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Biomedical subjects

H Lindeberg

Publications and source records attributed to H Lindeberg.

At least 19 recordsLinked to original sources

Laryngeal dysplasia and the human papillomavirus.

The relationship between the human papillomavirus (HPV) and cancer of the upper aerodigestive trace is controversial. There is no doubt that at least some nasal, oral, pharyngeal and laryngeal carcinomas contain HPV DNA. However, the diversity in the reported incidence of HPV in these tumours represents a major problem. In the present study we have examined 30 laryngeal dysplastic lesions for HPV by the polymerase chain reaction, using three different pairs of consensus primers (GP5+/GP6+, MY09/MY11 and CPI/CPII). The single HPV-positive specimen was from a recurrent laryngeal papilloma. The HPV type present could not be determined, but it was not type 6, 11, 16, 18, 30, 31, 33 or 45. Restriction fragment length polymorphy analysis suggested a yet unknown HPV-type in this lesion. This investigation does not support the idea of HPV as an oncogenic cofactor in most laryngeal carcinomas as HPV was present in only 1/30 precancerous laryngeal lesions.

Carcinoma

Carcinomas occurring in papillomas of the nasal septum associated with human papilloma virus (HPV).

Carcinomas arising in pre-existing sinonasal papillomas of the nasal septum are rare. To our knowledge only one case has been reported. We report two cases of carcinomas occurring in septal papillomas. In the first case a carcinoma developed in an exophytic papilloma 16 years after the first operation for a papilloma. In the second case a carcinoma was present at the first presentation within an inverted papilloma, and a metastasis had also developed. In the first case HPV type 6/11 was demonstrated by in-situ hybridisation and PCR in the original papilloma as well as in the recurrent papilloma and in the carcinoma. In the second case HPV type 18 was found in the nasal lesion as well as in the metastasis. All samples were examined for Epstein-Barr virus (EBV) by PCR, but with negative results. We believe that case one is the first reported case of carcinomatous transformation within an exophytic septal papilloma.

Adult

The presence of HPV in cervical biopsies, determined by histology and PCR with 2 different pairs of consensus primers.

The link between human Papillomavirus (HPV) and cervical carcinomas has become increasingly convincing recently, and the detection of infection with certain HPV types may become an important element in screening for cervical pre-cancer. We applied the polymerase chain reaction (PCR) technique to detect and type HPV-DNA in biopsies from the uterine cervix with a histological diagnosis of CIN and condylomatosis. Forty-eight consecutive cervical biopsies were analysed for HPV-DNA by PCR, using two different sets of consensus-primers. Typing was performed with HPV type-specific primers. Histological reevaluation revealed that 42 biopsies (87%) had condylomatous features. HPV was demonstrated in 46/48 (95.8%). HPV type 6/11 was found in seven biopsies, while HPV 16 was present in 23 samples, including two cases of double-infection. HPV type 18 was not found at all, and in 19 cases the HPV type present could not be determined. Apparently, HPV-DNA was absent in two cases. The results indicate that HPV-DNA screening is a valuable supplement to histopathological screening for cervical neoplasia. The value of different primer pairs is discussed.

Biopsy

Human papillomavirus (HPV) is rarely present in normal oral and nasal mucosa.

The association between human papillomavirus (HPV) and cervical carcinomas is well known. HPV has been found in oral carcinomas and paranasal papillomas, and the question of a causal role of HPV has yet to be answered. Reports on the frequency of HPV in oral and paranasal sinus tumours should be considered in relation to the frequency of HPV in normal oral and nasal mucosa. In the present study 61 normal individual had oral smears taken and 48 had nasal smears. These were examined for HPV by DNA amplification with HPV consensus primers. HPV was not found in the oral mucosa, while a single individual harboured HPV in the nasal mucosa. It is concluded that HPV is rarely present in normal oral and nasal mucosa.

Adult

Human papillomavirus (HPV) in sinonasal papillomas: a study of 78 cases using in situ hybridization and polymerase chain reaction.

To determine the role of human papillomavirus (HPV) in the etiology of sinonasal papillomas, 57 inverted papillomas including 5 cases associated with carcinomas, 16 exophytic papillomas, and 5 cases of columnar cell papillomas were examined for the presence of HPV DNA by in situ hybridization and polymerase chain reaction (PCR). The genetic studies were performed on the formalin-fixed, paraffin-embedded material. In only 6% of the 52 benign inverted papillomas was HPV DNA identified, whereas 69% of the exophytic papillomas were infected by HPV DNA. In none of the 5 cases with columnar cell papillomas could HPV be demonstrated. HPV 6/11 was identified in all of these HPV-positive cases. In the carcinoma area, HPV was detected in 2 (1 HPV 6/11 and 1 HPV 18) of the 5 inverted papillomas associated with carcinomas. The findings confirm the presence of HPV DNA in sinonasal papillomas. The results also indicate that HPV 6/11 may be involved in the pathogenesis of, solely, exophytic papillomas. We found that in situ hybridization and PCR seem equally sensitive in detecting HPV in sinonasal papillomas.

