p53 expression and cell proliferation as prognostic factors in laryngeal squamous cell carcinoma.

PURPOSE: To investigate the prognostic significance of p53 expression and proliferation markers in primary laryngeal squamous cell carcinoma. PATIENTS AND METHODS: Primary tumors for analyses were obtained from 103 patients, with complete follow-up data. All patients were treated between the years 1975 and 1990. The expression of p53 was analyzed with monoclonal D07 antibody and proliferative activity with Ki-67 (MIB-1) and PCNA (monoclonal 19A2) antibodies. Volume corrected mitotic (M/V) index and histological grade were determined in hematoxylin and cosin-stained slides. RESULTS: Sixty-eight percent of the tumors overexpressed p53. During a median follow-up of 62 months, 41 (40%) of patients relapsed. In univariate analysis site of the primary tumor, stage, p53 expression, histologic grade, and M/V index were significant predictors of disease-free survival. In multivariate analysis, only M/V index was a statistically significant predictor of disease-free survival. Overall survival was significantly better for those overexpressing p53 (10-year cumulative survival rate 68% v 44%, P = .004). In multivariate analysis, M/ V index (P = .02), p53 (P = .02), and stage (P = .007) were statistically significant predictors of overall survival. When this analysis includes stratification according to the type of treatment received, M/V index (P = .007), stage (P = .0002), and p53 (P = .006) were even more significant predictors of overall survival. No association between p53 status and proliferative activity was found. CONCLUSION: Overexpression of p53 is associated with favorable disease-free and overall survival in laryngeal squamous cell carcinoma. It may also have an independent prognostic value in laryngeal cancer. M/V index, p53 overexpression, and stage predict with significant accuracy the 10-year overall survival.

Clarithromycin vs. amoxicillin suspensions in the treatment of pediatric patients with acute otitis media.

Clarithromycin is a new macrolide antibiotic that is active in vitro against a variety of organisms that are responsible for acute otitis media in children. The parent compound is metabolized to microbiologically active 14-hydroxy clarithromycin, which is especially active against Haemophilus influenzae. The safety and efficacy of clarithromycin and amoxicillin suspensions were compared in the treatment of acute otitis media in children 1 to 12 years of age inclusive. This was a Phase III, single blind (investigator-blind), randomized, multicenter clinical trial. Clarithromycin oral suspension was given in a dose of 7.5 mg/kg (maximum, 500 mg) twice daily, and amoxicillin suspension in a dose of 20 mg/kg (maximum, 750 mg) was given twice daily for 7 to 10 days in a 1:1 ratio. Clinical evaluations were performed pretreatment, within 48 hours posttreatment and 10 to 14 days posttreatment. Myringotomy was performed in every child to obtain a microbiologic sample pretreatment and at subsequent visits as clinically indicated. A total of 79 children were enrolled, 39 in the clarithromycin and 40 in the amoxicillin treatment group. Thirty-two children were excluded from the efficacy analysis for various reasons. Clinical success (cure and improvement) rates at 0 to 4 days posttreatment were 93% for clarithromycin and 90% for amoxicillin (P > 0.999). Altogether 17 children (10 receiving clarithromycin, 7 receiving amoxicillin) experienced some adverse event, with gastrointestinal disorders being the most common complaint. No clinically significant differences in laboratory tests were found between the groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Serum levels and urinary excretion of mequitazine after a single oral dose.

Pharmacokinetics of mequitazine, a recently introduced peripheral H1-histamine receptor antagonist of phenothiazine type, was followed up to 72 h after the single oral dose of 5 mg of the drug to eight fasted healthy volunteers. Each subject was treated thrice with a dosing interval of 15 days or more. Thus all the results were triplicated. Serum mequitazine was measured by mass fragmentography using a gas-liquid chromatograph/mass spectrometer set in the electron impact mode. Urine phenothiazines were determined fluorometrically before and after cleaving phenothiazines from their glucuronide conjugates. Peak concentration of mequitazine in serum was 3.19 +/- 1.70 (s.d.) ng.ml-1, time to peak concentration 5.67 +/- 1.68 h, elimination half-life 45 +/- 26 h, and elimination rate constant 0.018 +/- 0.007 h-1. Only 10.9 +/- 3.3% of the dose appeared in urine in unconjugated plus the glucuronidated form during the first 72 h. About 46% of the urinary phenothiazines were glucuronide conjugates. The results suggested that after the oral administration only low mequitazine concentrations appeared in serum, most of the drug seemed to be deactivated by the extrarenal route, and the kinetic properties of the drug resembled those of several phenothiazines used for psychiatric therapy.

