Chocolate swelling during storage caused by fat or moisture migration.

Quantification of swelling in dark chocolate subjected to fat or moisture migration was conducted using a new method based on confocal chromatic displacement sensor. The nondestructive method allowed for the height profile of dark chocolate samples to be scanned with a sensitivity of ± 2.8 µm. By performing multiple scans on each sample prior to and after being subjected to fat or moisture migration, the induced swelling could be quantified. Applying the new method on confectionery systems revealed that fat and moisture migration generate different swelling behavior/kinetics in dark chocolate during storage. Moisture migration resulted in a rapid swelling once a water activity of 0.8 was reached in the chocolate, probably by interaction and absorption of moisture by the particulate solids. Fat migration also affected the swelling behavior in chocolate, possibly by inducing phase transitions in the continuous cocoa butter phase. Migrating fat also proved to induce a more pronounced swelling than the same amount of absorbed moisture which further consolidated that the observed swelling caused by fat or moisture migration is a result of significant different mechanisms.

A longitudinal study of the perimenopausal transition: altered profiles of steroid and pituitary hormones, SHBG and bone mineral density.

From a longitudinal prospective study, 160 women with spontaneous menopause and without steroid medication were followed during the transition from pre- to postmenopause. After 12 years 152 women were still participating in the study. Blood samples were drawn every 6 months until 1 year after the menopause and every 12 months thereafter. Measurements of bone mineral density (BMD) on the forearm were performed every second year. All women routinely completed a questionnaire concerning symptoms frequently attributed to the climacteric period. All data were grouped around the onset of the menopause, thereby allowing longitudinal evaluation of the changes in the variables from the premenopausal to the postmenopausal period. The beginning of the perimenopausal period was characterized by transitory elevations of follicle-stimulating hormone (FSH). A significant increase in serum levels of gonadotropins was observed for both FSH and luteinizing hormone (LH) from about 5 years before the menopause. Within the 6 month period around the menopause there was a further increase which culminated within the first postmenopausal year for LH and 2-3 years postmenopause for FSH. Thereafter, a continuous decrease in LH occurred over the following 8 years. With respect to FSH, there was a slight decline starting about 4 years postmenopause. During the premenopausal period an increasing frequency of inadequate luteal function or anovulation occurred and, in the postmenopausal years, the serum levels of progesterone (P) were invariably low. Gradually, the ratio between estrone (E1) and 17-beta-estradiol (E2) increased, reflecting the declining follicular steroidogenesis. A marked decrease in estrogen levels occurred during the 6 month period around the menopause, most pronounced in E2. During the next 3 years, the levels of E2 and E1 showed an essentially parallel, moderate decline. Around the menopause, serum levels of testosterone (T), delta4-androstenedione (A) and sex hormone-binding globulin (SHBG) showed small but significant decreases. From about 3 years postmenopause, the levels were relatively constant over the following 5 years. A decrease in BMD was observed in the postmenopause, and from about 3 years postmenopause, estradiol correlated positively with BMD. Before, as well as after the menopause, body mass index (BMI) showed an inverse correlation with SHBG. Postmenopausal androstenedione correlated positively with E1, E2 and T. BMI correlated positively with E1 and E2. The concentrations of the free fraction of E2 and T are dependent on the levels of SHBG, which in turn has a negative correlation with BMI. The impact of this will influence the severity of symptoms, the degree of bone loss and the need for supplementary therapy.

A prospective population-based management program including primary surgery and postoperative risk assessment by means of DNA ploidy and histopathology. Adjuvant radiotherapy is not necessary for the majority of patients with FIGO stage I-II endometrial cancer.

A management program for FIGO stage I-II nonserous, nonclear-cell adenocarcinomas was evaluated. Histopathology and DNA ploidy were used to estimate postoperatively the risk of progression or death of disease and to tailor treatment. The patient material was a population-based consecutive cohort of all women with endometrial cancer in the Southern Swedish Health Care Region diagnosed between June 1993 and June 1996 (n = 553). Of these, 335 were eligible for the management program. Patients estimated to be at low risk were treated by surgery only, while high-risk patients also received vaginal brachytherapy. A large low-risk group consisting of 84% (n = 283) of the patients with an estimated disease-specific 5-year survival of 96% (95% CI = 93-98%) was identified. The high-risk group (n = 52, 16%) showed a worse outcome with an 80% 5-year disease-specific survival (95% CI = 65-89%). The difference in survival between the groups was highly significant (P < 0.0001). Half of the progressions were distant in the high-risk group. Although there is a clear indication for adjuvant therapy for this group, locoregional radiotherapy could be expected to fail in cases with distant progression. Thus, effective systemic treatments need to be developed. Low-risk patients, constituting the majority (84%) of the patients, can be safely treated by surgery only.

