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In order to ascertain the dynamic relationship between the extracellular glucose in upper skin layers and blood glucose, skin suction blisters were raised in six Type 1 diabetic patients during a three-step glucose clamp. Blister glucose closely paralleled venous glucose (mean of r = 0.998). However, in three patients blister glucose was constantly lower than plasma glucose and this appeared to be related to their slower formation of skin blisters. A substantial difference in skin blister suction time was noted among patients and it was found that suction time was linearly correlated to glycosylated haemoglobin (HbA1C) (n = 6, r = 0.865, p = 0.026). It is concluded that a non-invasive blood glucose monitoring system could be successfully based on measurement of alterations in skin glucose contents.

The diagnostic accuracy for colorectal cancer (CRC) of rigid sigmoidoscopy and faecal occult blood test (Hemoccult-II) (H-II) was investigated in patients with irritable bowel syndrome in general practice in a three year period and the results were compared with those of the previous three years, where rigid sigmoidoscopy and double contrast barium enema (DCBE) were the initial preferred examinations. Colonoscopy was recommended in patients with positive H-II, but also in patients with repeated negative H-II within three months, provided that the symptoms persisted. CRC was detected in 141 of 630 patients with positive H-II and in 52 of 8697 with negative H-II. The number of CRC's in the two study periods was similar, in spite of a pronounced reduction in DCBE's from 12,196 to 5656 and a small increase in colonoscopies from 3053 to 4127. It was concluded that the new strategy was no worse than the previous one and the major savings in DCBE's could be used to exchange the rigid sigmoidoscopy with a 60 cm flexible sigmoidoscopy, increasing diagnostic accuracy, shortening delay of diagnosis and removing more adenomas, which eventually may reduce the future incidence of CRC and thereby the mortality from CRC.

A total of 151 postmenopausal women were randomly allocated to 3 groups for treatment with hormone replacement therapy. One group received combined therapy (2 mg oestradiol (E2) and 1 mg norethisterone acetate (NETA) daily), the second group was placed on sequential therapy (2 mg E2 for 12 days, 2 mgE2 and 1 mg NETA for 10 days and 1 mg E2 for 6 days), while the third was given placebo. Treatment was administered over 24 cycles of 28 days. The two active treatments were equally effective in relieving climacteric symptoms. In the combined therapy group, 62% of the women experienced spotting and/or breakthrough bleeding during the first 3 cycles; thereafter this proportion decreased to between 3 and 18% in each of the following three-cycle periods. Sixty-four percent (64%) of these women had no more bleeding after the first 3 cycles. Endometrial atrophy was detected in 93% of the women in this group after 24 cycles of therapy. Bleeding irregularities occurred during the first 3 cycles in 27% of the patients treated with sequential therapy and in 21% of those receiving placebo. In the subsequent 3-cycle periods these figures fell to below 10% in the 2 groups. In all 3 groups weight remained stable but blood pressure increased equally in the actively treated groups and the placebo group. The levels of follicle-stimulating hormone (FSH), sex-hormone-binding globulin (SHBG) and the free fraction of E2 in serum were significantly lower in the combined therapy group than in the sequential therapy group. The higher level of free E2 in the latter group may have been caused by a decrease in metabolism associated with the increased SHBG concentration. It was concluded that combined treatment with E2 and NETA might provide an alternative to sequential treatment in postmenopausal women willing to tolerate the initial high risk of breakthrough bleeding/spotting in order to avoid subsequent regular bleeding. In the subgroup of women in whom bleeding irregularities continue, sequential treatment should be considered.

Insulin-dependent diabetes is associated with other autoimmune diseases and subclinical hypothyroidism has been reported in pregnant diabetic women. We studied the thyroid function of 85 women with diabetes during pregnancy and after delivery, as well as various autoantibodies. During pregnancy, thyroid microsomal antibodies were present in 17/85, antibodies against thyroid peroxidase in 16/85, thyroglobulin antibodies in 2/85, parietal cell antibodies in 23/85, adrenal antibodies in 4/77, rheumatoid factor in 15/85, and thyroid-stimulating antibodies in 43/85. Presence of antibodies was not combined with thyroid dysfunction, but TSH and HbA1c was increased (p less than 0.005) in women with thyroid antibodies. The gestational age of the infants was lower (p less than 0.01) in women with positive thyroid-stimulating antibody titre, whereas the ponderal index was only lower in those with peroxidase antibodies (p less than 0.05). After delivery, microsomal and peroxidase antibodies were positive in 10 (17.5%) of 57 patients followed. Six women developed postpartum thyroiditis (10.5%), of whom 5 were positive for both microsomal and peroxidase antibodies; two of those showing a hyperthyroid phase also had positive thyroid-stimulating antibody titre. We conclude that autoantibodies occur with increased incidence in pregnant diabetic women. Thyroid antibodies are related to a slightly reduced thyroid capacity and involve a high risk of postpartum thyroiditis. Further, thyroid antibodies seem to influence the nutritional status of the infant.