Acute otitis media among rural children in Finland.

The occurrence of acute otitis media (AOM) and factors predisposing to the disease among children were studied in a small rural community in Finland. The annual incidence of AOM was 13.5% among children under 16 years of age and 28.7% under the age of 5. The highest incidences were found during the second and third years of life, with a subsequent decrease in incidences, but with the exception of peaks at the ages of 4 and 7 years. The following factors were found to predispose a child to AOM: atopic diathesis, attending a day-care center, a lack or short duration of breast-feeding, frequent respiratory infections, and housing in the center of a community, especially in an apartment. The smoking habits and otitis history of the parents did not significantly affect the occurrence of AOM in children.

Alteration of clinical picture and treatment of pediatric acute otitis media over the past two decades.

The clinical picture of acute otitis media (AOM) has changed greatly over the last few decades: serious complications have almost disappeared but more and more children suffer from recurrent middle ear infections and prolonged silent effusion. In this retrospective study we registered all AOM attacks among children under 10 in two rural municipal areas of Finland during 12-month-periods in 1978-79 and 1994-95. In addition to epidemiological data, the clinical picture and given treatments were recorded. Between study periods the number of children with recurrent AOM attacks increased heavily. The percentage of spontaneous otorrhea decreased from 6.0 to 3.3% (P=0.01) and the proportion of afebrile patients increased from 64.0 to 73.4% (P=0.002). In 1978-79 there were significantly more cases of diagnostic symptoms lasting over 24 h. Prescribing penicillin-V as a primary treatment decreased from 80.2 to 10.5% in favor of broad-spectrum antibiotics. The primary treatment with penicillin-V was associated with a decreased risk of recurrences. Acute tympanocentesis was performed less often and the incidence of surgical treatments (adenoidectomy and/or tympanostomy tube insertion) doubled from 6.2 to 12.4% of the acute cases. Although the clinical picture of AOM has become milder, children are treated with wider spectrum antibiotics. Nevertheless, a large number of children suffer from sequelae and there is a greater need for surgical treatments than 20 years ago.

Middle ear fluid bacteriology of acute otitis media in neonates and very young infants.

The middle ear fluid (MEF) bacteriology of 107 attacks of acute otitis media (AOM) in 101 infants less than 3 months old was analyzed. A total of 108 bacteria were isolated from 85 attacks. Major AOM-pathogens, S. pneumoniae (19%), H. influenzae (9%) or B. catarrhalis (7%) were cultured in approximately one-third of all the attacks. S. aureus (17%) and coagulase-negative staphylococci (22%) without the above pathogens were commonly found, whereas gram-negative enteric bacteria were culturable from only 5 attacks. Only 8% of the MEFs were polymicrobial. More than half of all the bacterial strains produced beta-lactamase. The bacteriology of those younger than one month was not different from that of the others. The same was true with attacks of out-patients and in-patients, except for a larger proportion of beta-lactamase producing strains in in-patients. Nasal-nasopharyngeal and MEF samples showed the same bacteriology in only 20% of cases. Two-thirds of AOM attacks were present in infants with perinatal or other concomitant morbidity, but their bacteriology was not different from those without other morbidity. In addition to the examination of ears in infants presenting with any illness before the age of 3 months, the study stresses the importance of bacteriological analysis of MEF in all cases of AOM at this age.

Clinical features of acute otitis media among children.

