Withdrawal of bromocriptine after long-term therapy for macroprolactinomas; effect on plasma prolactin and tumour size

The present study describes the effect on plasma prolactin values and tumour size of bromocriptine withdrawal in 12 patients who had been treated for macroprolactinomas for a period of 3.5-7 (mean 4.9) years. Pretreatment plasma prolactin values ranged from 12,000 to 210,000 (mean: 66,000) mU/l. Immediately before bromocriptine withdrawal plasma prolactin values were in the normal range (less than 350 mU/l for men; less than 450 mU/l for women). Bromocriptine treatment was associated with tumour reduction in all cases. The following observations were made upon withdrawal of bromocriptine: (1) In 11 patients hyperprolactinaemia redeveloped although plasma prolactin levels remained below 600 mU/l in two of these patients during a follow-up period of 1 year. In the other nine patients bromocriptine treatment was reinstituted after 4-12 weeks. (2) Hyperprolactinaemia was associated with tumour reexpansion in one case and increased density of the tumour in two cases. (3) In one patient plasma prolactin remained undetectable during a follow-up period of 1 year and no tumour re-expansion was found. It is concluded that tumour regrowth is uncommon and of small extent after cessation of long-term bromocriptine treatment for macroprolactinomas.     

Characterization of P-glycoprotein and multidrug resistance proteins in rat kidney and intestinal cell lines.

The activity of P-glycoprotein (Pgp/MDR1/ABCB1) and multidrug resistance proteins (MRP/ABCC) influence the pharmacokinetics and bioavailability of many drugs. Few suitable cell lines for the study of drug transport exist. Additional non-human cell lines may help clarify species differences and contribute to the current knowledge of drug transport. The aim of the present study was to characterize three rat epithelial cell lines for transporter expression and activity. Transporter expression was assessed in intestinal IEC-6 and renal GERP and NRK-52E cells using RT-PCR and Western blot analysis. Pgp and Mrp transport activity were analyzed by measuring calcein accumulation and glutathione-S-bimane efflux, respectively. The three cell lines showed Pgp expression and Pgp-dependent transport, both decreasing with culture time after reaching confluency. Besides Pgp, cells expressed Mrp1, Mrp3, Mrp4, and Mrp5, while Mrp2 and Mrp6 were absent. In addition, they showed temperature- and Mrp-dependent efflux of glutathione-S-bimane. Exposure to a panel of different inhibitors showed that this efflux was probably mediated by Mrp4. In conclusion, the three rat epithelial cell lines investigated showed Pgp and Mrp expression and transport. Mrp dependent transport was most likely mediated by Mrp4. In future, these cell lines may be used as in vitro models to study drug transport.     

An approach to protein restriction in children with renal insufficiency

Children with mild to moderate renal insufficiency may be at an increased risk for developing glomerulosclerosis and subsequent renal failure. Low protein diets (LPD) have been shown to delay the progression of renal insufficiency in laboratory animals and may be of benefit in adult humans. The nutritional costs of a LPD in adults are reportedly minimal. We review the protein and caloric requirements of growing children and discuss the potential harmful effects and benefits of an LPD in this population. We also discuss dietary adherence and the difficulty of designing an LPD for children. We conclude that the protein content of a typical American diet can safely be reduced to, but not below, the recommended daily allowance for protein if diets are carefully planned, patients and their parents extensively counseled, and if dietary supplements are given to help meet the caloric and vitamin-mineral nutrient needs of growing children. In addition, ongoing nutritional assessment, counseling, and frequent monitoring of growth, diet and biochemical indicators of protein status are essential for maintaining the health of these children.     

