Accidental intravenous administration of racemic adrenaline: two cases associated with adverse cardiac effects.

Accidental intravenous administration of racemic adrenaline (epinephrine) is a rare but potentially lethal complication. We describe a case of a 68-year-old man with chronic obstructive pulmonary disease who developed severe dyspnoea at home, and a case of an 81-year-old woman who had an allergic reaction associated with severe dyspnoea. The paramedics accidentally administered racemic adrenaline intravenously in both cases. Both patients suffered from severe cardiac adverse effects but their outcome was eventually favourable. Previous reports of accidental intravenous administration of racemic adrenaline are also reviewed. We discuss the potential risks of using racemic adrenaline, especially in the treatment of geriatric patients, and the possibilities of reducing the risk of accidents in drug administration.

Prediction of permanent hearing loss in high-risk preterm infants at term age.

UNLABELLED: The aim of this series was to assess hearing screenings; auditory brainstem responses (ABR), transient evoked otoacoustic emissions (TEOAE) and free field auditory responses (FF) for the prediction of permanent bilateral hearing loss in high-risk preterm infants at term post-conceptional age. A total of 51 preterm infants (gestational age < 34 weeks, birth weight < 1500 g) underwent examinations at term and hearing, speech and neurological development were followed up until a corrected age of 18 months. Significant hearing defects were verified by broader ABR examinations under sedation and by clinical ward observation including responsiveness to sounds and enhancement of hearing using an amplification device. Seven bilateral fails in ABR were found, together with nine bilateral fails in TEOAE and four fails in FF screening at term age. Six preterm infants were later confirmed to have a significant permanent bilateral hearing loss, four of whom had also cerebral palsy. Bilateral failure in ABR screening predicted hearing loss with a sensitivity of 100% and a specificity of 98%, TEOAE with a sensitivity of 50% and a specificity of 84% and in the FF examination at the levels of 50% and 98%, respectively. CONCLUSION: Transient evoked otoacoustic emissions alone seem not to be so applicable to the neonatal screening of hearing in high-risk preterm infants as shown earlier in full-term infants, possibly because a hearing defect may be due to retrocochlear damage. Consequently, auditory brainstem response screening seems to be more suitable for very low birth weight preterm infants.

Nasalance scores in snoring children with obstructive symptoms.

OBJECTIVE: Snoring and the sleep apnea syndrome (OSAS) in children are usually caused by adenotonsillar hypertrophy, which may affect air escape into the nose and nasal resonance. A microcomputer-based system makes it possible to objectively determine whether the oral passage is adequately separated from the nasal passage during phonation. The score thus obtained is called nasalance. This study was conducted to verify whether there exists differences in nasalance between primary snorers and OSAS-children. DESIGN: Fifty-three habitually snoring children (31 boys), mean age 6.1 years (range 3.2-10.5 years), were subjected to overnight sleep polygraphy (PG) and nasalance measurements with the Nasometer 6200. The study was successfully repeated 6 months later on 36 children. RESULTS: Nineteen children had obstructive apnea-h ypopneaindex (OAHI)> 1 on overnight polygraphy (OSAS-children), while 32 were considered primary snorers (PS), (OAHI<1). No statistically significant difference in nasalance scores was found between the OSAS- and PS children. Both groups of children had somewhat higher mean nasalance values both for oral and nasal passage sentences than the normative values for Finnish speech. In general, the most habitual snorers had lower nasalance scores than the less frequently snoring children (P=0.05). Earlier adenoidectomy or palatine tonsillar size did not have a significant influence on the nasalance. Adenotonsillectomy did not affect the nasalance scores of the nine children operated on during the follow-up period. CONCLUSIONS: According to the present study, nasalance measurements cannot be used to predict the incidence of OSAS among snoring children.

Epidemiology of moderate to profound childhood hearing impairments in northern Finland. Any changes in ten years?