The anamnestic and clinical data on all of the 2254 attacks of acute otitis media (AOM) registered among 14200 children (less than 16 years) at risk during a one-year period were analysed. On the basis of otoscopic findings AOM was classified into three grades: 25.0% of the cases were considered mild, 39.0% moderate and 36.0% severe. Spontaneous perforation was found in 4.6% of the cases. 76.2% of the attacks were preceded by a respiratory infection, but only 1.4% were sequelae of some epidemic childhood disease. Earache was present in 73.5% of the attacks; in 81.0% of these it had lasted less than 24 hours. 39.4% of all the attacks were bilateral; during the first 2 years of life the proportion was 53.7%, decreasing thereafter with increasing age, and being only 18.7% among those 10-15 years old. In unilateral attacks the right ear was affected slightly, but not significantly, more often.

Incidence of acute otitis media up to the age of 1 1/2 years in urban infants.

The object of this prospective cohort investigation of 1,642 infants was to study the incidence of acute otitis media (AOM) in urban children during the first 18 months of life. The monthly incidence of AOM was greatest at the age of 10 months, and the largest proportion of children with AOM was also found in this 10-month age group. Before the age of 18 months, 56.7% of the infants had had at least one episode of AOM, while 26.9% had had one or two episodes and 29.8% three or more. The corresponding figures before the age of 12 months were: 45.3%; 26.8%; 18.5%, and before the age of 9 months: 30.5%; 22.1%; 8.4%. The AOM incidence, particularly as regards recurrent AOM, was rather higher in boys than in girls.

Occurrence and recurrence of acute otitis media among children.

The occurrence and recurrence of acute otitis media among 37 570 Finnish children at risk who were under 15 years of age were studied. During a one-year period, 4 337 of the children experienced a total of 6 249 attacks of acute otitis media, giving an annual incidence rate of 16.6%. The highest incidence, 75.5%, was found among infants 6--11 months old. 50% of Finnish children had experienced at least one ear infection before their third birthday and 75% before the age of 10, and among this latter group the total number of otitis attacks per child-year during a lifetime was 0.71. Among children under 10, half of the index attacks were recurrences, and among children under 16, 28% of the index attacks were followed by recurrences during the study year. The highest relative recurrence rate was found during the second year of life. Before the second birthday both incidence and recurrence rates were significantly (p less than 0.001) higher among boys. Acute otitis media was most common in the higher social class families and the lowest incidence and recurrence rates were found among children of farmers.

Glottic and supraglottic laryngeal carcinoma: differences in epidemiology, clinical characteristics and prognosis.

In order to evaluate differences in epidemiology, clinical characteristics and prognosis, 166 glottic and 127 supraglottic cases of laryngeal squamous cell carcinoma diagnosed between 1962 and 1991 at Tampere University Hospital, Finland, were reviewed. The annual age-adjusted incidence in males decreased from 6.7/100,000 to 2.6/100,000 and the proportion of glottic tumours increased from one-third to two-thirds during the study period. The proportion of early stage lesions was greater among glottic tumours, and patients with a supraglottic tumour presented more often with neck node metastases. Hoarseness was the most common symptom, being more prevalent in patients with a glottic tumour. The symptom pattern of supraglottic carcinoma was altogether more diffuse. The 5-year disease-specific survival was 81% in glottic and 70% in supraglottic disease, but the difference in survival was not statistically significant. In the multivariate Cox regression analysis, higher T-category and presence of neck node metastases had adverse prognostic effect, while location of the tumour did not significantly affect the prognosis. Favourable changes in smoking habits seem to be the main reason for the incidence decrease and obviously also for the decrease in the proportion of supraglottic tumours.

Risk factors affecting the occurrence of acute otitis media among 2-3-year-old urban children.

The factors affecting the occurrence and recurrence of acute otitis media (AOM) were studied among 471 2-3-year-old children in two cities in Finland. Of these children, 188 had experienced greater than or equal to 3 attacks of AOM, 76 had had 1-2 attacks and 207 no otitis attacks (= control group). The study showed that the risk of recurrent AOM was increased among those children attending day-care nurseries as well as among those who had several siblings. Proneness to rhinorrhea and exposure to passive smoking at home was associated with an increased risk of AOM, while prolonged breast-feeding (greater than 6 months) seemed to reduce it. No correlation was found between the risk of recurrent AOM and the place of residence or type of housing, the parental otitis history, or atopic diathesis of a child. Thus the study suggested that to protect a young child from AOM we should promote breast-feeding and home-care for babies as well as avoid smoking in the home.

