Contemporary results of focal therapy for prostate cancer using cryotherapy.

With the increasing diagnosis of prostate cancer, there have been concerns expressed regarding the potential over-treatment that may ensue following the diagnosis of localized prostate cancer. Minimally invasive treatments such as cryotherapy have been used successfully to treat the entire gland, however complications such as incontinence and erectile dysfunction can still occur. Focal cryotherapy is a modification of the standard cryotherapy technique, aiming to only treat the portion of the prostate gland which has the cancer of clinical significance. The potential advantage of this is the minimization of complications; however the remainder of the prostate is still viable and so can develop cancer subsequently. There have been several published studies demonstrating promising efficacy with a low morbidity rate using focal cryotherapy to treat prostate cancer, however further follow up is required before definitive conclusions can be reached. The appropriate selection of patients and subsequent follow up are areas needing further research and the development of improved imaging modalities.

The development of the proximal oesophageal pouch in the adriamycin rat model of oesophageal atresia with tracheo-oesophageal fistula.

This study examined the morphological development of the proximal oesophagus in the Adriamycin-induced rat model of oesophageal atresia. The proximal oesophageal segment in oesophageal atresia with tracheo-oesophageal fistula (OA\TOF) has been assumed to be of similar embryological origin to the distal oesophagus. However, recent research using the Adriamycin model of OA\TOF has indicated that these structures may have a different origin. Time-mated Sprague-Dawley rats were administered either Adriamycin intraperitoneally or saline of an equivalent volume between days 6-9 of gestation. The rats were sacrificed between days 11-19 of gestation, their embryos removed and histologically sectioned. These sections were analysed to observe the morphological changes occurring in the proximal foregut. The proximal oesophageal pouch first appeared on day 15.25 as a dorsal outpouching of the proximal foregut immediately cranial to an area of apoptosis in the dorsal epithelium of the distal pharynx. It elongated through a process of cellular proliferation until it was clearly formed on day 16. Relatively little growth occurred from days 17-19. In the rat developing oesophageal atresia, the proximal oesophageal pouch has an origin different to that of the distal oesophagus. This study may explain the difference in immunohistological properties and intrinsic nervous supply between the proximal and distal oesophageal segments in oesophageal atresia.

Evidence of a common pathogenesis for foregut duplications and esophageal atresia with tracheo-esophageal fistula.

The pathogenesis of the alimentary tract duplications, including foregut duplications (FgD) remains speculative. The accidental finding of FgD in fetal rats with esophageal atresia and tracheoesophageal fistula (EA-TEF) induced by Adriamycin provided an animal model to investigate a possible relationship between these two entities. Timed-pregnant rats were intraperitoneally injected with Adriamycin (1.75 mg/kg) on gestational Days 6 to 9. Their embryos were harvested by Caesarean section from gestational Days 14 to 21. Forty-six of embryos were processed and serially sectioned in the transverse or sagittal planes. EA-TEF occurred in 43/46 (93%) embryos of which 11 (24%) were found to have an associated FgD located at the level where the esophagus was absent. Six FgDs communicated with the foregut or the trachea. Five noncommunicating FgDs were located between the foregut and the vertebral column. In the control embryo, the notochord was located in the centre of the vertebral column from Day 11 of the gestation. In Day 14, 15 and 16, however, embryos exposed to Adriamycin, an abnormal notochord or branch frequently was located within the mesenchyme of the maldeveloped foregut or attached to the duplication cyst. In some, it appeared that the notochord was drawing the cyst-like structure away from the foregut. The present study confirms that duplications adjacent to the esophagus arise from the foregut and that failure of the foregut to detach from the notochord at the normal time may contribute to the development of foregut duplications.

Demonstration of abnormal notochord development by three-dimensional reconstructive imaging in the rat model of esophageal atresia.

