Jukka Sipilä

Nasal insulin to prevent type 1 diabetes in children with HLA genotypes and autoantibodies conferring increased risk of disease: a double-blind, randomised controlled trial

BACKGROUND In mouse models of diabetes, prophylactic administration of insulin reduced incidence of the disease. We investigated whether administration of nasal insulin decreased the incidence of type 1 diabetes, in children with HLA genotypes and autoantibodies increasing the risk of the disease. METHODS At three university hospitals in Turku, Oulu, and Tampere (Finland), we analysed cord blood samples of 116 720 consecutively born infants, and 3430 of their siblings, for the HLA-DQB1 susceptibility alleles for type 1 diabetes. 17 397 infants and 1613 siblings had increased genetic risk, of whom 11 225 and 1574, respectively, consented to screening of diabetes-associated autoantibodies at every 3-12 months. In a double-blind trial, we randomly assigned 224 infants and 40 siblings positive for two or more autoantibodies, in consecutive samples, to receive short-acting human insulin (1 unit/kg; n=115 and n=22) or placebo (n=109 and n=18) once a day intranasally. We used a restricted randomisation, stratified by site, with permuted blocks of size two. Primary endpoint was diagnosis of diabetes. Analysis was by intention to treat. The study was terminated early because insulin had no beneficial effect. This study is registered with ClinicalTrials.gov, number NCT00223613. FINDINGS Median duration of the intervention was 1.8 years (range 0-9.7). Diabetes was diagnosed in 49 index children randomised to receive insulin, and in 47 randomised to placebo (hazard ratio [HR] 1.14; 95% CI 0.73-1.77). 42 and 38 of these children, respectively, continued treatment until diagnosis, with yearly rates of diabetes onset of 16.8% (95% CI 11.7-21.9) and 15.3% (10.5-20.2). Seven siblings were diagnosed with diabetes in the insulin group, versus six in the placebo group (HR 1.93; 0.56-6.77). In all randomised children, diabetes was diagnosed in 56 in the insulin group, and 53 in the placebo group (HR 0.98; 0.67-1.43, p=0.91). INTERPRETATION In children with HLA-conferred susceptibility to diabetes, administration of nasal insulin, started soon after detection of autoantibodies, could not be shown to prevent or delay type 1 diabetes.

Intranasally administered insulin intended for prevention of type 1 diabetes—a safety study in healthy adults

Intranasally applied insulin is one of the antigen‐specific therapies currently tested in clinical type 1 diabetes prevention trials, for example, in the Type 1 Diabetes Prediction and Prevention Study (DIPP). The possibility that the therapy may cause hypoglycaemia or local irritation and the poorly known immunological safety of mucosal application of the antigen in healthy subjects prompted this study.

Correlations between subjective sensation of nasal patency and rhinomanometry in both unilateral and total nasal assessment

The correlation between rhinomanometry and subjective sensation of nasal obstruction was studied. Patients assessed their nasal airway patency using a visual analogue scale (VAS). The VAS results and rhinomanometry correlated better when unilateral nasal obstruction was evaluated compared to total nasal evaluation. When rhinomanometric data were divided into four clinically relevant grades of obstruction (very patent, normal, obstructed and very obstructed) and the quartiles of the VAS results were compared to these, the agreement was good or fairly good in 75-85% of cases. A similar result was also encountered when, in an experimental study, 30 individuals were asked to breathe through four artificial nose models with a varying inner diameter of 9-3 mm. Again, most subjects assessed these models logically, but in 11% of the cases the subject assessed the narrowest tube as patent or the widest tube as very obstructed. Our results prove the necessity of having some sort of objective method to evaluate nasal patency; if we rely only on the patients sensation, we may get a misleading picture of his nasal function.

