Trimethoprim-sulphamethoxazole as primary Pneumocystis carinii prophylaxis does not increase serum homocysteine levels in HIV-positive subjects.

Background: We recently observed that a short course of trimethoprim 300 mg b.i.d. in healthy volunteers can cause a substantial increase in fasting plasma homocysteine levels, up to concentrations reportedly associated with atherothrombotic complications. The purpose of this study was to determine whether primary Pneumocystis carinii prophylaxis (PCP) with trimethoprim-sulphamethoxazole (TMP-SMX) adversely affects serum homocysteine levels in HIV-positive patients. Methods: We studied 34 subjects [29 male, 5 female, mean age 36.8+/-7.9 (S.D.) years] with no prior AIDS-defining disease who required primary PCP prophylaxis (CD4+ T-cell count <200/mm(3)). The common dose of TMP-SMX was 80/400 mg (80 mg trimethoprim and 400 mg sulphamethoxazole) once daily. Serum total homocysteine levels were determined in four samples: two collected prior to the start of TMP-SMX and two collected on average 2.6+/-2.2 and 5.3+/-3.5 months into the first year of prophylactic therapy. Results: Mean serum homocysteine was 13.9+/-3.7 &mgr;mol/l pre-treatment and 14.4+/-5.0 &mgr;mol/l during treatment with TMP-SMX, a non-significant increase of 0.5 &mgr;mol/l (95% CI: -0.5 to +1.4, P=0.34). Folate levels were equally unaffected by TMP-SMX (13.1+/-6.5 nmol/l versus 13.3+/-5.3 nmol/l, before and during therapy, respectively). Baseline folate levels did not predict the response of homocysteine to TMP-SMX, and neither did age, gender, or serum creatinine. Conclusion: Long-term therapy with 80/400 mg TMP-SMX does not adversely affect homocysteine levels.

Follow-up of GFR estimated from plasma creatinine after cimetidine administration in patients with diabetes mellitus type 2.

BACKGROUND: The glomerular filtration rate (GFR) can be estimated from plasma creatinine according to the formula of Cockcroft and Gault (CG). When tubular secretion of creatinine is inhibited by cimetidine the mean difference between the Cockcroft-Gault clearance (CG(Cim) and GFR approximates zero, but there is still some interindividual difference, especially in type-2-diabetic patients. We studied during longitudinal follow-up, whether the discrepancies between CG(Cim) and GFR per patient are consistent in time in type-2-diabetic patients. PATIENTS AND METHODS: In 1996 and 1998 (interval 20-26 months) GFR was measured in 21 patients as the urinary clearance of continuously infused 125I-iothalamate. Plasma creatinine was analyzed with an enzymatic assay before and after oral cimetidine 800 mg t.i.d. during 24 hours. GFR estimations were calculated with the Cockcroft-Gault formula before (CG) and after cimetidine (CG(Cim)) and expressed as means +/- SEM. RESULTS: GFR deteriorated from 89.7 +/- 5.7 to 81.3 + 5.8 ml/min/1.73 m2 and CG(Cim) from 85.3 +/- 5.7 to 81.1 +/- 6.6 ml/min/1.73 m2, whereas CG decreased from 102.4 +/- 6.8 to 98.4 +/- 7.0 ml/min/1.73 m2. Changes in GFR and changes in CG(Cim) were correlated (r = 0.72, p < 0.001) and were not significantly different from each other. The discrepancy between CG(Cim) and GFR per patient in 1996 also correlated with the discrepancy between CG(Cim) and GFR in 1998 (r = 0.85, p < 0.001 ). CONCLUSIONS: In individual patients the discrepancies between the CG(Cim) and GFR are consistent in time and the change in GFR is reflected by the change in CG(Cim). This small variability means that CG(Cim), based on an enzymatic plasma creatinine assay, would be suitable for follow-up of GFR in type-2-diabetic patients, independent of albuminuria.

Fasting and post-methionine homocysteine levels in NIDDM. Determinants and correlations with retinopathy, albuminuria, and cardiovascular disease.