The notochord (Nt) is believed to have a role in the development of axial organs. This study was undertaken to reconstruct in three dimensions (3D) the relationship of the Nt to abnormal development of the foregut (Fg) in the adriamycin-induced rat model of esophageal atresia (EA). Pregnant Sprague-Dawley rats were given 1.75 mg/kg adriamycin intraperitoneally on gestational days 6 9 inclusive; control rats received i.p. saline of equal volume, or no injection. Rats were killed between days 11 and 14 and their embryos harvested, histologically sectioned serially, and stained with hematoxylin and eosin. Digitized photographs were taken of serial transverse sections; these photos were traced and used as the basis for 3D reconstruction. From day 11 the normal Nt is no longer in contact with the respiratory or Fg mesenchyme. In adriamycin-treated embryos the Nt branches abnormally as it enters the Fg mesenchyme. Adherence of the Nt to the mesenchyme of the Fg exerts mechanical traction pulling the upper Fg dorsally. The severity of the Fg abnormalities correlates with the length of the ventral extension of the Nt within the Fg mesenchyme: the embryo develops atresia of the esophagus or trachea when the Nt is grossly abnormal. The Nt undergoes reactive thickening in the absence of Fg structures ventral to it. Thus, structural lesions of the Fg (e.g., atresias) are associated with abnormalities of the Nt. The relationship of the Nt to the Fg mesenchyme determines the severity of the abnormality induced by adriamycin: extensive adherence produces tracheal agenesis and EA.

Challenges of recruiting a vulnerable population in a grounded theory study.

Recruitment is a crucial and fundamental part of research and one that poses various degrees of difficulty. This is particularly so when the area of research is one that is either highly sensitive, or that involves participants who are deemed to be particularly vulnerable. This article explores the inherent tensions in matters of participant recruitment among meeting the demands of institutional ethics committees, satisfying the concerns of clinicians in the field and the need to maintain methodological rigor. A postgraduate research student's experience of these tensions underpins the discussion. The article concludes with an outline of the student's strategies and resolution of these issues.

Physiologic and behavioral effects of gentle human touch on preterm infants.

The purpose of this study was to evaluate the effects of a gentle human touch (GHT) intervention provided to 42 preterm infants (27-33 weeks gestational age), for 10 min, three times daily for 10 days. There was no significant difference in mean HR levels or in percent of abnormal heart rate (HR) or O2 saturation comparing 10-min baseline (B), GHT, and 10-min post-touch (PT) phases. There were significantly lower levels of active sleep, motor activity, and behavioral distress during GHT compared to B and P phases. There were no differences among the 42 infants in the GHT group and 42 infants in a randomly assigned control group on any outcome variable including weight gain, morbidity status, or behavioral organization. The findings suggest that GHT generally is a safe and soothing type of touch to provide to young preterm infants, but that individual infant responses to touch need to be continuously monitored by NICU staff and parents.

Does the urorectal septum fuse with the cloacal membrane?

PURPOSE: Traditional theories of cloacal embryogenesis assume that the urorectal septum fuses with the cloacal membrane before the anal membrane disintegrates. However, recent observations in humans and other species raise doubt about this assumption. We determined whether urorectal septum fusion occurs in rats. MATERIALS AND METHODS: Rat embryos were harvested at specific times between days 11 and 16 of gestation. We evaluated the morphology, growth and relationship of the urorectal septum to the cloacal membrane on serial histological sections. RESULTS: The urorectal septum consistently fused with the cloacal membrane on day 15 of gestation before the cloacal membrane began to disintegrate. CONCLUSIONS: In rats the urorectal septum fuses with the cloacal membrane, after which the urogenital membrane and anal membrane disintegrate by a process of apoptosis.

Factors associated with vagal tone responses in preterm infants.

The purpose of this study was to examine factors related to vagal tone (VNA) among preterm infants receiving a 10-minute gentle human touch (GHT) intervention three times daily for 10 days. VNA was measured continuously for 10 minutes before, during, and after each 10-minute GHT intervention. Findings indicated that there was a significant relationship between VNA and gestational age, although there were no relationships between VNA and measures of motor activity or behavioral distress. There was no difference in pattern of response to GHT or level of morbidity, average daily weight gain, or behavioral organization among infants with low, moderate, and high baseline VNA levels. There was no difference in VNA comparing infants in the GHT and control groups or during baseline, touch, and posttouch phases for infants in the GHT group. There is a need for further research to examine the usefulness of VNA as a measure of stress vulnerability among preterm infants.

