Preliminary investigations of the colonisation of upper respiratory tract tissues of infants using a paediatric formulation of the oral probiotic Streptococcus salivarius K12.

A powder preparation of the oral probiotic Streptococcus salivarius K12 has been given to 19 young otitis media-prone children following a 3-day course of amoxicillin administered as a preliminary to ventilation tube placement. In two subjects, the use of strain K12 appeared to effect the expansion of an indigenous population of inhibitory S. salivarius. In other children, strain K12 colonisation extended beyond the oral cavity to also include the nasopharynx or adenoid tissue. The relatively low proportion (33%) of subjects that colonised was attributed to failure of the amoxicillin pre-treatment to sufficiently reduce the indigenous S. salivarius populations prior to dosing with strain K12 powder.

Subannular tube insertion: anatomical considerations.

OBJECTIVES: To assess the distance between the bony groove created during subannular tubes placement and the chorda tympani, and examine the depth of the hypotympanum and retrotympanum. METHOD: Grooves drilled in cadaver temporal bones at two levels were imaged to measure: the distance between the chorda tympani nerve and the tympanic sulcus, and the depth of the hypotympanum and the retrotympanum relative to the annulus. RESULTS: The chorda tympani was between 0 and 5 mm from the groove cut across the annulus. The hypotympanum average depth was 2 mm (0.44-6.40 mm) and the retrotympanum average depth was 1 mm (0-2.53 mm). CONCLUSION: Grooves drilled across the tympanic sulcus should be placed at a point 20 per cent of the height of the tympanic membrane or lower; this will ensure least risk of injury to the chorda tympani nerve. The depth of the hypotympanum and retrotympanum dictates that the posteroinferior part of a subannular tube flange should be approximately 2 × 1 mm.

Sinonasal Lymphoma Presenting as a Probable Sanctuary Site for Relapsed B Acute Lymphoblastic Leukaemia: A Case Report and Review of the Literature.

Sinonasal lymphoma is a non-Hodgkin lymphoma (NHL) representing 1.5% of all lymphomas. It presents as an unremitting ulceration with progressive destruction of midline sinonasal and surrounding structures. Poor prognosis warrants early treatment although diagnosis is challenging and frequently delayed. It is usually primary in origin and to our knowledge the sinonasal region has never been reported as a sanctuary site in leukaemia/lymphoma relapse. We present a unique case of B-cell ALL (acute lymphoblastic leukaemia) with late relapse to the nasal septum as a sinonasal lymphoblastic lymphoma and with genetic support for this as a sanctuary site.

CHOP-based chemotherapy is as effective as alternating PEEC/CHOP chemotherapy in a randomised trial in high-grade non-Hodgkin's lymphoma. Scotland and Newcastle Lymphoma Group.

The aim of this study was to test whether survival for patients with high-grade non-Hodgkin's lymphoma (NHL) can be improved with a non-cross-resistant regimen as compared to a CHOP-based regimen. This is a multicentre study comprising 325 adult patients, median age 58 years, with high-grade non-Hodgkin's lymphoma: patients of any age and performance status were eligible provided they were able to receive the drugs in the regimens. Patients were randomised to either B-CHOP-M (bleomycin, cyclophosphamide, doxorubicin, vincristine, prednisolone and methotrexate) or PEEC-M (methylprednisolone, vindesine, etoposide, chlorambucil and methotrexate) alternating with B-CHOP-M. At a median follow-up of 9 years, there was no significant difference in overall survival or disease-free survival between the two arms. Toxicities for the two regimens were equivalent. This study confirms that for relatively unselected patients with high-grade non-Hodgkin's lymphoma, an alternating multidrug regimen does not improve upon the results obtained with B-CHOP-M.

Misonidazole in patients receiving radical radiotherapy: pharmacokinetic effects of phenytoin, tumor response and neurotoxicity.

In 1978, a pilot study began of 29 patients with advanced tumors of the head and neck. The study showed a initial peripheral neuropathy rate of 55%, despite a dose limitation of 12g/m2 of misonidazole. Tumor response at 9 months was most encouraging. We are now able to examine tumor response and persistence of neuropathy in these patients 2 1/2 years after radical radiotherapy. The results are comparable with those obtained with hyperbaric oxygen in a clinical trial at this center during the 1970's. Neuropathy was a serious side effect but the drug phenytoin has been shown to shorten the half-life of misonidazole. We have examined the effect of phenytoin on the pharmacokinetics of misonidazole in 13 patients who received radical radiotherapy for advanced head and neck tumors or oesophageal tumors. Misonidazole was given in multiple doses, i.e. daily or weekly as it would be used in conventional therapy. Phenytoin was given either daily throughout treatment, or it was withdrawn during treatment. There were dramatic changes in the half-life of misonidazole, but the concentration at the time of irradiation was little affected. The significant changes in the half-life of misonidazole and the increased concentration of the metabolite desmethylmisonidazole are discussed.

