DEPRESSION DURING THE TRANSITION TO MENOPAUSE: A Guide for Patients and Families David A. Kahn, MD, Margaret L. Moline, PhD, Ruth W. Ross, MA, Lori L. Altshuler, MD, and Lee S. Cohen, MD www.womensmentalhealth.org It is a common myth that as women enter the menopausal years, it is “normal” to feel depressed. Serious depression, however, should never be viewed as a “normal
Cees.kau.edu.saEffect of enteral feeding on lipid subfractions in children with chronic renal failureJameela A. Kari1, Vanessa Shaw1, David T. Vallance2, and Lesley Rees11 Nephrourology Unit, Great Ormond Street NHS Trust, London WC1N 1EH, UK 2 Department of Biochemistry, Royal Free Hospital and School of Medicine, Hampstead, London NW3, UK Received August 19, 1997; received in revised form December 19, 1997; accepted January 2, 1998 Abstract. The anorexia of chronic renal failure (CRF) is (LDL), apoprotein B (apo B) and lipoprotein(a) [Lp(a)], frequently managed with enteral feeds using combinations and reduced high-density lipoprotein (HDL), apo A1 and of commercial preparations, glucose polymers and fat apo A2 , all of which are believed to predispose to emulsions. Such feeds might predispose to atherogenic atherosclerosis. Studies in children have demonstrated blood lipid profiles. Our aim, therefore, was to compare the similar findings, but with a higher incidence of hypercho- blood lipid profiles of enterally fed and non-enterally fed children. Plasma lipid subfractions were measured in As well as the metabolic effects of CRF, the blood lipid 37 children with CRF managed conservatively and 10 profiles of patients may be influenced by their diet. High managed with peritoneal dialysis (PD); 10 of the children intakes of saturated fatty acids (FAs) increase serum LDL were tube fed, 5 of whom were on PD. Results were and TGs. Polyunsaturated FAs reduce LDL, but at the same compared between these groups. Overall, triglycerides time also reduce HDL , which is protective against (TGs, mean + SD) were high (2.3+1.4 mmol/l) and total coronary heart disease . Monounsaturated FAs lower cholesterol (TC) was at the upper limit of normal both LDL and TGs, and are associated with higher levels of (5.2+1.5 mmol/l). Low-density lipoprotein (LDL), high- HDL. High intakes of refined carbohydrate (CHO) increase density lipoprotein (HDL), apoprotein A1 (apo A1), A2 (apo A2) and B (apo B), and lipoprotein (a) [Lp(a)] were It is our policy to institute early enteral feeding in within the normal range. There was an inverse correlation children with CRF with a declining growth velocity. Such between TGs and glomerular filtration rate (P = 0.0001).
feeds are based on whole-protein (and occasionally protein There were no differences in the levels of TC, TG, LDL, hydrolysate) complete feeds and are supplemented with HDL, apo A1, apo A2 or Lp(a) between tube-fed and non- glucose polymers and/or peanut oil emulsions as additional tube-fed children. We conclude that enteral feeding does energy sources. The children eat little or no complex CHO or non-starch polysaccharides (fibre), so most of their in- take of CHO is refined. We were concerned, therefore, that Key words: Chronic renal failure ± Lipids ± Lipoproteins ± while providing adequate nutrition for growth, tube feeding regimens might have an adverse effect on the blood lipid Our purpose was to study the lipid profiles of children attending our CRF clinic who were eating a high-energy, low-phosphate, but otherwise unrestricted diet and to compare the results with those of a group of children who were receiving at least 50% of their energy as an enteral Hyperlipidaemia is one of the factors believed to be re- sponsible for the high incidence of atherosclerosis in chronic renal failure (CRF) . Abnormalities of lipids and lipoproteins reported in CRF include: increased triglycer- ides (TGs), total cholesterol (TC), low-density lipoprotein Patients. Forty-seven children (32 boys) aged 1±17 years [mean 9.3+5.2 (SD)] with CRF [defined for the purposes of this study as a Correspondence to: J. A. Kari, Nephrourology Unit, Institute of Child plasma creatinine concentration 4150 mmol/l (1.7 mg/dl)] were Health and Great Ormond Street Hospital for Children, 30 Guildford studied. Thirty-seven were managed medically, 5 of whom were ent- erally fed. The other 10 were receiving peritoneal dialysis (PD), 5 of ANOVA, Analysis of variance; SDS, standard deviation score; TG, * Insignificant when adjusted for age and creatinine by analysis of triglyceride; TC, total cholesterol; LDL, low-density lipoprotein; HDL, high-density lipoprotein; apo A1, apoprotein A1; Lp(a), lipoprotein (a) assessed formally: they were recommended to eat the family diet but with an emphasis on high-energy, low-phosphate foods.
