Voice Change Following Testosterone Supplementation in Women: A Multi-Institutional Case Series.

OBJECTIVES: To describe voice changes as a result of the off-label use of androgen supplementation in women. METHODS: A multi-institutional retrospective consecutive case series identified women taking androgen supplementation who presented to voice clinics at two institutions with a chief complaint of voice change between 2014 and 2019. Age, occupation, hormone therapy, indication, Voice Handicap Index-10, fundamental frequency, semitone pitch range, testosterone blood level, treatment undertaken, and long-term outcome were collected. RESULTS: Nine women presented with voice change after initiation of androgen hormone supplementation. The mean age was 55 and three patients were performers. All patients underwent hormone therapy with testosterone supplementation, most commonly subcutaneous testosterone pellets. Six patients (67%) were being treated for menopause symptoms, one patient for decreased libido, one patient for breast cancer, and one patient who desired additional muscle gain. Time of symptom onset after hormone therapy initiation was highly variable, ranging from 0 to 48 months with a mean of 15 months. Mean Voice Handicap Index-10 was 21, mean fundamental frequency at comfortable speaking level was 155 Hz and mean semitone pitch range was 22 semitones. Two patients had markedly elevated serum total testosterone levels. Hormone therapy discontinuation and voice therapy were recommended in six (67%) patients each. Five patients returned for follow-up after treatment and noted some subjective benefit. CONCLUSIONS: Female patients treated with androgen supplementation may experience unintended voice changes, most prominently reduction in fundamental frequency. Although some benefit may be obtained from voice therapy and cessation of hormone therapy, voice changes may be permanent. Caution should be exercised when prescribing these medications to women.

Uva-ursi extract and ibuprofen as alternative treatments for uncomplicated urinary tract infection in women (ATAFUTI): a factorial randomized trial.

OBJECTIVES: The aim was to investigate if offering symptomatic therapy (Uva-ursi or ibuprofen) alongside a delayed prescription would relieve symptoms and reduce the consumption of antibiotics for adult women presenting with acute uncomplicated urinary tract infection (UTI). METHODS: A 2 × 2 factorial placebo controlled randomized trial in primary care. The participants were 382 women aged 18-70 years with symptoms of dysuria, urgency, or frequency of urination and suspected by a clinician to have a lower UTI. The interventions were Uva-ursi extract and/or ibuprofen advice. All women were provided with a delayed or 'back-up' prescription for antibiotics. Missing data were imputed using multiple imputation methods (ISRCTN registry: ISRCTN43397016). RESULTS: An ITT analysis of mean score for frequency symptoms assessed on Days 2-4 found no evidence of a difference between Uva-ursi vs. placebo -0.06 (95% CI -0.33 to 0.21; p 0.661), nor ibuprofen vs. no ibuprofen advice -0.01 (95% CI -0.27 to 0.26; p 0.951). There was no evidence of a reduction in antibiotic consumption with Uva-ursi (39.9% vs. placebo 47.4%; logistic regression odds ratio (OR) 0.59 (95% CI 0.22-1.58; p 0.293) but there was a significant reduction for ibuprofen advice (34.9% vs. no advice 51.0%; OR 0.27 (95% CI 0.10 to 0.72; p 0.009). There were no safety concerns and no episodes of upper tract infection were recorded. CONCLUSIONS: We found no evidence of an effect of either intervention on the severity of frequency symptoms. There is evidence that advice to take ibuprofen will reduce antibiotic consumption without increasing complications. For every seven women given this advice, one less will use antibiotics.

Development of a portable blood salvage and autotransfusion technology to enhance survivability of personnel requiring major medical interventions in austere or military environments.

INTRODUCTION: Uncontrolled haemorrhage is the leading cause of death on the battlefield, and two-thirds of these deaths result from non-compressible haemorrhage. Blood salvage and autotransfusion represent an alternative to conventional blood transfusion techniques for austere environments, potentially providing blood to the casualty at point of injury. The aim of this paper is to describe the design, development and initial proof-of-concept testing of a portable blood salvage and autotransfusion technology to enhance survivability of personnel requiring major medical interventions in austere or military environments. METHOD: A manually operable, dual-headed pump was developed that removes blood from site of injury to a collection reservoir (upper pump) and back to casualty (lower pump). Theoretical flow rate calculations determined pump configuration and a three-dimensionally printed peristaltic pump was manufactured. Flow rates were tested with fresh bovine blood under laboratory conditions representative of the predicted clinical environment. RESULTS: Mathematical modelling suggested flow rates of 3.6 L/min and 0.57 L/min for upper and lower pumps. Using fresh bovine blood, flow rates produced were 2.67 L/min and 0.43 L/min. To mimic expected battlefield conditions, upper suction pump flow rate was calculated using a blood/air mixture. CONCLUSION: The authors believe that this technology can potentially enhance survivability for casualties in austere and deployed military settings through autotransfusion and cell concentration. It reduces negative effects of blood donation on the conventional donor pool, and potentially negates the logistical constraints associated with allogenic transfusions.

