Peritoneal fluid volume and levels of steroid hormones and gonadotrophins in peritoneal fluid of normal and norethisterone-treated women.

Peritoneal fluid and blood samples were collected at surgical sterilization from 30 untreated women at various stages of the luteal phase and from 43 women treated with 300 micrograms norethisterone daily. Levels of oestradiol, progesterone, luteinizing hormone (LH) and follicle stimulating hormone (FSH) were measured. The highest peritoneal fluid volume (mean, 23.1 ml) was found in the early luteal phase (LH 0 to + 3) and the lowest (mean, 5.9 ml) in the late luteal phase (LH + 12 to menses). The norethisterone treatment diminished the formation of peritoneal fluid and the degree of inhibition was dependent upon the type of ovarian reaction to norethisterone. Progesterone and oestradiol levels were higher in peritoneal fluid compared to plasma throughout the luteal phase and during norethisterone treatment. A comparison of the levels of these steroids between untreated controls (LH + 8 to + 11) and norethisterone-treated women demonstrated that the progesterone levels in peritoneal fluid were highly reduced by norethisterone treatment, while the oestradiol levels were not affected. The FSH and LH levels were, in contrast to the steroid hormones, significantly lower in peritoneal fluid than in plasma, both in the untreated and the treated women. No differences in the FSH or LH levels between the untreated and treated women were found. The results indicate that the peritoneal fluid volume and the steroid hormone levels in peritoneal fluid vary with the stages of the luteal phase. Norethisterone treatment significantly reduced the peritoneal fluid volume as well as its progesterone concentration, whereas the oestradiol and gonadotrophin levels remained unchanged.     

Take care in how you store your PD fluids: actual temperature determines the balance between reactive and non-reactive GDPs.

OBJECTIVE: During heat sterilization and during prolonged storage, glucose in peritoneal dialysis fluids (PDF) degrades to carbonyl compounds commonly known as glucose degradation products (GDPs). Of these, 3,4-dideoxyglucosone-3-ene (3,4-DGE) is the most cytotoxic. It is an intermediate in degradation between 3-deoxyglucosone (3-DG) and 5-hydroxymethyl-2-furaldehyde (5-HMF). We have earlier reported that there seems to be equilibrium between these GDPs in PDF. The aim of the present study was to investigate details of this equilibrium. METHODS: Aqueous solutions of pure 3-DG, 3,4-DGE, and 5-HMF were incubated at 40 degrees C for 40 days. Conventional and low-GDP fluids were incubated at various temperatures for up to 3 weeks. Formaldehyde, acetaldehyde, glyoxal, methylglyoxal, 3-DG, 3,4-DGE, and 5-HMF were analyzed using high performance liquid chromatography. RESULTS: Incubation of 100 micromol/L 3,4-DGE resulted in the production of 36 micromol/L 3-DG, 4 micromol/L 5-HMF, and 40 micromol/L unidentified substances. With the same incubation, 200 micromol/L 3-DG was converted to 9 micromol/L 3,4-DGE, 6 micromol/L 5-HMF, and 14 micromol/L unidentified substances. By contrast, 100 micromol/L 5-HMF was uninfLuenced byincubation. In a conventional PDF incubated at 60 degrees C for 1 day, the 3,4-DGE concentration increased from 14 to a maximum of 49 micromol/L. When the fluids were returned to room temperature, the concentration decreased but did not reach original values until after 40 days. In a low GDP fluid, 3,4-DGE increased and decreased in the same manner as in the conventional fluid but reached a maximum of only 0.8 micromol/L. CONCLUSIONS: Considerable amounts of 3,4-DGE may be recruited by increases in temperature in conventional PDFs. Lowering the temperature will again reduce the concentration but much more time will be needed. Precursors for 3,4-DGE recruitment are most probably 3-DG and the enol 3-deoxyaldose-2-ene, but not 5-HMF. Considering the ease at which 3,4-DGE is recruited from its pool of precursors and the difficulty of getting rid of it again, one should be extremely careful with the temperatures conventional PDFs are exposed to.     

Mantle cell lymphomas with clonal immunoglobulin V(H)3-21 gene rearrangements exhibit fewer genomic imbalances than mantle cell lymphomas utilizing other immunoglobulin V(H) genes.

