The peripheral portacath provides safe and convenient venous access in pediatric and adolescent patients.

INTRODUCTION: Adolescent patients with chronic conditions rely on permanent venous access for safe treatment and supportive care. Traditionally this is provided by a central venous access device (CVAD) e.g. Hickmann catheter or totally implanted subcutaneous port or also called Port-a-Cath (PaC). We reviewed the patient experience, safety and feasibility of insertion of peripheral inserted implanted subcutaneous port (peripheral PaC). METHODS: Medical records of patients who underwent insertion of peripheral PaC under ultrasound guidance at our institution since between 2012-2017 were reviewed to ascertain specific details including duration of insertion and complication rate. Short structured questionnaires were used to assess nursing and patient satisfaction. RESULTS: Twenty eight peripheral PaC were inserted at our institution. There were 17 female and 11 male patients aged between 12.3 and 18.7 years (median = 16.1). Six were inserted under local anesthetic (LA) in patients who were not fit for general owing to mediastinal mass or lung disease. At the time of analysis 2 PaCs remained in situ with a median duration of 8 months (range 3-48). Removal of 26 PaCs was under LA in 15 cases and under GA in 11. Complications were observed in 9 cases but only necessitated early removal or replacement in 3 cases (displacement and disconnection) and repositioning in 1 case. Thrombosis was seen in 2 patients who required systemic anticoagulation but had complete resolution. CONCLUSION: This study shows that the use of peripheral PaC is safe. The feedback from patients and nursing staff supports the use of the peripheral PaC. We are exploring additional patient groups that might benefit from this device.

RELATIVE DISSOLUTION RATES OF RADIOACTIVE MATERIALS USED AT AWE.

A simple in vitro dissolution test was used to provide a semi-quantitative comparison of the relative dissolution rates of samples of radioactive materials used at Atomic Weapons Establishment in a lung fluid surrogate (Ringer's solution). A wide range of dissolution rates were observed for aged legacy actinides, freshly produced actinide alloys and actinides from waste management operations.

The utility of the K6/ODC transgenic mouse as an alternative short term dermal model for carcinogenicity testing of pharmaceuticals.

The use of transgenic rodents may overcome many limitations of traditional cancer studies. Regulatory perspectives continue to evolve as new models are developed and validated. The transgenic mouse, K6/ODC, develops epidermal tumors when exposed to genotoxic carcinogens. In this study, K6/ODC mice were evaluated for model fitness and health robustness in a 36-week study to determine oncogenic risk of residual DNA in vaccines from neoplastic cell substrates. K6/ODC and C57BL/6 mice were treated with T24-H-ras expression plasmid, carrier vector DNA, or saline topically or by subcutaneous injection. One group of K6/ODC mice received 7,12-dimethylbenz-[a]anthracene [DMBA] dermally. Only DMBA-treated mice developed papillomas by six weeks, increasing in incidence to 25 weeks. By week 11, many K6/ODC mice showed severe dehydration and dermal eczema. By week 32, (6/8) surviving K6/ODC mice showed loss of mobility and balance. Microscopic evaluation of tissues revealed dermal/sebaceous gland hyperplasia, follicular dystrophy, splenic atrophy, and amyloid deposition/neutrophilic infiltration within liver, heart, and spleen, in all K6/ODC mice. Pathology was not detected in C57BL/6 mice. Progressive adverse health, decreased survival, and failure to develop papillomas to the H-ras plasmid suggest that K6/ODC mice may be an inappropriate alternative model for detection of oncogenic DNA and pharmaceutical carcinogenicity testing.

Hypericum perforatum L. extract - novel photosensitizer against human bladder cancer cells.

The polar methanolic fraction (PMF) of the Hypericum perforatum L. extract has recently been developed and tested as a novel, natural photosensitizer for use in the photodynamic therapy (PDT), and photodynamic diagnosis (PDD). PMF has been tested on HL-60 leukemic cells and cord blood hemopoietic progenitors. In the present study, the efficacy of PMF as a phototoxic agent against urinary bladder carcinoma has been studied using the T24 (high grade metastatic cancer), and RT4 (primary low grade papillary transitional cell carcinoma) human bladder cancer cells. Following cell culture incubation, PMF was excited using 630 nm laser light. The photosensitizer exhibited significant photocytotoxicity in both cell lines at a concentration of 60microg/ml, with 4-8 J/cm(2) light dose, resulting in cell destruction from 80% to 86%. At the concentration of 20microg/ml PMF was not active in either cell line. These results were compared with the results obtained in the same cell lines, under the same conditions with a clinically approved photosensitizer, Photofrin. Photofrin was used in the maximum clinically tolerable dose of 4microg/ml, and it was also excited with 630 nm laser light. In the T24 cell Photofrin exhibited slightly less photocytotocixity, compared with PMF, resulting in 77% cell death with 8J/cm(2) light dose. However, against the RT4 cells Photofrin resulted in minimal cell death (9%) with even 8J/cm(2) light dose. Finally, the type of cell death induced by PMF photoactivation was studied using flow cytometry and DNA laddering. Cell death by PMF photodynamic action in these two bladder cell lines is caused predominently by apoptosis. The reported significant photocytotoxicity, selective localization, natural abundance, easy, and inexpensive preparation, underscore that the PMF extract hold the promise of being a novel, effective PDT photosensitizer.

