The decline of smoking among Swedish men.

BACKGROUND: In 1987 the Association of the Nordic Cancer Registers (ANCR) predicted the incidence of lung cancer in the Nordic countries up to the years 2000 and 2010. The predictions for Sweden can now be considered against recent information on smoking habits. METHODS: Regular, question-based studies on the public's tobacco consumption are carried out by four separate institutions in Sweden. This article summarizes and updates the smoking habits among Swedish men in the age groups 35-54 and 55-70 years between 1963 and 1994, with special focus on smoking cessation. RESULTS: Between 1963 and 1994, there was a significant and continuous decrease in the prevalence of smoking among Swedish men. During this time ex-smoking men increased from 20% to 41%. The data reveal a continuous, unbroken and uniform increase in smoking cessation rates during the last 20 years, despite the small success of smoking cessation programmes and smoking-relapse rates of 75-80%. The explanation of this seems to be the surprisingly high frequency of smokers who attempted to stop smoking each year (about 30%). The best success rate in smoking cessation was achieved by occasional smokers and others with a low cigarette consumption. CONCLUSION: With the continuing fall in the numbers of smoking men, a greater drop in lung cancer incidence than predicted by the ANCR in 1987 may be expected in Sweden within the coming decade.

Auditory impairment in guinea pigs treated with isepamicin.

Groups of adult guinea pigs were treated intramuscularly with isepamicin at doses of 100, 150 and 225 mg/kg/day for 21 days. For comparison, two other groups were administered either saline or amikacin 225 mg/kg/day. Auditory function, as measured by the Preyer pinna reflex and the brain stem evoked response, was impaired in both the isepamicin and amikacin groups treated with 225 mg/kg/day, and to a lesser extent in the group receiving isepamicin 150 mg/kg/day. Morphological evaluation of the organ in Corti, performed either by scanning electron microscopy or by light microscopy, showed the typical pattern of damage associated with the aminoglycosides. The greatest damage was observed at 225 mg/kg/day, with no difference between isepamicin and amikacin. Isepamicin 100 mg/kg/day produced no impairment in auditory function and very little change in the morphology of the organ of Corti.

Subcutaneous interleukin-2 and alpha-interferon in advanced colorectal carcinoma. A phase II study.

Subcutaneous administration of low doses of recombinant interleukin-2 (IL-2) and interferon-alpha (IFN-alpha) on an out-patient basis has been reported not to significantly compromise the response frequency compared to intravenous IL-2 in patients with renal cell carcinoma and melanoma. As part of an ongoing program to develop a biotherapeutic concept in patients with colorectal carcinoma (CRC) we studied the clinical effects of such a regimen in 15 patients with metastatic CRC. The daily dose of IL-2 varied between 4.8-14.4 x 10(6) U/m2 and of IFN-alpha between 3-6 x 10(6) U/m2. The cycle length was 6 weeks. The course was repeated every 8 weeks until disease progression. Maximum 4 cycles were administered. Maintenance therapy was given to responding patients once a week every month. No patient showed a major response (CR or PR). Six patients had a stable disease ranging from 3 months to 18 months with a median duration time of 5 months. The median survival of all patients was 13 months. The main adverse reactions were fever, chills, anorexia and shortness of breath. No treatment related deaths occurred. 6/14 patients developed abnormal concentration of serum levels of thyroid hormones. It is concluded that the present treatment schedule using IL-2 and IFN-alpha in advanced CRC seemed not to be of clinical benefit.

Ototoxic antibiotics: a review.

Fifty years of experience with aminoglycoside antibiotics has confirmed their usefulness in many infections with Gram-negative bacteria. The ototoxic action has been investigated clinically in patients and in numerous animal studies. The increased knowledge about molecular structure, pharmacology and pharmacokinetics as well as information of the site of action in the labyrinth has resulted in reduced risks for severe toxic damage in kidneys and in the ear. Nevertheless, a number of cases of severe hearing loss and a few cases of deafness still occur every year. Further studies on modified molecular structure as well as site of action at the molecular level and ways of avoiding toxicity will make this group of antibiotics still more useful.

Haemorrhagic pituitary tumours.

In a group of 69 patients with pituitary tumours, 12 were found to have evidence of intratumoral haemorrhage on MRI, characterized by high signal intensity on short TR/TE sequences. This was verified in all but 1 patient. The majority of the bleedings occurred in macroadenomas. Five (42%) were prolactinomas and 4 (33%) were non-functioning adenomas. There were 2 GH- and 1 ACTH-secreting tumours. All 5 patients with prolactinomas were on bromocriptine medication. Two of the patients had a clinical picture of pituitary apoplexy. The haemorrhage was not large enough to prompt surgery in any of the patients. However, surgical verification of the diagnosis was obtained in 5 cases, while 6 patients were examined with follow-up MRI.

