Effects of nicotine nasal spray on atherogenic and thrombogenic factors during smoking cessation.

OBJECTIVES: To investigate changes in cardiovascular risk factor parameters when stopping smoking and to identify any impact of nicotine nasal spray on these factors. DESIGN AND SUBJECTS: In a placebo-controlled, double-blind 3-month prospective study, nicotine nasal spray (NNS) or a placebo was given to 157 subjects attending a smoking cessation programme. Blood samples from 46 subjects who remained abstinent for 3 months were analysed. Nasal spray use was given on an ad libitum basis. RESULTS: The haemoglobin (Hb) decreased from 149.0 to 143.2 g L(-1) (P<0.001). The haematocrit (Hct) decreased from 44.6 to 42.4% (P<0.001). The mean corpuscular volume (MCV) decreased from 93.4 to 92.3 fl (P<0.001). The mean corpuscular haemoglobin concentration (MCHC) increased from 333.9 to 338.1 g L(-1) (P = 0.029). The white blood cell count (WBC) decreased from 8.4 to 6.6x10(9) L(-1) (P<0.001). The total cholesterol decreased from 5.92 to 5.65 mmol L(-1) (P = 0.015). The high-density lipoprotein cholesterol (HDL) increased from 1.29 to 1.44 mmol L(-1) (P = 0.48) and low-density lipoprotein cholesterol (LDL) decreased from 4.00 to 3.54 mmol L(-1) (P = 0.004). The HDL/LDL ratio increased from 0.36 to 0.46 (P = 0.011). CONCLUSION: Stopping smoking resulted in positive effects on cardiovascular risk factors. Nicotine treatment for as long as 3 months did not have any significant effect on these 'stopping smoking changes'. In smoking cessation, nicotine substitution up to 3 months seems to be safe.

alpha(2)-macroglobulin and alpha(1)-inhibitor-3 mRNA expression in the rat liver after slow interleukin-1 stimulation.

In this study we have investigated total fiver RNA and the expression of mRNA in the rat fiver in vivo after a slow stimulation of interleukin-1. A total dose of 4 mug interleukin-1beta was administered via a subcutaneously implanted osmotic minipump over a period of 7 days. Plasma concentrations of alpha(2)-macroglobulin manifested a rapid increase, reaching a peak on day 2, while alpha(1)-inhibitor-3 manifested a marked initial decrease to 50% of the baseline level, followed by a tendency to increase again. For measurement of total RNA and specific mRNAs from the fiver, rats were sacrificed at different times during the experimental period. Total RNA peaked at 6 h, the level being approximately 60% higher than baseline value. Specific mRNA from the liver for alpha(2)-macroglobulin and alpha(1)-inhibitor-3 were quantified using laser densitometry on slot blots. The amounts measured during the experimental period agreed with the pattern of corresponding plasma protein levels. From barely detectable amounts at baseline, alpha(2)-macroglobulin mRNA peaked on day 1, and then declined. Levels of alpha(1)-inhibitor-3 mRNA manifested an initial increase at 3 h, but then declined and remained low until day 5 when there was a tendency towards an increase. It was concluded that the levels of plasma concentrations of alpha(2)-macroglobulin and alpha(1)-inhibitor-3 are mainly regulated at the protein synthesis level, and that long-term interleukin-1beta release could not override the initial acute phase protein counteracting mechanism triggered.

Methodological aspects of flow cytometry DNA analysis in endometrial carcinoma, with special reference to sampling and reproducibility.

