Neuropsychological dysfunction in systemic lupus erythematosus is not associated with changes in cerebral blood flow.

Cognitive dysfunction is found in a considerable proportion of patients with systemic lupus erythematosus (SLE). SPECT provides an estimate of regional cerebral blood flow (rCBF) which has been claimed to be sensitive to detect brain involvement in SLE. It is, however, uncertain if these perfusion defects are related to cognitive dysfunction. In the present study we investigated whether cerebral dysfunction assessed by neuropsychological measures was associated with changes in rCBE Fifty-two SLE patients were examined with a battery of neuropsychological tests and MRI of the brain. For each patient 99mTC-HMPAO-SPECT was performed with the visual cortex as reference, and a reduction in rCBF of > 15% was considered abnormal. Regional CBF was performed with an automated computer program quantitatively estimating blood perfusion in 16 symmetrical sectors of the brain. Several sectors of the brain showed varying areas of reduced rCBF with the temporal lobes most frequently involved. There were generally no associations between cognitive level of functioning and reduced rCBF. MRI demonstrated cerebral infarcts in 9 (17%) patients. In general rCBF was reduced in all sectors of the brain in patients with infarcts, although statistical significant difference in rCBF between patients with and without infarcts was only seen in the parietal lobe. Several neuropsychological functions were influenced by the presence of cerebral infarcts. There was no significant association between immunological measures and SPECT findings or neuropsychological measures. Neuropsychological dysfunction in SLE was associated with the presence of cerebral infarcts detected by MRI, but not by changes in rCBF. SPECT seems to add little if any information to that obtained by clinical examination, neuropsychological testing, and MRI. Since anticoagulation may prevent cerebral infarcts, such prophylactic intervention may be of importance in preventing cognitive deterioration.

A simplified serum-free method for preparation and cultivation of human granulosa-luteal cells.

A simplified method for the preparation and long-term cultivation of granulosa-luteal cells in serum-free medium is described. The cells were harvested from women undergoing in-vitro fertilization, enriched by sedimentation and dissociated by enzymatic treatment. We demonstrated, by introducing a synthetic serum replacement (SSR2), that these primary cell cultures cultivated in monolayers on an extracellular matrix may be used in experiments exceeding 7 days with low cell loss and cell death. No adverse effect on progesterone production was found. There was a high diversity in progesterone production between cells from individual patients. After several days in culture, the cells were challenged with human chorionic gonadotrophin which revived the rapidly decreasing progesterone production. We were unable to demonstrate an increase in cell number after 7 days of cultivation when the cells were grown in medium supplemented with either serum or SSR2. The mitogens epidermal growth factor and basic fibroblast growth factor had no influence on proliferation. We also found that the present method prevents leukocyte contamination in the granulosa-luteal cell cultures. Compared with the common method based on the enrichment of granulosa-luteal cells on a density gradient (Ficoll/Percoll), this method saves time, labour and expense, in addition to augmenting purity.

Plasma brain natriuretic peptide as an indicator of left ventricular systolic function and long-term survival after acute myocardial infarction. Comparison with plasma atrial natriuretic peptide and N-terminal proatrial natriuretic peptide.

BACKGROUND: Elevated plasma levels of atrial natriuretic peptide (ANP) and the N-terminal fragment of the ANP prohormone (N-ANP) are associated with decreased left ventricular function and decreased long-term survival after acute myocardial infarction (AMI). Previous data suggest that plasma brain natriuretic peptide (BNP) may increase proportionally more than plasma ANP after AMI and in chronic heart failure. The diagnostic and prognostic value of plasma BNP as an indicator of left ventricular dysfunction and long-term survival after AMI, relative to that of ANP and N-ANP, remain to be established. METHODS AND RESULTS: Venous blood samples for analysis of ANP, N-ANP, and BNP were obtained on day 3 after symptom onset from 131 patients with documented AMI. Left ventricular ejection fraction was determined by echocardiography in a subsample of 79 patients. Twenty-eight cardiovascular and 3 noncardiovascular deaths occurred during the follow-up period (median, 1293 days). All three peptides proved to be powerful predictors of cardiovascular mortality by univariate Cox proportional hazards regression analyses (ANP: P < .0001; N-ANP: P = .0002; BNP: P < .0001). In a multivariate model, plasma BNP (P = .021) but not ANP (P = .638) or N-ANP (P = .782) provided additional prognostic information beyond left ventricular ejection fraction. Logistic regression analysis showed that ANP (P = .003) and N-ANP (P = .027) but not BNP (P = .14) were significantly associated with a left ventricular ejection fraction < or = 45%. CONCLUSIONS: These results suggest that plasma BNP determination provides important, independent prognostic information after AMI. Although plasma ANP appears to be a better predictor of left ventricular dysfunction, plasma BNP may have greater potential to complement standard prognostic indicators used in risk stratification after AMI because of its strong, independent association with long-term survival, enhanced in vitro stability, and simplicity of analysis.