Solubilization and partial characterization of human and porcine thyrotrophin receptors.

Thyrotrophin (TSH) receptors have been extracted from human and porcine thyroid membranes by treatment with Triton X-100. 125I-Labelled bovine TSH was used to monitor receptor activity. Analysis by gel filtration and electrophoresis on acrylamide gels containing sodium dodecyl sulphate suggested that Triton extracts of human thyroid membranes contained TSH receptors with a molecular weight in the region of 50 000 closely associated with Triton micelles of approximate molecular weight 300 000. Isoelectric focusing studies indicated that the Triton-solubilized TSH binding activity had an isoelectric point of pH 4--4.5. The soluble TSH receptors were heat-labile, showed optimum TSH binding at pH 7.4 and reduced hormone binding at high ionic strength. The TSH binding characteristics of membrane-bound and solubilized human TSH receptors were similar and both preparations gave curved Scatchard plots. Solublized porcine TSH receptors appeared to have a similar molecular weight to the human receptors and were also closely associated with Triton micelles of approximate molecular weight 300 000. Scatchard analysis of TSH binding to membrane-bound or solubilized porcine TSH receptors gave approximately linear plots with association constants of 2.8 +/- 0.95 (S.E.M.) X 10(9) and 1.7 +/- 0.27 x 10(9) l/mol respectively. Comparison of the binding capacities of the solubilized and membrane-bound porcine receptors indicated that the 0.5% Triton extracts contained 40% of the original TSH binding activity and that this was present at a concentration of 25 ng/ml.

Early post-operative brachytherapy and free flap reconstruction in the management of sarcomas.

Brachytherapy delivered within the early post-operative period has been associated with delayed healing and wound breakdown. The objective of this study was to determine whether reconstruction with a microvascular free flap reduced the incidence of wound breakdown after early post-operative brachytherapy and wide excision of soft tissue sarcomas. Four patients with sarcomas underwent excision and free flap reconstruction. Brachytherapy was administered in the early post-operative period using Iridium-192 wires via tubes inserted intraoperatively. In three of the four patients the wounds healed uneventfully, demonstrating that brachytherapy can be delivered in the early post-operative period following free flap reconstruction without an increase in the frequency of wound breakdown. There has been no local recurrence to date in this group of patients.

Acute pulmonary distress following high-dose irradiation of the upper half of the body.

Two cases of acute pulmonary distress following very shortly after irradiation of the upper half of the body are described. The first occurred one hour and forty minutes after irradiation and led to the patient's death three hours after irradiation. The second occurred 15 minutes after irradiation and was successfully treated with hydrocortisone and Frusemide. The features are the sudden onset of dyspnoea and cyanosis associated with pyrexia. Auscultatory evidence of pulmonary oedema was not apparent initially. The response to steroid alone is transitory. High single-dose pulmonary irradiation causes transudation of extracellular fluid and diapedesis of red cells from the alveolar capillaries. The supervention of these effects on severly compromised pulmonary function can well prove dangerous.

The role of computed tomography and coronal plane tomography in radiotherapy for laryngeal cancers.

The results of a study undertaken prospectively in 1983 and 1984 to assess the value of computed tomography (CT) and conventional tomography in the planning of radiotherapy for laryngeal cancer are presented. Of 32 cases treated in 1983, 23 had both CT scans and coronal plane tomography prior to radiotherapy. At the end of 1983 these radiographs were reviewed and an assessment made of their value in treatment planning. As a result of this review it was decided that cancers of the larynx confined to the vocal cords should routinely have conventional coronal plane tomograms rather than CT scans. All other cases were to have CT scans and not tomograms. The results of following this policy in 1984 confirm that it is effective. There was no detriment to patients with early vocal cord cancers in performing coronal plane tomograms rather than CT scans. The survival at 24 months of both cohorts was 93%. In the more invasive cancers of the larynx, greater information about the extent of the disease was obtained using CT scans, and improved treatment plans resulted. When compared with a historical group, there appears to be an advantage for local control, 27.3% of the study group suffering local recurrence as opposed to 53.6% of the historical group.

Gynaecological treatments using the Selectron remote afterloading system.