Two adjacent paraffin-embedded sections manifested concordance in ploidy status in 96% of cases (45/47), and the standard deviation (SD) for SPF was 2.7%. Analysis of 'micro-heterogeneity', within a distance of < or = 700 microm, yielded results for concordant ploidy status in 94% of cases, and the SD for SPF was 1.9% (n = 17). Frozen and paraffin-embedded material yielded concordant results for ploidy status in 87% (39/45) of cases, and SPF values were significantly lower (mean difference 1.5%) in the frozen samples. Diagnostic and repeat curettage material yielded concordant results for DNA ploidy status in 85% (40/47) of cases, and no significant difference in mean SPF (12% vs. 11%) was found. Discordant DNA ploidy results were attributable to small differences in the DNA histograms influencing the interpretation of near-diploid, near-tetraploid and small non-diploid cell populations, and the influence of debris on SPF estimation. On the basis of our findings and the practical advantage we recommend paraffin-embedded material from diagnostic curettage for FCM DNA analysis; the results are available sooner and the handling and transportation of tumor samples is more convenient.

Identification of small areas of solid growth has a strong prognostic impact in differentiated endometrial carcinomas. A histopathologic and morphometric study.

A large, consecutive series of 562 patients with endometrial adenocarcinomas was investigated with respect to prognostic factors. In the histopathologic evaluation the World Health Organization (WHO) classification system was used. In addition to that, in moderately differentiated (MD) tumors small areas of solid growth were identified and the proportions of these out of the whole areas of tumor (in the predominant number of cases this being less than 5%) were later determined by morphometry, showing a good accordance with the subjective estimations. Differentiated tumors with small solid areas (MD + S tumors) implied a significantly worse prognosis compared to tumors without a solid component (P < 0.001), which was also confirmed in a multivariate analysis. In the multivariate analysis MD+S differentiation had an independent prognostic impact, as strong as age, clinical stage and myometrial invasion. It is suggested that the occurrence of even a very small solid component is an ominous sign, the presence (or absence) of which might be an important parameter to take into consideration in the discrimination between high- and low-risk endometrial carcinomas.

The prognostic information of DNA ploidy and S-phase fraction may vary with histologic grade in endometrial carcinoma.

DNA ploidy and S-phase fraction (SPF) were determined by flow cytometry on paraffin-embedded tumor material from 243 patients treated during 1980-1985. Patients with well differentiated and moderately differentiated tumors without solid areas (n = 351) formed a low-risk group (corrected 5-year survival 90%). Twenty-four patients, dead of disease within 5 years, were compared with 52 survivors. The estimated death risk was higher for those with SPF > or = 8.0% compared with those with SPF < 8.0% (odds ratio = 18.2; p < 0.001). SPF was the only independent prognostic factor in a multivariate analysis also including age, clinical stage and grade of differentiation. Patients with moderately differentiated tumors with solid areas or poorly differentiated tumors (n = 208) were regarded as a high-risk group. There was a difference in survival according to ploidy; the corrected 5-year survival was 75% for 106 patients with diploid tumors compared with 44% for those with non-diploid tumors (p < 0.0001). In a multivariate analysis DNA ploidy, age and clinical stage were independent prognostic factors, whereas SPF was no longer significant. Thus, DNA ploidy and SPF have different prognostic values depending on histological grade of endometrial carcinoma.

[Clinical chemistry and bacteriological testing in Iceland 1990.].

In this article we present the number and composition of clinical laboratory testing, both haematological, biochemical and bacteriological, performed at hospitals, primary care centers and private clinics in Iceland, in the year 1990. Inquiries were sent to 85 institutions, 52 (61%) responded. The number of assays performed at the laboratories/institutions not responding was estimated. The total number of assays performed in 1990 at these Icelandic institutions was 1.7 million which equals to 6.7 tests per person. Comparison to a similar investigation of assays done in 1982 showed that for those institutions which participated both years the number of tests other than bacteriological tests had increased by 23.2%. Tests done at larger hospitals had increased by 30%, at intermediate sized hospitals they had increased by 14.5%, and testing at primary care centers had decreased by 10% between 1982 and 1990. Bacteriological and clinical chemistry tests increased significantly or by 53% and 49% respectively. On the other hand hematological tests increased only by 1% and tests on urine decreased by 25%. By far the most common assay performed was blood count, ESR came second both years.

[Congenital hypothyroidism in Iceland 1979-1993.].