Panendoscopy and synchronous second primary tumors in head and neck cancer patients

Endoscopy techniques are used to diagnose and to determine the extent and exact location of malignancies in the head and neck region, bronchial tree and esophagus. Panendoscopy is used to find the primary tumor in the case of metastatic disease from unknown primaries or to detect a simultaneous second primary tumor at the time of diagnosis of a malignancy in the upper aerodigestive tract (UADT). The value of panendoscopy has been debated lately because of the relatively small proportion of malignant findings and because of the lack of convincing data concerning its effect on survival rates. However, despite the relatively low proportion of positive findings, their significance is often crucial for the individual patient. The significant number of late metachronous, second primaries, especially in the lungs, also emphasizes the importance of follow-up endoscopies. This study consists of 203 consecutive patients with squamous cell cancer (SCC) of the upper aerodigestive tract who underwent panendoscopy in Turku University Central Hospital as part of the initial diagnostic workup from 1992–1999. Eight patients with synchronous second primaries were found to represent a prevalence of 3.9%, and in addition, 19 patients with metachronous tumors were diagnosed. In the case reports we illustrate the importance of some of these findings.

Early percutaneous endoscopic gastrostomy nutrition in head and neck cancer patients

Objective Many head and neck cancer patients suffer from poor nutrition. Nutrition is a problem during and after therapy, especially when it consists of extensive surgery, intensive (chemo)radiotherapy or their combination. Additional enteral nutrition has been provided by means of either nasogastric tube feeding, surgical gastrostomy, radiologic percutaneous gastrostomy or percutaneous endoscopic gastrostomy (PEG). Because of the straightforward, easy technique involved and its low complication rate, PEG has become established as the primary route of nutrition in these patients. Previously, the aim of assisted enteral nutrition was to compensate for already existing malnutrition; nowadays, an additional purpose is to diminish or prevent the development of malnutrition. The main objective of this study was to evaluate the safety of pre-treatment PEG in a sample of patients with an upper aerodigestive tract area malignancy treated in a tertiary referral centre. Material and methods A total of 79 patients with an upper aerodigestive tract area malignancy were treated with a total of 80 PEGs during the period 1997–2001. Results Most of the PEGs (62/80; 77.5%) were performed by an otolaryngologist. An open gastrostomy was needed in five cases because of unsuccessful gastroscopy due to oesophageal stricture (n=4) or severe trismus (n=1). Both acute and late complications were minor and the respective complication rates (1/80; 1.3% and 12/80; 15%) were low. In addition, all complications were easily managed and did not seriously affect the actual treatment. Conclusions A major advantage of having the PEG performed by the otorhinolaryngologist was the possibility to combine it easily with other necessary procedures, such as panendoscopy, tracheostomy and additional biopsy. In addition, the timing of the procedure was easy to schedule.

MicroRNA profiles in nasal mucosa of patients with allergic and nonallergic rhinitis and asthma.

Rhinitis and asthma commonly coexist and are often regarded as “unified airways disease.” Evidence exists that microRNAs are important in controlling inflammatory processes, but little is known about their role in airway inflammation. The present study evaluated the inflammatory profiles of patients with allergic rhinitis (AR), with and without concomitant asthma, and of patients with nonallergic rhinitis (NAR).

Mediastinoscopy Its Role and Value Today in the Differential Diagnosis of Mediastinal Pathology

Mediastinoscopy has been an important method in the differential diagnosis of mediastinal pathology since it was presented by Carlens in 1959. Present investigation methods in radiology such as computed tomography and magnetic resonance imaging as well as the new developments in ultrasonography have resulted in a decrease in the number of mediastinoscopies performed. In addition, better results of fine-needle aspiration and core-needle biopsy investigations together with new techniques in thoracoscopy have brought alternative possibilities in examining mediastinal masses. To evaluate the role of mediastinoscopy today, a retrospective study was conducted comprising 249 consecutive patients who had undergone mediastinoscopy in the years 1989-1997 at Turku University Central Hospital. Mediastinoscopy was technically possible in 229 of the 249 cases (92.0%) and a definitive diagnosis was obtained in 210 cases (84.3%). The mortality rate was zero and only 13 complications (5.2%) were reported. Six cases of paresis of the left recurrent nerve were reported, four of which were temporary. There were also five minor intraoperative and two postoperative bleedings, which were easily controlled. We still consider mediastinoscopy as a safe and efficient way of examining mediastinal pathology.Mediastinoscopy has been an important method in the differential diagnosis of mediastinal pathology since it was presented by Carlens in 1959. Present investigation methods in radiology such as computed tomography and magnetic resonance imaging as well as the new developments in ultrasonography have resulted in a decrease in the number of mediastinoscopies performed. In addition, better results of fine-needle aspiration and core-needle biopsy investigations together with new techniques in thoracoscopy have brought alternative possibilities in examining mediastinal masses. To evaluate the role of mediastinoscopy today, a retrospective study was conducted comprising 249 consecutive patients who had undergone mediastinoscopy in the years 1989 1997 at Turku University Central Hospital. Mediastinoscopy was technically possible in 229 of the 249 cases (92.0%) and a definitive diagnosis was obtained in 210 cases (84.3%). The mortality rate was zero and only 13 complications (5.2%) were reported. Six cases of paresis of the left recurrent nerve were reported, four of which were temporary. There were also five minor intraoperative and two postoperative bleedings, which were easily controlled. We still consider mediastinoscopy as a safe and efficient way of examining mediastinal pathology.