The epidemiology of childhood hearing impairments was studied in a clinical series of the birth cohorts for 1973-82 and 1983-92 from a geographically well-defined area. The overall prevalence of hearing impairments with PTA0.5-4 kHz > or = 40 dB was 1.2/1000 live births. Even in the later cohort, the median age ascertainment was 2.6 years for the congenital or early acquired group and 3.0 years for all impairments. Risk indicators for hearing impairment were present in half of the children, and those referred for the risk were ascertained at the median age of 1.1 years. The delay from suspicion to ascertainment was over a year in about one fifth of cases, while the median time from referral to ascertainment was only 1.8 months. The planning and implementation of neonatal hearing screening are suggested, and general information is given on paedoaudiology for both parents and professionals. A database could be beneficial in increasing the systemacy of the diagnostic process.

HLA types in women with cervical human papillomavirus (HPV) lesions prospectively followed up for 10 years.

Certain genotypes of HPV have been recently implicated in the etiology of carcinoma of the uterine cervix. In order to determine whether HLA antigen-controlled immunoregulatory functions have a role in the pathogenesis of HPV infections, class I and II HLA antigen typing was carried out on a series of 96 randomly selected women who were part of a cohort of 530 women prospectively followed up for cervical HPV infections in our clinic since 1981. The frequency of the DQ3 antigen, which has previously been reported to be increased among cervical cancer patients, was decreased in our HPV patients compared with the control group of Finnish women, but it was slightly increased in HPV16-infected women (P = 0.0812). However, we were able to demonstrate that HLA-DR5 antigen is significantly increased (i) in patients with high grade cervical intraepithelial neoplasia (CIN) (P < 0.02), and (ii) in women harbouring the high risk HPV type 16 (P = 0.0003), thus confirming earlier reports of an association of this HLA antigen and cervical cancer. Such a close association between the high risk HPV type 16 with an HLA antigen might have important implications in the possible immunogenetic basis of the increased risk for squamous cell carcinoma of the uterine cervix.

Two cases of placenta accreta managed conservatively.

Placenta accreta is a rare complication of pregnancy. Traditionally treatment has been operative, commonly total abdominal hysterectomy, in order to prevent serious haemorrhage or infection. Reproductive function can, however, be preserved by conservative management which is possible in carefully selected cases without risking maternal welfare. We report two cases of placenta accreta managed conservatively--both women delivered after this treatment.

Medical student abuse: an international phenomenon.

OBJECTIVE: To evaluate the prevalence of physical and psychological mistreatment of medical students at two medical schools in Finland. STUDY DESIGN AND SETTING: To enable comparison between Finnish and American students, we used the American Medical Association's Office of Education Research questionnaire. RESULTS: Three of every four students surveyed reported experiencing some kind of mistreatment during their medical education. Students most commonly reported sexual mistreatment, usually as slurs and sexual discrimination, from classmates, preclinical teachers, clinical teachers, clinicians, nurses, and patients. Other forms of verbal abuse, psychological mistreatment, and physical threats were also reported. CONCLUSIONS: All forms of mistreatment were reported occurring less frequently than in the United States; still, the level of such behavior was high. The results suggest the need for more international awareness and debate regarding the habits and behavior of teaching staff in medical schools.

Combined intraperitoneal interferon alpha-2b and mitoxantrone in refractory ovarian cancer.

In a non-randomized clinical trial, combined intraperitoneal therapy with recombinant interferon alpha-2b (20-50 MU) and mitoxantrone (20-50 mg) was studied for recurrent ovarian cancer with ascites. Altogether 19 patients were treated. After primary operation, all patients had received intravenous chemotherapy, 16 of which included cisplatin. One patient had complete response, seven patients partial response, four no change and seven progressive disease. The mean duration of the responses was 5+ months (range 1-12), and mean survival time 4.5+ months (range 1-14+). Eight patients had side effects (flu-like symptoms, dyspnea, abdominal pain, vomiting, diarrhea, fever and bowel obstruction). It was concluded that the formation of ascites in refractory ovarian cancer can be reduced with intraperitoneal administration of interferon alpha-2b and mitoxantrone, with tolerable side effects.

