Using historical tropical cyclone climate datasets to examine wind speed recurrence for coastal Australia.

Likelihood estimates of extreme winds, including those from tropical cyclones (TCs) at certain locations are used to inform wind load standards for structural design. Here, wind speed average recurrence intervals (ARIs) determined from TC climate data dating back to the 1970s in two quantile-quantile adjusted reanalysis datasets (ERA5 and BARRA [1990]), and best-track observations for context, were compared with Standardized ARIs (AS/NZS) across seven tropical and two subtropical Australian inland coastal regions. The novelty of this work lies in determining TC-wind speed ARIs from a range of datasets that are not typically used to evaluate this metric. Inherent differences between the data used to determine the Standard ARIs (large sample size allow for larger extrapolations; GEV function) and TC data ARIs (smaller sample size and less certain data; the more asymptotic Lognormal/Weibull functions are used) led to the use of different extreme value functions. Results indicated that although these are two distinct ways of determining design wind speeds, when they are considered equivalent, there was a moderate reproduction of the ARI curves with respect to the Standard in both reanalysis datasets, suggesting that similar analyses using climate model products can provide useful information on these types of metrics with some caveats. Trends in TC wind strength affecting coastal Australia were also analyzed, indicating a potential slight downtrend in tropical West coast TC wind strength and slight uptrend for tropical East coast TC wind strength, noting considerable uncertainty given the short time period and limitations of data quality including over longer time periods. Such trends are not only limited to the relationship between TC intensity and anthropogenic warming, but also to regional changes in TC frequency and track direction. This could lead to significant trends emerging in regional Australian TC wind gust strength before several decades of warming have occurred. It is hoped that climate models can provide both longer-term and a more homogenous base for these types of evaluations and subsequent projections with respect to climate change simulations.

Modification of auditory pathway functions in patients with hearing improvement after middle ear surgery.

We recorded auditory-evoked magnetic responses with a whole-scalp 122-channel neuromagnetometer from seven adult patients with unilateral conductive hearing loss before and after middle ear surgery. The stimuli were 50-msec 1-kHz tone bursts, delivered to the healthy, nonoperated ear at interstimulus intervals of 1, 2, and 4 seconds. The mean preoperative pure-tone average in the affected ear was 57 dB hearing level; the mean postoperative pure-tone average was 17 dB. The 100-msec auditory-evoked response originating in the auditory cortex peaked, on average, 7 msecs earlier after than before surgery over the hemisphere contralateral to the stimulated ear and 2 msecs earlier over the ipsilateral hemisphere. The contralateral response strengths increased by 5% after surgery; ipsilateral strengths increased by 11%. The variation of the response latency and amplitude in the patients who underwent surgery was similar to that of seven control subjects. The postoperative source locations did not differ noticeably from preoperative ones. These findings suggest that temporary unilateral conductive hearing loss in adult patients modifies the function of the auditory neural pathway.

Imaging of olfactory neuroblastoma--an analysis of 17 cases.

A total of 17 histologically confirmed olfactory neuroblastomas treated at Helsinki University Central Hospital between 1962 and 1996 were reviewed retrospectively. The tumors displayed a variety of imaging characteristics and aggressiveness. Imaging evolved from plain X-rays at the beginning of the study period to CT and MRI during the latter part of the study. CT provided the best information about the tumor and its local invasion especially into surrounding bony structures. MRI allowed an estimate of tumor spread into surrounding soft-tissue areas, such as the anterior cranial fossa and the retromaxillary space. However, signal intensity characteristics were not specific for olfactory neuroblastomas. Bone scintigraphy and MIBG scan allowed us to detect distant metastases. Olfactory neuroblastoma is an aggressive malignancy and the prognosis is poor in most cases, as shown by the short survival rates (average 45.3 months) in our study group. The tumor can be detected, delineated and its characteristics suspected by modern radiology. Definite diagnosis is based on histopathology. This study proposes general imaging strategies for detecting this disease.

Labelling of bleomycin with Auger-emitter increases cytotoxicity in squamous-cell cancer cell lines.