Modern injection augmentation for glottic insufficiency.

PURPOSE OF REVIEW: A number of technological advancements in recent years have spurred renewed interest in vocal fold injection augmentation. The present review discusses the characteristics of currently available short-term and long-term injection materials, and the advantages and disadvantages of each. RECENT FINDINGS: Many of the newer laryngeal injectable substances were originally used as dermal fillers born out of the plastic surgery and dermatologic literature. Clinical outcomes have improved as a result of exciting advancements in vocal fold injection material availability and design. New substances now closely mimic the native viscoelastic properties of the vocal folds, but the search for the ideal material is ongoing. SUMMARY: The wide array of injectable materials available is both daunting and exciting. Many variables must be considered in choosing the best temporary or long-term injectable material to meet each patient's needs. Surgeons will be better able to optimize patient outcomes by understanding the advantages and disadvantages each has to offer.

Vagal nerve stimulation: clinical and electrophysiological effects on vocal fold function.

More than 16,000 vagal nerve stimulators (VNSs) have been implanted for refractory epileptic seizures. The most commonly reported side effect is hoarseness. This study examines the effects of VNS placement on vocal fold function. Eleven patients who had undergone VNS placement at our institution were recruited. Subjective evaluation by a panel of speech and language pathologists of both connected speech and videolaryngoscopy recordings were used both at rest and during VNS activation. Additional subjective evaluation included use of the Voice Handicap Index for the study group. These results were compared to data from age- and sex-matched controls. Objective data included maximum phonation time in the study and control groups, as well as laryngeal electromyography performed on the VNS-implanted patients only. Motor unit potential morphology and recruitment, as well as spontaneous activity, were analyzed bilaterally for the cricothyroid and thyroarytenoid muscles. Significant differences were found between the study and control groups subjectively for vocal quality and videolaryngoscopy parameters. Vocal fold tension, supraglottic muscular hyperfunction, and reduced vocal fold mobility were the most common findings during VNS activation. Two of 10 patients had immobile left vocal folds in the absence of active stimulation. The maximum phonation time was generally reduced in the subject group, but this reduction did not reach statistical significance. Finally, 6 of 10 patients had abnormal electromyographic results, including large-amplitude polyphasic motor unit potentials and decreased recruitment. We conclude that implantation of a VNS can affect vocal fold function. The effects are magnified during periods of active stimulation. There is the potential for nerve degeneration after prolonged repetitive stimulation, and there may be a trend toward greater vocal fold dysfunction with higher stimulation parameters.

Splicing signals and factors in plant intron removal.

Constitutive splicing of the potato invertase mini-exon 2 (9 nt long) requires a branchpoint sequence positioned around 50 nt upstream of the 5' splice site of the adjacent intron and a U(11) element found just downstream of the branchpoint in the upstream intron [Simpson, Hedley, Watters, Clark, McQuade, Machray and Brown (2000) RNA 6, 422-433]. The sensitivity of this in vivo plant splicing system has been used to demonstrate exon scanning in plants, and to characterize plant intronic elements, such as branchpoint and poly-pyrimidine tract sequences. Plant introns differ from their vertebrate and yeast counterparts in being UA- or U-rich (up to 85% UA). One of the key differences in splicing between plants and other eukaryotes lies in early intron recognition, which is thought to be mediated by UA-binding proteins. We are adopting three approaches to studying the RNA-protein interactions in plant splicing. First, overexpression of plant splicing factors and, in particular, UA-binding proteins, in conjunction with a range of mini-exon mutants. Secondly, the sequences of around 65% of vertebrate and yeast splicing factors have high-quality matches to Arabidopsis proteins, opening the door to identification and analysis of gene knockouts. Finally, to discover plant-specific proteins involved in splicing and in, for example, rRNA or small nuclear RNA processing, green fluorescent protein-cDNA fusion libraries in viral vectors are being screened.

Patient perception of local anesthesia for prostate brachytherapy.