A preferential use of one particular immunoglobulin variable heavy chain gene, V(H)3-21, has recently been reported in mantle cell lymphoma, where almost all of these V(H)3-21+ mantle cell lymphomas showed usage of the same light chain Vlambda gene (Vlambda3-19) and also had a tendency towards improved prognosis. These findings suggested that V(H)3-21+ mantle cell lymphomas constitute a distinct subgroup, possibly with antigen stimulation involved in disease pathogenesis. In this study, we applied the comparative genomic hybridization (CGH) method on 37 mantle cell lymphoma tumors in order to investigate if the V(H)3-21+ tumors are different at the genomic level. Interestingly, V(H)3-21+ mantle cell lymphomas (n=14) showed significantly fewer genomic aberrations (mean 2.4) compared to non-V(H)3-21 mantle cell lymphomas (n=23) (mean 4.9). The chromosomal aberrations identified in our study were generally in accordance with previous CGH studies of mantle cell lymphoma; the most frequent aberration was complete or partial loss of chromosome 13, followed by recurrent losses within 6q, 9p, 9q and 11q and frequent gains in 3q, 7p, 8q and 15q. Deletions within 8p and 9p as well as gains in 7p and 15q were found exclusively in the non-V(H)3-21-utilizing tumors. In summary, V(H)3-21+ mantle cell lymphomas demonstrated both a lower number and a different spectrum of genomic aberrations than mantle cell lymphoma in general, thus supporting the hypothesis that V(H)3-21+ mantle cell lymphomas constitute a new subgroup. The findings presented in this report may explain the tendency for a better clinical outcome for patients whose tumors utilize V(H)3-21.     

PD fluids contain high concentrations of cytotoxic GDPs directly after sterilization.

OBJECTIVE: Glucose degradation products (GDPs) in peritoneal dialysis (PD) fluids are cytotoxic and affect the survival of the peritoneal membrane. One of the most reactive GDPs in PD fluids is 3,4-dideoxyglucosone-3-ene (3,4-DGE). 3,4-DGE has been reported as an intermediate between 3-deoxyglucosone (3-DG) and 5-hydroxymethyl furaldehyde (5-HMF) during degradation of glucose. In PD fluids, 3,4-DGE exists in a temperature-dependent equilibrium with a pool of unidentified substances.The aim of this study was to explore this equilibrium and its temperature dependence during the first months of storage after the sterilization procedure. METHODS: GDPs and inhibition of cell growth (ICG) were measured directly after sterilization of the PD fluid and during storage at different temperatures for 60 days. The following GDPs were analyzed: 3-DG, 3,4-DGE, 5-HMF, formaldehyde, acetaldehyde, glyoxal, and methylglyoxal. RESULTS: Immediately after sterilization, the concentration of 3,4-DGE was 125 micromol/L. During the first weeks of storage, it decreased by about 80%. At the same time, the 3-DG concentration increased. None of the other GDPs were significantly affected. Cytotoxicity correlated well with the concentration of 3,4-DGE. When pure 3,4-DGE was substituted for the lost amount of 3,4-DGE after 30 days of storage, the initial ICG was almost completely regained. CONCLUSIONS: Heat sterilization of PD fluids promotes the formation of large quantities of 3,4-DGE, rendering the fluid highly cytotoxic. During storage, the main part of 3,4-DGE is reversibly converted in a temperature-dependent manner to a less cytotoxic pool, consisting mainly of 3-DG. Cytotoxicity seems to be dependent exclusively on 3,4-DGE. In order to avoid higher levels of 3,4-DGE concentrations, PD fluids should not be used too soon after sterilization and should not be stored at temperatures above room temperature.     

Experimental study of two methods of data collection by questionnaire

The aim of the present study was to compare the results obtained using two different methods of data collection about caries preventive services provided in general dental practice. A questionnaire was mailed to a random national sample of 479 dentists resident in Norway in January 1985. The sample was divided into two groups by random allocation. All dentists, irrespective of group, were requested to give background information. One group, comprising 287 dentists (GR), was asked to complete a separate form for every adult patient (greater than or equal to 20 yr) treated in the course of 1 day. The demographic characteristics and dental visiting habits of the patients, as well as the number of teeth present, caries lesions and preventive services rendered were recorded. The other group, 192 dentists (GE), was requested to make general estimates of the time spent on caries prevention and the proportion of patients receiving various types of caries preventive services. The dentists were unaware of the methodologic aspect of the survey and everyone received one reminder in order to guarantee anonymity. The estimation method (GE) did not give the expected advantage over the registration method (GR) in response rate (51.7% vs 46.2%, P greater than 0.40), and gave a gross overestimation of the frequency with which adult patients received different types of caries preventive procedures (P less than 0.005). Thus, even though the estimates of the proportion of total treatment time spent on caries prevention were comparable for the two methods, and the estimation approach is labor-saving, it cannot be recommended for the collection of data on caries prevention in the dental office.     

Shwachman-Kulczycki score and resting energy expenditure in cystic fibrosis.