PURPOSE: To investigate the cytotoxicity of bleomycin (BLM), two Auger-emitting bleomycin complexes (indium-111 ((111)In)-BLMC) and (111)InCl3 in three squamous cell cancer (SCC) cell lines. MATERIAL AND METHODS: Three recently established SCC cell lines were investigated using the 96-well clonogenic assay. Concentrations causing 50% inhibition in cell survival (IC50) were calculated for BLM and two specific activities of (111)In-BLMC (40 MBq/mg BLM (low) and 195 MBq/mg BLM (high)). RESULTS: (111)In-BLMC (low) was the most toxic to the SCC cell lines. (111)In-BLMC containing 4.9-fold more activity of (111)In (195 MBq/mg BLM) was more effective than BLM (p=0.0029), but not as toxic as (111)In-BLMC (low) (p=0.0023). UT-SCC-19A had a IC50 value for BLM as low as 4.1 nM, whereas IC50 values for (111)In-BLMC (low) and (111)In-BLMC (high) were 2.0 nM and 2.6 nM, respectively. The most chemoresistant cell line UT-SCC-12A had a IC50 value for BLM of 18.8 nM, for (111)In-BLMC (low) 10.7 nM and for (111)In-BLMC (high) 12.7 nM. (111)InCl3 had no cell killing effect. CONCLUSIONS: This study shows that (111)In-BLMC is superior in SCC cell killing compared with BLM. These data provide the basis for further clinical investigations of (111)In-BLMC.

Expression profile of vascular cell adhesion molecule-1 (CD106) in the middle ear using radiolabeled monoclonal antibody.

Adhesive interactions between leukocytes and endothelium are required for subsequent leukocyte extravasation toward inflammatory sites. Understanding the possible kinetic expression of vascular cell adhesion molecule-1 (VCAM-1) in the middle ear cavity during an inflammatory cascade in vivo may be important for clarifying local immunological responses in otitis media. Two inflammatory models were produced in the rat and involved acute middle ear mucosal and cutaneous inflammation induced after inoculation or intradermal injection of lipopolysaccharide (LPS). After intravenous injection of both 125I-labeled anti-VCAM-1 and 131I-labeled control monoclonal antibody (mAb), the kinetic expression of VCAM-1 in the middle ear and skin was assessed by local radionuclide uptake. The biodistribution of an 125I-labeled anti-VCAM-1 mAb as a potential detector of focal inflammation was examined in normal rats. Both inflammatory lesions were characterized by early and sustained (up to 24 h) expression of VCAM-1, with maximal expression at 4 h after LPS stimulation. The kinetics of VCAM-1 expression was similar among the middle ear mucosa or skin specimens studied and different stimulation methods. A similar biodistribution and clearance of radioactivity between 125I-labeled anti-VCAM-1 mAb and 131I- or 99mTc-labeled control mAb were observed. The present result suggest that functional VCAM-1 induced by LPS is expressed in both middle ear tissue and skin lesions and may play a role in the initial stage of inflammatory response produced. Although VCAM-1 upregulation is a very early event in the inflammatory cascade, 125I-labeled anti-VCAM-1 mAb may be useful for the early detection of focal inflammation in the middle ear.

Radioimmunoimaging of glomus tympanicum tumors by In-111 labeled monoclonal antibody using single photon emission computed tomography.

OBJECTIVE: This study aimed to evaluate the diagnostic value of radioimmunoimaging by radionuclide-labeled monoclonal antibody F023C5 (MAb), raised originally against carcinoembryonic antigen (CEA), in patients with glomus tympanicum tumors. STUDY DESIGN: Prospective. SETTING: Preoperative imaging versus radioactivity of removed tumor. PATIENTS: Two patients with paraganglioma (glomus tympanicum). INTERVENTION: Diagnostic. MAIN OUTCOME MEASURE: Radiolabeled MAb accumulates in paraganglioma tissue. Single photon emission computed tomography (SPECT) provides improved detection of lesions. RESULTS: SPECT using F023C5 MAb detected the abnormal accumulation of radioactivity in the middle ear region. This method detected paraganglioma less than 1 cm in diameter. CONCLUSIONS: Successful detection of glomus tympanicum in two patients using In-111-labeled F023C5 MAb is reported. The result suggests the radioimmunoimaging using this antibody is useful for the detection of not only primary glomus tumors, but also of local recurrence and unsuspected lesion in patients with paragangliomas.

Biokinetics of indium-111-bleomycin complex in head and neck cancer--implementations for radiochemotherapy.