Neural activity in speech-sensitive auditory cortex during silence.

That auditory hallucinations are voices heard in the absence of external stimuli implies the existence of endogenous neural activity within the auditory cortex responsible for their perception. Further, auditory hallucinations occur across a range of healthy and disease states that include reduced arousal, hypnosis, drug intoxication, delirium, and psychosis. This suggests that, even in health, the auditory cortex has a propensity to spontaneously "activate" during silence. Here we report the findings of a functional MRI study, designed to examine baseline activity in speech-sensitive auditory regions. During silence, we show that functionally defined speech-sensitive auditory cortex is characterized by intermittent episodes of significantly increased activity in a large proportion (in some cases >30%) of its volume. Bilateral increases in activity are associated with foci of spontaneous activation in the left primary and association auditory cortices and anterior cingulate cortex. We suggest that, within auditory regions, endogenous activity is modulated by anterior cingulate cortex, resulting in spontaneous activation during silence. Hence, an aspect of the brain's "default mode" resembles a (preprepared) substrate for the development of auditory hallucinations. These observations may help explain why such hallucinations are ubiquitous.

Mutations at the GABA receptor selectivity filter: a possible role for effective charges.

An important feature of ligand-gated ion channels is their exquisite ability to discriminate between ions. Still, little is known about the mechanisms underlying, or structural determinates of, this ability. We examined the structural elements underlying the ionic selectivity of rho1 GABA receptors expressed in Xenopus oocytes and human embryonic kidney cells using site-directed mutagenesis and two-electrode voltage-clamp or patch-clamp techniques. The wild-type GABA receptor was chloride selective, with a small but significant permeability to potassium (PNa+ : PK+ : PCl- = 0 : 0.03 :1). Mutation of an alanine to glutamate at position 291 (thought to be located at the intracellular end of the second transmembrane domain), formed a channel that exhibited little discrimination among ions (0.70:0.87:1), while deletion of a neighbouring proline (290) was chloride selective, but had elevated cation permeabilities compared to the wild-type channel (0.12 : 0.14 : 1). Together, the two mutations (DeltaP290/A291E) caused a reversal of selectivity (2.72 : 3.59 : 1). We also examined the effects of neutralizing and reversing the charge of the adjacent, and highly conserved, arginine. Mutation of the neighbouring arginine to glutamate (R292E) increased the cation permeability similar to the DeltaP290/A291E double mutant (2.4 : 3.0 : 1), whereas neutral mutations at this position (R292M or R292C) retained chloride selectivity (0 : 0.11 : 1.0 and 0 : 0.14 : 1.0, respectively). Our experiments suggest that the effective charge near the presumed intracellular mouth of the pore is critical for ionic selectivity.

Visual function is stable in patients who continue long-term vigabatrin therapy: implications for clinical decision making.

PURPOSE: Vigabatrin (VGB) has been shown to cause visual field constriction and other forms of mild visual dysfunction. We determined the safety of continuing VGB therapy in patients who had received prolonged treatment (>2 years) with the drug by serially monitoring changes in visual function over a 1-year period of continued therapy. We also followed up patients who discontinued VGB to see whether alternative therapies are effective. METHODS: Fifteen of 17 patients who continued VGB therapy had visual-function testing (visual acuity, color vision, kinetic and static perimetry) every 3 months for 1 year. Eighteen patients who discontinued VGB were given alternative antiepileptic drugs (AEDs); their seizure responses were measured after > or =3 months of treatment. RESULTS: Patients continuing VGB showed no worsening of visual acuity, color vision, or visual-field constriction beyond that measured in the initial test. Many patients who discontinued VGB had good seizure control with either newer or previously unsuccessful AEDs. CONCLUSIONS: For patients who have an excellent response to VGB and only mild visual changes, continued therapy may be safe with close visual monitoring. Patients who do not have a significant reduction in seizures or who experience considerable visual dysfunction with VGB may respond well to alternative therapies.

Neoadjuvant therapy for organ preservation in head and neck cancer.