Plasma proatrial natriuretic factor (1-98) concentration after myocardial infarction: relation to indices of cardiac and renal function.

OBJECTIVES: (a) To assess the relation between plasma concentrations of proatrial natriuretic factor (1-98) and non-invasively derived indices of left ventricular systolic and diastolic performance and (b) to assess the potential confounding effect of renal function and age on this relation in patients with acute myocardial infarction. DESIGN: Cross sectional comparison of biochemical and echocardiographic indices of cardiac function. SETTING: Norwegian central hospital. PATIENTS: Sixty four patients with acute myocardial infarction. MAIN OUTCOME MEASURES: Relation between plasma proatrial natriuretic factor (1-98) concentrations and echocardiographic indices of left ventricular systolic function as assessed by univariate and multivariate linear regression analysis. Sensitivity and specificity of plasma proatrial natriuretic factor (1-98) concentration as a measure of left ventricular systolic and diastolic dysfunction. RESULTS: Plasma proatrial natriuretic factor (1-98) concentrations were significantly related to left ventricular ejection fraction (r = -0.33; P = 0.008), age (r = 0.43; P < 0.001), and creatinine clearance (r = - 0.53; P < 0.001). In a multivariate model left ventricular ejection fraction and creatinine clearance were both independently related to plasma values. The mean concentration of proatrial natriuretic factor (1-98) was significantly higher in patients with an ejection fraction of < 40% than in those with an ejection fraction of > or = 40% (1876 (1151) v 1174 (530) pmol/l; P = 0.03) and in patients with an abnormal transmitral E/A ratio ( < 0.65 or > 1.65, where E/A is ratio of peak early filling velocity to peak atrial component) compared with those with a normal ratio (1572 (895) v 1137 (523) pmol/l, respectively; P = 0.02). When patients were subdivided according to the median concentration of proatrial natriuretic factor (1192 pmol/l) the sensitivity and specificity were 89% and 56% respectively for detecting a left ventricular ejection fraction of < 40% and 75% and 61% respectively for detecting an abnormal E/A ratio. Concentrations below the median had a negative predictive value of 97% in excluding an ejection fraction of < 40% and of 84% in excluding an abnormal E/A ratio. CONCLUSION: These results suggest that soon after myocardial infarction left ventricular ejection fraction and indices of renal function are independently related to plasma concentrations of proatrial natriuretic factor (1-98). Plasma concentrations of proatrial natriuretic factor (1-98) seem to reflect renal and cardiac performance rather than specific haemodynamic variables assessed by noninvasive methods. Plasma proatrial natriuretic factor (1-98) measurements may be a useful screening tool to identify patients with normal cardiac function soon after myocardial infarction.

Prognostic significance of N-terminal pro-atrial natriuretic factor (1-98) in acute myocardial infarction: comparison with atrial natriuretic factor (99-126) and clinical evaluation.