Prostate brachytherapy is an increasingly popular treatment for early-stage prostate cancer. Until now, spinal or general anesthesia for the procedure has been the standard of care. For patient safety, patient convenience, and to limit use of operating facilities, the authors started performing implants routinely with local anesthesia. We present here an evaluation of patients' acceptance of prostate brachytherapy under local anesthesia. On arrival at our department on the morning of the procedure, the patient is brought into the simulator suite, an intravenous line is started, and a urinary catheter is inserted. With the patient in the lithotomy position, a 5-by-5-cm patch of perineal skin and subcutaneous tissue is anesthetized by local infiltration of 10 mL of 1% lidocaine, using a 25-gauge 5/8-inch needle. Immediately following injection into the subcutaneous tissues, the deeper tissues, including the pelvic floor and prostate apex, are anesthetized by injecting 15 mL lidocaine solution with approximately 8 passes of a 20-gauge 1-inch needle. Following subcutaneous and periapical lidocaine injections, the transrectal ultrasound (TRUS) probe is positioned to reproduce the planning images and a 3.5- or 6-inch, 22-gauge spinal needle is inserted into the peripheral planned needle tracks, monitored by TRUS. When the tips of the needles reach the prostatic base, about 1 mL of lidocaine solution is injected in the intraprostatic track, as the needle is slowly withdrawn. The lidocaine infiltration procedure takes approximately 10 to 15 minutes. Seed implantation is then performed as previously described. At the time of this report preparation, 58 of the 71 patients (81%) were interviewed, with a median follow-up of 6 months since the implant procedure. On a scale of 1 to 10, the median biopsy pain score was 4.5 compared with a median pain score with the implant procedure of 3.0. There was no clear correlation between the two scores (r = .26). There was no correlation between patients' implant pain score and the number of implant needles used, the pre-implant prostate size, or patient age. The prostate radiation dose coverage, calculated as the percent of the post-implant volume covered by the prescription isodose, averaged 88% (range, 75% to 99%). Five of the 55 patients interviewed (9%) stated that they would have preferred to have the procedure under general anesthesia. Ranked on a 1 to 5 scale, the median patient satisfaction was 5 and the average was 4.4. The substitution of local anesthesia has facilitated rapid introduction of a high-volume brachytherapy program at an institution, without requiring the allocation of significant operating room time. We are pleased with the overall level of patient comfort and satisfaction.

Requirements for mini-exon inclusion in potato invertase mRNAs provides evidence for exon-scanning interactions in plants.

Invertases are responsible for the breakdown of sucrose to fructose and glucose. In all but one plant invertase gene, the second exon is only 9 nt in length and encodes three amino acids of a five-amino-acid sequence that is highly conserved in all invertases of plant origin. Sequences responsible for normal splicing (inclusion) of exon 2 have been investigated in vivo using the potato invertase, invGF gene. The upstream intron 1 is required for inclusion whereas the downstream intron 2 is not. Mutations within intron 1 have identified two sequence elements that are needed for inclusion: a putative branchpoint sequence and an adjacent U-rich region. Both are recognized plant intron splicing signals. The branchpoint sequence lies further upstream from the 3' splice site of intron 1 than is normally seen in plant introns. All dicotyledonous plant invertase genes contain this arrangement of sequence elements: a distal branchpoint sequence and adjacent, downstream U-rich region. Intron 1 sequences upstream of the branchpoint and sequences in exons 1, 2, or 3 do not determine inclusion, suggesting that intron or exon splicing enhancer elements seen in vertebrate mini-exon systems are absent. In addition, mutation of the 3' and 5' splice sites flanking the mini-exon cause skipping of the mini-exon, suggesting that both splice sites are required. The branchpoint/U-rich sequence is able to promote splicing of mini-exons of 6, 3, and 1 nt in length and of a chicken cTNT mini-exon of 6 nt. These sequence elements therefore act as a splicing enhancer and appear to function via interactions between factors bound at the branchpoint/U-rich region and at the 5' splice site of intron 2, activating removal of this intron followed by removal of intron 1. This first example of splicing of a plant mini-exon to be analyzed demonstrates that particular arrangement of standard plant intron splicing signals can drive constitutive splicing of a mini-exon.

Local anesthesia for prostate brachytherapy.