OBJECTIVES/HYPOTHESIS: We designed two sequential trials of induction chemotherapy followed by definitive radiation in patients with potentially resectable head and neck cancer to determine whether organ preservation is feasible without apparent compromise of survival Study Design Both trials were Phase II studies. METHODS: Two clinical trials were conducted sequentially at the University of Michigan. Fifty-two patients enrolled in the first study and were treated with a planned three cycles of carboplatin and 5-fluorouracil. Patients who achieved at least 50% reduction in the size of the primary tumor received definitive radiation therapy, to a dose of 6600 to 7380 cGy. Patients with minimal response or progression had immediate salvage surgery. Thirty-seven patients enrolled in the second trial, in which the chemotherapy consisted of carboplatin, 5-fluororuracil, and leukovorin. Responders were treated with accelerated radiation therapy, to a total dose of 7120 cGy delivered in 41 fractions over 5.5 weeks. RESULTS: Toxicity and response were similar in both trials; therefore, the results are reported first separately and then combined for all 89 patients. Tumor sites included: oropharynx, 55 patients; hypopharynx, 34 patients. Eighty-three percent of patients tolerated all three cycles of chemotherapy and toxicity was mild. Response to chemotherapy was: 48% complete response at the primary tumor site, and 34% partial response at the primary tumor site. Initial organ preservation at individual tumor sites was: oropharynx, 58%; hypopharynx, 59%. Median survival was 28 months, and survival at 3 and 5 years was 40% and 24%, respectively. CONCLUSIONS: These two regimens were well tolerated, and survival did not appear to be compromised by organ preservation treatment compared with historical controls. This approach warrants further investigation, particularly in those patients for whom surgery could be functionally debilitating.

Diagnosis of prostate adenocarcinoma using transurethral resection of the prostate after multiple negative transrectal biopsies and persistently elevated prostate-specific antigen level.

We report a case of prostate cancer diagnosis by transurethral resection of the prostate in a man who underwent more than 50 needle biopsies by three different physicians for an increasing prostate-specific antigen level. Radical prostatectomy resulted in removal of an organ-confined tumor (T2aN0M0), and a short follow-up revealed an undetectable prostate-specific antigen level.

Changes of fermentation pathways of fecal microbial communities associated with a drug treatment that increases dietary starch in the human colon.

Acarbose inhibits starch digestion in the human small intestine. This increases the amount of starch available for microbial fermentation to acetate, propionate, and butyrate in the colon. Relatively large amounts of butyrate are produced from starch by colonic microbes. Colonic epithelial cells use butyrate as an energy source, and butyrate causes the differentiation of colon cancer cells. In this study we investigated whether colonic fermentation pathways changed during treatment with acarbose. We examined fermentations by fecal suspensions obtained from subjects who participated in an acarbose-placebo crossover trial. After incubation with [1-13C]glucose and 12CO2 or with unlabeled glucose and 13CO2, the distribution of 13C in product C atoms was determined by nuclear magnetic resonance spectrometry and gas chromatography-mass spectrometry. Regardless of the treatment, acetate, propionate, and butyrate were produced from pyruvate formed by the Embden-Meyerhof-Parnas pathway. Considerable amounts of acetate were also formed by the reduction of CO2. Butyrate formation from glucose increased and propionate formation decreased with acarbose treatment. Concomitantly, the amounts of CO2 reduced to acetate were 30% of the total acetate in untreated subjects and 17% of the total acetate in the treated subjects. The acetate, propionate, and butyrate concentrations were 57, 20, and 23% of the total final concentrations, respectively, for the untreated subjects and 57, 13, and 30% of the total final concentrations, respectively, for the treated subjects.

The value of imagery in perioperative nursing.

Body/mind medicine is rapidly becoming one of the catalysts that will integrate conventional and complementary health care. Interactive Imagery, in particular, offers many potent healing opportunities for nurses and patients in the perioperative continuum. Within this holistic approach, nurses play a pivotal part in providing to patients self-care tools that can be applied in and out of the hospital. Imagery adds value to the health care system by offering nurses and other health care practitioners a way to empower themselves and their patients. It is harmless, time and cost-effective, and often fun, and it focuses on patient satisfaction.

Antenatal triiodothyronine improves neonatal pulmonary function in preterm lambs.