Apoptosis during regression of the tailgut and septation of the cloaca.

PURPOSE: Apoptosis is involved in the embryonic morphogenesis of many organs. The current study was undertaken to ascertain the role of apoptosis during cloacal development in the rat. METHODS: One hundred five rat embryos, ranging from gestational days 11 to 16, were sectioned serially in the transverse or sagittal planes and stained with H&E. The cloaca, urorectal septum, rectum, urogenital sinus, Wolffian ducts, and tailgut (TG) were examined consecutively in temporospatial sequence. RESULTS: The tailgut immediately distal to the hindgut starts to regress by apoptosis on day 12 of gestation in a craniocaudal direction and has regressed completely by day 13.5. A large number of apoptotic cells and debris can be identified in the urorectal septum during cloacal septation. Vacuoles are formed by coalescence of apoptotic cells at the tip of urogenital sinus from day 15 to 16, and, at the same time, sporadic apoptotic bodies in the anal membrane contribute to its thinning. CONCLUSION: Results of the current study confirm that apoptosis occurs in a specific temporo-spatial sequence in the hindgut and cloaca and appears to be an important mechanism in TG regression, uro-rectal separation, urethral opening, and rupture of the anal membrane.

Temporospatial aberrations of apoptosis in the rat embryo developing esophageal atresia.

BACKGROUND/PURPOSE: Recent work has shown that apoptosis is a key component of the normal development of the foregut. This study was designed to compare the patterns of apoptosis in the normal foregut with those in the fetus developing esophageal atresia and tracheoesophageal fistula (EA-TEF) using 3-dimensional reconstructive techniques. METHODS: Timed pregnant rats that received no treatment (control group) or received Adriamycin intraperitoneally (experimental group) had their embryos removed between days 11 and 14 of gestation. The embryos were sectioned serially and stained with H&E. Three-dimensional reconstructions were made of the foregut and areas of apoptosis were marked on them to facilitate analysis of apoptotic patterns. RESULTS: Apoptosis was evident in control embryos in the region in which tracheoesophageal separation occurs from days 12 and 12.5. Experimental embryos showed no apoptosis until day 13 when apoptosis was observed immediately posterior to the foregut within the esophageal mesenchyme and in the laryngeal mesenchyme ventral to the foregut. CONCLUSIONS: The pattern, timing and location of apoptosis in rats developing EA-TEF is abnormal. Our work indicates that it is actually a complete lack of apoptosis at the crucial stage of development that leads to this abnormality rather than an alteration in the patterning of apoptosis at this crucial time. The observation of apoptosis only within the mesenchyme raises the possibility that apoptosis in the foregut developing EA-TEF may be a reaction to that abnormal development rather than its cause.

Development of the bones and synovial joints in the rat model of the VATER association.

The adriamycin-induced rat model of the Vertebral, Anorectal, Tracheo-Esophageal, Radial and Renal (VATER) association produces a variety of vertebral, rib, and limb abnormalities. This study was designed to document accurately the nature of these abnormalities and to determine whether synovial joints are affected. Fetuses from pregnant Sprague Dawley rats that had received intraperitoneal injections of 1.75 mg/kg of adriamycin on days 6-9 or 10-13 of gestation were harvested. Double-stained skeletal preparations and histological sections were examined for vertebral, rib, and limb anomalies. The incidence of anomalies was high in the group treated on gestational days (GD) 6-9, while it was low in the GD 10-13 group. The length and thickness of the long bones were reduced, with bowing and reduction in their endochondral ossification. Sirenomelia occurred in the group treated on GD 6-9, and was often associated with a short tail and anal atresia. The joint cavities, and intra-articular structures such as menisci and the cruciate ligaments developed normally from the mesenchymal interzone. These data indicate that adriamycin inhibits skeletal growth and differentiation without any interference in the differentiation of the mesenchymal interzone, thus producing normal synovial joints.