Bleomycin (BLM) has been used successfully for treatment of head and neck cancer. Combining radionuclide therapy with chemotherapy is a fascinating possibility. We have studied the biokinetics of BLM labeled with indium-111 (In-111). A complex formed at low pH had an activity of 100 MBq/mg BLM. This substance was intravenously injected into 10 head and neck cancer patients in escalating doses of 75, 175, and 375 MBq. Scintigraphic data from these patients were compared with tissue samples obtained at surgery. The activity distribution and penetration into tumor tissue was not affected by increasing the injected activity. In-111-BLMC uptake was directly proportional to Ki-67/MIB-1 activity and number of mitoses in tumor tissue. Based on the biokinetics, dosimetric calculations for In-111 and In-114m have been performed. S values for realistic geometry (a phantom designed from Patient CT) have been calculated. In-114m could deliver a 4-fold absorbed radiation dose into the tumor compared with In-111. We think that In-111-BLMC could be used for radiochemotherapy in head and neck cancer or adjuvant Auger-electron therapy using In-114m combined with BLM. Further studies on cellular dosimetry should be undertaken.

Squamous cell cancer cell lines: sensitivity to bleomycin and suitability for animal xenograft studies.

Bleomycin (BLM) is a natural antibiotic, toxic to dividing cells (G2/M-phase), also proven effective in squamous cell carcinomas (SCC). We have clinically shown that a short-range beta-emitting radionuclide combined to bleomycin (In-111-BLMC) is a tumor-targeting agent in SCCs. With higher radionuclide activities it may be possible to develop a more effective agent, to be tested in animal studies. Using a 96-well clonogenic assay we investigated three SCC cell lines, grown in our own laboratory. IC20, IC50 and IC90 values for BLM were determined. The UT-SCC-12A and UT-SCC-12B cells were originated from a primary tumor and a metastasis of the same patient. UT-SCC-12A cells were also inoculated subcutaneously into nude mice and the tumor growth was analysed. The IC50 value for UT-SCC-19A cell line was 4.0 +/- 1.3 nM. UT-SCC-12A and UT-SCC-12B were both more resistant to BLM; IC50 values were 14.2 +/- 2.8 nM and 13.0 +/- 1.1 nM, respectively. Within 35 days the weight of nude mice increased 2.8 +/- 0.6g. At 25 and 35 days after tumor inoculations the tumor volumes were 111 +/- 51 mm3 and 874 +/- 577 mm3, respectively. The calculated doubling time was 3.86 +/- 0.76 days. SCC cell lines demonstrate different sensitivity to BLM. Our SCC tumor xenograft model showed a rapid growth proper for radiochemotherapeutic studies using In-111-BLMC. The uptake of In-111-BLMC in vivo has been directly proportional to proliferation activity, and the tumors with high binding capacity could be predicted from animal model dose calculations.

Somatostatin receptor imaging of olfactory neuroblastoma.

Neural-crest tumours, including neuroblastomas, express somatostatin receptors. This can be shown by radionuclide labelling of octreotide, a somatostatin analogue. Studies on imaging with this substance have dealt with childhood neuroblastomas. Olfactory neuroblastoma (aesthesioneuroblastoma) is a rare tumour in which somatostatin receptor content has not been analysed, nor have radionuclide methods for diagnostic purposes been described. We report a case of olfactory neuroblastoma, in which scanning with 111In-labelled octreotide was performed. A strong uptake was seen at the base of the skull. This was confirmed as a recurrent tumour by magnetic resonance (MR) imaging. Uptake was also observed in the neck and chest, indicating extensive spread of the disease. Somatostatin receptor expression has been shown to correlate with prognosis in childhood neuroblastoma. The accuracy of labelled octreotide in the diagnosis of olfactory neuroblastoma indicates that it might be useful in radionuclide therapy of patients with advanced disease, when no other treatment modalities are available.

Imaging and staging of head and neck cancer using a low pH In-111-bleomycin complex.