OBJECTIVE: To evaluate the prognostic significance of plasma N-terminal pro-atrial natriuretic factor (1-98) concentrations measured in the subacute phase after acute myocardial infarction, and to compare the predictive value of measurement of N-terminal pro-atrial natriuretic factor (1-98) with the measurement of atrial natriuretic factor (99-126) and with clinical assessment of the degree of heart failure. DESIGN: Prospective observational. SETTING: Norwegian central hospital. PATIENTS: 139 patients (mean (SD) age 66.9 (11.1) years, 71.2% males) with acute myocardial infarction. Patients in cardiogenic shock or with severe heart failure (New York Heart Association class IV) were excluded. MAIN OUTCOME MEASURE: Cardiovascular death within 12 months. RESULTS: During the follow up period 15 patients died. In a univariate Cox proportional hazards model N-terminal pro-atrial natriuretic factor (1-98) was significantly related to mortality (p = 0.0003). In a multivariate model the prognostic value of N-terminal pro-atrial natriuretic factor (1-98) was better than that of atrial natriuretic factor (99-126) and clinical assessment of heart failure (N-terminal pro-atrial natriuretic factor (1-98), p = 0.0003; atrial natriuretic factor (99-126), p = 0.4513; heart failure, p = 0.0719). The odds ratio estimate of patients in whom plasma concentrations of N-terminal pro-atrial natriuretic factor (1-98) were greater than 2000 pmol/l was 25 (95% confidence interval 2.8-225.0) compared with patients with plasma concentrations less than 1000 pmol/l. CONCLUSIONS: These results suggest that determination of plasma N-terminal pro-atrial natriuretic factor (1-98) in the subacute phase of myocardial infarction may provide clinically relevant prognostic information that is superior to that obtained from atrial natriuretic factor (99-126) measurements and clinical evaluation.

Physiological levels of immunoreactive ANH-like peptides in human follicular fluid.

The concentrations of immunoreactive C-terminal (ANH-(99-126)) and N-terminal (ANH-(1-98] portions of pro-ANH were measured in follicular fluid and plasma samples from 9 young women undergoing in vitro fertilization. ANH-(99-126) and ANH-(1-98)-like immunoreactivity levels in plasma were 6.0-25.4 (mean 12.2 pmol/l and 184-427 (mean 300) pmol/l, respectively, whereas the corresponding levels in follicular fluid were 3.8-8.0 (mean 4.9) pmol/l and 169-385 (mean 262) pmol/l. The concentrations of both ANH-like peptides were consistently lower (p less than 0.01) in the follicular fluid than in the matched plasma samples, but within the variation found in plasma controls. It is concluded that ANH-like peptides in the follicular fluid, whether secreted locally or derived from circulating ANH, might play a physiological role in the biosynthesis of ovarian steroid hormones or follicular maturation and fluid dynamics.

Identification and plasma concentrations of the N-terminal fragment of proatrial natriuretic factor in man.

A specific RIA was developed to measure plasma atrial natriuretic factor (ANF) N-terminal immunoreactivity in man. Antibodies raised in rabbits against a rat ANF N-terminal fragment [ANF-(11-37)] had 100% cross-reactivity with human ANF-(1-30) and purified plasma N-terminal ANF immunoreactivity. The ED80 and ED50 of standard curves prepared using [125I]human ANF-(1-30) and human ANF-(1-30) were 31.5 +/- 5.4 (+/- SD) and 132.5 +/- 20.4 fmol/tube, respectively. The plasma ANF N-terminal peptide concentrations were assayed directly, without extraction, since dilution of plasma and addition of standard to plasma yielded parallel dose-responses in the RIA and virtually 100% recovery of ANF-(1-30) added to plasma. Purification of ANF N-terminal immunoreactivity from 1.5 L human plasma by affinity chromatography and amino acid sequencing suggested that it was closely related to ANF-(1-98), although some degraded peptides were also detected. The mean basal plasma ANF N-terminal peptide level measured in 34 normal subjects was 420 +/- 157 (+/- SD) pmol/L. The values were higher in plasma from patients with congestive heart failure (grades III and IV; 7,041 +/- 6,136 pmol/L; n = 13) or chronic renal failure (10,079 +/- 4,942 pmol/L; n = 20). In 9 patients with chronic renal failure, hemodialysis resulted in a 30% (P less than 0.05) decrease in plasma ANF-(99-126) levels, from 34.7 +/- 12.3 (+/- SD) to 23.2 + 6.1 pmol/L, but no changes in plasma ANF N-terminal peptide concentrations. These data indicate that the N-terminal portion of pro-ANF is cosecreted with ANF-(99-126). Its higher plasma levels in the basal state and during chronic renal failure suggest a different process of elimination than that of ANF-(99-126), which may be partly mediated by the kidney.

