Perfusion SPECT in cochlear implantation and promontory stimulation

BACKGROUND: Recent studies of profoundly deaf patients with cochlear implants have demonstrated that these patients are able to process sound in the auditory cortex in a similar way to normal subjects. However, there are large variations in outcome. Various clinical criteria are used for subject selection and the decision as to which ear is to be implanted involves electrical stimulation of the promontory which is used to confirm the persistence of auditory neurones and fibres that can be utilized by the cochlear implant. In this study we have used SPECT with Tc-HMPAO to investigate activation of the auditory cortex in cochlear implantees post-surgery. In addition we also investigated whether electrical stimulation of the promontory does produce change in blood flow in the auditory cortex in pre-surgery candidates, which would indicate viable auditory networks that can be utilized by a cochlear implant device. METHODS AND RESULTS: Image analysis was performed with SPM99. Results of a simple subtraction paradigm indicated bilateral activation of auditory cortex and Wernicke's area in the post-implant group during auditory stimulus (speech) and bilateral activation of the ventral lateral posterior thalamus and bilateral auditory association cortex BA21/22/42, in the pre-implant group during electrical stimulus but no activation of the primary auditory cortex. A conjunction analysis used to investigate the common areas of activation across both groups during the stimulus condition showed that there was a common bilateral activation of the primary auditory cortex in both groups (BA22/41/42). In addition, analysis of a subset of the seven post-implant subjects who did not comprehend the speech in our study showed an activation (Pu<0.05, where Pu is the peak voxel threshold, uncorrected for multiple comparisons) in the left auditory cortex that extended into area BA22 synonymous with Wernicke's area. This supports the theory that this region has a sensory role.     

Mammary tumorigenesis in growth hormone deficient spontaneous dwarf rats; effects of hormonal treatments

This study was carried out to investigate mammary tumorigenesis in growth hormone (GH) deficient spontaneous dwarf rats (SDR). At 50–60 days of age, the rats were divided into five groups. Group 1 received bovine (b) GH (prolonged release formulation) administered at a dose of 40–50 mg/kg body wt. in 50 l weekly injections; group 2 received recombinant human insulin-like growth factor-I (IGF-I) at a dose of 1 mg/kg body wt./day administered via osmotic pumps; animals in group 3 were fitted with subcutaneous silastic capsule containing 30 g 17-estradiol (E2) plus 30 mg progesterone (P4), replaced every 2 months; group 4 received both bGH and E2 plus P4 treatments at the same doses as above, and control animals (group 5) received sham treatments (vegetable oil injection, silastic capsules containing cellulose). After 1week of treatment, all animals were injected intraperitoneally with the carcinogen N-methyl-N-nitrosourea (MNU) at a dose of 50 mg/kg body wt. Other groups of animals, receiving identical hormonal treatment to those exposed to MNU, were treated for 10 days only and then sacrificed for assessment of circulating concentrations of hormones and mammary gland characteristics at the time of carcinogen exposure. The hormonal treatments of the animals exposed to the MNU were continued for an additional 20 weeks and mammary tumor development monitored by weekly palpation and tumors collected as necessary. The rats were weighed weekly. At the end of the treatment period, all animals were sacrificed and remaining tumors were collected. Rats in all groups continued to gain weight throughout the experimental period, but the largest weight gain was see in animals receiving GH either alone or with E2 and P4. Animals treated with IGF-I also gained weight compared to controls, but this weight gain was less than that seen in GH-treated rats. GH treatment alone increased mammary tumor incidence from 4.8% in controls to 100%. Average tumor load and latency in the GH-treated rats were 7.0 ± 0.8 tumors/tumor-bearing rat (mean±SEM) and 57.3 ± 2.7 days (mean±SEM), respectively. As in intact Sprague–Dawley rats, approximately 90% of the tumors that developed in the GH-treated rats were ovarian dependent for growth. IGF-I treatment also increased mammary tumor development to 62.5%. Average tumor load and latency in the IGF-I-treated rats were 1.6 ± 0.4 tumors/tumor-bearing rat (mean±SEM) and 96.2 ± 14.5 days (mean±SEM), respectively. However E2+P4 treatments did not significantly alter tumorigenesis and, surprisingly, simultaneous treatment with E2+P4 and GH obliterated the GH-stimulated increase in tumor development. Prolactin (PRL) did not appear to influence mammary tumorigenesis in the SDRs, as untreated SDRs had significantly elevated serum concentration of PRL as compared with normal Sprague–Dawley (SD) rats, whereas GH-treated SDRs had PRL levels similar to that of normal SD rats. No obvious structural characteristics were associated with high or low susceptibility to mammary tumorigenesis, as assessed by mammary gland whole mounts from the different animal groups sacrificed at the time of carcinogen administration.Enhanced expression of the extracellular signal-regulated kinase 1/2 (ERK1/2), and activation (phosphorylation) of ERK1/2 were associated with an increase in mammary tumorigenesis. Similarly, the expression of the estrogen receptor- (ER) was significantly elevated in animal groups with the highest susceptibility to tumorigenesis, whereas the levels of cyclin D1 expression were not related to mammary tumorigenesis.     

