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.     

Unproven Nutritional Remedies and Cancer

Questionable dietary remedies for cancer decreased quality of life and did nothing to improve cancer outcomes in patients with extensive disease.     

Terminal deletion of chromosome 4p (4p16.3) shows a breakpoint between loci linked to Huntington disease

A 15-year-old boy with a terminal deletion of the short arm of chromosome 4 is described. The patient has a mild clinical phenotype that is incompatible with Wolf-Hirschhorn syndrome. Careful neurological examination including CT scan did not show any signs of Huntington disease. The chromosomal breakpoint was analyzed by means of polymorphic DNA probes localized close to the tentative Huntington (HD) locus. The breakage has occurred between D4S43 and D4S90 loci and thus deletes part of the chromosomal candidate regions for the HD locus. © 1992 Wiley-Liss, Inc.     

Identification of individual benzo[c]phenanthrene dihydrodiol epoxide-DNA adducts by the 32P-postlabeling assay.

Purine deoxyribonucleoside 3'-phosphates were reacted separately with the four configurational isomers of benzo[c]phenanthrene 3,4-dihydrodiol 1,2-epoxide. Products resulting from the cis and trans opening of the epoxide ring by the exocyclic amino groups of deoxyadenosine and deoxyguanosine 3'-phosphates were separated by high-pressure liquid chromatography and identified by comparison of the observed circular dichroism spectra with the known spectra for the corresponding nucleoside adducts. The 16 structurally identified benzo[c]phenanthrene-purine deoxyribonucleoside 3'-phosphate adducts were then separately postlabeled according to the Randerath method, and the positions of the individual bisphosphates were mapped by thin-layer chromatography. Chromatographic conditions were developed that allowed separation of the four adducts for 3 of the 4 dihydrodiol epoxide isomers.     

Three-year results of bracing in scoliosis

We treated 107 patients with idiopathic scoliosis with the Boston brace. The primary correction was good in all the curve patterns. The follow-up time after weaning averaged 3 years. The best final result was achieved in thoracic and lumbar curves (mean 2°). The final correction was worse in patients with an initial curve less than 30° when compared with the patients with larger curves. Except the double major curves, there was a positive correlation between the primary correction, duration of the treatment, and the final result. The results in 14 patients with bracing for 12 hours daily did not differ from the remainder. Progression of the initial curve more than 5° after the treatment was noted in 24 patients. Three patients were operated on later because of progression. We conclude that bracing can prevent progress of scoliosis.     

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.     

Early complications of stenting in patients with congenital heart disease: a multicentre study.

AIMS: Stenting has become an established interventional cardiology procedure for congenital heart disease. Although most stent procedures are completed successfully, complications may occur. This multicentre study evaluated early complications after stenting in patients with congenital heart disease, including potential risk factors. METHODS AND RESULTS: In this combined Dutch-Belgian retrospective study, 309 consecutive patients had undergone 366 catheterizations and received 464 stents in 13 different anatomical positions (418 sites). Seventy-two stenting-related complications (19%) occurred, of which 24 (5.7%) were major. Seven procedure-related deaths were documented (2.3%). Stent malpositioning and embolization were most common (7.7%). The use of non-premounted stents tended to be associated with higher complication rates. Centre inexperience with stenting and stenting of native vs. post-surgical stenosis tended to be associated with increased major complication rates. CONCLUSION: After stenting, complications are common for congenital heart disease. The vast diversity of stenotic sites combined with relatively small patient populations makes these procedures sensitive to complications. Combining operator experience may reduce the risks of stenting in congenital heart disease. The availability of premounted stents for greater vessel diameters will likely reduce incidences of stent migration and embolization.     

Metabolic alkalosis after pediatric cardiac surgery.

OBJECTIVE: To determine occurrence, causes and associated mortality of postoperative metabolic alkalosis in pediatric cardiac surgery. METHODS: We retrospectively analyzed clinical and biochemical variables of 186 consecutive cardiac operations other than ductal ligations on children less than 2 years old during the years 1999 and 2000. Metabolic alkalosis was defined as a pH>7.48 corrected for PCO2, with a base excess > or =5 on two or more consecutive measurements during an 8h period. RESULTS: Median age was 15 weeks [range 2 days-95 weeks] and median weight 4.5 kg [range 2.1-15.7 kg]. In 157 cases, cardiopulmonary bypass was used. In 92 [49%] procedures, metabolic alkalosis occurred with the highest corrected pH 24.3h after operation. Multivariate regression analysis associated age [P<0.001], cardiopulmonary bypass [P<0.001] and preoperative ductal dependency [P=0.04] with postoperative metabolic alkalosis. Of the surgical procedures the arterial switch for transposition of the great arteries [n=19] was strongly associated with metabolic alkalosis [100%, P<0.001]. Hemodilution appeared to enhance the development of alkalosis: those who experienced alkalosis had been hemodiluted to a greater extent [P=0.007]. Nearly 95% of patients experienced some increase in bicarbonate, but patients with metabolic alkalosis experienced more than those without [5.9 versus 3.5 mmol/l, P<0.001]. There were four postoperative deaths, only one coincidental with metabolic alkalosis. CONCLUSIONS: Metabolic alkalosis has a high incidence after pediatric cardiac surgery, strongly associated with younger age, cardiopulmonary bypass, preoperative ductal dependency and perioperative hemodilution. Early recognition allows for timely therapeutic intervention.     

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.