Older children were fasted overnight prior to blood sampling, but younger children were fasted for at least 4 h (although they were allowed water). This length of time has been used in other large studies . Serum TC, TG, LDL, HDL, apo A1, apo A2, apo B and Lp(a) and Lipid subfractions were compared between the four patient groups (Table 2) using analysis of variance. Analysis of covariance (AN- COVA) was used to adjust for age and creatinine when a significant difference was found between groups. A significant P value was defined as 50.05. Each subject and/or their parents gave informed consent to the study, which was approved by the local committee on Methods. TC was measured using the cholesterol C system high-per- formance cholesterol oxidase 4-aminophenazone method and TG by FA, Fatty acid; trans, transpolyunsaturated FA glyceryl phosphate oxidase 4-aminophenazone high-performance en- zymatic colorimetric test (both Boehringer Mannheim Diagnostica) b Dietary reference values for food energy and nutrients for the United . HDL was measured following precipitation of apo B-containing lipoproteins and LDL was calculated using the Friedewald formula .
c The Dietary and Nutritional Survey of British Adults  apo A1 and apo B were measured using immunoturbidimetry (Im- d Maximum recommended 10% of total energy intake muno, Sevenoaks, Kent, UK) , and Lp(a) by enzyme-linked im- munosorbent assay (Immuno) . GFR was estimated from the clearance of 51chromium EDTA  or by the Schwartz formula .
whom were enterally fed (Table 1). The mean (range) glomerular fil- tration rate (GFR) of the medically managed children was 15 (5±35) ml/min per 1.73 m2. Children with nephrotic syndrome were excluded because of its effect on lipid metabolism .
The mean (range) length of time on enteral feeds was 18.2 (6±32) months. The feeds were prepared from whey-based infant formulae or Children who were managed medically and on PD without cows' milk protein-based adult enteral feeds, and were delivered by enteral feeds (groups 1 and 2) were older than the enterally pump overnight. One child received a soya-based feed because of fed children. Medically managed children were taller, but parental suspicion of cows' milk protein intolerance. One received a there was no difference in body mass index among the four whey hydrolysate to enhance stomach emptying. All feeds included a comprehensive range of vitamins and minerals. The aim was to offer adequate nutrition for growth, while maintaining blood chemistry The results of the lipid subfractions are shown in Table 1.
within acceptable parameters by the provision of at least the estimated TGs were elevated in all groups. Figure 1 illustrates the average requirement for energy for chronological age using additional relationship between serum TGs and method of feeding, glucose polymers and peanut oil emulsions, and reference nutrient plasma creatinine and treatment modality. There was an intake for protein for height age (dietary reference values, Table 2).
overall positive correlation between TGs and creatinine Table 2 shows the tube feed composition for protein, CHO and FAs, and the corresponding United Kingdom recommended dietary (r = 0.63, P 50.0001). However, there was no difference intakes for a healthy population. Also shown are the observed dietary among the patient groups when the results were corrected intakes of British adults (comparable figures are not available for for age and creatinine (ANCOVA P = 0.07). There was also children). The dietary intake of the non-tube-fed children was not a negative correlation between TGs and GFR in children in However, we achieved a balanced energy intake with our enteral formula composition, which did not differ sig- nificantly from published recommendations for dietary in- take for a normal population. Indeed, the total fat intake, and particularly the saturated fat intake, was less in the tube-fed children than in a normal adult population eating an unrestricted diet (Table 2). Despite a CHO intake comprised mainly of refined sugars rather than a mixture of sugars, starch and fibre, there was no adverse effect on Although the children were under regular dietary re- view, we were not able to fully analyse the intakes of those who were not tube fed because there are only a few foods that have been analysed for their FA composition. As these children were eating a relatively free diet rather than re- ceiving a precisely prescribed enteral feed, it is possible that their diet was less balanced than that of the tube-fed It might be expected that the glucose load during PD Fig. 1. Effect of method of feeding, plasma creatinine and treatment would have an adverse effect on plasma lipids, resulting in modality on serum triglycerides. EF, Enteral feeding; PD, peritoneal hypertriglyceridaemia and decreased HDL . Although the patients on PD were the only group to have levels of atherogenic lipids above the normal range, those on PD group 1 (P = 0.0001), even when age was taken into con- who were enterally fed did not. One possible explanation is that the enteral feed was beneficial to the plasma lipids, but Children managed by PD (group 3) were the only group the numbers are too small to draw any conclusions.