Risk factors associated with cervical human papillomavirus infections: a case-control study.

As a part of the long-term prospective follow-up study conducted for women with genital human papillomavirus (HPV) infections in Kuopio University Hospital, Finland, since 1981, a case-control study was designed to assess risk factors for genital HPV infections. The cases (n = 691) were women who had been invited to attend the follow-up program on the basis of an abnormal cervical smear consistent with HPV-induced cytopathic changes, i.e., had a clinical HPV infection. The controls (n = 706) were a randomly selected group of women who had normal smears in the screening. Both groups were asked to fill in an extensive questionnaire focusing on detailed epidemiologic data on previous gynecologic and obstetric history, sexual practices, sexual partners, and smoking habits. In the multivariate analysis, eight variables emerged as independent risk factors for prevalent HPV infection. These variables could explain over 80% of the risk for infection. The risk for the infection varied with age, being highest in the age group 20-29 years, thereafter declining in the following 10-year age groups. The strongest independent risk factor was the number of sexual partners during the past 2 years (adjusted odds ratio = 12.1; 95% confidence interval 4.3-33.8 for five or more vs. one or no partners). Among the independent risk factors that increased the risk were also current smoking (adjusted odds ratio = 2.7; 95% confidence interval 1.7-4.3), warts in sexual partner(s) (adjusted odds ratio = 3.2; 95% confidence interval 1.6-6.5), and increasing frequency of sexual intercourse per week. Independent risk factors with a protective effect included a normal result in the last Papanicolaou smear, regular use of an intrauterine device as a contraceptive method, and good personal hygiene. No significant association between oral contraceptive use and risk for HPV infection was found. Condom use did not result in protection from the infection. The results of this study support the concepts that sexual intercourse is the main form of transmission among adults and that sexual promiscuity is the most important determinant for genital HPV infections.

ICRU reference points and maximum doses of rectum and bladder in intracavitary radiotherapy.

The absorbed doses in the reference points of the rectum and bladder defined by ICRU report 38 for reporting intracavitary radiotherapy were compared with the calculated maximum doses of these organs. The calculations were validated by a thermoluminescent probe. A good correlation between the doses at the reference points and the calculated maximum doses was found.

Expression of p53 protein related to the presence of human papillomavirus (HPV) DNA in genital carcinomas and precancer lesions.

The E6 protein of the high-risk human papillomavirus (HPV) types 16 and 18 is capable of complexing with the wild-type p53 tumor suppressor gene product, leading to loss of the normal p53 function as an anti-oncogene, whereas the low-risk HPV types 6 and 11 lack this binding property. The malignant potential of HPV 16 and 18 has been ascribed to this complexing of E6 with p53, which regularly leads to undetectable expression of the latter in HPV-positive lesions. To assess the role of p53 in HPV-associated genital carcinogenesis, the expression of p53 protein was studied immunohistochemically in 22 genital carcinomas and precancer lesions; 8 vulvar carcinomas, 1 VIN (vulvar intraepithelial neoplasia), 5 cervical carcinomas and 8 CIN (cervical intraepithelial neoplasia) using monoclonal antibody PAb 1801. Presence of HPV was demonstrated by PCR using HPV consensus primers, and amplified HPV-DNA was digested with the restriction enzymes giving distinct patterns for various HPV-types in gel electrophoresis. HPV-typing was confirmed by in situ hybridization with biotinylated DNA probes. Altogether, 17 of the 22 specimens (77%) showed p53 expression: 67% of the precancer lesions and 83% of carcinomas. Expression was more frequent (89%) in the vulvar than (70%) in cervical lesions. Using PCR,HPV DNA was detected in 19/22(86%) of the samples. The following HPV types were identified: HPV 6 (2 samples), HPV 11 (3 cases), HPV 16 (5 cases), HPV 33 (3 cases), and 6 contained unidentified HPV types. All HPV DNA-negative specimens showed p53 expression. Of the 19 HPV DNA-positive lesions, 5 were p53-negative, three of these being HPV 16 positive CIN lesions. The remaining two HPV 16 lesions were invasive carcinomas with a weak p53 expression. HPV 6 and 11-positive lesions showed a weak p53 expression more frequently than HPV-negative cases and HPV 33 lesions. The results indicate that p53 expression is detectable, but it is less frequent and less intense in HPV DNA-positive genital precancer lesions and carcinomas (particularly those with HPV 16 DNA) as compared with HPV DNA-negative lesions.