Wound healing and soft tissue effects of CO2, contact Nd: YAG and combined CO2-Nd: YAG laser beams on rabbit trachea.

Rabbit trachea was used as an experimental model to study tissue effects and healing of full-thickness tracheal lesions produced by CO2, contact Nd: YAG and combined, coaxial CO2-Nd: YAG (Combo) laser beams. Two power settings (10 W and 16 W) were used with CO2 and contact Nd: YAG lasers. Three different CO2/Nd:YAG power ratios (1:1, 1:2 and 1:4) and power settings (12 W 15 W and 16 W) were used with the Combolaser. Histological specimens for light and transmission electron microscopy were prepared immediately and 1, 3, 5, 7, 14 and 21 days postoperatively. The wound with the most precise and fastest healing was produced by contact Nd: YAG laser. CO2 laser produced a moderate amount of charring and the largest amount of coagulated tissue with a slightly prolonged healing period. In the acute phase, tissue defects produced by the Combolaser with power ratios 1:1 and 1:2 resembled the CO2 laser lesions but with slightly less charring. The power ratio 1:4 diminished the cutting properties of the beam considerably. During the healing period the Combolaser produced the most intensive inflammation and granulation tissue formation resulting in delayed regeneration of the lesion. In transmission electron micrographs the most severe damage to chondrocytes was seen after using the Combolaser. These findings indicate that the Combolaser produces deeper tissue damage than CO2 or contact Nd:YAG laser. However, the Combolaser appears to be suitable for tracheobronchial operations, owing to its good simultaneous cutting and haemostatic properties.

The Bayesian approach to the evaluation of risk factors in acute and recurrent acute otitis media.

A multivariant modelling method was used to analyse the risk, associated with 22 different factors, of contracting acute otitis media (AOM) in a prospective cohort of 1294 urban children followed up to the age of 17-32 (mean 25) months. By far the most important risk factor was the caring of the child at a day-care centre. The importance of this factor further increased with increasing recurrence of the attacks. Next in order came the existence of sibling(s) with AOM attacks during the follow-up. Prolongation of breastfeeding increased the protection against AOM during the first year of life. The frequency of AOM attacks was lowest around midsummer and highest in early winter.

Pneumococcal middle ear fluid antibodies after pneumococcal acute otitis media in infants.

Forty-one infants, who during their first (initial) acute otitis media (AOM) had culturable S. pneumoniae (Pn) in 57 middle ear fluids (MEFs) which prolonged or recurred during the follow-up, were observed for 7-15 months for the presence of Pn, Pn-antigens (Pn-ags) and initial-type/group Pn-antibodies (Pn-abs) in these MEFs. Initially, Pn-abs were found in only 3 MEFs. During the follow-up a total of 20 ears (35%) were, at various time-intervals, positive for Pn-abs; they belonged to all three major Ig-classes, but were often slight in quantity. Most regularly, and often with distinct positivity, Pn-abs were found to type 3, 9N and 14. Secretory abs were detected in 5 ears. Within one month after initial AOM, Pn-abs appeared in 9 of the 41 ears with MEF (22%); six of them cleared soon after that. MEFs with Pn-abs usually did not show initial-type Pn/Pn-ag, but new Pn/Pn-ag could later be simultaneously present in recurrent MEF. So, pneumococcal AOM may cause a local and/or systemically mediated immune response in the middle ear in infants. The response may protect the ear from homologous, but still be present in apparently non-homologous otitis media.

Speech articulation after subtotal glossectomy and reconstruction with a myocutaneous flap.

Speech samples of 9 subjects (8 males, 1 female) were recorded before and 0.5-2 years after a partial glossectomy and reconstruction with a pectoralis major myocutaneous flap. A reading sample, a list of meaningful and nonsense words, and a list of sustained vowels were recorded. The speech samples were evaluated by pairs of naive listeners and using acoustic analysis of the vowel production. Each pair listened to the recordings of only one patient. Inter-rater agreement was satisfactory. The general impression of the speech outcome varied from normal to moderately impaired. The perceptually estimated impairments of speech articulation in the after/before comparisons were statistically significant. Only the first formant of the vowel /i/ (rise) and the second formant of the vowel /a/ (drop) changed significantly at the group level. There was a negative correlation (r = -0.79) between the extent of tongue resection and the drop of the second formant of the vowel /a/. The perceptual variables showed a relationship (r = 0.74-0.82) with the changes in the level of the second formant of the vowel /i/. The relationship that emerged between the perceptual estimates and the objective acoustic parameters suggests that it will be possible to develop clinically relevant test batteries for articulatory quality analysis.