with levels of the atherogenic lipids TC, LDL and apo B All the children had high TG levels. The importance of that were above the normal range, although TC levels were TGs in atherogenesis is controversial, but recently it has at the upper limit of normal in the other groups. However, been found that hypertriglyceridaemia is associated with a only apo B was significantly higher in children on PD when high proportion of small, dense LDL, which is now rec- adjusted for age and creatinine (ANCOVA P = 0.01). No ognised to be particularly atherogenic. Although overall the other lipid subfractions were abnormal in any other group.
lipid fractions that we measured were at acceptable levels, There was no correlation between GFR and any lipid we did not study those subfractions that are now recognised In conclusion, this small study would suggest that an enteral feeding regimen providing an appropriate energy intake with a balanced profile of fat and CHO can be ad- ministered to children with CRF who are both con- servatively managed and on PD, without detrimentally af- In this study we have confirmed previous reports that hy- pertriglyceridaemia correlates inversely with GFR in CRF, and that TC is at the upper limit of the normal range [2, 3].
Acknowledgements. We acknowledge Dr. Sarah E. Lederman and Dr.
Our patients did not, however, have abnormalities of Judith Taylor for their help in recruiting patients from their clinics, and apo A1, apo A2, apo B and Lp(a), which have been found Dr. Richard Morris for his help with the statistics.
in some, although not all, previous studies [2, 3]. Angio- graphic studies have shown that low apo A and high apo B (or their ratio) may be better indicators of future coronary heart disease than HDL levels . HDL, high levels of which protect against vascular disease, was reduced in previous studies [2, 3], but was also normal in our patients.
1. Lemos JA de, Hillis LD (1996) Diagnosis and management of We were concerned that the enteral feeds we give to our coronary artery disease in patients with end-stage renal disease on patients might have an adverse effect on their blood lipids hemodialysis. J Am Soc Nephrol 7: 2044±2054 and lipoproteins. The value of tube feeding in the promo- 2. Attman PO, Samuelsson O, Alaupovic P (1993) Lipoprotein me- tabolism and renal failure. Am J Kidney Dis 21: 573±592 tion of catch-up growth is well established [13, 14].
3. Querfeld U (1993) Disturbance of lipid metabolism in children However, such feeds contain added glucose polymerase and with chronic renal failure. Pediatr Nephrol 7: 749±757 fat emulsions which may be atherogenic. Ingestion of a 4. Grundy MS, Denke MA (1990) Dietary influences on serum lipids bolus of refined CHO causes an increase in TGs and re- and lipoproteins. J Lipid Res 3: 1149±1172 duces HDL, and a high intake of saturated fat raises TGs 5. Querfeld U, Gnasso A, Haberbosch W, Augustin J, SchaÈrer K and LDL . Furthermore, an imbalance of mono- and (1988) Lipoprotein profiles at different stages of the nephrotic polyunsaturated fat can also promote atherogenesis by re- 6. Lapinleimu H, Viikari J, Jokinen E, Salo P, Routi T, Leino A, Ronnemaa T, Seppanen R, Valimaki I, Simell O (1995) Pro- spective randomized trial in 1062 infants of diet low in saturated 13. Claris-Appiani A, Ardissino GL, Dacco V, Funari C, Terzi F fat and cholesterol. Lancet 345: 471±476 (1995) Catch up growth in children with chronic renal failure 7. Warnick GR (1986) Enzymatic methods for quantification of li- treated with long-term enteral nutrition. J Parenter Enteral Nutr poprotein lipids. Methods Enzymol 129: 101±123 8. Friedewald WT, Levy RI, Fredrickson DS (1972) Estimation of 14. McCarey DW, Buchanan E, Gregory M, Clark BJ, Weaver LT the concentration of low density lipoprotein cholesterol in plasma (1996) Home enteral feeding of children in the west of Scotland.
without use of the preparative ultracentrifuge. Clin Chem 18: 15. Lindholm B, Norbeck HE (1986) Serum lipids and lipoprotein 9. Labeur C, Shepherd J, Rosseneu M (1990) Immunological assays during continuous ambulatory peritoneal dialysis. Acta Med Scand of apolipo proteins in plasma: methods and instrumentation. Clin 16. Nourooz-Zadeh J, Rahimi A, Tajaddini-Sarmadi J, Rosen P, Hal- 10. Dagen MM, Packard CJ, Shepherd J (1991) A comparison of liwell B, Betteridge DJ (1997) Relationships between plasma commercial kits for the measurement of lipoprotein(a). Ann Clin measures of oxidative stress and metabolic control in NIDDM.