In a retrospective study of femoro-popliteal bypass surgery in Denmark during the period 1983 to 1987, a total of 1,532 operations were performed. Approximately 2/3 of the patients were operated upon for limb salvage, the remainder for severe disabling claudication. The perioperative lethality was below two per cent in all departments. Early occlusion rate was found to be between 21 and 11 per cent, leading to major amputation in about half of the patients.

Iron-depleted donors are at increased risk of developing anemia; if these donors could be identified by a screening test, iron supplementation or decreased donation frequency could be considered. Tests to determine serum ferritin, blood hemoglobin, and erythrocyte (Erc)-zinc protoporphyrin concentrations were examined in 679 consecutive female blood donors to identify donors with non-anemic iron deficiency. The test to determine serum ferritin is expensive and slow, whereas the two latter tests are rapid and less costly and could therefore be used for screening. Women in the fertile age groups had the lowest average serum ferritin values. In all, 93 women (13.7%) had depleted iron stores, as indicated by serum ferritin concentrations less than 14 micrograms/L. In these women, a much better correlation was found between Erc-zinc protoporphyrin and serum ferritin (rs = -0.49, P less than 0.001) than between blood hemoglobin and serum ferritin (rs = 0.31, P less than 0.01). These findings suggest that measurement of Erc-zinc protoporphyrin is superior to that of blood hemoglobin in identifying donors with non-anemic iron deficiency.

Eight insulin-dependent diabetic patients were given two constant infusions (each 1 IU/h) of 125I-labeled insulin into the abdominal subcutaneous tissue for about 12 h. Insulin was infused in pulses into one side of the abdomen in 6-min intervals (by means of an Auto-Syringe pump) and in the other side of the abdomen, insulin was infused in 1-h intervals (by means of a Medix pump). The size of the subcutaneous depots was continuously measured by counting the radioactivity at the infusion sites. After starting the infusions, the two depots were built up to steady-state levels at the same time and of the same size (approximately 3 IU) and with similar absorption rates. Thus, during basal rate insulin infusion, identical insulin absorption kinetics was achieved, irrespective of a 10-fold difference in the pulse rate.

Twenty-five lead-exposed Danish battery production workers and 25-age-matched controls were examined to evaluate subclinical effects on blood formation. Blood lead levels averaged 2.14 mumol/L and 0.35 mumol/L in the two groups; the lead workers also showed high levels of erythrocyte protoporphyrin, as compared to the controls. Otherwise, the hematological parameters indicated an appropriate iron status and no other deviations. From all subjects, 0.45 L of blood was bled as part of a normal blood donation. Five and 11 days later, reticulocyte counts were significantly higher in the control group than in the lead-exposed workers. On day 15, the lead workers showed a significant delay in blood regeneration, as evidenced by lower hemoglobin concentration, and erythrocyte and reticulocyte counts. The lead exposure in the present study was within legal limits, and lead-induced anemia would be expected only at much higher exposure levels. Thus, despite the normal hematological findings in the initial examination, the lead exposure caused a decreased reserve capacity for blood formation, and this effect became evident only after the blood loss.

Nine cases of thoracic actinomycosis treated in the period 1966-1987 are reported. Three of the patients presented with a clinical picture of empyema and six were admitted for suspected primary pulmonary neoplasm. No case was correctly diagnosed preoperatively. The final diagnosis was based on direct microscopy (2) or culture (1) of drained pus in the empyema cases and on histologic examination of resected tissue in the others. In one case the correct diagnosis was missed when a palpable tumour mass was not extirpated at exploratory thoracotomy, and was made only when clinical deterioration necessitated a second operation. Good clinical results can be expected from surgical eradication of an intrathoracic focus of actinomycosis in conjunction with appropriate antibiotic therapy.

Eight insulin-dependent diabetic patients were simultaneously given subcutaneous infusions (1.12 IU/h each) of 125I-labeled Actrapid insulin in each side of the abdominal wall. After 24 h of infusion, the size of the infused insulin depots was measured by external counting for 5 h. The basal infusion rate was then doubled in one side and halved in the other for the next 4 h. Finally, 1.12 IU/h of insulin was given in both sides of the abdominal wall for an additional 3 h. The changes in the size of the depots were measured, and the absorption rates for each hour were calculated. During the first 5 h of infusion, the depot size was almost constant (approximately 5 IU) with an absorption rate that equaled the infusion rate. Doubling the infusion rate led to a significant increase in depot size, but the absorption rate remained unchanged for the first 3 h, and only thereafter was a significant increase seen. When the infusion rate was reduced to the initial 1.12 IU/h, the absorption rate remained elevated during the next 3 h. Correspondingly, when the infusion rate was decreased, the depot size also decreased, but the absorption rate remained unchanged for the first 3 h. The results show that a change in the basal insulin infusion rate does not lead to any immediate change in the insulin absorption rate. This should be considered when planning an insulin-infusion program that includes alteration(s) in the basal-rate setting.

