. DESIGN: A multicenter, prospective case load analysis and chart review, identifying operations performed by 6 advanced laparoscopic surgeons over a 12-month period (1/1/05 to 12/31/05). SETTING: Surgical cases were performed in 5 hospitals in Sydney, New South Wales. PATIENTS: One thousand two hundred sixty-five women underwent a variety of major and advanced operative procedures. MEASUREMENTS AND MAIN RESULTS: A total of 1265 major and advanced laparoscopic procedures were performed. Laparoscopic hysterectomy accounted for 364 cases (28.8%), pelvic floor repair and Burch colposuspension 280 cases (22.2%), excisional endometriosis surgery 354 cases (28%), adnexal surgery 177 cases (13.9%), adhesiolysis 75 cases (5.9%), and miscellaneous cases 15 (1.2%). Overall major complications in terms of bowel, urologic, or major vessel injuries accounted for 8 cases (0.6%). There were 4 injuries of the bowel, 2 injuries to the bladder, and 2 injuries to ureters. There were no major vessel injuries. There were no injuries associated with primary trocar or Veres needle insertion. The most common perioperative morbidity reported was the requirement for blood transfusion (11 cases [0.9%]), and the second most common was venous thromboembolism (4 patients [0.3%]). Six (0.5%) cases were converted to laparotomy, 2 as a result of a complication and 4 for technical reasons. Six of the 8 complications were managed laparoscopically, and a multidisciplinary input was sought only in 4 of the 8 complications. CONCLUSIONS: Despite the advanced nature of laparoscopic procedures performed by our group, the complication rate and conversion to laparotomy remain low. There is an increasing feasibility to perform traditional open operations laparoscopically. An increasing number of these complications are now being managed laparoscopically by the gynecologist.     

Olfactomotor activity during imagery mimics that during perception

Neural representations created in the absence of external sensory stimuli are referred to as imagery, and such representations may be augmented by reenactment of sensorimotor processes. We measured nasal airflow in human subjects while they imagined sights, sounds and smells, and only during olfactory imagery did subjects spontaneously enact the motor component of olfaction--that is, they sniffed. Moreover, as in perception, imagery of pleasant odors involved larger sniffs than imagery of unpleasant odors, suggesting that the act of sniffing has a functional role in creating of olfactory percepts.