Electrophysiological and neuropsychological effects of a central alpha 2-antagonist atipamezole in healthy volunteers.

We studied the electrophysiological and neuropsychological effects of acute modulation of central noradrenergic (NA) transmission using a specific alpha 2-antagonist atipamezole (ATI) in sic healthy volunteers. ATI had effects on resting EEG, auditory event-related potentials and neuropsychological tests. Quantitative EEG revealed increased total power in frontal, parietal and temporo-occipital areas without significant changes in the mean or peak frequencies. Event-related potentials showed no effects on the active attention-related processing negativity or the passive mismatch negativity, but frontally recorded mean amplitude of target-P300 was decreased. Neuropsychological tests after ATI revealed improvement in Digit Span, more errors in Word Recognition task, and no effects on Moss spatial recognition task. In healthy subjects with intact NA systems and without any attention deficit, ATI produced evident NA overactivity. ATI decreased the spontaneous thalamocortical oscillation of EEG and improved focused attention (Digit Span). It impaired, however, more divided attention (decreased mean P300 amplitude, increased errors in Word Recognition).

Colposcopic analysis of genital human papillomavirus infections during an 8-year prospective follow-up.

A long-term prospective follow-up program has been conducted for genital human papillomavirus (HPV) infections in 532 women in Kuopio since 1981. By regular examinations (at 6-month intervals) using colposcopy, cytology and/or punch biopsy, 426 of these women have been followed up for the minimum of 48 months (mean 71 +/- 19 months). These 426 women were included in the present report. The colposcopic data of all women at the first and the latest visits were recorded from the colpophotographs, analysed and correlated with cytology, histology, HPV DNA detection and clinical behavior (i.e. prognosis) of the disease. Colposcopic abnormalities were found in 313 (73.5%) women at the first visit and in 138 (32.4%) patients at the latest visit. HPV infections were diagnosed in 368 (86.4%) women at the first visit and in 75 (17.9%) at the latest visit on light microscopy (i.e. biopsy and/or PAP smear). CIN was found in 54.7% of the women at the first visit. HPV DNA was detected by in situ hybridization in 38.2% of the biopsies assayed. Colposcopical multicentric lesions were found in one third of the women upon examination of the entire lower genital tract. The majority of the lesions were situated within the transformation zone. HPV infection and CIN were most frequently encountered in women with multiple lesions. Progression to CIN III was most frequent in large lesions (28.6%). No colposcopic pattern was able to distinguish HPV infections from CIN lesions, or predict the progression of the former. The results implicate that: (1) colposcopy is an essential method to disclose abnormalities due to CIN and HPV infections, but histological changes cannot be predicted on a single colposcopy; (2) HPV infection is a multicentric disease, making the careful examination of the entire lower genital tract mandatory on every colposcopy; and (3) the HPV progressors cannot be predicted on the basis of the colposcopic patterns.

Placebo-controlled study on the efficacy of the pyrimido-pyrimidine derivative RA 233 in ovarian cancer.