C-myc oncoprotein expression and prognosis in patients with carcinoma of the cervix: an immunohistochemical study

OBJECTIVE: Evaluation of the prognostic significance of c-Myc expression in carcinoma of the cervix. MATERIALS AND METHODS: 132 patients with carcinoma of the cervix presenting at the Cancer Institute in Chennai from 1996-1999 were included in the study. All the cases were treated with a radical course of radiotherapy and had a median follow-up of 36 months. Paraffin blocks obtained from the punch biopsies from the tumours were used for immunohistochemistry. RESULTS: c-Myc nuclear immunoreactivity was observed in 44/132 (33.3%) of tumours. Patients with tumours in Stages 11 B and III B accounted for 112/132 (84.8%) of the cases. Patients with tumours expressing c-Myc nuclear immunoreactivity were found to have more advanced disease; less likely to achieve complete remission (54.5% vs. 78.4%; p < 0.005) and lower disease-free status (52.3% versus 73.8%; p < 0.014). The poor prognostic feature of c-Myc nuclear immunoreactivity was seen in both stage II B (52.9% vs. 76.3%) and stage III B (38.1% vs. 69.4%; p < 0.025). CONCLUSIONS: c-Myc nuclear immunoreactivity is a predictor of poorer response to radiotherapy and poorer disease free status in stage II B and III B carcinoma of the cervix.     

A new surgical treatment of an acute dislocation of the proximal tibiofibular joint

Acute dislocation of the proximal tibiofibular joint is rare, and although most dislocations are treated by closed reduction, open reduction and internal fixation is sometimes required. We present the case of an injury to a professional football player where open reduction and internal fixation with bioabsorbable pins was performed.     

Management of osteoporosis in an orthopaedic department: audit improves practice

Patients presenting with an osteoporosis-related fracture are at increased risk of further fractures. We performed a retrospective survey to determine if elderly patients presenting to the orthopaedic unit at Manchester Royal Infirmary with low energy hip or distal radius fractures were being managed appropriately with regards to assessment, investigation and treatment for possible osteoporosis. The initial survey demonstrated that only 16% of elderly female patients with low energy hip fractures and none of those (0%) with distal radius fractures were started on treatment or referred for further investigations for possible osteoporosis. After changes in our practice, 76% (p < 0.00001) of patients with hip fractures and 81% (p < 0.00001) of those with distal radius fractures were investigated, started on treatment or referred to a consultant physician for the management of osteoporosis.     