A nationwide screening for congenital hypothyroidism (CHT) was initiated in Iceland on January 1st 1979. From the beginning the screening consisted of TSH measurements from blood samples obtained on the fifth day of life on filter paper. TSH was initially assayed by RIA but since 1990 DELFIA fluoroimmunoassay has been used. During the 15 year period 1979-1993, a total of 65,892 children were born in Iceland. Participation in the screening program was 99.5%. The diagnosis of CHT was established in 21 cases, eight boys and 13 girls or 1/3138. Elevated TSH was found in 33 infants in the initial screening program, but on recall, thyroid function proved to be normal in 12 infants. Two infants had transient hypothyroidism presumably caused by TSH blocking antibodies of maternal origin. In one infant CHT was diagnosed on the first day of life because of a large goiter. Goiter was found in six infants on diagnosis, ectopia in six and no uptake on thyroid scan in three infants. In six infants thvroid scan was not performed. The diagnosis was delayed for 71 and 131 days respectively in two infants. Both infants had severe neonatal problems needing intensive care. On follow-up, those two children have a mild developmental delay. In the remaining 19 children mental development has been normal as judged by school performance and developmental tests. Growth has been within normal limits in all cases, mean SDS for height is 0.3. The incidence of CHT in Iceland is comparable to the results published recently in most of the other Nordic countries.

Acute phase protein response and polymorphonuclear leukocyte cathepsin g release after slow interleukin-1 stimulation in the rat.

In this work we have studied the acute phase protein response and degranulation of polymorphonuclear leukocytes in vivo in the rat after a slow interleukin-1beta stimulation. A total dose of 1 mug, 2 mug, 4 mug and 0 mug (controls with only vehicle) of interleukin-1beta was released from osmotic minipumps over a period of 7 days. The pumps were implanted subcutaneously. A cystic formation was formed around the pumps that contained interleukin-1beta whereas no tissue reaction was seen around pumps containing only vehicle. Besides flbroblasts the cyst wall contained numerous polymorphonuclear leukocytes which were positively stained for cathespin G. alpha(2)-macroglobulin, alpha(1)-inhtbitor-3, alpha(1)-proteinase inhibitor, albumin and C3 were measured by electroimmunoassay and all showed plasma concentration patterns that were dose-dependent to the amount of interleuktn-1beta released. Fibrinogen in plasma was elevated in the control group but showed decreased plasma values with higher doses of interleukin-1beta released. All animals showed increased plasma levels of cathespin G but the lowest levels for cathespin G were seen for the highest interleukin-1beta dose released. It was clearly seen that a slow continuous release of interleukin-1beta in vivo caused an inflammatory reaction. Plasma levels for the proteins analysed all showed a similar pattern, namely an initial increase or decrease of plasma concentration followed by a tendency to normalization of plasma values. It was concluded that a long-term interleukin-1beta release could not sustain the acute phase protein response elicited by the initial interleukin-1beta release.

Quality status of serum cholesterol analysis in Iceland.

Eight laboratories participated in the first Icelandic quality assessment survey of serum cholesterol analysis in 1989. Quality control material, lyophilized animal serum and frozen human serum, was distributed three times over a period of one year and analyzed each time over 10 consecutive days. After two distributions of control material the laboratories were advised to start using a common calibrator from the U.S. National Bureau of Standards, and six months later the third lot of control material was analyzed. All laboratories use the same enzymatic methods for estimating serum cholesterol. Average total imprecision within and between laboratories improved throughout the survey, but did not reach the quality goal of the U.S. National Cholesterol Education Panel of +/- 3% for imprecision and +/- 3% for bias leaving scope for further improvement.

Influence of dietary cod liver oil on fatty acid composition of plasma lipids in human male subjects after myocardial infarction.