The Manchester method of gynaecological treatment using radium 226, ovoids and a flexible intrauterine tube has been used in many centres. In Newcastle, the Manchester technique was used until 1971, when a manually afterloaded system (MAS) using caesium 137 and two source trains was introduced. In 1985, the MAS was replaced by the Selectron remote afterloading system (RAS), which also uses caesium-137 sources. The dosimetry of this remote system has been designed to produce the same shape of isodose distributions as the MAS, but shorter treatment times. The applicator design and the dosimetry of the system used in Newcastle are discussed. Dose rates achieved by the RAS are more than double those currently produced by the MAS, and a reduction in prescribed dose of 10-20% is being made. The percentage of ward staff receiving monthly doses of more than 0.2 mSv has fallen from 78% to 18% since the introduction of the remote afterloading system. The almost-cylindrical isodose distributions facilitate matching of external beam treatments using a central lead wedge to the intracavitary treatments, and work is in progress to develop this technique.

Results of treatment of carcinoma of the uterine cervix using the Newcastle afterloading technique.

Eighty-seven patients with carcinoma of the uterine cervix were seen between 1 August 1977 and 31 December 1985. Seventy-one patients were treated radically. A combination of intracavitary radiotherapy, using the Newcastle manual afterloading technique, and external-beam radiotherapy was used. The actuarial 4-year survival for all Stage 1 cervical carcinomas was 84.9%. For Stage 2 cancers the actuarial local control rate was 71.1% and the survival 49.2% and for Stage 3 cancers the 4-year actuarial local control rate was 24.3% and the survival 14.8%. Complications of treatment were confined to the bowel and bladder and occurred in 11.5% of cases. The results of treatment of Stage 1 cancer suggest that the intracavitary technique gives a satisfactory distribution of radiation. The results of treatment of more advanced cases are disappointing and suggest that improvements are possible for some patients (i.e. wedge malalignment patients). There is sufficient flexibility in the technique for it to be applied satisfactorily for most anatomical situations.

A pilot study of accelerated fractionation in the radiotherapy of invasive carcinoma of the bladder.

24 patients with muscle invasive carcinoma of the bladder were treated in a pilot study of twice daily fractionation at radiation doses of 1.8-2.0 Gy per fraction to total doses of 54-64 Gy to the bladder and 39.6-44 Gy to the whole pelvis. The treatment aim was to give 32 fractions in 22 days. The interfraction interval was a minimum of 6 h. The principle objective was to record acute and late tolerance, but local control and survival data is also presented. Acute radiation morbidity was scored according to the RTOG system. Grade 2 large bowel effects were seen in 52% of patients, Grade 3 effects in 26% and there was one Grade 4 and one Grade 5 effect. The mean duration of effect was 4.5 weeks although the more severe reactions were also more protracted. Grade 2 urinary effects occurred in 30% and Grade 3 in 17% of patients. The mean duration of effect was 7.2 weeks. There were no Grade 4 or 5 acute urinary effects. Late radiation morbidity was scored according to the EORTC/RTOG system and was assessable in 16 cases who survived more than 6 months. There were two cases (12%) of Grade 1 bowel toxicity, two cases of Grade 1 and three of Grade 2 urinary toxicity. There were no cases of late skin effects. Actuarial analysis at 2 years shows a local control probability of 56% and survival probability of 35%.

MRI appearances of the axilla in treated breast cancer.

Differentiation between recurrent axillary disease and changes due to radiotherapy or surgery has major implications for management in patients following breast cancer treatment, but clinical examination of the axilla may be difficult. This study was undertaken to correlate the MRI appearances of the axilla following breast cancer treatment with clinical outcome. 74 women with treated breast cancer were evaluated by MRI (0.5 T) and the appearances defined by consensus. Outcome was assessed by long-term clinical follow-up. 62 women had symptoms related to the axilla while 12 were scanned to stage the axilla. None of the axillary staging group had abnormal MRI appearances and none of these subsequently developed recurrence. The 62 symptomatic women were subdivided according to MRI appearances. 22 had normal axillary appearances, 18 had an axillary mass and 22 women had abnormal axillary appearances (rated mild, moderate and severe) in the absence of a mass. Normal axillary appearances on MRI excluded recurrent disease as the cause of symptoms with a specificity of 94.7% and a positive predictive value (PPV) of 95.5%. The presence of an axillary mass was commonly but not exclusively due to recurrent disease (sensitivity 68.4%, specificity 88.4%, PPV 72.2%). Sensitivity for diagnosis of axillary recurrence was increased to 89.5% with a specificity of 76.7% if the criteria for recurrent disease were taken as either the presence of an axillary mass or severe axillary changes in the absence of a mass lesion.

Tracheostomy and radiotherapy in the management of laryngeal carcinoma causing airway obstruction.