BACKGROUND: Disease severity assessed by clinical scores in cystic fibrosis (CF) has been a topic of investigation for many years, although a correlation of clinical scores with resting energy expenditure (REE) has not been described yet. We aimed to assess disease severity as evaluated by the Shwachman-Kulczycki (SK) score and to correlate these findings with REE and forced expiratory volume in 1 s (FEV1). METHODS: Twenty-eight patients performed respiratory function testing (FEV1), and assessment of REE with open circuit indirect calorimetry. The SK score was evaluated according to general activity, physical examination, nutrition and conventional chest X-ray findings. RESULTS: Mean SK score was 75.3 +/- 15.7. Mean REE was 109.1% of predicted vs. 96.5% predicted in 16 healthy subjects (P = 0.002). There was a significant correlation between the SK score and REE (P = 0.001), the SK score and FEV1 (P < 0.001) and REE and FEV1 (P = 0.034). CONCLUSIONS: The correlations between the SK score, REE and FEV1 demonstrate a close connection between disease severity, caloric requirement and lung damage. They confirm the clinical value of the SK score, which is easy to assess in a clinical setting.     

The effect of tolterodine on the pharmacokinetics and pharmacodynamics of a combination oral contraceptive containing ethinyl estradiol and levonorgestrel.

BACKGROUND: Tolterodine is an antimuscarinic agent for the treatment of overactive bladder, a chronic condition that is particularly common in women. Given the prevalence pattern of overactive bladder and the widespread use of oral contraception, circumstances are likely to arise in which physicians may wish to prescribe tolterodine for patients already taking oral contraceptives. Based on a search of MEDLINE from 1990 to 2001, there have been no studies of whether concomitant use of these agents entails a risk of drug-drug interaction or conception. OBJECTIVE: This study investigated the effects of tolterodine on the pharmacokinetics and pharmacodynamics of a low-dose combination oral contraceptive (ethinyl estradiol 30 microg/levonorgestrel 150 microg). METHODS: This was an open-label, randomized, 2-period crossover study in healthy women. Oral contraception was given for 21 days either alone or in combination with oral tolterodine 2 mg BID (on days 1-14) over two 28-day contraceptive cycles. Pharmacokinetic assessments were performed on day 14 based on plasma levels of ethinyl estradiol and levonorgestrel up to 24 hours after dosing and serum tolterodine levels at 1 to 3 hours after dosing. The potential for pharmacodynamic interaction was assessed in terms of the risk of failure of suppression of ovulation based on serum levels of estradiol and progesterone measured throughout each cycle. RESULTS: Twenty-four healthy women (age, 23-41 years [mean, 30 years]; height, 155-178 cm [mean, 167 cm]; body weight, 51-75 kg [mean, 64 kg]) participated in the study. There was no evidence of a pharmacokinetic interaction between tolterodine and the steroid hormones in the oral contraceptive used, nor did the oral contraceptive show any relevant pharmacokinetic interaction with tolterodine. Serum levels of estradiol and progesterone indicated suppression of ovulation in both treatment periods. CONCLUSION: In this selected population. coadministration of tolterodine did not affect the contraceptive efficacy of a low-dose combination oral contraceptive containing ethinyl estradiol and levonorgestrel.     

Low threshold afferent projections from the oral cavity and the face to the cerebral cortex of the cat

Summary The projections of low threshold afferents from the oral cavity and the face to the cerebral cortex of cats anaesthetized with chloralose were investigated. The projection fields of the ipsi- and contralateral lingual, inferior alveolar, mental, superior alveolar, infraorbital, (separate branches from whiskers and nose), ophthalmic, great auricular and the contralateral superficial radial nerves were localized. Surface potentials of short latency and maximal amplitude were recorded and their location traced on photographs of the rostral part of the right cerebral hemisphere. Reference points were indicated with india ink punctures.The extent of the cytoarchitectonic areas was determined on histological serial sections and the borders transferred to the photographs of the hemisphere. The features of the projections were related to the cytoarchitecture and to the pattern of the gyri and sulci.It was observed that the low threshold afferents from the oral cavity and the face projected via fast conducting, presumably three synaptic paths, to separate locations in areas 3a, 3b, 5a and 6a. The projections to area 3b were somatotopically organized starting with the auricular and the ophthalmic nerve projections lateral to the 3b projection of the forelimb in the posterior sigmoid gyrus and continuing with the maxillary nose, maxillary whiskers, mental nerve, superior alveolar, inferior alveolar and lingual nerve fields along the coronal gyrus towards the presylvian sulcus. The somatotopy was, however, not isomorphic with the body surface but displayed consecutive, overlapping bands across area 3b. The projections to area 3a were similarly organized. The somatotopy was less obvious in area 5a and 6a. Convergent projections with responses of slightly longer latency were observed in area 43 (gyrus orbitalis).This work was supported by the Swedish Medical Research Council (Proj. B79-14X-00045-15)