A randomized crossover study was carried out to investigate the fatty acid profile and concentrations of plasma lipids in male patients with myocardial infarction (MI) who supplemented their diet with 20 ml cod liver oil daily for 6 weeks. Subjects were divided into two groups, A and B. Group A received cod liver oil daily for 6 weeks after hospital discharge, but none for the subsequent 6 weeks. Group B did not start taking cod liver oil until 6 weeks after hospital discharge, and they then took cod liver oil for 6 weeks. Diet, medication or smoking habits were kept as constant as possible during the study. During the period of cod liver oil intake, eicosapentaenoic acid (20:5 (n-3), EPA) and docosahexaenoic acid (22:6 (n-3), DHA) increased significantly in phospholipids (PL), triglycerides (TG) and cholesterol esters (CE), whereas linoleic acid (18:2 (n-6), LA), dihomo-gamma-linolenic acid (20:3 (n-6), DHGLA) and arachidonic acid (20:4 (n-6), AA) were significantly decreased in phospholipids. The plasma level of TG was significantly decreased during the cod liver oil intake. Total cholesterol, high density lipoprotein (HDL) cholesterol, and levels of apolipoproteins A1 and B were not affected by cod liver oil in these MI patients.

Staging in local endometrial carcinoma. Assessment of magnetic resonance and ultrasound examinations.

Possible deep (more than an inner third of the uterine wall) myometrial invasion and cervical extension of endometrial carcinoma were evaluated prospectively using magnetic resonance (MR) and transabdominal real-time sonography (US) in 20 and 10 patients, respectively. The data obtained from these examinations were compared with hysterosalpingography (HSG) and clinical modalities including hysteroscopy, sounding and histopathologic findings after surgery. The concordance of outlining cervical extension was between MR and hysteroscopy 85 per cent, and between US and hysteroscopy 50 per cent. Deep myometrial tumor invasion was suggested in 4/10 patients by US and in 6/20 by MR, and was confirmed in all but one in each group at histologic examination of the resected uterus. There were no false negative US or MR examinations. Transabdominal US did not prove accurate in defining local endometrial carcinoma (distinguishing between stages I and II), but it may be used as an additional tool in revealing myometrial invasion. MR, however, seems to refine the delineation of uterine tumor growth.

Doxorubicin-cisplatin combination chemotherapy for recurrent carcinoma of the cervix.

A total of 31 patients with recurring or metastasizing squamous cell carcinoma of the cervix were treated with doxorubicin and cisplatin. Sixteen patients (Group 1) had previously been treated with external irradiation and two intracavitary radium applications, and 15 patients (Group 2) had been treated with radiotherapy plus chemotherapy with bleomycin plus mitomycin, peplomycin, or melphalan. The overall frequency of response was approximately 16% (five of 31 patients). In Group 1, two of 16 patients had complete remission for 14+ and 28 months, and survival for 36+ and 45+ months. One of 16 patients had partial remission for 8 months, and survival for 16+ months. In Group 2, two of 15 patients achieved partial remission for 16 and 18 months, and survival for 28 and 35 months. No serious side effects were noted in the two groups.

Familial elevation of serum thyroxine binding globulin in an Icelandic family.

A kindred of four generations with inherited elevation of serum thyroxine binding globulin (TBG) is reported. To our knowledge this is the twelfth kindred reported with this disorder. Of the 35 family members studied, 10 females and 5 males had elevated serum TBG. The patients were clinically euthyroid. The pedigree data was consistent with an X-chromosome linked mode of inheritance.

Long-term effect of clofibrate on albumin turnover and distribution in man.

The long-term effect of clofibrate (at least 6 months' treatment) on albumin metabolism was investigated in 7 subjects and the results were compared with those from 15 control subjects. Human albumin labelled with 131I was used as a tracer. A significant difference between the groups was found in the following parameters: The clofibrate-treated group had a prolonged rapid component (t1 1/2) of the disappearance curve (p less than 0.05), relatively increased albumin in the extravascular space (i.e. decreased distribution ratio, p less than 0.01) and increased extravascular albumin space when corrected for body size by calculating it as per cent of the extravascular bromide space (p less than 0.01). There was no significant difference between the groups in albumin synthesis, fractional catabolic rate or the slow component (t2 1/2) of the disappearance curve. The results suggest that long-term treatment with clofibrate causes changes in the intercellular matrix.