Low dose cyclophosphamide, alpha-interferon and continuous infusions of interleukin-2 in advanced renal cell carcinoma.

Pretreatment with a low dose of cyclophosphamide (CY) has been claimed to inhibit suppressor functions and augment various immune functions. A combination of a low dose of CY, alpha-interferon (IFN-alpha) and continuous infusion of interleukin-2 (IL-2) was used to treat patients with advanced renal cell cancer (RCC) (stage IV). Sixteen patients received four cycles consisting of CY (500 mg m-2) three days prior to daily i.m. injections of alpha-IFN (3 x 10(6) U), and continuous infusion of 18 x 10(6) IU rIL-2 for five days. The cycle interval was three weeks. Two patients had partial response (13%) (26+ and 12+ months), two had a minor response (9+ and 4 months), and three patients achieved stable disease (19+, 14+ and 8+ months). No patients required intensive care. Side effects were mainly fever, malaise, capillary leak syndrome and diarrhoea. Non-responders showed significantly higher eosinophil and platelet counts compared to responders. Serum concentration of IL-2 was significantly higher in responders. 5/11 patients had abnormally low values of serum thyroxine after therapy. Two patients needed thyroid hormone substitution. The difference between the initial and the lowest thyroxine values correlated significantly to survival (p < 0.03). The addition of CY to rIL-2 and IFN-alpha in the present protocol did not contribute to an increased major response rate.

Hair cell damage after continuous and interrupted pure tone overstimulation: a scanning electron microscopic study in the guinea pig.

In our earlier investigations [Fredelius et al., Hear. Res. 30, 157-167 (1987)] acoustic trauma was studied after continuous 3.85-kHz pure tone exposures of different intensities and durations. In the present investigation, the importance of the introduction of a break during longer 3.85-kHz pure tone exposures was studied. Female pigmented guinea pigs were exposed to 108, 114, or 120 dB SPL for 6 h with or without a 1-h break after the first 3 h. Four weeks after exposure the cochleas were prepared for scanning electron microscopy and the resulting hair cell damage was evaluated according to a 4-grade damage scale. Significant differences could be demonstrated in the hair cell damage in the animals exposed to continuous acoustic overstimulation and those exposed to intermittent overstimulation. The importance of rest periods to decrease hair cell damage during long periods of acoustic overstimulation was clearly demonstrated.

Glycoconjugates in the human fetal endolymphatic sac as detected by lectins.

The distribution of glycoconjugates in the 11 to 16 weeks old human fetal endolymphatic sac (ES) was analyzed using six biotinylated lectins; Wheat germ agglutinin (WGA), Abrus precatorius agglutinin (APA), Ulex europaeus agglutinin I (UEA-I), Ricinus communis agglutinin 120 (RCA120), Helix pomatia agglutinin (HPA), Concanavalin A (ConA). In the 11 week old human fetus, fluorescent reactions with WGA, APA, RCA120 and ConA were detected in the ES. There was almost no reaction with HPA and UEA-I. In the 14 week old human fetus, however fluorescent reactions with HPA and UEA-I appeared. This result suggests that the presence of glycoconjugates changes during the maturation process of the ES. Glycoconjugates detected with HPA were related to the epithelial cell elements of the ES epithelium. The reaction with UEA-I suggests that the stainable substance present in the ES lumen may be secreted locally by the ES itself.

Long-term effects of radiotherapy and bromocriptine treatment in patients with previous surgery for macroprolactinomas.

The long-term effect of radiotherapy and bromocriptine treatment was retrospectively evaluated in 25 patients who had previously undergone transsphenoidal surgery for treatment of macroprolactinomas. Surgery had reduced the median serum prolactin (PRL) value from 613 micrograms/l, a reduction of 53%. Postoperative bromocriptine was administered to 21 of the 25 patients. In 14 of these patients, serum PRL values became normal or almost normal with medication. There were no radiological or ophthalmological signs of progressive tumor growth during bromocriptine treatment. Fourteen patients received postoperative radiotherapy. After withdrawal of bromocriptine in 13 of these patients an average of 7 years after radiotherapy, the median serum PRL value had further decreased by 95%. The PRL reduction was similar for all doses applied, 38 to 52 Gy. After withdrawal of bromocriptine in 8 patients not receiving radiotherapy an average of 7 years after operation, the median serum PRL level had further decreased by 75%. At follow-up, 18 additional instances of pituitary insufficiency had developed in the group receiving radiotherapy, compared with 8 cases of insufficiency in the group not receiving radiotherapy. Thus, because bromocriptine has a long-standing effect on prolactin secretion, and radiotherapy is associated with a notably high incidence of pituitary insufficiency, we propose that photon irradiation should be considered mainly for patients who are not candidates for surgical or medical treatment.