Islet autoantibodies in cord blood from children who developed type I (insulin-dependent) diabetes mellitus before 15 years of age.

Islet autoantibodies are early markers for Type I (insulin-dependent) diabetes mellitus. The aim of this study was to establish whether islet autoantibodies were present at birth in children who developed Type I diabetes before 15 years of age. Cord blood sera from 81 children who developed Type I diabetes between 10 months and 14.9 years of age were tested for glutamic acid decarboxylase autoantibodies (GAD65Ab), islet cell antigen 512 autoantibodies (ICA512Ab), insulin autoantibodies (IAA) all by quantitative radioligand binding assays and islet cell autoantibodies (ICA) by indirect immunofluorescence. Cord blood sera from 320 randomly selected matched children were controls. The children who developed Type I diabetes had an increased frequency of cord blood islet autoantibodies compared with control subjects: Glutamic acid decarboxylase autoantibodies were detected in 6% (5/81) patients and 2% (5/320) control subjects (p = 0.03); islet cell antigen 512 autoantibodies in 5% (4/73) patients and 1% (4/288) control subjects (p = 0.06); insulin autoantibodies (IAA) in 0% (0/79) patients and 0.3% (1/320) control subjects (p = 0.36); and islet cell autoantibodies in 10% (8/81) patients compared with 0.6% (2/320) control subjects (p = 0.0001). Taken together, 17% (14/81) patients had one or more islet autoantibody compared with 4% (12/320) control subjects (p = 0.0001). Whereas none of the control children had more than one antibody, 4% (3/81) children who later developed Type I diabetes were double positive (p = 0.002). Although glutamic acid decarboxylase autoantibodies' concentrations in cord-blood correlated to those in the mothers' blood at the time of delivery, no corresponding correlation was found for the other two types of autoantibodies. The increased frequency of cord blood islet autoantibodies suggests that the Type I diabetes process could already be initiated in utero.

Ten-year clinical, developmental, and intellectual follow-up of children with congenital cytomegalovirus infection without neurologic symptoms at one year of age.

OBJECTIVE: This study was undertaken to ascertain whether children with congenital cytomegalovirus (CMV) infection at birth, but without neurologic symptoms at 1 year of age, differed in somatic, neurologic, developmental, or intellectual status from matched control children at long-term follow-up. MATERIAL AND METHODS: Congenital CMV infection, as demonstrated by isolation of the virus within the first week of life, was diagnosed in 44 (0.5%) of 9806 infants. From this basic CMV-infected population, children who developed neurologic disturbances including sensorineural deafness before 1 year of age were excluded (n = 7), as were those unwilling to participate (n = 2). Congenitally infected infants (n = 35) and matched control infants (n = 53) were followed up clinically and neurologically. At 21 months, development was assessed with the Griffiths' Developmental Scale and at 7 years of age neurologic status was assessed with the Stott test and intellectual development with the Wechsler Intelligence Scale for Children. RESULTS: As reported previously, 18% (8/44) of the CMV-infected infants manifested symptoms at birth, as compared to 8% (4/53) in the control group. In the congenital CMV group 7% (2/30) children tested had abnormal Stott test results, as compared to 2% (1/43) in the control group. Thirty-two CMV-infected and 51 control group children were assessed with the Griffiths' scale at 21 months of age. The two groups did not differ significantly, either in mean scores (6.3 +/- 2.3 vs 6.1 +/- 1.9) or in the proportion of children with scores below normal (19% [6/32] vs 16% [8/51]). Twenty-five CMV-infected and 41 control group children were assessed with the Wechsler Intelligence Scale for Children at 7 years of age (median 86 months; range, 82 to 90 and 82 to 91, respectively). The two groups did not differ significantly, either in mean scores (5.8 +/- 2.0 vs 6.4 +/- 1.6) or in the proportion of children with scores below normal (12% [3/25] vs 5% [2/41]). CONCLUSION: Children with congenital CMV infection are unlikely to be at an increased risk of subsequent neurodevelopmental or intellectual impairment if they show normal development at 12 months of age.

Retrospective diagnostics of congenital cytomegalovirus infection performed by polymerase chain reaction in blood stored on filter paper.