The clinical acceptability and the influence on diabetes control were investigated in 50 women with insulin-dependent diabetes mellitus (IDDM) during intake of a combined nonalkylated estrogen/progestogen compound (4 mg 17-beta estradiol, 2 mg estriol and 1 mg norethindrone) for one year. In 6 IDDM women, the influence of the hormonal treatment on diabetes control and on ovarian function was investigated by measuring the concentration of glycosylated hemoglobin (Hb-Alc), fasting plasma glucose, serum estradiol, serum estrone, serum progesterone and sex hormone binding globulin (SHBG) capacity. No pregnancy occurred during the study and the overall continuation rate of 60% compare well with the continuation rate normally found in non-diabetic women after administration of conventional type oral contraceptives. No difficulties with diabetes control was registered and no significant changes in insulin requirements, 24-h urinary glucose excretion nd Hb-Alc were found. Ovulation was inhibited during the hormonal intake as judged by serum progesterone measurements. Serum estrone increased (p less than 0.05), but this had no influence on SHBG capacity, indicating that the estrogen/androgen balance was unchanged during treatment.

To compare the metabolic control and the pharmacokinetics of infused insulin using an insulin pump (Auto-Syringe AS 6C) which provides the basal rate in pulses every 2-10 min with a pump (Medix Syringe Driver 209) providing the basal rate in pulses every 15-60 min, 6 C-peptide negative diabetic patients received, in random order, identical, but individual, insulin treatment during one 4-day period using the Auto-Syringe pump and another 4-day period using the Medix pump. On the fourth day of each period, blood glucose and plasma-free insulin were estimated every 30 min for 7 hr and every 5 min for the next hour. Plasma-free insulin was significantly higher on 3 time points out of the 26 possible when using the Medix pump, but this was not reflected in the blood glucose concentrations which were similar in the 2 periods. The results indicate that, from a metabolic and pharmacokinetic point of view, insulin pumps working with larger intervals between the basal rate pulses are just as good as the more technically advanced and hence often more expensive pumps which provide the basal rate in more and smaller pulses.

Severe congenital malformations occur more often in infants of diabetic mothers than in infants of non-diabetic mothers. Fetuses exhibiting early fetal growth delay are in increased risk to be malformed and the early fetal growth rate seems to be related to the degree of metabolic control around the time of conception and in the early pregnancy. Nine insulin-dependent diabetic women (White classes B-F) were treated by means of continuous subcutaneous insulin infusion (CSII) initiated at least two months prior to conception and continued throughout pregnancy in order to evaluate the influence of optimized metabolic control on the course and outcome of diabetic pregnancy. Eleven conventionally treated pregnant diabetics (White classes B-D) served as controls. In the pump group the mean blood glucose values in the 4 weeks immediately before and after the conception were 7.7 +/- 0.2 mmol/l and 8.0 +/- 0.3 mmol/l, respectively, the HbA1c was 7.3 +/- 0.5% at the time of conception and 6.9 +/- 0.2% 6-10 weeks later. In the control group the HbA1c 6-10 weeks after conception was 7.2 +/- 0.5%. In the pump group two fetuses exhibited early growth delay while all of the 11 fetuses in the control group were of normal early growth. There were no malformations in either group. All pregnancies were uncomplicated except for one case of toxaemia in the control group. Thus, during CSII treatment the metabolic control was improved in all patients. A possible beneficial effect of this improved control on the early fetal growth delay was not demonstrated. Both groups are, however, still small and definite conclusions must await further results.

Donaldson, D. M. (Brigham Young University, Provo, Utah), R. S. Jensen, B. M. Jensen, and A. Matheson. Serological relationships among beta-lysin, plakin, and leukin. J. Bacteriol. 88:-1049 1055. 1964.-beta-Lysin is a substance which has been separated from normal serum and which is bactericidal for a variety of gram-positive bacteria including Bacillus subtilis. Purified beta-lysin is not denatured at 97 C for 15 min. The bactericidal activity of six of nine beta-lysin preparations was unaltered at 97 C for 30 min and was depressed 50% in the other three preparations. After 120 min at 97 C, the bactericidal activity was between 13 and 25% of normal. beta-Lysin was completely inactivated at 120 C for 15 min. Antisera prepared in guinea pigs against purified rabbit beta-lysin neutralized the bactericidal activities of purified beta-lysin, normal rabbit serum, platelet extracts, and purified plakin. This serological relationship between beta-lysin and plakin was also demonstrated by the observation that antisera against platelets neutralized the bactericidal activities of serum, platelet extracts, and purified beta-lysin. When anti-beta-lysin serum was tested against crude bactericidal extracts of leukocytes and purified leukin, no neutralization of these bactericidal substances was measurable. The results of this study are in accord with conclusions made in previous studies that platelets are a primary source of serum beta-lysin and that leukocytes contribute little, if any, to this type of serum bactericidal activity. Ouchterlony tests, in combination with the neutralization studies, indicated that the antigen-antibody system involved in the neutralization of beta-lysin may be a nonprecipitating system.