The presence of laminin in the fetal human inner ear.

The expression of laminin was analyzed in the human fetal inner ear using immunohistochemical methods. In the 11-week-old human fetus, the presence of laminin was found in the basement membrane of the immature cochlea, endolymphatic sac and vestibular end organs. The reaction of the basement membrane of the endolymphatic sac was strong in the 15-week-old human fetus. A laminin reaction was seen in the cochlea, Reissner's membrane, epithelial cells of the limbus spiralis, the basilar membrane and the stria vascularis. In particular, the capillaries and basement membrane of the stria vascularis were strongly positive. These results suggest that laminin may be an essential component in the development of the inner ear and may possibly be related to filtration of the endolymph.

Time-related changes in the guinea pig cochlea after acoustic overstimulation.

Forty-eight female pigmented guinea pigs were used to study the development of the morphologic and electrophysiologic changes occurring during a 4-week period after exposure to a 3.85-kHz pure tone at an intensity of 120 dB sound pressure level for 22.5 minutes. The morphologic results suggest an alteration in the permeability of ions between the inner ear fluids through gradual development of holes in the reticular lamina.

Electron microscopic demonstration of sialic acid residues in the organ of Corti with lectin from Limax flavus.

The localization of sialic acid (N-acetyl- and N-glyconylneuraminic acid) in the organ of Corti of the mongolian gerbil was examined with electron microscopy by postembedding labeling using Limax flavus agglutinin and feutin-gold. Gold labeling was observed on the fibrous structure of the tectorial membrane, the basilar membrane and the spiral limbus. The labeling was also observed on the cuticular plate of the hair cells, the head and cone of the pillar cells and the head plate of Deiters' cells and other supporting cells. Collagen or cytoskeletal glycoproteins are suggested to be the source of the sialic acid in these structures.

Effect of acoustic overstimulation on the glycocalyx and the ciliary interconnections in the organ of Corti: high resolution scanning electron microscopic investigation.

Changes in ciliary interconnections in the organ of Corti are described after acoustic overstimulation using a special high resolution scanning electron microscope and tannic acid-osmium staining technique, giving an almost three dimensional view. Guinea pigs were exposed to a 3.85 kHz pure tone at an intensity of 120 dB for 22.5 minutes. The first detectable change was a disarrangement of the cilia with a loosening of the interconnections. The ciliary plasma membrane presented with an abnormally smooth appearance. The tip links connecting the tips of the stereocilia to their taller neighbours were also affected showing elongation or even disappearance. The fine granules which cover the tips of the tallest stereocilia of the outer hair cells were decreased. These findings suggest that acoustic overstimulation may affect the carbohydrate metabolism exceeding to degeneration of ciliary interconnections resulting in a disarrangement and detachment of cilia. The tip links, which may participate in sensory cell transduction, seem also to be affected by acoustic overstimulation.

DNA evaluation in growth hormone producing pituitary adenomas: flow cytometry versus single cell analysis.

DNA patterns were analysed in 26 GH-producing pituitary adenomas by flow cytometry as well as by microspectrophotometry. Twelve tumours (46%) were diploid according to both methods, whereas 5 tumours (19%) showed aneuploid DNA patterns. Nine tumours were classified differently by the two methods: flow cytometry resulted in diploidy in 2 and aneuploidy in 7 patients, whereas microspectrophotometry showed diploidy in 5 tumours, tetraploidy in 3 and aneuploidy in 1. Methodological limitations may explain the discrepancy in the results obtained by the two methods. However, both the flow cytometry and the microspectrophotometry method show the presence of aneuploid DNA patterns in GH-producing pituitary adenomas despite their benign growth characteristics and the clinically benign course of the disease. This comparative study with two methods measuring DNA content, shows that depending on the criteria used for diploidy-aneuploidy, the frequency of aneuploidy will vary. In this material of 26 GH-producing adenomas, 46% were aneuploid according to flow cytometry and 23% according to microspectrophotometric. However, no correlation to tumour size or GH levels was found with either method when patients with aneuploid and diploid tumours were compared. Therefore, no clinical significance can so far be drawn from these results.