Capillary blood samples from 63 infants collected 3-7 days after birth, and thereafter stored on filter papers for 12-18 y, were tested for the presence of CMV DNA by the polymerase chain reaction (PCR) method. Of 16 infants with proven congenital CMV infection (positive virus isolation test in urine sampled within 1 week of age), 13 (81%) had a positive CMV PCR test and 3 (19%) a negative PCR test. All blood samples from 16 control infants without congenital CMV infection (negative virus isolation test in urine sampled within 1 week of age) were CMV PCR-negative. When 31 samples on filter papers stored above or below the samples of the infected infants were tested, 6 (19%) had a weak reactivity. This suggests that CMV DNA can be transferred from one filter paper to another during storage. We conclude that PCR performed on dried blood stored on filter paper is a useful method in the retrospective diagnostics of congenital CMV infection. Consideration must be given, however, to the possibility of transfer of CMV DNA from blood samples stored nearby.

Glutamate decarboxylase antibodies in non-diabetic pregnancy precedes insulin-dependent diabetes in the mother but not necessarily in the offspring.

We studied the risk for diabetes of glutamate decarboxylase (GAD65Ab) and islet cell (ICA) autoantibodies in non-diabetic pregnant mothers and their children. Pregnancy and cord blood sera were collected in 1970-87 from about 35,000 mothers who delivered a child in the city of Malmö, Sweden. A total of 42 mothers were identified in 1988 who, 1-18 years after their pregnancies, had developed either insulin-dependent (n = 22) or non-insulin dependent (n = 20) diabetes mellitus. First, in 123 pregnant mothers selected as controls, 0.8% had GAD65Ab and 0.8% ICA. Second, among the mothers with non-insulin dependent diabetes, 7/20 (35%) had GAD65Ab eight months to 13 years, 10 months before clinical diagnosis. Third, in mothers who later developed insulin-dependent diabetes, 12/22 (55%) had GAD65Ab and 10/22 (45%) had ICA in pregnancies preceding the clinical diagnosis by 13 months to 9 years, 4 months. In 1996, none of the children born to the 42 mothers have developed diabetes. GAD65Ab and ICA in non-diabetic pregnancies may predict insulin-dependent diabetes in the mother but not necessarily in the offspring.

Indications that maternal coxsackie B virus infection during pregnancy is a risk factor for childhood-onset IDDM.

In a population-based setting, we traced serum samples collected at time of birth from 55 mothers whose children later developed insulin-dependent diabetes (IDDM) and matched them pairwise to control subjects who gave birth at the same hospital during the same month. The sera were analysed for IgM antibodies to coxsackie B virus serotypes 2, 3 and 4 (CBV-2, 3 and 4) using a type-specific mu-antibody-capture radioimmunoassay. Despite a decreased power due to the close matching by time of birth we found a significantly higher frequency of CBV-3 IgM at delivery in mothers whose children later became diabetic compared to their matched control subjects. When using the presence of CBV-3 IgM as a risk factor the Mantel-Haenszel odds ratio estimate (95% confidence limits) was 2.57 (1.02; 7.31), p = 0.043. For CBV-2 and CBV-4, respectively no significant difference was found between mothers of patients and control subjects. According to the odds ratio estimate for CBV-3 and the proportion of exposed mothers among patients estimated in this study the aetiological fraction for this risk determinant would be 27%. In conclusion, this study indicates that children of mothers who expressed CBV IgM at delivery are at increased risk for developing childhood onset IDDM. A fetal infection with CBV similar to rubella virus may initiate autoimmunity or cause persistent infection that may lead to progressive beta-cell destruction.

Thyroid antibodies are not a risk factor for pregnancies with Down syndrome.

The observation that thyroid disease is frequent in mothers of children with Down syndrome (DS) has suggested that maternal thyroid antibodies could be a factor predisposing to trisomy 21 in their offspring. In this study, the incidences of thyroglobulin (Tg) and thyroid peroxidase (TPO) antibodies were analysed with a sensitive solid-phase immunosorbent radioassay in sera from 29 mothers giving birth to children with trisomy 21 and 87 control mothers. The serum samples were collected at delivery. There was no statistical difference regarding the proportion of thyroid antibodies (against Tg and/or TPO) in the two groups. Thyroid antibodies were detected in 6/29 (20.7 per cent) of the DS mothers and in 23/87 (26.4 per cent) of the control mothers. Among the women with thyroid antibodies, 4/6 (66.7 per cent) of the DS mothers and 12/23 (52 per cent) of the control mothers had antibodies against both Tg and TPO. There was no increase in the relative risk of having a child with DS if the titre of either Tg or TPO antibodies or both were positive, i.e. > or = 1/5. The results indicate that the presence of thyroid antibodies in the serum of a pregnant women has no prognostic value for the birth of an infant with DS.

A longitudinal study of the perimenopausal transition: altered profiles of steroid and pituitary hormones, SHBG and bone mineral density.