Iontophoretic in Vivo Transdermal Delivery of β-Blockers in Hairless Rats and Reduced Skin Irritation by Liposomal Formulation

Purpose. To demonstrate the in vivo transdermal delivery and establish the comparative pharmacokinetics of five -blockers in hairless rat. Methods. Intravenous dosing was initially done via jugular cannula. For iontophoretic delivery, current (0.1 mA/cm²) was applied for 2 h through a drug reservoir patch containing the -blocker (10 mg/ml). Blood samples were collected and analyzed by stereoselective HPLC assays. Any irritation resulting from patch application was quantified by a chromameter. Multilamellar liposomal formulation was prepared by the thin-film hydration method and converted to unilamellar liposomes by extrusion. Results. With transdermal iontophoresis, therapeutically relevant amounts of propranolol (83.78 ± 7.4 ng/ml) were delivered within an hour and lasted for up to 4 h. C_max (185.1 ± 56.8 ng/ml) was reached at hour 3. A significantly higher amount (p < 0.05) of sotalol HCl was delivered compared to other -blockers. There was no significant difference in the S/R ratio of AUC_0-t for enantiomers after both intravenous and transdermal delivery. Skin irritation was significantly reduced (p < 0.05) when a liposomal formulation of the propranolol base was used rather than the base itself. Conclusions. The comparative pharmacokinetics of intravenous and transdermal iontophoretic delivery of five -blockers in hairless rats was established. It was shown that there is no stereoselective permeation.     

Interleukin-10 receptor signaling through STAT-3 regulates the apoptosis of retinal ganglion cells in response to stress

PURPOSE: Interleukin (IL)-10 has recently been shown to promote survival of neurons and glia. The purpose of this report is to investigate whether IL-10 has any role in protecting retinal ganglion cells (RGCs) from death under conditions in which growth factors are removed, or in which oxidative stress is present. Signal transduction pathways that activate IL-10 signaling in RGCs were studied in both stress conditions. METHODS: Effects of various interleukins on the viability of the RGC cell line was determined, and apoptotic cells were quantified. Immunoblot analysis was preformed to identify the IL-10 receptor (IL-10R) and phosphorylated or nonphosphorylated Akt and STAT-3 proteins in RGC extracts. Immunohistochemistry was performed on the rat retinal sections to identify native IL-10R. RESULTS: Apoptosis of RGCs in the absence of growth factors with or without dexamethasone (1 microM) occurred in 68.5% +/- 3.4% and 53.4% +/- 2.6% of cells, respectively, after 96 hours. Addition of IL-10 at a concentration of 50 ng/mL significantly reduced the apoptotic population of RGCs to 28.2% +/- 2.3% in the absence of growth factors with dexamethasone and to 31% +/- 2.7% in the absence of growth factors alone. RGCs as well as native retina expressed functional IL-10R as determined by immunoblot analysis and by the ability of IL-10 to phosphorylate Stat-3. However, IL-10 failed to phosphorylate Akt in these cells. CONCLUSIONS: IL-10 caused a 59% and 42% reduction in the apoptotic population of serum-deprived cells with and without dexamethasone treatment, respectively. These observations establish that activation of IL-10R promotes survival of RGCs and this survival-promoting activity is due to IL-10 signaling through the Stat-3 pathway, which inhibits the cell death and not through the Akt cell survival pathway.     

Human papillomavirus and risk factors for cervical cancer in Chennai,India: a case-control study

To evaluate the role of human papillomavirus (HPV) and other risk factors in the aetiology of invasive cervical carcinoma (ICC), we conducted a hospital-based case-control study in Chennai, Southern India. A total of 205 ICC cases (including 12 adenocarcinomas) and 213 frequency age-matched control women were included. HPV DNA in cervical cells was evaluated by means of a polymerase chain-reaction assay. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were computed by means of unconditional multiple logistic regression models. HPV infection was detected in all but one ICC cases and in 27.7% of control women (OR = 498). Twenty-three different HPV types were found. HPV 16 was the most common type in either cases or controls, followed by HPV 18 and 33. The association of ICC with HPV 18 and HPV 16-associated types was somewhat stronger than the one with HPV 16. Multiple HPV infections did not show a higher OR for ICC than single infections. Other than HPV infection, high parity (OR for >4 vs. /=45 years = 4.2) were significantly associated with ICC, also after restricting the analysis to HPV-positive cases and controls. Poor hygienic conditions were associated with an increased risk of HPV infection among control women but not with ICC risk among HPV-positive women. A vaccine against HPV 16 and 18 may be effective in more than three-quarters of ICC in the study area.