OBJECTIVE: The increased cardiovascular risk in subjects with NIDDM is partly explained by an association with established risk factors like hypertension, dyslipidemia, and obesity. Mild hyperhomocysteinemia has emerged as a new risk factor for cardiovascular disease. The purpose of this study was to assess its role in NIDDM. RESEARCH DESIGN AND METHODS: We studied predictors of homocysteine levels and correlations between homocysteine and (micro-)albuminuria, retinopathy, and history of cardiovascular disease in normotensive NIDDM subjects under stable metabolic control. This was done in 85 NIDDM subjects by measuring fasting and post-methionine-loading homocysteine levels together with blood pressure, BMI, serum cholesterol, triglyceride, HDL cholesterol, folate, vitamin B12, pyridoxal-5-phosphate, HbA1c, and (micro-)albuminuria and creatinine clearance in triplicate 24-h urine samples. The relationship between micro- and macrovascular complications and fasting homocysteine only was studied in an additional 65 subjects, giving a total of 150 subjects. RESULTS: In multiple regression analysis, significant (P < 0.05) predictors of fasting homocysteine were low-normal values of creatinine clearance (threshold effect at < 80 ml.min-1 .1.73 m-2), folate (< 20 nmol/l), and vitamin B12 (< 350 pmol/l), and postmenopausal status in women. Determinants of post-methionine homocysteine were pyridoxal-5-phosphate levels < 80 nmol/l, creatinine clearance, and sex (higher levels in women). Hyperhomocysteinemia did not cluster with other cardiovascular risk factors, like hypertension, obesity, or dyslipidemia. Regarding cardiovascular complications, fasting homocysteine, but not post-methionine homocysteine, was higher in subjects with a history of cardiovascular disease. There was a stepwise increase in the prevalence of subjects with cardiovascular disease with increasing fasting homocysteine. The prevalence of cardiovascular disease was 19.4% in the bottom quartile of fasting homocysteine, versus 55.0% in the top quartile (P for trend < 0.01). Neither fasting homocysteine nor post-methionine homocysteine correlated with (micro-)albuminuria or with retinopathy. CONCLUSIONS: The findings suggest that homocysteine levels in NIDDM rise even with modest deterioration of renal function and when vitamin status is in the low to low-normal range. Fasting homocysteine correlates with macrovascular disease, but we found no evidence of a correlation with retinopathy or (micro-)albuminuria. Post-methionine homocysteine levels do not show a correlation with micro- or macrovascular complications.

Glomerular filtration rate estimation from plasma creatinine after inhibition of tubular secretion: relevance of the creatinine assay.

BACKGROUND: Estimation of glomerular filtration rate (GFR) from plasma creatinine concentration after inhibition of tubular creatinine secretion with cimetidine provides a good assessment in patients with various nephropathies and with non-insulin-dependent diabetes mellitus (NIDDM). The aim of this study was to compare cimetidine-aided GFR estimations using various creatinine assays. METHODS: In 30 outpatients with NIDDM GFR was measured as the urinary clearance of continuously infused [125I]iothalamate. Plasma creatinine concentration was analysed after oral cimetidine with an alkaline picrate (AP) method, with an enzymatic (PAP) assay and with HPLC. GFR estimations were calculated with the Cockcroft Gault formula (CG). RESULTS: AP creatinine concentrations were significantly higher than PAP or HPLC values. GFR estimations by AP (CG(AP) 66 +/- 19 ml/min/1.73 m2, mean SD) were significantly lower than GFR (89 +/- 30), whereas CG(PAP) (85 +/- 30) and CG(HPLC) (84 +/- 34 ml/min/1.73 m2) were not. Bland and Altman analysis showed a difference between CG(AP) and GFR of -22.4 +/- 17.7 ml/min/1.73 m2; this difference becomes larger when the GFR increases. The difference between CG and GFR was only -3.8 +/- 14.8 ml/min/1.73 m2 for PAP and -4.4 +/- 17.5 ml/min/1.73 m2 for HPLC, without any systematic difference. CONCLUSION: A good assessment of the GFR from plasma creatinine after cimetidine administration is possible when creatinine is measured with an enzymatic assay or with the less convenient HPLC method. The more widespread and cheaper alkaline picrate assay is not suitable for GFR-estimation.

Short-term variability and sampling distribution of various parameters of urinary albumin excretion in patients with non-insulin-dependent diabetes mellitus.