Bleomycin (BLM), a natural antibiotic toxic to dividing cells has been used for treatment of several forms of cancer. BLM has been labelled with various cations but most have turned out to be unstable in vivo. In-BLM has demonstrated high bone marrow uptake, but by using an In-111-bleomycin complex (BLMC) formed at low pH, the low in vivo stability and high bone marrow uptake can be avoided. Our premise is to combine radiotherapy and chemotherapy by using radionuclide-BLMC. In this study we used In-111-A'2a-c-BLMC in 28 head and neck cancer patients. Scintigraphic findings were compared to those of surgery, pre-operative radiology and proliferation markers. The injected patient activity was approximately 85 MBq, 100 MBq/mg. The half-life of In-111 activity in serum varied from 1.5 to 3.1 h, and in urine from 1.4 to 3.7 h. More than 95% of the urine activity was excreted within 24 h. From biopsies obtained from surgical specimens of 22 patients the absolute uptakes in tumour tissues varied between 0.10 and 0.95 x 10(-3)% ID/g. Uptakes in normal tissues varied from 0.01 to 0.32 x 10(-3)% ID/g, and were always lower than in malignant tissues of the same patients. All patients were examined on the injection day with ultrasonography of the neck. Using In-111-BLMC we missed small metastatic lymph nodes (< 1 cm) in 2 patients, but there were no false positive findings. The critical organ from the dosimetric point of view was the kidney. The absorbed radiation doses with these injected activities were 19 mGy in liver, 75 mGy in kidney and 1.0 mGy in whole body (5 h mean residence time). Our results indicate that In-111-BLMC targets head and neck cancer, and identifies metastatic spread. It could possibly be applied with higher activities for adjuvant Auger-electron therapy of head and neck cancer.

Indium-111 bleomycin complex for radiochemotherapy of head and neck cancer--dosimetric and biokinetic aspects.

Bleomycin (BLM) is used for the treatment of head and neck cancer. In order to improve the effectiveness of this chemotherapeutic drug, BLM was combined with indium-111. A complex of these agents (111In-BLMC), formed at low pH, was injected intravenously into ten head and neck cancer patients in escalating activities of 75, 175 and 375 MBq. The internally delivered dose to the tumours varied from 0.20 to 2.73 mGy at 75 MBq, from 0.33 to 2.51 mGy at 175 MBq, and from 0.87 to 31.3 mGy at the 375 MBq activity level. Uptake of radioactivity was 0.45+/-0.24x10(-3)% ID/g in primary tumours and 0. 52+/-0.20x10(-3)% ID/g in metastases (at 48 h). Tumour volumes varied from 0.51 to 49.0 cm3. The radioactivity half-lives in the tumours were 30+/-7 h. The activity distribution and penetration into tumour tissue were not affected by increasing the injected activity. There was a positive correlation between BLMC uptake and Ki-67/Mib activity as well as number of mitoses in tumour tissue. These data indicate that 111In-BLMC has potential as a radiochemotherapeutic agent in head and neck cancer and that adjuvant Auger-electron therapy is possible using 114mIn-labelled BLMC.

Imaging of olfactory neuroblastoma by In-111 bleomycin complex.

No other successful nuclear method, besides bone scanning, has been reported in the literature for in vivo imaging of olfactory neuroblastoma. In this article, excellent uptake is reported by an In-111 labeled bleomycin complex (BLMC) in the ethmoid region of a histologically confirmed olfactory neuroblastoma. The uptake of BLMC was 0.7 x 10(-3)% ID/g at 48 hours after injection, and tumor-to-muscle and tumor-to-fat ratios were 6:1 and 11:1, respectively. The authors conclude that BLMC should be considered as a useful imaging agent, and the BLMC has potential as a radiochemotherapeutic agent against an olfactory neuroblastoma.

Cytotoxicity of bleomycin and external radiation in squamous cell cancer cell lines of head and neck.

Bleomycin, a natural antibiotic toxic to dividing cells, has been successfully used in combinations for treatment of recurrent head and neck cancer. In this study, we investigated five recently established head and neck squamous cell cancer lines (UT-SCC-2, UT-SCC-8, UT-SCC-9, UT-SCC-12A, UT-SCC-19A) in terms of response to bleomycin and radiation treatment. Experiments were carried out using the 96-well plate clonogenic assay for concentration determinations causing 20% (IC20), 50% (IC50), and 90% (IC90) inhibition of clonogenic survival and dose-response calculations for bleomycin. Survival fraction after a radiation dose of 2 Gy (SF2) was used as a measure for radiation sensitivity. The sensitivity for bleomycin was in good accordance with radiation sensitivity except for cell line UT-SCC-9. This was the cell line most sensitive to radiation (SF2 = 0.25 +/- 0.03) but was fairly resistant to chemotherapy (IC50 = 11.5M). Sensitivity patterns may suggest partly different mechanisms of action.

Effect of epidermal growth factor on tympanic membranes with chronic perforations: a clinical trial.