OBJECTIVE: To characterize 1) pulmonary gas exchange, 2) pulmonary function, 3) lung fluid and tissue phospholipid content, and 4) thyroid hormone in the premature lamb (0.85 of term) after intra-amniotic administration of 100 micrograms of triiodothyronine (T3) 2 weeks before delivery. METHODS: Nine fetal lambs were given 100 micrograms of intra-amniotic T3 under ultrasound guidance at 112 +/- 1 days' gestation and delivered at 126 +/- 1 days (term = 149 days). Five saline-injected animals served as controls. Arterial blood gases, pulmonary mechanics, and lung volumes were compared between groups for 1 hour after delivery. At delivery, tracheal fluid and blood was taken for T3, and thyroxine (T4) levels. Tracheal fluid and lung tissues were assayed for total phosphorus and disaturated phosphatidylcholine. RESULTS: Triiodothyronine-treated lambs had significantly higher mean arterial pH and lower PCO2 than controls (P < .05) with a trend toward higher mean PO2. The dynamic lung compliance was increased by 54% with a 40% proportional increase in tidal volume and minute ventilation in the T3-treated group (P < .05). Functional residual capacity increased 69% (P < .05) without a change in specific compliance. The tracheal fluid and pulmonary phospholipids and tracheal fluid and plasma T3 and T4 levels were not different between the two groups. CONCLUSION: A single 100 micrograms dose of antenatal T3 significantly improves neonatal gas exchange and lung compliance. The improvement in lung function was not accompanied by an increase in pulmonary surfactant production. It is inferred that T3 improved lung function via accelerated structural development of the lung with an alternative possible effect on parenchymal connective tissue matrix.

Gastric injury and protection against alcohol and acid: influence of perturbations in glutathione metabolism.

This study assessed the role that inhibition of glutathione (GSH) synthesis and decreased GSH peroxidase (GPX) activity in the rat played in modulating gastric injury induced by ethanol and acid and its prevention by 16,16-dimethyl PGE2 (dmPGE2) and the mild irritant, 25% ethanol. Although numerous studies have proposed that GSH may be important in maintaining gastric mucosal defense, the exact role of this antioxidant in protecting the stomach from injury remains undefined. The present study addressed this consideration by blocking the synthesis of GSH and altering the major pathway by which it exhibits its antioxidant activity and determining the effect of these perturbations on gastric injury and protection. Four to six rats were used for each experimental group. GSH synthesis was blocked by the potent and specific inhibitor L-buthionine sulfoximine (BSO), 2 or 6 mmole/kg intraperitoneally. The activity of the major form of GPX, which is selenium dependent and utilizes GSH as a substrate to detoxify hydrogen peroxide and other hydroperoxides, was inhibited by placing animals on a selenium-deficient diet for 6 weeks. Gastric damage was induced by 100% ethanol, 50% ethanol in 150 mM HCl, and 0.75 M HCl. Prevention of such injury was accomplished with oral pretreatment using 25% ethanol or dmPGE2 (5 microgram/kg). The damaging effects of 100% ethanol, 50% ethanol/150 mM HCl, or 0.75% M HCl were not adversely affected by BSO pretreatment even though GSH synthesis was inhibited by as much as 80%. Similarly, inhibition of GPX activity by 58% in adult rats and 98% in weanling rats failed to potentiate the damaging effect of 100% ethanol. Furthermore, with both perturbations in GSH metabolism, the protective action of dmPGE2 and 25% ethanol was maintained. Our results indicate that profound alterations in gastric GSH metabolism by themselves do not aggrevate the injurious effects of ethanol or acid, nor do they prevent the protective action of a prostaglandin or mild irritant.

Effects of some components of the essential oil of chamomile, Chamomilla recutita, on histamine release from rat mast cells.

The influence of three compounds of the essential oil of Chamomilla recutita (L.) Rauschert on the protamine sulphate-provoked degranulation of mast cells from Lewis-1a rats was investigated. The effect was determined by measuring histamine liberation fluorometrically. Chamazulene and (-)-alpha-bisabolol had no distinct effects. The en-yne dicycloether partly inhibited the degranulation in concentrations above 10(-4) M.

Accuracy of presumed uveal melanoma diagnosis before alternative therapy.

AIMS/BACKGROUND: This study was performed to ascertain the diagnostic accuracy rate of non-invasive tests in patients with presumed uveal melanomas scheduled to be treated with either irradiation or cyclochoroidectomy. METHODS: One hundred consecutive patients who had non-invasive tests followed by fine needle aspiration biopsy (FNAB) as prior alternative treatment were analysed retrospectively. RESULTS: In 86 cases the diagnosis of uveal melanoma was confirmed on FNAB. In five cases false negative results were obtained. In nine patients a diagnosis other than a uveal melanoma was made on the basis of cytopathology. No significant morbidity and no evidence of tumour spread occurred. CONCLUSION: In presumed uveal melanomas eligible for treatment with alternative therapies, the diagnostic accuracy of non-invasive tests is not as good as with larger tumours that require enucleation. Fine needle aspiration biopsy data resulted in correct management of 9% of cases that were thought to have uveal melanomas on non-invasive tests, but had other lesions on cytopathological evaluation.