We determined the degree of variability and sampling distribution of several commonly used parameters of microalbuminuria in patients with non-insulin-dependent diabetes mellitus (NIDDM) and proposed a sampling strategy for estimating the level of albuminuria. Four patients with NIDDM with previously documented microalbuminuria collected 30 consecutive split (overnight and daytime) 24-hour urine samples (experiment A). These samples were analyzed for total 24-hour albumin excretion; daytime, overnight, and 24-hour albumin concentration; and daytime, overnight, and 24-hour albumin-to-creatinine ratio. In a second experiment (B), 10 patients collected 10 consecutive overnight urine samples. Finally, a total of 300 separate triplicate urine samples were analyzed for the variability of 24-hour albumin excretion (100 samples) and albumin-to-creatinine ratios in 24-hour urine (100 samples) and overnight urine (100 samples). We found that the sampling distribution shape of all parameters of albuminuria is positively skewed, without consistent evidence of log-normality. When two methods were used for quantifying day-to-day variability (the interquartile range/median ratio and the chance of a single measurement being >50% off the actual value of albuminuria), the overnight albumin-to-creatinine ratio is the least-variable parameter of albuminuria, scoring 0.38% and 10% on both methods, respectively, in experiment A. Collecting multiple samples of overnight urine improves accuracy. The largest gain in precision in estimating the actual value of albuminuria is obtained for sample sizes of three and five and does not increase with nonconsecutive sampling of urine. Based on the combined data from experiments A and B, the expected mean deviation of the median of three and five overnight samples from the actual level of the overnight albumin-creatinine ratio is 17.9% and 12.1%, respectively. An analysis of variability in three sets of 100 triplicate 24-hour urine samples shows that the overnight albumin-to-creatinine ratio is a significantly more-constant parameter of microalbuminuria than the amount of albumin excreted in 24 hours or the albumin-to-creatinine ratio in 24-hour urine (p < 0.05). We concluded that the parameters of diabetic albuminuria have positively skewed, non-log-normal sampling distributions. The overnight albumin-to-creatinine ratio is the least-variable parameter of microalbuminuria. We recommend collecting three consecutive early morning urine samples, using the median value of the albumin-to-creatinine ratio in these samples for quantifying albuminuria.

Estimation of the glomerular filtration rate in NIDDM patients from plasma creatinine concentration after cimetidine administration.

OBJECTIVE: Glomerular filtration rate (GFR) can be estimated in patients with renal disease from plasma creatinine concentration, age, sex, and body weight according to the formula of Cockcroft and Gault. The hypothesis that this method can be improved when tubular secretion of creatinine is inhibited by cimetidine was studied in NIDDM patients. RESEARCH DESIGN AND METHODS: In 30 outpatients with NIDDM and normo- (n = 10), micro- (n = 9), or macroalbuminuria (n = 11), GFR was measured as the urinary clearance during continuous infusion of 125I-labeled iothalamate. Plasma creatinine concentration was analyzed with an enzymatic assay before and after 800 mg t.i.d. oral cimetidine was given during a 24-h period. RESULTS: Plasma creatinine rose in all patients after cimetidine administration and, as a consequence, the clearance calculated with the Cockcroft-Gault formula fell. The ratio of this formula and GFR decreased from 1.16 +/- 0.20 to 0.97 +/- 0.16 (means +/- SD). This ratio tended to be smaller in the normo- (0.93) than in the micro- (0.98) and macroalbuminuric (1.00) groups. Also, 20 patients with a BMI < 30 kg/m2 had a smaller ratio than those with a BMI > 30 kg/m2 (0.92 vs. 1.07; P < 0.05). Bland and Altman analysis showed a difference of the Cockcroft-Gault formula and GFR of 12.0 +/- 17.4 ml.min-1 (1.73 m2)-1, which decreased to -3.8 +/- 14.8 ml.min-1.(1.73 m2)-1. The same analysis of 24-h creatinine clearance with urine collection and GFR showed larger standard deviations. CONCLUSIONS: GFR can be estimated in an acceptable way from plasma creatinine concentration after cimetidine administration in outpatients with NIDDM. Despite a nonsignificant underestimation in normoalbuminuric and overestimation in overweighted patients, this method is superior to 24-h creatinine clearance with outpatient urine collection.

Determinants of progression of microalbuminuria in patients with NIDDM.A prospective study.