Der Einfluß von N1-n-Butylbiguanid auf das Verhalten der Unveresterten Fettsäuren (UFS) bei Normalpersonen und bei Diabetikern und am epididymalen Fettgewebe der Ratte

Zusammenfassung Das Verhalten der Unveresterten Fettsäuren an Gesunden und Diabetikern und am epididymalen Fettgewebe der Ratte unter N₁-n-Butylbiguanid wurde untersucht. Normalpersonen mit und ohne Biguanid reagieren bei Blutzuckerabfall mit einem Anstieg der UFS, der unter Biguanid signifikant höher ist. Diabetiker zeigen einen geringfügigen Abfall der UFS nach Biguanid. Unter Biguanidkonzentrationen, die der therapeutischen Serumkonzentration entsprechen (5/ml), werden vom Fettgewebe in Gegenwart von Glucose vermehrt UFS utilisiert. Bei hohen Konzentrationen (100 bis 1000/ml) tritt ein Wirkungsumschlag ein, die Fettsäureutilisation wird gehemmt.Teile dieser Arbeit sind in den Dissertationen vonM. L'age undJ. Stehr enthalten.     

Die Inkorporation von markiertem Sauerstoff aus Wasser in die ATP-, Kreatinphosphat- und Orthophosphat-Fraktion intakter Muskeln bei Ruhe,tetanischer Reizung und Erholung

Ohne ZusammenfassungMit 7 TextabbildungenDie vorliegenden Studien am Physiologischen Institut Freiburg i. Br. wurden durch einen Bundeszuschuß des Ministeriums für Atomkernenergie und Wasserwirtschaft (Bonn) ermöglicht. Die Untersuchungen in Zürich wurden aus Mitteln des Schweizer Nationalfonds getragen. Den genannten Institutionen gilt unser besonderer Dank. Vorläufige Mitteilungen über die Methode und die hier dargestellten Ergebnisse wurden bereits früher gegeben [siehe Fleckenstein, A. E. Gerlach, u. J. Janke gemeinsam mit P. Marmier: Naturwissenschaften 46, 365 (1959); Pflügers Arch. ges. Physiol. 270, 20 (1959); P. Marmier gemeinsam mit E. Gerlach, J. Janke u. A. Fleckenstein: Pflügers Arch. ges. Physiol. 270, 19 (1959); A. Fleckenstein: University of London Special University Lectures in Physiology 26–28. Oct. 1959: The turnover rates of high energy phosphate compounds during activity and rest as indicated by the oxygen exchange with H₂O¹⁸. Bericht von E. Gerlach sowie von J. Janke vor der Freiburger Med. Ges. vom 24. 11. 1959, vgl. Klin. Wschr. 38, 341–342 (1960)].     

Client feedback on physiotherapy counselling in primary health care

The extent of rehabilitation services is adequate, but little feedback is available on these services and service users. This paper is based on a client feedback survey of physiotherapy services conducted in Spring 2000. The purpose of the paper is to compare patients' perceptions of the physiotherapy instruction they received in a private outpatient facility and in a public physiotherapy facility. The results of the study showed that physiotherapy clients were satisfied with the therapy and instruction they received. They felt they received an adequate amount of instructions and advice. The rehabilitee's strong commitment to care, high motivation and a support network are important to independent rehabilitation in the future. As for the point of contact, the majority of clients in the private physiotherapy facility were gainfully employed while the health centre had almost as many retired clients. Client instruction was not dependent on the point of contact.     

Self-reinforced polylactide/polyglycolide 80/20 screws take more than 1(1/2) years to resorb in rabbit cranial bone

The aim of this study was to assess tissue reactions to bioabsorbable self-reinforced polylactide/polyglycolide (SR-PLGA) 80/20 miniscrews in rabbit cranial bone. One PLGA screw was implanted on one side and one titanium screw on the other side of the sagittal suture (n = 21). Three animals were sacrificed after 2, 4, 8, 16, 24, 54, and 72 weeks. In histological examination the numbers of macrophages, giant cells, active osteoblasts, and fibrous tissue layers were assessed and degradation of the bioabsorbable screws was evaluated. After 2 weeks, macrophages were seen near the heads of both screws. After 4 and 8 weeks, the bioabsorbable screws were surrounded by fibrous tissue. Osteoblastic activity and groups of several giant cells were seen. After 24 weeks, a significant change in the morphology of the PLGA screws had occurred. Osteoblastic activity and the amount of giant cells had decreased. After 1 year, some PLGA biomaterial was still present. PLGA screws had been replaced by adipose tissue, fibrous tissue, and "foamy macrophages" that had PLGA particles inside them. After 1(1/2) years, the amount of biomaterial remaining had decreased remarkably. The particles of biomaterial were inside foamy macrophages. SR-PLGA 80/20 screws are biocompatible and have no clinically manifested complications when used in the cranial bone of rabbits. No contraindications as regards their clinical use in craniofacial surgery was found when these screws were studied in the cranial bones of rabbits.     