This prospective double-blind, multicenter study was aimed at evaluating the clinical efficacy of RA 233 (a derivative of dipyridamole) in ovarian cancer. Following primary surgery, 497 patients with ovarian cancer were treated with combination cytotoxic chemotherapy; those in clinical stage II were also treated with pelvic irradiation. The patients were randomly allocated to receive RA 233 (N = 251) or placebo (N = 246) for 2 years. The groups did not significantly differ from each other in any of the clinical, therapeutic, or histopathological variables evaluated. There were no significant differences between RA 233-treated patients and placebo-treated patients with respect to appearance of new metastases, progressive growth of malignancy, or survival of all patients, in any of the clinical stages of the disease, in radically operated patients or in nonradically operated patients, in different histopathological groups, or in different age groups. Hence, supplementation of carcinoma therapy with long-term administration of the antiplatelet drug RA 233 has no clinical benefit in this malignancy. Using Cox's multifactorial stepwise analysis, this study revealed that the clinical stage of the disease, the extent of surgery, and the histopathology of the tumor, but not the age of the patient or the use of RA 233, were significant and independent predictors of survival. With respect to the histopathology, the poor prognosis of serous and mesonephric carcinomas appeared to be independent of the other prognosis indicators.

Prevalence, incidence, and estimated life-time risk of cervical human papillomavirus infections in a nonselected Finnish female population.

The authors derived prevalence and incidence figures for cervical human papillomavirus (HPV) infections in an unselected Finnish population of women aged 22. This paper is an epidemiologic study utilizing the mass-screening program that has been conducted in Finland for cervical cancer since the early 1960s. The authors estimated the lifetime risk of cervical HPV infections based on the figures in this program and on those derived from a random sample of 2,084 (out of 28,861) routine Papanicolaou (Pap) smears examined in their laboratory. The mass-screening program was performed between 1985-1986 focusing on a total cohort of 22-year-old women (born in 1963) in Kuopio province. In 1985, 2,013 women were invited of which 1,289 attended. One year later, 1,768 women of those 2,013 were reinvited, and the number of women screened at the second round was 1,069. The routine cervicovaginal Pap smears were taken, including a cell sample from the vagina, exocervix, and endocervix. All smears were screened for the HPV-induced cytopathic changes by the same cytopathologist. The prevalence of HPV infection among the 22-year-old women was about 3% at the beginning of the follow-up and about 7% one year later. The crude annual incidence was 7.0%. According to the estimates for the life-time risk, half of the sexually active women would experience at least one HPV infection within 10 years. Up to 79% of the Finnish females would contract at least one HPV infection between ages 20 and 79 years. This indicates that factors, which are poorly understood at the moment, exist that regulate the development of an invasive carcinoma from a CIS lesion.

Reliability of the moiré method in study of tooth and palatal morphology.

The purpose of the present study was to determine reproducibility of the photographic technique, intra- and inter-examiner reliability of the moiré method for investigating tooth and palatal morphology as well as the agreement between the moiré method and the palatometer in measuring palatal height. Intraclass correlation coefficients (ICC) of 0.88 to 0.95 for three separate photographs for each of the same 40 casts taken by three examiners and measured by a single examiner exhibited high reproducibility of the photographic technique. For studying tooth morphology, the moiré lines were counted from the cusp tips to the mesiobuccal and distolingual fossae. ICC of 0.92 to 0.99 with 95% confidence limits for triple measurements and Pearson correlation coefficients of 0.92 to 1.00 for double measurements showed high intra- and inter-examiner consistency, respectively. For palatal height at the level of the first maxillary molars ICC with 95% confidence limits for triple measurements was 0.98 and correlation coefficient between two examiners 0.98, respectively. Correlation coefficients between the moiré method and the palatometer were also high, with a value of 0.98. In summary, with careful calibration before use, the moiré method proved to be useful and reliable in studying tooth and palatal morphology.

Primary invasive and in situ vaginal carcinoma. Flow cytometric analysis of DNA aneuploidy and cell proliferation from archival paraffin-embedded tissue.