OBJECTIVE: To assess the degree of interindividual variation in the rate of progression of microalbuminuria and to identify determinants of progression of microalbuminuria in patients with NIDDM. RESEARCH DESIGN AND METHODS: In a prospective cohort study, 58 microalbuminuric NIDDM patients were followed for a period of at least 24 months. During this period, the level of microalbuminuria in these patients was assessed in triplicate 24-h urine samples on at least four separate visits. All patients had stable metabolic control and controlled blood pressure during follow-up. Microalbuminuria was defined as an albumin-to-creatinine ratio in 24-h urine of between 3 and 30 mg/mmol. The individual rates of progression of microalbuminuria were calculated from linear regression analysis. At baseline, the following data were collected for all patients: age, sex, ethnicity, time since diagnosis of NIDDM, smoking habits, drug use, blood pressure, BMI, HbA1c, serum creatinine, cholesterol, triglyceride, and HDL cholesterol concentrations. RESULTS: Microalbuminuria was found to progress linearly in time. Considerable differences in rates of progression of microalbuminuria were found, the absolute yearly change in albumin-to-creatinine ratio ranging from -5.2 to 12.9 mg/mmol. In bivariate analyses, serum triglyceride concentration, use of ACE inhibitors, mean arterial blood pressure, HDL cholesterol, and time since diagnosis of NIDDM correlated with progression of microalbuminuria (P < or = 0.05). In stepwise multiple regression analysis, a high triglyceride-to-HDL cholesterol ratio at baseline (P = 0.006) and the use of ACE inhibitors (P = 0.007) were identified as the only independent predictors of progression of microalbuminuria. CONCLUSIONS: The rate of progression of microalbuminuria in NIDDM differs considerably between subjects. Diabetic dyslipidemia (high serum triglyceride and low HDL cholesterol) is a predictor of more rapid progression of microalbuminuria in patients with well-controlled blood pressure.

Can reduction in hypertriglyceridaemia slow progression of microalbuminuria in patients with non-insulin-dependent diabetes mellitus?

The objective of this study was to investigate whether reduction in hypertriglyceridaemia is associated with a slower rate of progression of microalbuminuria in patients with non-insulin-dependent diabetes mellitus (NIDDM). Fifteen normotensive NIDDM patients with hypertriglyceridaemia (> 2.5 mmol L-1) and microalbuminuria were randomly selected to receive either placebo (eight patients) or gemfibrozil 600 mg b.i.d. (seven patients). Progression of microalbuminuria was assessed during a 12-month follow-up period with measurements, consisting of blood tests and triplicate 24-h urine collections, at 1, 3, 6, 9 and 12 months. All but one patient in the treatment group showed a favourable response (> or = 20% reduction) of hypertriglyceridaemia to gemfibrozil. One patient in the placebo group showed a spontaneous reduction in triglyceride levels. Progression of microalbuminuria was lower, although not statistically significantly so, in the treatment group (36%) than in the placebo group (65%). In the group with > or = 20% reduction in triglyceride levels, progression of MA was significantly lower than in the group with stable or increasing triglyceride levels (+1%, range -56% to +49% vs. +97%, range -35% to +202% respectively) (P = 0.03). Continued follow-up data of patients switching from placebo to gemfibrozil after the trial further support the role of serum triglyceride reduction in stabilizing albumin excretion. In conclusion, the results indicate that, in microalbuminuric NIDDM patients, effective treatment of dyslipidaemia could be associated with stabilization of urinary albumin excretion.

Renal tubular acidosis. Pathophysiology and diagnosis.

The pathophysiology of renal tubular acidosis is slowly being unraveled, which has implications for the traditional classification of the condition. Nonetheless, the diagnosis of renal tubular acidosis is still easy to establish, and identification of the specific pathophysiological subtype is relatively straightforward. The diagnostic information required usually includes only urinary pH and sodium, potassium, and chloride concentrations and serum potassium level. The urinary pH is not a diagnostic test for renal tubular acidosis, but it serves to distinguish between the various subtypes.

Hypovitaminosis D in immigrant women: slow to be diagnosed.

Hypovitaminosis D osteopathy should be considered in immigrant women with musculoskeletal pain.

Reduced complement activation and improved postoperative performance after cardiopulmonary bypass with heparin-coated circuits.