From a longitudinal prospective study, 160 women with spontaneous menopause and without steroid medication were followed during the transition from pre- to postmenopause. After 12 years 152 women were still participating in the study. Blood samples were drawn every 6 months until 1 year after the menopause and every 12 months thereafter. Measurements of bone mineral density (BMD) on the forearm were performed every second year. All women routinely completed a questionnaire concerning symptoms frequently attributed to the climacteric period. All data were grouped around the onset of the menopause, thereby allowing longitudinal evaluation of the changes in the variables from the premenopausal to the postmenopausal period. The beginning of the perimenopausal period was characterized by transitory elevations of follicle-stimulating hormone (FSH). A significant increase in serum levels of gonadotropins was observed for both FSH and luteinizing hormone (LH) from about 5 years before the menopause. Within the 6 month period around the menopause there was a further increase which culminated within the first postmenopausal year for LH and 2-3 years postmenopause for FSH. Thereafter, a continuous decrease in LH occurred over the following 8 years. With respect to FSH, there was a slight decline starting about 4 years postmenopause. During the premenopausal period an increasing frequency of inadequate luteal function or anovulation occurred and, in the postmenopausal years, the serum levels of progesterone (P) were invariably low. Gradually, the ratio between estrone (E1) and 17-beta-estradiol (E2) increased, reflecting the declining follicular steroidogenesis. A marked decrease in estrogen levels occurred during the 6 month period around the menopause, most pronounced in E2. During the next 3 years, the levels of E2 and E1 showed an essentially parallel, moderate decline. Around the menopause, serum levels of testosterone (T), delta 4-androstenedione (A) and sex hormone-binding globulin (SHBG) showed small but significant decreases. From about 3 years postmenopause, the levels were relatively constant over the following 5 years. A decrease in BMD was observed in the postmenopause, and from about 3 years postmenopause, estradiol correlated positively with BMD. Before, as well as after the menopause, body mass index (BMI) showed an inverse correlation with SHBG. Postmenopausal androstenedione correlated positively with E1, E2 and T. BMI correlated positively with E1 and E2. The concentrations of the free fraction of E2 and T are dependent on the levels of SHBG, which in turn has a negative correlation with BMI. The impact of this will influence the severity of symptoms, the degree of bone loss and the need for supplementary therapy.

The prevalence of type 1 diabetes mellitus at follow-up of Swedish infants congenitally infected with cytomegalovirus.

In a Swedish prospective study of congenital cytomegalovirus (CMV) infection, 76 infants were shown to be infected among 16,474 newborns screened by virus isolation in urine. Seventy-three of the excreters were followed up and one developed Type 1 diabetes, as compared to 38 of the 19,483 children born during the same period (p = 0.14, Fisher's one-tailed test). Thus we found no evidence that the combined finding of congenital CMV infection and Type 1 diabetes mellitus was related.

Endonuclease cleavage pattern of cytomegalovirus DNA of strains isolated from congenitally infected infants with neurologic sequelae.

A prospective study of congenital cytomegalovirus infection in Malmö, Sweden, was performed from 1977 through 1985. The diagnosis was based on isolation of cytomegalovirus soon after birth. Congenital cytomegalovirus infection was identified in 76 infants, and as of September 1986 CNS symptoms have been experienced by nine of them. In at least seven of these infants, the disturbances can be referred to the cytomegalovirus infection. The strains from eight of the nine infants have been further studied by restriction endonuclease analysis of cytomegalovirus DNA. The cleavage patterns obtained with BamHI, EcoRI, and HindIII showed a unique pattern for each one of the eight strains. No common pattern could be associated with these eight strains in comparison with strains from postnatally infected children.

Single dose bromocriptine microcapsules in postpartum lactation inhibition.

The clinical efficacy and safety of a single intramuscular injection of Parlodel LA, Pravidel 50 mg, were studied in the prevention of lactation in 10 postpartum women. The overall efficacy at the end of the 28 day observation period was very good in 8 postpartum women and good in 2 women and no rebound lactation occurred. The prolactin plasma levels decreased to normal levels within 4 days in 9 women. Menstrual bleeding occurred in 9 women 4 to 6 weeks after treatment. Laboratory data recorded in this study support that Pravidel is effective in suppressing postpartum lactation.

A prospective long-term study in women from pre-menopause to post-menopause: changing profiles of gonadotrophins, oestrogens and androgens.