Carcinoma, Squamous Cell

Urethral condylomata, due to human papilloma virus (HPV) type 6/11., associated with transitional cell tumors in the bladder and ureter. A case report.

Condylomata in the urethra usually occur as a complication to genital warts on the external genitals and are most often situated in the distal part of the urethra. This is a report of a male patient with recurring papillomatous transitional cell tumors, stage Ta and T1, grade 2 and 3 in the bladder and the right ureter, who presented with extensive condylomatosis in the urethra from the meatus to the verumontanum, without simultaneous presence of condylomata at the external genitals. Condylomatous fragments were also present in the TUR specimen from the bladder, but may have been displaced from the urethra during cystoscopy. Using PCR technique and in situ hybridisation, HPV types 6/11 were detected in the condylomata, but no virus was present in the transitional cell tumors.

Adult

Human papillomavirus and normal nasal mucosa: detection of human papillomavirus DNA in normal nasal mucosa biopsies by polymerase chain reaction and in situ hybridization.

To determine a possible etiological role of human papillomavirus (HPV) in sinonasal papillomas and squamous cell carcinomas, it is necessary to investigate normal nasal mucosa of healthy persons for the presence of HPV. The material in the present study consists of 21 biopsies taken from the inferior concha of 21 otherwise healthy persons who underwent surgery for nose fractures or nasoseptal deviations. In addition, five inferior conchae were obtained from persons who had died of non-neoplastic diseases. HPV was not detected in any of these specimens, either by polymerase chain reaction or by in situ hybridization. Histologic evaluation showed that squamous metaplasia was a common finding in the biopsies. The presence of HPV in sinonasal papillomas and carcinomas may indicate that HPV is an etiological factor in these lesions.

Adolescent

The presence of human papillomavirus in sinonasal papillomas, demonstrated by polymerase chain reaction with consensus primers.

The frequency of human papillomavirus (HPV) in sinonasal papillomas seems to vary considerably. The highest frequencies have been reported by investigators using in situ DNA or RNA hybridization. Few studies have used polymerase chain reaction, and in these reports the frequency of HPV detection is rather low. We have investigated the presence of HPV in sinonasal papillomas using the polymerase chain reaction with a set of degenerated consensus primers, which amplify the vast majority of the known HPV types. Human papillomavirus was found in three of 14 papillomas. By in situ hybridization the same three papillomas were positive for HPV type 6/11.

Humans

Calcitonin gene-related peptide in small cell lung carcinomas.

OBJECTIVE: Calcitonin gene-related peptide (CGRP) is a regulatory peptide encoded by the calcitonin gene. CGRP is expressed in increased amounts by the cells of medullary thyroid carcinomas and has been demonstrated by immunohistochemistry to occur in neuroendocrine cells and nerve fibres of lung tissue. MEASUREMENTS: Serum CGRP levels were measured in patients with small cell lung carcinomas before treatment (n = 74) and immediately before the second course of chemotherapy (n = 30). In-situ hybridization and immunohistochemistry were performed on tumour tissue and CGRP was extracted from two tumours and characterized by gel chromatography and high pressure liquid chromatography. RESULTS: Serum CGRP levels were elevated in small cell lung carcinomas when compared with healthy controls of similar age and sex (median values 55.0 vs 36.6 pmol/l, P < 0.001), and 27% had levels above the upper normal range. Serum CGRP levels decreased following the initial course of chemotherapy (P < 0.05) but remained elevated when compared to the controls (P < 0.001). In-situ hybridization for CGRP mRNA was positive in three of 17 tumours and immunohistochemistry was positive in seven of 31 tumours investigated. CGRP immunoreactivity extracted from two tumours was characterized by gel chromatography and high pressure liquid chromatography. A major part of the immunoreactivity was demonstrated to represent the intact molecule. CONCLUSIONS: We found that patients with small cell lung carcinomas had elevated concentration of serum calcitonin gene-related peptide but only 27% had values above the upper normal range. Serum CGRP is therefore of limited value as a tumour marker. Intact CGRP can be extracted from tumour tissue, but in-situ hybridization and immunohistochemistry showed positive reactions in only a few of the tumours investigated. The elevated serum CGRP levels are therefore likely to be largely of extratumoral origin.

Adult

Myocardial ultrastructure in the isolated rabbit heart exposed to dopamine, dobutamine, isoprenaline, G-strofanthin, xamoterol and hypoxia.