Epidermal growth factor is an important modulator of cell growth, and its role in normal wound healing is well documented. Epidermal growth factor receptors have been identified in tympanic membranes of different animals. The ability of epidermal growth factor to promote healing of tympanic membrane perforations has recently been shown in experimental animals. We performed a double-blind, placebo-controlled study of the effect of epidermal growth factor applied locally on the tympanic membrane for 1 week in patients with chronic perforations. Seventeen adult patients took part in the study, eight in the epidermal growth factor group and nine in the placebo group. Three placebo-treated patients were later treated with epidermal growth factor, and five patients received repeated epidermal growth factor treatment. Perforation size was measured as a percentage of the tympanic membrane area before and at least 1 month (mean, 2.6 months) after treatment. One perforation in the placebo group healed completely, but none of the epidermal growth factor-treated perforations closed. Perforations became slightly smaller in both groups (mean decrease, 0.3% and 2.7% for epidermal growth factor and placebo, respectively), but these changes in size were not statistically significant for either group. At otomicroscopy, a proliferation reaction with thickening of the tympanic membrane and pseudomembrane formation at the perforation edge could be seen in some ears. Histologically, a sample from one epidermal growth factor-treated ear demonstrated signs of hypertrophic epithelium when compared with the morphology of a placebo-treated tympanic membrane. The only complications were two mild infections in the placebo group. Hearing remained stable after epidermal growth factor treatment.

Mixed hearing loss in otosclerosis: indication for long-term follow-up.

This retrospective study of 146 ears with long-term follow-up after otosclerosis surgery evaluated the stability of hearing results, the incidence of sensorineural hearing loss, and the effect of fluoride treatment. Follow-up was at least 15 years (mean, 25.2 yr; range, 15-44 yr). There were 97 large fenestra stapedectomy operations, 23 lateral canal fenestrations, 7 mobilizations, and 19 revision stapes operations. The level of air-bone gap achieved at surgery remained stable over time; the mean deterioration rate was only 0.2 dB per year. Profound sensorineural hearing loss ( > or = 65 dB bone conduction average) at the most recent follow-up occurred in 13 ears (8.9%). Such hearing loss occurred in all operative groups. Mean bone conduction average immediately postoperatively was significantly higher in these ears than in others in the study. This finding indicates that a mixed hearing loss at surgery is a factor that increases the risk of later profound cochlear loss. Only 3 percent of ears with pure conductive hearing loss, but 28 percent of patients with mixed hearing loss at surgery eventually suffered profound cochlear loss. Sodium fluoride was used to treat 11 ears with progressive cochlear loss. The rate of bone conduction hearing deterioration decreased in all ears after treatment, and none developed profound hearing loss. Follow-up after the first postoperative year is not necessary if pure conductive hearing loss is present at surgery. Annual follow-up with audiograms is recommended if a mixed hearing loss is present. Fluoride treatment is recommended if inner ear hearing loss progresses.

Osteoma of the internal auditory canal. A case report.

Osteomas of the petrous temporal bone are rare and seldom symptomatic. This report describes an osteoma of the internal auditory canal, causing compression of the eighth nerve, leading to auditory and vestibular complaints. The symptoms were abolished by surgical decompression of the internal auditory canal and removal of the osteoma.

Treatment of acoustic tumours in elderly patients: is surgery warranted?

Controversy regarding the best and safest treatment of acoustic tumours in elderly patients still exists. These patients may therefore end up having either microsurgical tumour removal, stereotactic radiosurgery or no treatment at all, depending on where the treatment decision is made. We evaluated the results of microsurgery for acoustic tumour removal in 65 patients who were 70 years of age or older. Surgery was performed between 1982 and 1989, using the translabyrinthine approach. Total tumour removal was achieved in 61 patients (94 per cent). No deaths due to surgery occurred. Other than one case of meningitis, there were no serious complications. Seven cases had post-operative CSF leaks, and three required surgery for correction of the problem. Facial nerve function pre-operatively, at the time of discharge and at one year or more post-operatively was compared to that in a younger age group. No differences between the groups were found. Nor was there any significant difference in mean operative time, blood loss, or hospital stay between the older and younger patients. We believe that total microsurgical tumour removal is the treatment of choice in patients who are in good health, regardless of age. Partial removal is acceptable only if the tumour is adherent to the facial nerve or if vital-sign changes occur during surgery. Other forms of treatment are reserved for cases where surgery is contraindicated or refused by the patient.