Influence of age on length and passive elastic stiffness characteristics of the calf muscle-tendon unit of women.

BACKGROUND AND PURPOSE: Therapeutic stretching of the calf muscle-tendon unit is used to increase its length and to ameliorate decreased dorsiflexion range of motion (ROM), but the influence of age on the passive properties of the calf muscle-tendon unit has not been studied adequately The purpose of this study was to examine the influence of age on length and passive elastic stiffness (PES) characteristics of the calf muscle-tendon unit when stretched through the full, available dorsiflexion ROM. SUBJECTS: Twenty-four younger women (aged 20-39 years), 24 middle-aged women (aged 40-59 years), and 33 older women (aged 60-84 years) participated. METHODS: An isokinetic dynamometer was used to passively stretch the right calf muscle-tendon unit from relaxed plantar flexion to the maximal angle of available dorsiflexion at 5(ús-1. The maximal passive resistive torque was measured, and passive angle-torque curves were constructed for a full ROM from an initial angle of passive resistive torque to the maximal dorsiflexion angle. The full ROM represented length extensibility. The average PES was calculated for this full stretch ROM and for the first half and the last half of this stretch ROM. The maximal passive dorsiflexion angle, maximal passive resistive torque, angular change for the full stretch ROM, and average PES for the full stretch ROM and the first half and the last half of the full stretch ROM were examined for group differences and their relationships with age. RESULTS: The maximal passive dorsiflexion angle, maximal passive resistive torque, angular change for the full stretch ROM, and average PES within the last half of the full stretch ROM were less for the older women than for the younger women. Age was negatively associated with these variables. CONCLUSION AND DISCUSSION: Decreased maximal passive dorsiflexion ROM in older women was associated with decreased maximal passive resistive torque, decreased calf muscle-tendon unit length extensibility, and decreased average PES within the last half of their available passive dorsiflexion ROM.

Concentric isokinetic torque characteristics of the calf muscles of active women aged 20 to 84 years.

STUDY DESIGN: Descriptive, comparative, and correlational study of nonimpaired, active women in 3 age groups. OBJECTIVES: We described age-related concentric isokinetic torque of plantar flexion (PF) of active women and examined the proposal that PF torque at slow to rapid velocities would be influenced by age-related slower muscle contractile properties. We also examined the relationship of age to passive and active force characteristics of the calf muscle. BACKGROUND: Aging is associated with decreased calf muscle strength, slower muscle contractile properties, and decreased dorsiflexion (DF) range of motion. Clinical methods of measuring these changes in the calf muscles have not been described adequately. METHODS AND MEASURES: 24 younger women (20 to 39 years), 24 middle-aged women (40 to 59 years), and 33 older women (60 to 84 years) performed maximal concentric PF of the right ankle from maximal passive DF at randomly ordered velocities of 30 degrees.s-1, 60 degrees.s-1, 120 degrees.s-1, and 180 degrees.s-1. The peak and mean torques and "angular delay" (degree) from the onset of movement to peak torque were examined using ANOVA. Age was correlated (Pearson product moment r) with the peak and mean torques, "angular delay," velocity at peak torque for 180 degrees.s-1, and the maximal passive DF angle and torque. RESULTS: The peak and mean torques decreased with increasing age and velocities. The angular delay at 180 degrees.s-1 decreased with increasing age. Age was negatively correlated with the peak and mean torques (range, r = -0.60 to -0.73), the "angular delay" at all velocities (range, r = -0.44 to -0.64), the maximal passive DF angle (r = -0.73) and torque (r = -0.60), and with the peak torque velocity at 180 degrees.s-1 (r = -0.29). CONCLUSIONS: The results indicate age-related changes for the concentric isokinetic torque of the calf muscles of active women. The angular delay at 180 degrees.s-1 may show changes influenced by slower muscle contractile properties. Concurrent age-related declines in passive and active calf muscle force characteristics were demonstrated.