Operative Treatment of Frontal Sinusitis

When the medical therapy fails trephination is the primary operation indicated in acute eroding sinusitis when drainage is necessary to avoid severe complications. In recent years also endoscopic transnasal surgery has been recommended for exenteration of the underlying disease in the ostiomeatal unit as well as for opening of the obstructed nasofrontal duct in acute phase of the disease. In Turku University Central Hospital endoscopic frontal sinus surgery is still reserved for cases with prolonged or delayed disease performed as a secondary operation after trephination and CT examination. Failures are common after these operations and both types of surgical treatment may be needed. Three percent of our patients developed a persistent chronic infection inside the frontal sinus. In these cases external osteoplastic approach is recommended. In these operations we have used bioactive glass as obliteration material with promising clinical results.

Sleep disorders in patients with severe nasal obstruction due to septal deviation.

The role of nasal obstruction in etiology of the sleep apnea disease is controversial in literature. Forty-six subjects (3 women, 43 men) with severe nasal obstruction due to septal deviation were evaluated. The examination included case history, clinical ORL examination by ENT specialist, rhinomanometry and whole night sleep recording (SCSB, oximetry, EKG). Mean age of the patients was 40.0 years (from 17 to 68 years) and body mass index 26.0 kg/m2 (from 20.3 to 34.6 kg/m2). The chief complaint of the patients was a severe nasal obstruction. Thirty-one patients (67%) had also heavy disturbing snoring, and apnea periods during sleep were reported by 10 cases. The evaluation of the sleep recordings revealed 12 cases with partial upper airway obstruction (26%), 1 case with severe airway obstruction, 1 case with mixed type of obstructive apnea and 3 cases with periodic limb movements. Evaluation of the oxygen desaturation of the blood revealed only 6 cases with significant disturbance (pO2 below 90% level). As a final result we conclude that severe nasal obstruction can lead to breathing disturbance during sleep.

The Effect of Laser-uvulopalatopharyngoplasty on the Nasal and Nasopharyngeal Volume Measured with Acoustic Rhinometry

Nasal breathing is considered as an important factor in sleep apnea and snoring, and nasal obstruction can lead to an increased respiratory resistance and to inflammatory reactions in the nasal mucosa. Uvulopalatopharyngoplasty is an effective treatment for sleep apnea and snoring. Different operation techniques with minor variations have been introduced during the last few years. Uvulopalatopharyngoplasty with laser technique (LUPPP) has made it possible to perform the operation in local anesthesia. Acoustic rhinometry is a new method for the evaluation of the nasal cavities and the nasopharynx. We measured the volume of nasal cavities and nasopharynx of 29 patients using acoustic rhinometry before and 6 months after the LUPPP operation. There was a tendency to a better nasal patency in the turbinate area, but no change was found in the nasopharyngeal volume. Acoustic rhinometry is a useful tool for measuring the turbinate area, and this part of the nasal cavities seems to be influenced by the LUPPP operation, maybe due to a better ventilation or reduction of the inflammation of the nose. However, technical and methodological improvements are needed before reliable measurements are achieved from the nasopharynx area.