To permit a more detailed hormonal characterization of the peri-menopause, 30 healthy women were examined at regular intervals over a 7-yr period, starting about 3 yr before the menopause. Even though most of the subjects periodically experienced climacteric symptoms, no hormonal supplementation was given. The serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), oestradiol and oestrone that were recorded essentially confirmed previous data obtained in cross-sectional studies. Within the 6-mth period around the menopause the serum levels of testosterone and androstenedione showed small but significant decreases of 18 and 16%, respectively. These decreases continued over the following years and amounted to about 30% after 3 yr. In contrast, neither the mean level of dehydroepiandrosterone (DHA) nor the DHA/DHA sulphate (DHAS) ratio changed significantly at the menopause, but DHA and DHAS concentrations declined slowly by about 20% over the 7-yr observation period. The mean level of DHAS showed an isolated increase during the last few months before the menopause. A similar, although not significant, increase was also seen in DHA and testosterone levels. After the first post-menopausal year a significant positive correlation was found between the levels of oestrone and androstenedione. This longitudinal study of individual women appeared to lend itself well to the investigation of even subtle hormonal fluctuations during the gradual transition to an established post-menopausal pattern.

Neonatal chlamydial conjunctivitis.

Maternal chlamydial antibodies were determined in cord sera of 41 infants who developed neonatal chlamydial conjunctivitis and compared with the antibody profile of infants who had been exposed to Chlamydia trachomatis at birth by their isolation positive mothers but in whom conjunctivitis did not develop. No protective effect could be attributed to maternal antibodies transferred to the infants. Paired sera samples were collected from 18 infants with chlamydial conjunctivitis. Chlamydial IgM antibodies were detected in four of these 18 cases at the time diagnosis was established by isolation. An additional eight cases had developed chlamydial IgM at the time the convalescent sera samples were taken, on average on day 40. At that time symptoms had disappeared after systemic treatment had been given. Thus chlamydial IgM antibodies were eventually shown in two thirds of infants with chlamydial conjunctivitis who were all systemically treated and clinically healed. These data suggest a cautious assessment of chlamydial IgM in the diagnosis of chlamydial pneumonia.

A prospective study of rotavirus infections in neonatal and maternity wards.

The occurrence and symptomatology of rotavirus infections was studied at three maternity wards and one neonatal unit. Rotavirus was identified in 12.7% of 553 infants and 1.3% of 542 mothers at the maternity wards. Infections were more frequent in a mixed obstetric/gynecology ward than in the pure obstetric wards. Only 10% of the infants had symptomatic infections. Subgroups of rotavirus was determined in 41 infants: 22 of subgroup I and 19 of subgroup II, which is the subgroup accounting for the majority of childhood gastroenteritis. Rotavirus was found in faecal samples from 37% of the infants at the neonatal unit during an eight-month survey. A seasonal variation with most infections during colder months was seen. Subgroup determination was possible in 29 cases, 14 subgroup I and 15 subgroup II. Fifteen per cent of the infections demonstrated diarrheal symptoms. No significant difference among other clinical data registered was seen among rotavirus infected compared to the non-infected infants. We conclude that neonatal rotavirus infections occur as an endemic infection at our maternity wards possibly combined with infections due to external sources of virus in mixed wards and neonatal units.

On resorption and the effects of vaginally administered terbutaline in women with premature labor.

In a randomized, single-blind study, of a pilot nature, the administration of terbutaline sulphate was found to cause significant inhibition of contractions in premature labor. This effect became evident within 30 min when the dosage was 0.1 mg in 1 ml cellulose gel, applied vaginally, and within 2 h when released from a 5-g medicated vaginal polymer ring containing 10% terbutaline sulphate. No generalized effects of the terbutaline were noted (such as increased blood pressure or tachycardia) and the level of terbutaline in peripheral venous blood remained low. Vaginally administered terbutaline can obviously be quickly resorbed, giving a localized effect. Thus applied, terbutaline would appear to offer a number of advantages as regards treatment procedure.

Congenital cytomegalovirus infection and sensorineural hearing loss.

In a prospective study still in progress, infants with congenital cytomegalovirus (CMV) infection were followed with audiological, ophthalmological, neurological, and psychological tests; 10,328 infants were investigated within a 5-year period (1977-1982) by virus isolation in urine within the first week of life. Fifty (0.5%) had a congenital CMV infection. In this group four children turned out to have total deafness and a fifth possibly a mild hearing disorder. In one case the deafness was associated with severe mental retardation and spastic tetraplegia. The mother of the child had a primary CMV infection in the first trimester. In one of the other cases of severe deafness it could be proven that the mother had had a secondary CMV infection and in further two cases, presumed secondary infections. Prospective serological tests of the mothers would not have revealed more than one of the high risk pregnancies. The value of vaccination against congenital CMV infection is questioned. Screening of newborn infants for congenital CMV infection is recommended in order to reveal infants at high risk for deafness and make an early habilitation possible.