Age, gender and litter-related variation in T-lymphocyte cytokine production in young pigs

The capacity of farm animals to produce cytokines could be an important determinant of robustness and health. From research in rodents and humans it appears that the production and the balance of T helper 1 (Th1) and T helper 2 (Th2)-type cytokines influences susceptibility to autoimmune and infectious diseases. It is known that pigs show a large variation in many immune response parameters. So far the extent of individual variation in the production of Th1- and Th2-type cytokines in commercial outbred pigs has not been reported. In the current experiment we determined mRNA expression, as well as protein production of cytokines in 32 pigs from eight litters. From each litter two male and two female pigs were tested at 2, 5 and 8 weeks of age. Two Th1-type cytokines, interleukin (IL)-2 and interferon (IFN)-gamma, and two Th2-type cytokines, IL-4 and IL-10, were measured after phytohaemagglutinin (PHA)-stimulation of blood mononuclear cells. Cytokine production and the Th1/Th2-ratio were highly variable. The variation in cytokine protein production was moderately consistent across ages, i.e. pigs that produced high levels of cytokine at 2 weeks of age tended to do so as well at 5 and 8 weeks of age. Cytokine production tended to increase with age, and gilts and boars differed in their IL-2/IL-4 ratio. Unexpectedly, age, gender and litter effects often differed for mRNA and protein production data. We hypothesize that cytokine production is a consistent trait in pigs, especially at the protein production level. Future investigations in more animals and across a wider age range are necessary.     

Estimating the relative frequency of leukodystrophies and recommendations for carrier screening in the era of next‐generation sequencing

Leukodystrophies are a heterogeneous group of heritable disorders characterized by abnormal brain white matter signal on magnetic resonance imaging (MRI) and primary involvement of the cellular components of myelin. Previous estimates suggest the incidence of leukodystrophies as a whole to be 1 in 7,000 individuals, however the frequency of specific diagnoses relative to others has not been described. Next generation sequencing approaches offer the opportunity to redefine our understanding of the relative frequency of different leukodystrophies. We assessed the relative frequency of all 30 leukodystrophies (associated with 55 genes) in more than 49,000 exomes. We identified a relatively high frequency of disorders previously thought of as very rare, including Aicardi Goutières Syndrome, TUBB4A‐related leukodystrophy, Peroxisomal biogenesis disorders, POLR3‐related Leukodystrophy, Vanishing White Matter, and Pelizaeus‐Merzbacher Disease. Despite the relative frequency of these conditions, carrier‐screening laboratories regularly test only 20 of the 55 leukodystrophy‐related genes, and do not test at all, or test only one or a few, genes for some of the higher frequency disorders. Relative frequency of leukodystrophies previously considered very rare suggests these disorders may benefit from expanded carrier screening.     

No evidence for allelic association between bipolar disorder and monoamine oxidase a gene polymorphisms

We have tested the hypothesis that DNA markers in the MAOA gene show allelic association with bipolar affective disorder. Eighty-four unrelated Caucasian patients with DSM III-R bipolar disorder and 84 Caucasian controls were typed for three markers in MAOA: a dinucleotide repeat in intron 2, a VNTR in intron 1, and an Fnu4HI RFLP in exon 8. No evidence for allelic association was observed between any of the markers and bipolar disorder. © 1995 Wiley-Liss, Inc.