PURPOSE: To demonstrate the technique and feasibility of prostate brachytherapy performed with local anesthesia only. METHODS AND MATERIALS: A 5 by 5 cm patch of perineal skin and subcutaneous tissue is anesthetized by local infiltration of 10 cc of 1% lidocaine with epinephrine, using a 25-gauge 5/8-inch needle. Immediately following injection into the subcutaneous tissues, the deeper tissues, including the pelvic floor and prostate apex, are anesthetized by injecting 15 cc lidocaine solution with approximately 8 passes of a 20-gauge 1.0-inch needle. Following subcutaneous and peri-apical lidocaine injections, the patient is brought to the simulator suite and placed in leg stirrups. The transrectal ultrasound (TRUS) probe is positioned to reproduce the planning images and a 3.5- or 6.0-inch, 22-gauge spinal needle is inserted into the peripheral planned needle tracks, monitored by TRUS. When the tips of the needles reach the prostatic base, about 1 cc of lidocaine solution is injected in the intraprostatic track, as the needle is slowly withdrawn, for a total volume of 15 cc. The implants are done with a Mick Applicator, inserting and loading groups of two to four needles, so that a maximum of only about four needles are in the patient at any one time. During the implant procedure, an additional 1 cc of lidocaine solution is injected into one or more needle tracks if the patient experiences substantial discomfort. The total dose of lidocaine is generally limited to 500 mg (50 ml of 1% solution). RESULTS: To date, we have implanted approximately 50 patients in our simulator suite, using local anesthesia. Patients' heart rate and diastolic blood pressure usually showed moderate changes, consistent with some discomfort. The time from first subcutaneous injection and completion of the source insertion ranged from 35 to 90 minutes. Serum lidocaine levels were below or at the low range of therapeutic. There has been only one instance of acute urinary retention in the patients treated so far, and no unplanned admissions to the hospital or need to reschedule a patient to be implanted under general or spinal anesthesia. CONCLUSIONS: The substitution of local anesthesia has facilitated rapid introduction of a high-volume brachytherapy program at an institution that previously had none, without requiring the allocation of significant operating room time. Although the patients reported here were implanted without conscious sedation, we are starting to try various sedatives and analgesics for patients who we anticipate will have substantial anxiety with the procedure.

Acute care has an innovative approach to the bed crisis!

The regionalization of healthcare in Alberta has been instrumental in changing the way we deliver healthcare to the population. In Calgary, the restructuring involved the closing of three acute care hospitals and a significant reduction in beds per capita. This reduction in inpatient beds behooved Senior Management in acute care to be innovative and responsive to the utilization of existing resources. The Department of Patient Transition Services was conceived with a mandate to provide assistance and support in utilization management and discharge planning, administrative coordination, system support and integration support. The evolution of this unique department is described.

Living the art of the human becoming theory.

The author shows through examples how quality of life is enhanced when the nurse lives the art of the human becoming theory through composing and playing music with persons and families. Also demonstrated is Parse's practice methodology as lived through music.

Integrating chiropractic in managed care.

Alternatives to traditional health care are emerging as an important element in the mix of services offered by managed care plans. Integrating these nontraditional services, such as chiropractic, presents special challenges for plan managers. ChiroNet, an Oregon-based chiropractic specialty PPO network, has formed partnerships with a variety of managed care plans bringing managed chiropractic services to the PPO, EPO, and HMO environments. Practical experience with benefit design, access protocols, utilization management, quality assurance, provider credentialing, and administrative integration has been developed over the period of the network's cooperation with its managed care partners. Successful integration of these nontraditional provider groups depends on alignment of goals and incentives among all players in the system, including providers, their network, the patients, and the managed care plan.

Neuropeptide Y, the hypothalamus and the regulation of energy homeostasis.

Neuropeptide Y (NPY) neurones in the arcuate nucleus of the rodent hypothalamus may play a key role in responding to reductions in body energy stores with appropriate changes in energy homeostasis, namely an increase in food-seeking behaviour and hyperphagia, together with a reduction in heat production by brown adipose tissue. These adaptive responses are mimicked by the injection of NPY into the main sites of projection of the NPY neurones, and animals that are threatened by energy deficits (e.g. through starvation or insulin-deficient diabetes) show increased activity of these neurones. Genetically obese rodents also show hyperactivity of the NPY neurones, which is inappropriate to their energy needs and may contribute to their hyperphagia, reduced energy expenditure and excessive weight gain. The NPY neurones may be inhibited by insulin and leptin, which may both serve as signals of peripheral fat mass. Ultimately, characterization of the specific "feeding' receptors which mediate NPY's central effects on energy homeostasis may provide opportunities for designing drugs to manipulate and appetite and energy balance in man, notably obesity and the cachexia commonly associated with malignancy and chronic infection.

Complementary deletions in expressed potato U2snRNA gene variants support the hypothesis that stem-loop IIb is dispensable for splicing.