The infectious bronchitis virus nucleocapsid protein binds RNA sequences in the 3' terminus of the genome.

The infectious bronchitis virus (IBV) nucleocapsid protein was expressed as a bacterial fusion protein which differed from the native protein only in the addition of six amino terminus histidine residues. Using RNA overlay protein blot assays, the recombinant protein was shown to bind to RNA fragments specific for the positive sense 3' noncoding end of the IBV genome. At greater concentrations of sodium chloride, the native and fusion nucleocapsid proteins similarly bound to G RNA, representing the terminal 1805 3' nt of the genome, whereas bovine serum albumin and allantoic fluid protein did not bind to labeled G RNA. Competitive gel shift assays with labeled G RNA indicated that the protein interacted with several unlabeled RNA representing sequences at the 3' noncoding end of the IBV genome. Cache Valley virus (a bunyavirus) mRNA transcribed from the small segment cDNA also inhibited the interaction with IBV G RNA to approximately the same extent as homologous unlabeled G RNA, whereas reactions with bovine liver RNA and yeast tRNA were considerably weaker. Whereas yeast tRNA did not inhibit the interaction with the labeled large G RNA, interactions of the fusion protein with EF, a region from 78 to 217 nt from the 3' terminus of the IBV genome, were also apparently weaker than interactions with fragment CD which consisted of the 3' terminal 155 nt. On a molar basis, the latter interacted in an identical nature to a RNA consisting of CD and an additional 1053 nt of plasmid sequences. Compared to bovine liver RNA, unlabeled G specifically inhibited binding to the two smaller labeled IBV fragments in gel shift assays. The binding of IBV nucleocapsid protein with RNA probably requires specific sequences and/or structures that are present on the genome, and may represent a common mechanism used by similar viral nucleoproteins whose functions depend on binding to RNA.

Influence of age on concentric isokinetic torque and passive extensibility variables of the calf muscles of women.

The purpose of this study was to investigate the influence of age on concentric isokinetic torque (CIT) and passive extensibility (PE) variables of the calf muscles of healthy women. Ten younger women [31.9 (SD 6.1) years] and ten older women [71.1 (SD 6.6) years] were tested using a KIN-COM 500H dynamometer. The PE was tested by stretching the muscles from relaxed plantarflexion to the maximal dorsiflexion (DF) angle at 5 degrees.s-1 without raw electromyogram (EMG) activity exceeding 0.05 mV. The maximal CIT was tested from the maximal DF angle 60 degrees into plantarflexion at four randomly ordered velocities of 30,60, 120, and 180 degrees.s-1. Separate analysis of variance (ANOVA) tests showed that the standardized (% body mass) concentric peak and mean torques were lower for the older women for all isokinetic velocities (p < 0.001). The "angular delay" from the onset of concentric activation to peak torque was smaller for the older women at 120 and 180 degrees.s-1 (p < 0.05). Age showed negative relationships (Pearson r) with all standardized peak torques (p < or = 0.001) and mean torques (p < 0.001), and the "angular delay" at 120 and 180 degrees.s-1 (p < or = 0.05). Independent t-tests showed that the maximal DF angle and the change in the PE angle from an initial angle (defined at 10% of the maximal passive torque) to the maximal DF angle were less for the older women (p < 0.05). Age was negatively related to the maximal DF angle and the change in the PE angle (p < 0.01). The results suggest an age-related decrease in calf muscle CIT, muscle length and PE. The smaller "angular delay" for the older women at 120 and 180 degrees.s-1 indicates that CIT testing at rapid velocities can be used to examine age-related changes in calf muscle contractile properties in relation to rapid velocities of movement.

Interactions between the IBV nucleocapsid protein and RNA sequences specific for the 3' end of the genome.