Eleven invasive and five non-invasive primary vaginal carcinomas were studied by DNA flow cytometry using archival paraffin-embedded tissue as starting material. Overall frequency of DNA aneuploidy in the invasive carcinomas was 8/11 (73%). DNA aneuploidy occurred in all four advanced stage (III-IV) and in 4/7 (57%) of the early stage (I-II) carcinomas. Among the squamous cell carcinomas aneuploid DNA content was also associated with non-keratinizing tumor type. Invasive vaginal carcinomas showed a high median S-phase fraction (SPF) (18.4%, range 6.9-31.8%). High SPF values were associated with advanced stage and non-keratinizing tumors. Corrected 5-year survival rate in invasive vaginal cancer was 44%, with no significant relation to DNA ploidy or SPF. In situ carcinomas were almost as often DNA-aneuploid (3/5, 60%) as the invasive carcinomas and had comparable median SPF value (13.4%, range 5.5-24.6). One in situ carcinoma with a high DNA-index and SPF relapsed, but overall 5-year survival rate was 100%. In conclusion, both invasive and in situ vaginal carcinomas frequently contain DNA-aneuploid stemlines and show a high SPF. Although DNA aneuploidy and high SPF correlate with advanced stage and non-keratinizing tumor type, they do not have much prognostic relevance in vaginal neoplasia.

Prospective follow-up of cervical HPV infections: life table analysis of histopathological, cytological and colposcopic data.

A total of 532 women with established cervical HPV infection have been prospectively followed (without treatment) since 1981 for a mean of 45 (SD 21) months. The patients were examined by colposcopy, PAP smears and/or punch biopsy every 6 months. The life-table method was applied to analyze the clinical course (i.e. regression and progression) of the HPV lesions, stratified by their colposcopic pattern, PAP smear findings and grade of CIN. During the follow-up, 107 (41.8%) of 256 patients with HPV-NCIN lesion in the first punch biopsy, experienced spontaneous regression. The corresponding proportions for HPV-CIN I, HPV-CIN II and HPV-CIN III lesions were 31.1%, 34.2%, and 20.7%, respectively. In the overall comparison between these four groups, the heterogeneity in the probability of regression was statistically significant (p = 0.0005). Clinical progression was also associated significantly with the histological grade of the lesions in the first biopsy. Progression rate was only 5.8% for HPV-NCIN lesions, as compared to 12.3% for HPV-CIN I, 20% for HPV-CIN II, and 55.2% for HPV-CIN III. The probability of progression varied significantly between the four groups (p less than 0.00001). Cumulative proportion of regression was 46% for patients with PAP smear class I, 84% with class II, and 82% for those with class III, cells, i.e. PAP smear was not of value in predicting the regression. However, PAP smears predicted clinical progression (p = 0.006 overall).(ABSTRACT TRUNCATED AT 250 WORDS)

Factors associated with progression of cervical human papillomavirus (HPV) infections into carcinoma in situ during a long-term prospective follow-up.

In the course of a prospective study of 508 women with papillomavirus (HPV) lesions of the uterine cervix, 66 lesions that progressed into carcinoma in situ (CIS) were identified and treated by conization during a mean follow-up period of 35 months. The lesions were investigated with light microscopy and with in-situ DNA hybridization using 35S-labelled probes for HPV 6, 11, 16, 18, 31 and 33. After radical cone treatment, 11 of the 66 women (16.7%) have presented with a recurrent HPV infection. The recurrence rate increased with the duration of the follow-up period from less than 10% at the mean follow-up of 25 months to 16.7% at the most recent follow-up at 35 months. Most of these 66 HPV lesions (89%) presented with concomitant CIN in the first punch biopsy, but it is noteworthy that the other 11% presented without concomitant CIN. HPV DNA of at least one of the six types examined was found in 73% of the first biopsies and it is noteworthy that the so-called 'low-risk' types, HPV 6 and 11, were found as frequently as the 'high-risk' types, HPV 16 and 18 (18% and 17%, respectively). This would suggest a similarity in the biological behaviour of these two HPV groups. Although the concept of the 'high-risk' and 'low-risk' HPV types may remain at least partially valid, it is imperative to realize that infection by HPV 6 and 11 by no means excludes the possibility for clinical progression into CIS and eventually to an invasive carcinoma.