A polymerase chain reaction (PCR) strategy designed to amplify DNA sequences between closely linked U2snRNA genes has generated extensive coding and 5' regulatory sequence information on the potato U2snRNA multigene family. Two of the U2snRNA coding sequences isolated differed substantially from normal U2snRNAs by containing both complementary deletions and regions of novel sequence. However, sequences such as Sm-binding sites and loops of stem-loops III and IV, which are some of the most highly conserved regions in U2snRNA, remain highly conserved in these genes. The complementary deletions would effectively remove stem-loop IIb which has been shown in yeast to be unnecessary for pre-mRNA splicing. Transcripts from one of the genes have been detected by reverse transcriptase-PCR (RT-PCR) in total RNA. These novel U2snRNA genes represent the first reported example of naturally occurring structural variants and provide support for the proposed non-essential role of U2snRNA stem-loop IIb.

Complexity of the healthcare crisis in rural America.

Because osteopathic physicians comprise 15.3% of all physicians in small rural counties, while making up only 5.1% of the nation's physicians, the solutions to the healthcare crisis for rural America are of special interest to them. The authors explore the incredible diversity of rural communities and the difficulty with defining the term "rural." They give the background of efforts to address rural health problems and the reasons accessible healthcare--available, acceptable and affordable--has been so elusive in rural settings. The authors also explain the relative success of the osteopathic medical profession and address the role osteopathic physicians can play in the future. Finally, they explore the exciting new possibilities that telemedicine offers.

Prostaglandins and hypothalamic neurotransmitter receptors involved in hyperthermia: a critical evaluation.

The role of a prostaglandin of the E series (PGE) in the hypothalamic mechanisms underlying a fever continues to be controversial. This paper reviews the historical literature and current findings on the central action of the PGEs on body temperature (Tb). New experiments were undertaken to examine the local effect of muscarinic, nicotinic, serotonergic, alpha-adrenergic, or beta-adrenergic receptor antagonists at hypothalamic sites where PGE1 caused a rise in Tb of the primate. Guide tubes for microinjection were implanted stereotaxically above sites in and around the anterior hypothalamic, preoptic area (AH/POA) of male Macaque monkeys. Following postoperative recovery, 30-100 ng of PGE1 was micro-injected unilaterally in a volume of 1.0-1.5 microliter at sites in the AH/POA to evoke a rise in Tb, and once identified, pretreated with a receptor antagonist. PGE1 hyperthermia was significantly reduced by microinjections of the muscarinic and nicotinic antagonists, atropine, or mecamylamine, at PGE1 reactive sites in the AH/POA. The serotonergic antagonist, methysergide, injected at PGE1 sensitive sites in the ventromedial hypothalamus also attenuated the rise in Tb. However, the 5-HT reuptake blocker, fluoxetine, and the beta-adrenergic receptor antagonist, propranolol, injected in the AH/POA failed to alter the PGE1 hyperthermia. In contrast, the alpha-adrenergic antagonist, phentolamine, potentiated the increase in Tb at all PGE1 reactive sites in the hypothalamus. An updated model is presented to explain how the concurrent actions of aminergic neurotransmitters acting on their respective receptors in the hypothalamus can interact with a PGE to elicit hyperthermia. Finally, an evaluation of the current literature including recent findings on macrophage inflammatory protein (MIP-1) supports the conclusion that a PGE in the brain is neither an obligatory nor essential factor for the expression of a pyrogen fever.

Detection of antisense transcripts in transgenic plants by RT-PCR.

A reverse transcriptase-polymerase chain reaction (RT-PCR) where one oligonucleotide primer is end-labelled has been used to analyse expression in transgenic plants carrying antisense gene constructs. Specific detection of both sense and antisense RNA transcripts of the spliceosomal protein gene, U2B'', was achieved using the same pair of oligonucleotide primers. To maintain specificity, a reaction step in which reverse transcriptase was inactivated and RNA digested was found to be essential.

Plant pre-mRNA splicing and splicing components.

Pre-mRNA splicing or the removal of introns from precursor messenger RNAs depends on the accurate recognition of intron sequences by the plant splicing machinery. The major components of this machinery are small nuclear ribonucleoprotein protein particles (snRNPs) which consist of snRNAs and snRNP proteins. We have analysed various aspects of intron sequence and structure in relation to splice site selection and splicing efficiency and we have cloned snRNA genes and a gene encoding the snRNP protein, U2B". In the absence of an in vitro splicing system for plants, transient expression in protoplasts and stable plant transformations have been used to analyse splicing of intron constructs. We aim to address the function of the UsnRNP-specific protein, U2B", via the production of transgenic plants expressing antisense U2B" transcripts and epitope-tagged U2B" protein. In addition, we have cloned genes encoding other proteins which potentially interact with RNA, such as RNA helicases, and strategies involving transgenic plants are being developed to analyse their function.