Bone scintigraphy, radiographic survey and prostatic acid phosphatase in patients with prostatic carcinoma. A comparison of sensitivity.

In 62 patients with histologically confirmed carcinoma of the prostate bone scintigraphy, radiographic survey and serum prostatic acid phosphatase determinations were carried out to evaluate the progression of the disease and to compare the relative sensitivity of the diagnostic tools. Thirty-five patients had scintigraphic evidence of skeletal metastases, whereas abnormal X-ray survey and elevated prostatic acid phosphatase levels were found in only 4 and 19 patients, respectively, all of whom had positive scintigraphic findings. Radiographic evidence of metastases was not found in any of the patients with normal scintigraphy, while elevated prostatic acid phosphatase was found in two patients. It is concluded that bone scintigraphy is far more sensitive than either radiographic survey or determination of prostatic acid phosphatases in the diagnosis of skeletal involvement in prostatic carcinoma, and should be the method of choice for this purpose.

A study on oedema mechanism in nephrotic syndrome.

Colloid osmotic pressure in plasma (COPp) and interstitial fluid (COPi), plasma volume (PV) and interstitial fluid volume (IFV) were measured in 14 patients with hypoproteinaemia due to glomerulonephritis and in five healthy controls. In controls, COPp averaged 24.2 mmHg and COPi 12.0 mmHg. In patients with COPp above 12 mmHg, COPi was reduced nearly identical to the fall in COPp. The transcapillary COP gradient (COPp-COPi) was maintained, and PV and IFV were unchanged. When COPp was reduced below 12 mmHg, the transcapillary COP gradient was decreased. Both IFV increased and renal fluid retention occurred. This study demonstrates the relationship between COPp, transcapillary fluid transport, and renal fluid retention in nephrotic syndrome.

Ectopic thyroid tissue in the head and neck.

A review has been performed of thyroid ectopia seen during a 10 year period. There were five cases of total ectopia; three of these were lingual thyroids, one situated in the perihyoid region had been clinically diagnosed as a thyroglossal cyst, while the fifth presented as a tumor in the lateral neck. In the same period 41 thyroglossal cysts were removed. None of these showed uptake on technetium scintigraphy. Thyroid tissue was present in the cyst walls in 41% of cases. Scintigraphy should be performed routinely if the clinical picture is at all compatible with thyroid ectopia.

Seasonal changes in T3, FT4, and cortisol in free-ranging Svalbard reindeer (Rangifer tarandus platyrhynchus).

Serum levels of 3,5,3'-triiodothyronine (T3), free thyroxine (FT4), and cortisol were determined for free-ranging Svalbard reindeer during winter (March), summer (June-July), and autumn (October). A total of 48 animals representing adult males, adult barren, pregnant, and lactating females, and calves were shot, and blood sampled from their hearts. T3 and FT4 were found to vary seasonally, the levels being lower in winter than in summer or autumn. Differences due to state of pregnancy, sex, or age were represented by low FT4 levels in lactating females (summer) and rutting males (autumn), and high T3 levels in young calves (summer). Serum cortisol levels were found to change seasonally, summer levels being higher than winter or autumn levels in all groups of animals. This finding suggests that glucocorticoids (cortisol) do not affect the deiodination from T4 to T3 in reindeer. The seasonal changes in T3 and FT4 in wild animals were similar to the changes in captive animals. It is therefore concluded that the changes in thyroidal hormone levels do not indicate changes in basal metabolic rate in this species.

Regulation of metabolic rate in Svalbard and Norwegian reindeer.