Incidence of acute otitis media.

The occurrence of acute otitis media was studied over a one-year period in a total population of 146822 persons living in different parts of Finland. Of these 146822 persons, 4583 experienced a total of 6518 otitis attacks giving an annual incidence rate of 4.44% (4.48% in males and 4.07% in females, P less than 0.001). Acute otitis media was strikingly concentrated in the youngest age groups, with the highest annual incidence rates, in the order of 50%, found in infants younger than 2 years. Half of all the episodes occurred before the age of 33 months. The relative risk of getting acute otitis media was about 200 times higher during the first 2 years of life than as an adult. The occurrence of otitic episodes followed seasonal variations, and in urban areas the incidence was significantly (P less than 0.001) higher than in the countryside.

Occurrence of tracheal carcinoma in Finland.

During the period 1967-1985, 95 primary tracheal carcinomas occurred in Finland. The mean annual incidence rate was one per one million inhabitants, the male:female ratio being 7:3. There was a significant increase of the disease by increasing age with the exception of 70-79 years. The most common location was the lower third of the trachea. Over two-thirds of the tumours were squamous carcinomas. Smoking seems to be an important risk factor at least in males.

Branhamella catarrhalis in acute otitis media.

A total of 5217 middle ear fluid (MEF) samples obtained from 1203 children with otitis media, aged 3 months to 6 years, were studied for the presence of Branhamella catarrhalis (Br) between Oct. 1977 and Sept. 1981. Br grew in 10.2% of 3497 MEFs of acute otitis media (AOM), with almost the same frequency in the very first and subsequent attacks. During the first 4 years of life the percentage did not vary much; among older children it seemed to decrease. The overall prevalence of Br in AOM did not change during the study period. Br alone grew in 72.4% of acute MEFs with Br; with other bacteria the respective figure was 82.9% (p less than 0.001). Acute attacks with bilateral Br were found in 22.8% of attacks with Br. In 1720 non-acute MEFs obtained at postacute control visits, Br was isolated in only 7.0%. The proportion of beta-lactamase-producing strains among the 2419 otitis-Br strains tested in two laboratories of the two study regions showed an increase from 27.1% and 21.1% in 1980 to 57.6% and 38.6% in 1983, respectively (p less than 0.001).

Haemophilus influenzae in acute otitis media.

We studied the occurrence of Haemophilus influenzae (Hi) in 2625 middle ear fluid (MEF) specimens obtained from 523 children with otitis media, aged 3 months to 6 years, between October 1977 and May 1979. In clinically acute cases 12.3% of the MEFs grew Hi; 6.3% (13/206) of the strains were of type b and 4.9% (10/206) were beta-lactamase producing. In the very first acute case of a child 8.0% (21/263) of the MEFs grew Hi, but in acute recurrences it was cultured in 17.0% (184/1082) (p less than 0.001). In non-acute persistent MEFs obtained during control visits Hi was found in no less than 21.7% (198/913); as many as 12.6% (25/198) of them were beta-lactamase producing. Both of these figures, but not the proportion of type b strains (8.6%), were significantly (p less than 0.001 and p less than 0.01, respectively) greater than in clinically acute MEFs. Hi was grown in 13.1% of the acute MEFs taken from children less than 4 years old, but in only 8.6% of the older children (p less than 0.05). The annual survey of all the 1816 Hi strains isolated from the MEFs of acute or subacute cases of otitis media in one laboratory in 1976-81 showed the proportion of beta-lactamase producing strains of all Hi strains to be gradually increasing from 8.0% (17/212) in 1976 to 15.2% (16/105) in 1981 (p less than 0.05).