A randomized controlled trial that involved 30 patients undergoing elective coronary artery bypass grafting was done to determine the effect of heparin-coated circuits and full heparinization on complement activation, neutrophil-mediated inflammatory response, and postoperative clinical recovery. Peak concentrations of terminal complement complex were 38% lower (p = 0.004) in 15 patients treated with heparin-coated circuits (median 775 micrograms/L, interquartile range 600 to 996) compared with those in 15 patients treated with uncoated circuits (median 1249 micrograms/L, interquartile range 988 to 1443). Although no significant intergroup differences in concentrations of polymorphonuclear neutrophil elastase were found, a positive correlation (rs = 0.74, p < 0.0007) was calculated between peak concentrations of terminal complement complex and polymorphonuclear neutrophil elastase. Differences in patient recovery were analyzed with use of a score composed of fluid balance, postoperative intubation time, and the difference between rectal temperature and skin temperature. The score was significantly lower in patients treated with heparin-coated circuits (p = 0.03), whereas its components showed no intergroup significance. We conclude that the use of heparin-coated circuits with full systemic heparinization results in improved biocompatibility, as assessed by complement activation, and leads to an improved postoperative recovery of the patient.

The response of the pituitary-ovarian axis to pulsatile administration of gonadotropin-releasing hormone in long-term oral contraceptive users.

OBJECTIVE: Our purpose was to differentiate between pituitary and hypothalamic feedback effects of oral contraceptives. STUDY DESIGN: Twenty micrograms of gonadotropin-releasing hormone was administered intravenously at 90-minute intervals for 4 days to 14 long-term users of a combined oral contraceptive (30 micrograms of ethinyl estradiol and 150 micrograms of levonorgestrel), starting at different moments in the pill cycle. On the fourth day of administration the pulsatile release of luteinizing hormone was determined by blood sampling every 10 minutes for 6 hours. The sensitivity of the pituitary was determined before, during, and after treatment with gonadotropin-releasing hormone by a 100 micrograms gonadotropin-releasing hormone challenge test. On each sampling day serum estradiol, progesterone, and prolactin levels were measured, and ovarian ultrasonography was performed. RESULTS: After 4 days of pulsatile gonadotropin-releasing hormone administration every exogenous gonadotropin-releasing hormone bolus was followed by an endogenous luteinizing hormone pulse of high amplitude (median 3.30 U/L). Both serum luteinizing hormone and follicle-stimulating hormone levels increased significantly (p < 0.001). The increase in follicle-stimulating hormone levels was accompanied by an increase in serum estradiol (p < 0.01). The luteinizing hormone response to a 100 micrograms bolus of gonadotropin-releasing hormone decreased during gonadotropin-releasing hormone treatment (p < 0.01), whereas the follicle-stimulating hormone response did not change. CONCLUSION: Pituitary sensitivity is not impaired during oral contraceptive use, suggesting that oral contraceptives exert their negative feedback effects predominantly at the hypothalamic level.

A simple method for the quantification of portosystemic shunting (PSS) in patients with portal hypertension.

Portosystemic shunting (PSS) was evaluated in 32 patients with chronic liver disease by the rectal administration of iodine-123 I-amphetamine (IMP method), a radionuclide which is rapidly absorbed from the sigmoid and extracted by liver and lungs. Simultaneous measurement of pulmonary and hepatic uptake supplies a shunt fraction (SF) as an index of PSS. The IMP method was compared with the ammonia tolerance test (NH3TT), and there proved to be a significant correlation between these two methods (r = 0.75, p < 0.001). Assuming that an increase of > 7 mumol/l in arterial ammonia concentration after NH3TT represents PSS, the IMP method had a sensitivity of 0.93. When fasting (NH3) was > 50 mumol/l, all patients showed pathological PSS with either method, but this was also the case in 50% of patients with normal basal arterial ammonia. There was also a significant correlation between the IMP method and the Child-Pugh classification (r = 0.75, p < 0.001). Endoscopy in 28 patients revealed absence of varices in 11, of whom, however, 7 (64%) had an increased SF and although all 15 patients with ascites had increased SF, this was also the case in 12 of the 17 patients without ascites. In conclusion, PSS evaluation using IMP is a non-invasive, sensitive method without patient discomfort which might be used in the staging and follow-up of chronic liver disease.

The effects of levonorgestrel, desogestrel and gestodene on the pulsatile release of luteinizing hormone in oral contraceptive users.