The isolated spontaneously beating heart was used for comparing the effects of hypoxia and positive inotropic drugs on myocardial ultrastructure. Hypoxia gives a significant decrease in the volume fractions of mitochondrial cristae relative to the total mitochondrial volume (Vvmcristae) and a significant increase in the volume fraction of mitochondrial matrix relative to the total mitochondrial volume (Vvmmatrix), but changes in volume fractions of mitochondria (Vvmitochondria) and myofibrils (Vvmyofibrils) were absent. Significant changes in ultrastructure in hearts treated with dopamine (0.6 microM), dobutamine (90 nM), G-strofanthin (0.25 microM), xamoterol (32 nM) and isoprenaline (0.15 microM or 15 nM) were absent. Furthermore, myocardial effects in the isolated rabbit heart without exposure to any treatment showed a significantly decrease in oxygen consumption after 90 min. and a significant decrease in frequency of contractions after 120 min. perfusion time, but no change in contractility was seen. We conclude that this experimental model is useful in studies of positive inotropic drugs.

Adrenergic Agonists

Laryngeal papillomas: histomorphometric evaluation of multiple and solitary lesions.

Laryngeal papillomas from 20 patients (162 papillomas) were subjected to histomorphometric analysis: Based on clinical parameters, the papillomas were divided into juvenile multiple papillomas, adult multiple papillomas and adult solitary papillomas. The volume fractions of basal cells, koilocytes and nuclei as well as the mean nuclear volume were determined for each group. Significant differences between the 3 groups were not found and it is therefore concluded that they all represent the same basic lesion.

Adult

Malignant tumours in patients with a history of multiple laryngeal papillomas: the significance of irradiation.

For a period of more than 30 years irradiation was used in the treatment of multiple laryngeal papillomas, especially in children. The treatment was discontinued because a number of irradiated patients developed laryngeal carcinomas. There are however a number of reports of laryngeal and even bronchial carcinomas arising in patients with laryngeal papillomas who had not been irradiated. In addition, HPV type 11 has recently been found in laryngeal papillomas as well as in laryngeal and bronchial carcinomas, subsequently arising in the same patients, both irradiated and non-irradiated. The analysis of a series of 113 patients with laryngeal papillomas has shown that irradiated patients have a 16-fold increased risk of a subsequent carcinoma in the respiratory system.

Adolescent

Human papillomavirus types in cervical biopsy specimens from Pap-smear-negative women with external genital warts.

Cervical biopsy specimens were taken from 55 Pap-smear-negative women with external genital warts in order to diagnose a concomitant cervical human papillomavirus (HPV) infection. HPV-DNA was demonstrated by in situ hybridization in 17 (31%) of the samples: HPV types 16/18 in 9, HPV types 6/11 in 5 and double infection (16/18 and 6/11) in 3. HPV-DNA was found in 10 (43%) of 23 biopsy specimens with koilocytotic atypia and in 5 (29%) of 17 specimens showing chronic inflammatory reaction, whereas only 2 (13%) of 15 women with normal cervical histology had HPV-DNA in the biopsy specimen. Overall histology and in situ hybridization indicated the presence of a cervical HPV infection in at least 30 (55%) of the 55 women examined. Colposcopic examination revealed abnormal acetowhite epithelium in 17 (74%) of 23 women with koilocytosis and/or HPV-DNA positivity, compared with 7 (32%) of 22 HPV-DNA-negative women with histology showing either chronic inflammatory changes or normal epithelium (p less than 0.01). It is concluded that a cervical focus of HPV infection is frequent among Pap-smear-negative women with external genital warts.

Biopsy

Laryngeal papillomas: the epidemiology in a Danish subpopulation 1965-1984.

The incidence rate of laryngeal papillomas in a Danish subpopulation (approximately 2.8 million inhabitants) was 3.84 x 10(-6) per year in the period 1968-1984. For juvenile papillomas the incidence rate was 3.62 x 10(-6), compared with 3.94 x 10(-6) for laryngeal papillomas of adult onset. When comparing different time periods a significantly low incidence was found in the time 1965-1968, while the incidence remained constant in 1969-1984. The low incidence rate in the early period may be real, but selectional bias may have played a part. It is general anticipated that maternal genital HPV-infections may serve as an HPV-reservoir, and that juvenile laryngeal papillomas is a result of HPV transmission from the mother to the child during birth. In the period in question cervical HPV-infections have been recorded with increasing frequency in younger women, indicating that the prevalence is rising. However, this is not reflected in the incidence of laryngeal papillomas.

Adolescent

The presence of human papillomavirus (HPV) in solitary adult laryngeal papillomas demonstrated by in-situ DNA hybridization with sulphonated probes.

Human papilloma virus (HPV) types 6 and 11 have been repeatedly demonstrated in multiple laryngeal papillomas, and there is little doubt that these lesions are caused by HPV. It has been clearly demonstrated in recent reports that the clinical course of solitary adult onset laryngeal papillomas is entirely different from that of multiple papillomas of juvenile as well as of adult onset. We here report the presence of HPV types 6 and 11 in 19 out of 20 solitary papillomas from 16 patients, while HPV types 16 and 18 were totally absent. We conclude that the milder clinical course in such patients is most likely to be due to host factors, rather than to viral factors.

DNA Probes, HPV