The infectious bronchitis virus (IBV) nucleocapsid protein was expressed as a fusion protein in bacteria. The coding sequence differed from the native protein only in the addition of six histidine residues at the amino terminus which were used for enrichment with a nickel affinity column. In gel shift assays, the mobility of labelled G RNA was decreased with increasing concentrations of the fusion protein. Competitive gel shift assays with labelled G RNA indicated that the protein interacted with relatively high avidities to several unlabelled RNAs representing sequences at the 3' noncoding end of the IBV genome. Cache Valley virus (a bunyavirus) mRNA transcribed from the smaller segment cDNA also inhibited the interaction with IBV G RNA to the same extent as homologous unlabelled G RNA. In contrast, interactions of the fusion proteins with a region from 99 to 249 bases from the 3' terminus of the IBV genome and bovine liver RNA were relatively weak. The binding of IBV nucleocapsid protein with RNA probably requires specific sequences and/or structures that are present at a number of sites on the genome, and may represent a common mechanism used by similar viral proteins whose functions depend on binding to RNA.

HIV/AIDS: knowledge and attitudes of accident and emergency healthcare professionals.

The knowledge and attitudes of healthcare professionals in accident and emergency departments in Australia are poorly understood. The authors assessed knowledge of and attitudes toward HIV/AIDS and homophobia were assessed in a convenience sample of 111 healthcare professionals in three New South Wales teaching hospitals. Results indicated that respondents with low knowledge of HIV/AIDS used the media as their major source of education and had higher levels of fear of infection than their colleagues with higher knowledge. The study findings imply that quality health care for people with HIV/AIDS requires programs that provide correct information and address the fear of infection.

Analysis of a hypervariable region in the 3' non-coding end of the infectious bronchitis virus genome.

Previous studies on infectious bronchitis virus (IBV) cDNA have identified a region of about 184 bases in the 3' non-coding terminus of both the U.S. prototype strain (Beaudette) and a Japanese strain (KB8523), that was not present in an antigenically closely related U.S. strain, Massachusetts (Mass) 41 (Boursnell et al., 1985; Sutou et al., 1988). In order to investigate the origin and function of this region and its occurrence in nature, the cDNA sequences of the 3' non-coding regions of three additional strains of IBV, Gray, Arkansas (Ark) 99 and Holland (Holl) 52, were determined and compared to the sequences of the Beaudette, KB8523 and Mass41 strains. Not only was this Urich sequence absent from the 3' non-coding region of the Mass41 strain, it was also highly variable, especially in comparison to the highly conserved 3' non coding region downstream of this sequence. Computer analyses of the sequences adjacent to this hypervariable region (HVR) showed that the 3' end of the IBV genome was highly conserved downstream of this region, with 94.3 to 97.8% similarity. However, the similarities for the HVR ranged from 53.2% between Holl52 and Ark99, to 92.8% between Beaudette and Gray. The flanking sequences were not only conserved but these sequences upstream and downstream of the HVR also formed mirrored images.

Comparative analyses of the nucleocapsid genes of several strains of infectious bronchitis virus and other coronaviruses.

The natural sequence variations of the nucleocapsid genes of the Gray, Arkansas99 (Ark99), and Holland52 (Holl52) strains of infectious bronchitis virus (IBV) were determined. These were compared with previously published sequencing data of other IBV strains, as well as other coronaviruses, in order to correlate the serological and evolutionary relationship of coronaviruses. IBV nucleotide sequence alignment shows that overall the sequences are highly conserved, with homologies from 91.1 to 96.5%. However, there are also two regions (730 to 800 and 1138 to 1166) that appear to be even more highly conserved. Overall, the nucleocapsid protein is highly variable both in size and composition between coronavirus major antigenic groups but is conserved within these groups. A phylogenetic tree of the nucleocapsid protein of various coronaviruses indicates that the coronaviruses fall into distinct groups that correspond to the three major antigenic groups; however, a phylogenetic tree of the IBV nucleocapsid shows that this does not hold true for the type specific antigenic groups of IBV.