The dynamics of luteinizing hormone (LH) and follicle stimulating hormone (FSH) release were investigated in 60 long-term oral contraceptive (OC) users. Five different types of OC, all containing the same amount of estrogens were studied: three monophasic preparations containing levonorgestrel, desogestrel and gestodene, respectively, and two triphasic formulations, containing levonorgestrel or gestodene. Thirteen healthy, normally cycling volunteers served as controls. Blood sampling was performed at 10-min intervals during a 6-h period to determine the pulsatile release of LH. LH and FSH were measured using a sensitive immunoradiometric assay. Pulse patterns were classified on the basis of the overall LH level, as well as on the character of the LH pulses, according to both frequency and amplitude characteristics. Pulsatile LH release was maintained during OC use. After the 7-day pill-free interval, FSH levels as well as the LH pulse patterns were comparable to those of early follicular-phase controls. FSH levels and FSH release in response to a gonadotropin releasing hormone (GnRH) challenge were profoundly suppressed in all OC users, as early as day 8 of the pill cycle. LH release during the pill cycle was characterized by either a low frequency (median 1 pulse/6 h), high amplitude (median 2.5 IU/l) pulse pattern or by a pattern of low-amplitude pulses (median 0.2 IU/l) and low basal LH levels (median 0.2 IU/l). The distribution of these pulse patterns showed marked differences between different OC preparations and depended on both the type and dose regimen of the gestagenic component of the OC.

Pulsatile luteinizing hormone secretion during the first and the fourth cycle on two different oral contraceptives containing gestodene.

Oral contraceptives inhibit ovarian follicular growth by suppressing the release of gonadotropins from the pituitary. We studied basal and gonadotropin-releasing hormone-stimulated gonadotropin release, as well as pulsatile luteinizing hormone (LH) secretion, in ten healthy volunteers who had not used oral contraceptives before. Subjects received either a monophasic preparation containing 30 micrograms of ethinylestradiol and 75 micrograms of gestodene (group 1) or a triphasic formulation containing 30-40 micrograms of ethinylestradiol and 50, 70 and 100 micrograms of gestodene (group 2). Blood sampling at 10-min intervals during 6-h periods was performed on days 1, 8, 15 and 21 of both the first and fourth pill cycle. Thirteen healthy volunteers with regular ovulatory cycles served as normal controls. Both LH and follicle-stimulating hormone (FSH) were measured by a sensitive immunoradiometric assay. Pulsatile LH secretion was observed in all oral contraceptive users. Mean serum LH and FSH levels, number of pulses/6 h and the amplitude of LH pulses on day 1 in both the first and fourth pill cycle did not differ from early follicular phase controls in both groups. The FSH levels were suppressed rapidly in both groups, even in first cycles, while LH serum levels progressively declined in all cycles studied. In both groups, amplitudes of LH pulses decreased from day 8 onwards, with a substantial number of low-amplitude pulses (< 0.75 U/l) interspersed between large-amplitude pulses. On day 1 of the fourth pill cycle a significant number of pulses were of low amplitude.(ABSTRACT TRUNCATED AT 250 WORDS)

Pulsatile luteinizing hormone patterns in long term oral contraceptive users.

Oral contraceptives (OC) inhibit folliculogenesis by a central suppressive action on the release of gonadotropins. To characterize the nature of these central effects, we studied 40 long term OC users on 3 different OCs: two monophasic preparations with 30 micrograms ethinyl estradiol and 150 micrograms l-norgestrel (group 1; n = 15), 150 micrograms desogestrel (group 2; n = 10), and a triphasic formulation containing 30-40 micrograms ethinyl estradiol and 50, 75, and 125 micrograms l-norgestrel (group 3; n = 15). Blood sampling at 10-min intervals during 6-h periods was performed at different moments in the pill cycle. Thirteen healthy volunteers with regular ovulatory cycles served as normal controls. FSH and LH were measured by a sensitive immunoradiometric assay. Pulsatile LH release was observed in all OC users. Mean serum LH and FSH levels, number of LH pulses per 6 h, and the amplitude of LH pulses on day 1 of the pill cycle did not differ from early follicular phase control values. FSH levels were rapidly suppressed from day 2 onward in all three groups, whereas LH levels progressively declined in groups 1 and 2 from day 8 onward. In group 3, however, LH levels were only significantly suppressed after day 13. The number of LH pulses per 6 h decreased in all groups starting on day 2, whereas the amplitude of LH pulses increased. A substantial percentage of LH pulses observed in OC users after day 1 were of low amplitude (< 0.75 IU/L). From these results, we conclude that 1) pulsatile release of LH is maintained during OC use; 2) FSH levels are suppressed equally early and equally effective by all OCs studied; 3) during OC use, the number of LH pulses per 6 h is reduced; 4) modulation of LH pulse amplitudes, and subsequently of serum LH levels, is mainly mediated by a dose- and time-dependent effect of the gestagenic component of the OC; and 5) after the 7-day pill-free interval, a normal early follicular phase pulse pattern is found, even in long term OC users, suggesting that in this period, most of the steroidogenic feedback effects wear off.