11. Chantler C, Barratt TM (1972) Estimation of glomerular filtration 17. Report of Health and Social Subjects (1991) HMSO, London, rate from plasma clearance of 51-chromium edetic acid. Arch Dis 18. Office of Population Censuses and Surveys (1990) HMSO, Lon- 12. Schwartz GJ, Haycock GB, Edelmann CM, Spitzer A (1976) A simple estimate of glomerular filtration rate in children derived from body length and plasma creatinine. Pediatrics 58: 259±263 Literature abstractsNephrol Dial Transplant (1997) 12: 1668±1671 Pharmacokinetics of tacrolimus (FK 506) in children and adolescents with renal transplants G. Filler, R. Grygas, I. Mai, H. J. Stolpe, C. Greiner, S. Bauer, and J. H. H. Ehrich Background. Only few data exist on pharmacokinetics of tacrolimus At the time of switch, median serum creatinine was 234+82 mmol/l and 6 months after switch 201+99 mmol/l. All grafts are still func- Patients. In 1995 and 1996, 14 children (mean age 13 years, range tioning. Mean FK-506 dose was 0.16 mg/kg body weight/day (range 5±23 years) received tacrolimus after renal transplantation; 10 of these 0.036 ±0.30 mg/kg). Mean trough level was 7.1+2.6 ng/ml in the after biopsy-proven steroid-resistant rejection (2 with vascular rejec- morning and 6.5+2.0 ng/ml in the evening. Median time of maximum tion), two for cyclosporin A (CsA)-induced severe nephrotoxicity, one concentration (tmax) was 120 min after application, and the mean for untreatable gingival hyperplasia on CsA, and one child was treated maximum concentration (Cmax) was 15.2+6.7 ng/ml. Mean area under primarily after transplantation because of severe liver involvement in the curve (AUC) was 104+33 ng * h/ml, with a range from 65 to nephronophthisis. Pharmacokinetic investigations were performed 169 ng * h/ml. No patient had unsatisfactorily low trough levels during after establishing a stable maintenance dose with trough levels in the the study. There was only a weak but significant (P 50.05) correlation between dose per kg body weight and AUC and, as expected, an ex- Results. Mean follow-up time was 6 months (range 3±25 months).
cellent correlation (r = 0.73, P 50.001) between AUC and trough Eleven patients are still on tacrolimus. Two were discontinued because of severe aggravation of chronic persistent hepatitis C (one of them Conclusion. Because of interindividual variation between patients, also developed diabetes mellitus), and one patient was subsequently therapeutic drug monitoring of tacrolimus is mandatory. In this study, a switched to conventional immunosuppression because of tacrolimus- daily dose of 0.15 mg/kg was sufficient in most patients. We rec- associated nephrotoxicity. All tacrolimus levels were measured by a ommend the performance of at least one pharmacokinetic study after modified assay (MEIA, Tacrolimus, Abbott) with improved sensitivity.
establishing stable FK 506 trough levels to ascertain a safe profile.
Immunity of diphtheria and tetanus in a young population on a dialysis regimen Luciana Ghio, Chiara Pedrazzi, Baroukh M. Assael, Alfonso Panuccio, Marina Foti, and Alberto Edefonti In 54 transplant recipients diphtheria and tetanus immunity after pri- bodies developed in the transplant recipients and dialysis patients but mary vaccination was significantly lower than in 57 control subject no diphtheria antibodies developed in two transplant recipients. No and 35 patients on a dialysis regimen. After a booster, tetanus anti- adverse reactions, including acute graft rejection episodes, occurred.
Secretary: Joy Woodward P O Box 53219, Kenilworth 7745, South Africa. Editorial Team: Mick Dower with Coen Calitz, Johan Schoombee and John Winter (The views expressed in this publication do not necessarily reflect the views of the Cape Cliivia Club) The year end meeting was held at Kirstenbosch, followed by the traditional braai. Over a 100 members attended and enjoyed Johan Scho