Between 1977 and 1985, 66 patients presenting with airway obstruction due to laryngeal squamous cell carcinoma were treated by tracheostomy and subsequent radiotherapy. Female survival (64% at 2 years and 35% at 5 years) was significantly better than male survival (19% at 2 years and 10% at 5 years). When four forms of management were compared, it appeared that 40 Gy in ten fractions over 21 days was associated with better survival. Because two of the treatment groups contained few patients, these were excluded from further analysis. When adjustments were made for sex, delay between tracheostomy and treatment, and residual disease, the difference in treatment response between those receiving 60+ Gy in 28-30 fractions over 42 days and those receiving 40 Gy in ten fractions over 21 days was not significant (hazard ratio 1.37; 95% CI 0.64-3.91).

Combined external beam and intracavitary radiotherapy in oesophageal carcinoma.

Seventy patients (40 males, 30 female; age 36-87 years, median 72 years) who were unsuitable for surgery were referred to the Regional Radiotherapy Centre, Newcastle General Hospital with oesophageal carcinoma (54 squamous cell; tumour length 2-14 cm). Sixty-seven patients received combined external beam radiotherapy (20-50 Gy in 5-20 fractions over 1-4 weeks) followed by intracavitary radiation (66 patients received 10 Gy at 1 cm; the remaining 4 received less) using an endoscopically inserted afterloading technique at 6.4 Gy/hour. Swallowing was restored in 65 patients (92%), although 39 patients (55.7%) subsequently required dilatation. Four developed fistulae (1 day, 2 months, 11 months, 17 months post-treatment). The actuarial survival was 71% at 6 months and 42% at 1 year. The combined treatment is well tolerated, with few complications and provides good palliation.

A comparison of active anterior rhinomanometry and nasometry in the objective assessment of nasal obstruction.

Nasometry is an objective technique that was originally devised for assessing nasality of speech. It is based on a comparison of the acoustic output from the nose and the mouth for a given spoken word or phrase. Subjects with nasal obstruction tend to have "hyponasal" speech and this study compares the standard technique of active anterior rhinomanometry with nasometry in the objective assessment of nasal obstruction. There was a significant association between the Total Nasal Resistance (TNR) and the nasality measurements using nasophonemically enhanced test phrases in 15 adult subjects. This test has obvious advantages over rhinomanometry which can be difficult, time consuming and unreliable particularly in the younger and severely congested patient.

Vestibular schwannoma screening: closing the audit loop.

Completion of an audit loop assessing vestibular schwannoma screening practice in a sub-regional ENT centre shows good agreement between the guidelines given and indications used for selecting patients to undergo screening MRIg. The proportion of cerebellopontine angle tumours diagnosed is consistent with other reports from the United Kingdom. During the audit period the proportion of patients screened because of unilateral tinnitus increased, but not beyond a reasonable estimate of the proportion that could expect to be screened because of this symptom. There was a reduction in the number of inappropriate scan requests after introduction of a guideline reminder. During the initial period after introducing screening guidelines there is increased screening activity, but this plateaus at a steady level.

The early complications of inferior turbinectomy.

A retrospective study has assessed the early complications occurring in 90 patients who underwent inferior turbinectomy during a 3-year period. The operation was complicated by haemorrhage, adhesions, crusting, infection and septal perforation in a proportion of cases, the overall incidence being 20 per cent, and that of significant reactionary or secondary haemorrhage was 9 per cent. Attention has been directed towards possible aetiological factors and measures proposed that may minimise the occurrence of complications.

Myringostapediopexy: surgical expectation.

Myringostapediopexy may occur as a result of incus erosion with medialization of the tympanic membrane and is recognized as often producing serviceable hearing. The technique may be used as part of tympanoplasty following either canal wall up or canal wall down surgery for chronic otitis media. The use of this type of reconstruction is influenced by the anatomy of the ear after disease excision. This review of the hearing levels associated with myringostapediopexy shows that there is a similar range of hearing level both for naturally formed as well as surgically fashioned myringostapediopexy. For both 'naturally formed' and following canal wall up surgery about 80 per cent of patients will have an air-bone gap of 20 dB or less compared to 60 per cent of those who undergo canal wall down surgery.

Early complications of surgery for chronic otitis media.

This audit report details early post-operative complications following surgery for chronic otitis media. One hundred and forty-five cases were assessed. There were no facial nerve palsies, a bone conduction threshold elevation occurred in 4.6 per cent of cases. A wound infection occurred in six per cent of cases as did BIPP allergy. Twenty-six per cent of patients reported symptoms consistent with chorda tympani trauma. Short-lived symptoms of jaw discomfort were reported by 46 per cent of patients and imbalance or vertigo by 10 per cent of patients. The findings are compared with other published reports of complications following ear surgery.