PIP: Oral contraceptives (OCs) inhibit folliculogenesis by a central suppressive action on the release of gonadotropins. To characterize the nature of these central effects, the authors studied 40 long-term OC users different OCs: 2 monophasic preparations with 30 mcg ethinyl estradiol and 150 mcg 1-norgestrel (group 1, n + 15), 150 mcg desogestrel (group 2; n = 10), and a triphasic formulation containing 30-40 mcg ethinyl estradiol and 50, 75, and 125 mcg 1-norgestrel (group 3; n = 15). Blood sampling at 10-minute intervals during 6-hour periods was performed at different moments in the pill cycle. 13 healthy volunteers with regular ovulatory cycles served a normal controls. FSH and LH were measured by a sensitive immunoradiometric assay. Pulsatile LH release was observed in all OC users. Mean serum LH and FSH level,s number of LH pulses per 6 hours, and the amplitude of LH pulses on day 1 of the pill cycle did not differ from early follicular phase control values. FSH levels were rapidly suppressed from day 2 onward in all 3 groups, whereas LH levels progressively declined in groups 1 and 2 from day 8 onward. In group 3, however, LH levels were only significantly suppressed after day 13. The number of LH pulses per 6 hours decreased in all groups starting on day 2, whereas the amplitude of LH pulses increased. A substantial percentage of LH pulses observed in OC users after day 1 were of low amplitude (0.75 IU/L). From these results, the authors conclude that 1) pulsatile release of LH is maintained during OC use; 2) FSH levels are suppressed equally early and equally effective by all OCs studied; 3) during OC use, the number of LH pulses per 6 hours is reduced; 4) modulation of LH pulse amplitudes, and subsequently of serum LH levels, is mainly mediated by a dose--and time-dependent effect of the gestagenic component of the OC; and 5) after the 7-day pill-free interval, a normal early follicular phase pulse pattern is found, even in long-term OC users, suggesting that in this period, most of the steroidogenic feedback effects wear off.

[Fructosamine values in hyperthyroidism, hypothyroidism and gammopathy]. / Fructosaminwerte bei Hyperthyreose, Hypothyreose und Gammopathie.

Fructosamine values in two groups of hypo- and hyperthyroid patients were compared with the values in a reference group of non-diabetics. In hyperthyroid patients the fructosamine values were significantly lower than in the reference group. Also the mean concentrations of albumin and total protein in serum are significantly lower for hyperthyroid patients compared to hypothyroid patients. The results do not provide evidence for a simple relationship between fructosamine and protein values in these patient groups. Therefore we do not recommend to relate fructosamine to protein or albumin using correction factors. Under conditions of thyrotoxicosis fructosamine is no reliable indicator of previous serum glucose concentrations. The test is not affected by monoclonal IgG gammopathy.

Acute pancreatitis in a case of Werner's syndrome with severe hyperlipidaemia.

A patient with Werner's syndrome and acute pancreatitis due to severe hyperlipidaemia is reported. Special attention is paid to early recognition of the syndrome and the prevention of complications of the several metabolic disorders that occur in this syndrome.

Adenosine deaminase activity, not diagnostic for tuberculous pleurisy.

We have measured adenosine deaminase (ADA) in pleural effusions of 95 patients, using a method optimalised for rapid determination on a Hitachi 705 analyzer. High ADA activity was found in four of the five patients with tuberculous pleurisy, in four of the seven with empyema and in three of the seven patients with mesothelioma. One patient with very high serum ADA activity due to liver disease also had a high activity in the pleural effusion. Low activity was found in all patients with other neoplastic pleural effusions, parapneumonic pleural effusions, transudates, and in pleural effusions due to some other diseases. We conclude that in a country with a low tuberculosis incidence a high ADA activity in pleural effusion in neither sensitive nor specific enough to rely on the diagnosis of tuberculous pleurisy. Routine determination of ADA is not recommended; in selected cases, however, it may be useful.