Food intake, body weight, serum levels of triiodothyronine (T3) and free thyroxine (FT4), and metabolic rate were measured at intervals in Svalbard (SR) and Norwegian (NR) reindeer. From summer to winter food intake decreased 57 (SR) and 55% (NR), while body weight decreased 8.6 (SR) and 3.8% (NR). In SR T3 and FT4 changed seasonally, whereas this was only evident for T3 in NR. Resting (standing) metabolic rate (RMR) in winter was 1.55 (SR) and 2.05 W X kg-1 (NR), lower critical temperature (TLC) being -50 (SR) and -30 degrees C (NR). RMR in summer was 2.15 (SR) and 2.95 W X kg-1 (NR), TLC being -15 (SR) and 0 degrees C (NR). Seasonal changes in T3 and FT4 did not coincide with changes in food intake or RMR in either SR or NR. RMR did, however, correlate with food intake. This indicates that seasonal changes in RMR are due to the thermic effects of feeding and represent no physiological adaptation aimed at conservation of energy during winter.

Relief from pain in Sudeck's posttraumatic syndrome by fasciotomy. A clinical, radiographic, and scintigraphic study.

Twenty-three consecutive patients aged 33-80 years with a presumed Sudeck's syndrome of one hand or one foot were seen. A fracture initiated the syndrome in three-quarters of them, and the median duration of suffering was 3.5 months in the hand and 7 months in the foot. Osteoporosis and marked 99mTc-labeled methylene diphosphonate uptake were seen in radiographs and scintigrams respectively. Thirteen of the patients were operatively treated; distal fasciotomy on the volar aspect of the forearm or the ventral aspect of the lower leg gave rapid relief from pain at rest in nine of ten patients thus affected. All the patients became symptom-free, except two who underwent closed treatment. At follow-up 2-8 years later radiographic and scintigraphic findings were usually normal.

The influence of dihydralazine and angiotensin-II blockade on renal extraction of [131I]hippuran.

The renal extraction of [131I]ortho-iodohippuran ([131I]OIH) was measured during the first minutes after the bolus injection during renal vein catheterization of two groups of hypertensive patients. Concomitantly the hippuran clearance (effective renal plasma flow (ERPF) was determined with a quantitative renographic technique based on net kidney uptake between 1 1/2 and 2 1/2 min and plasma radioactivity 2 min after the bolus injection of hippuran. The study was repeated 30 min after intravenous administration of dihydralazine (0.1 mg/kg body weight) in 14 subjects (group A) and during continuous infusion of the angiotensin II blocking agent Saralasin (5 micrograms/kg . min) in 10 subjects (group B). Before dihydralazine was given, the rate of [131I]OIH extraction was (Mean +/- S.D.) 74.0 +/- 16.7% in the 2 min sample after bolus injection of hippuran, 67.5 +/- 17.3% after 10 min, falling to 53.0 +/- 15.3% after 30 min. There was no difference after dihydralazine administration, as the extraction values were 75.6 +/- 17.5 and 65.6 +/- 21.4% 2 and 10 min after the bolus injection of hippuran. The extraction values before Saralasin infusion were 74.2 +/- 15.7%, 59.8 +/- 18.2% and 47.1 +/- 16.6% at 2, 10 and 25 min after bolus injection of hippuran. Saralasin elicited no change in the extraction, as the values were 74.1 +/- 18.6% and 64.3 +/- 23.2%, 2 and 10 min after hippuran injection. For kidneys with ERPF above 100 ml/min . 1.73 m2 the extraction 2 min after hippuran injection was at the level of 82%, whereas the extraction fell rapidly with further reduction in ERPF. It is concluded that ERPF determined with the renographic technique, reflects the renal plasma flow when the clearance for the individual kidney exceeds 100 ml/min . 1.73 m2. This is the case also after dihydralazine and Saralasin administration.

To the management of the solitary thyroid nodule.

Excisional biopsy with peroperative frozen section and later paraffin section examination was performed in 107 consecutive cases of solitary thyroid nodules. Frozen section gave a correct diagnosis in 99 cases (92%). A false benign diagnosis was made in 6 cases, one was inconclusive and one was false malignant (Hürthle cell tumor). Technetium scintigraphy was of no definite diagnostic value. Malignancy was found in 25 cases (23%) in which the whole gland was removed. Multicentric bilateral lobe involvement was encountered in 7 patients. Lack of reliable preoperative diagnostic methods makes liberal excisional biopsy of all solitary thyroid nodules advisable.

The effect of secretin on renal haemodynamics in man.

Five young males were studied after no overnight fast on 2 separate days with a 3 h intravenous infusion of secretin 2 CU per kg body weight per h in saline and of saline alone. Urinary outputs of water, sodium, potassium, calcium, inorganic phosphate, creatinine and solutes were determined, and the creatinine clearance was calculated. Glomerular filtration rate (GFR) and renal plasma flow (RPF) were determined by constant infusion of [51Cr]EDTA and [125I]o-iodohippurate, respectively. Secretin induced a significant increase in urinary water, sodium, calcium and solute excretion, and a significant decrease in free water clearance. Both creatinine and [51Cr]EDTA clearance rose slightly but non-significantly, whereas [125I]o-iodohippurate increased 2 fold and significantly. This study confirms that secretin has a diuretic effect in man, and it is concluded that this effect is most likely due to impairment of sodium reabsorption in the renal tubule caused by the increase in RPF. Furthermore, this increase in RPF is probably secondary to a direct vasodilatation of the renal arterioles.

Evaluation of the endocrine functions in dystrophia myotonica.

Investigation of several endocrine functions was performed in seven patients with dystrophia myotonica (DM). All patients had hyperinsulinemia. Whereas the four female patients had normal pituitary-gonadal function, all three male patients presented evidence of a primary gonadal failure. Thyroid function was normal in all patients. Four patients displayed abnormal diurnal variations of cortisol secretion. Basal prolactin levels were elevated in three patients, one of whom also had consistently elevated levels of growth hormone. The investigation adds some new evidence of neuroendocrine dysfunction at the hypothalamic level in DM.

Renin levels and spironolactone treatment in general practice: similar blood pressure lowering effect of spironolactone in low and normal renin patients.

We examined the predictive value of plasma renin activity (PRA) in ambulatory patients in the selection of hypertensive patients for treatment with spironolactone. The patients were classified as frusemide responders or non-responders according to their PRA response to 80 mg frusemide orally. After an initial 4 weeks placebo period forty-five patients with the clinical diagnosis of benign hypertension (WHO stage I-II) entered a 4 X 4 week double blind treatment period during which they received spironolactone (Aldactone) 400, 300, 200 and 100 mg/day, respectively. Five out of the forty-five patients who started the trial were withdrawn on account of side-effects and five patients for other reasons. Of the thirty-five patients who completed the study eighteen belonged to the group of non-responders to frusemide, seventeen to the responders. A gradual and significant decrease in mean blood pressure occurred during the period with the high doses of spironolactone, without any significant difference between the groups. The blood pressure lowering effect obtained with the initial high doses was maintained during the consecutive periods when the doses was reduced to a half or even a fourth, in both groups. We conclude that PRA measurement in ambulatory patients is of little, if any, value for the selection of hypertensives for spironolactone treatment; this in contrast to similar selections performed on hospitalized patients.

The effect of spironolactone (Aldactone) and methyldopa in low and normal renin hypertension.

The effect on BP of 100 and 200 mg spironolactone/day has been compared with that of methyl-dopa, 750 mg/day, and with combined treatment with both drugs in 32 patients with essential hypertension. The 28 patients who completed the entire investigation were treated for 30 weeks, divided into 4 treatment periods and 4 placebo periods of equal duration. BP did not fall significantly during the initial placebo period, and at the end of each of the intervening placebo periods it rose to pretreatment levels. A signifcant decrease in mean BP was found during the 4 treatment periods. A fall exceeding 14% was registered in 32% of the patients after methyldopa, 750 mg/day, in 50% of the patients after spironolactone, 200 mg/day, in 89% after combined treatment with both drugs, and in 29% after spironolactone, 100 mg/day. Low renin hypertension was found in 9 of the 28 patients. The average decrease in mean BP after sironolactone, 200 mg/day, methyldopa, 750 mg/day, and after combined treatment did not differ significantly between the low and the normal renin group. The rationale for using diuretics such as spironolactone or thiazide as the basic therapy in essential hypertension is discussed. It is concluded that both are useful in the treatment of essential hypertension and might be used alone or in combination.