Hypocalcaemia of acute pancreatitis: the effect of hypoalbuminaemia.

Hypoalbuminaemia has been consistently observed in a prospective study of 130 patients with acute pancreatitis. A study was initiated, therefore, to find out if the hypocalcaemia of acute pancreatitis could be explained by the associated hypoalbuminaemia. 64.4% of all serum calcium results were in the apparently hypocalcaemic range. A comparable incidence of hypoalbuminaemia was observed. The 'uncorrected' total serum calcium and serum albumin showed a similar pattern in their daily changes and also a significant correlation overall. When correction of serum calcium was made for albumin levels, only 10.9% of all results represented varying degrees of 'true' hypocalcaemia. Mortality and severity of acute pancreatitis related as closely to hypoalbuminaemia as to uncorrected hypocalcaemia. It is concluded that a low serum albumin should be regarded as the most common cause of a low serum calcium in acute pancreatitis. Routine albumin administration is proposed, a procedure which has been shown to be associated with improved mortality rate and morbidity in this disease.

Abnormalities in mineral metabolism suggestive of parathyroid over-activity in rheumatoid arthritis.

A three-part study on mineral metabolism in patients with classical rheumatoid arthritis is described. In the first two parts, biochemical abnormalities were revealed suggestive of parathyroid over-activity, and in the third part, observation on calcium absorption provides a hyperparathyroid pattern. The importance of these findings in relation to demineralisation of bone in rheumatoid arthritis is discussed.

Effects of conjugated equine oestrogens with and without the addition of cyclical norgestrel on serum and urine electrolytes, and the biochemical indices of bone metabolism and liver function.

Serum and urine electrolytes, and biochemical indices of bone metabolism and liver function were measured in 51 post-menopausal women treated with two hormone replacement therapy regimens for 24 wk. Twenty-six of the women were treated continuously with conjugated equine oestrogens (0.625 mg/day) and the remainder were treated as above with the addition of norgestrel (0.15 mg/day) during the last 12 days of each 28-day cycle. Both treatment regimens affected electrolytes in a similar manner. The most consistent effect was a reduction in serum sodium levels and a reduction in urinary sodium/creatinine ratios. The combined regimen appeared to have a greater effect on sodium reabsorption. Both regimens decreased all the biochemical indices of bone metabolism measured, viz serum calcium (corrected for albumin), phosphate and alkaline phosphatase and urinary calcium/creatinine and hydroxyproline/creatinine ratios. The preparations used decreased the parameters by similar amounts over the 24 wk indicating that both were equally effective in reducing bone turnover. The data suggested, however, that the combined regimen had a more profound effect on bone metabolism during the early phase of treatment. The two treatment regimens had broadly the same effects on the biochemical indices of liver function, reducing albumin levels and all the liver enzymes. Judging by these indices neither regimen had a deleterious effect on liver function. We conclude that the two hormone replacement regimens have similar effects on the biochemical indices measured, but there are subtle differences between the two treatments which merit further research.

Do anticonvulsant drugs commonly induce osteomalacia?

Twenty adult epileptic out-patients who had received anticonvulsant therapy for a mean duration of 15 years were assessed for clinical, biochemical, radioisotopic and bone biopsy evidence of osteomalacia. Occasional biochemical abnormalities were demonstrated but no individual subject was found to have osteomalacia. There is increasing evidence to cast doubt on the existence of a strong relationship between anticonvulsant drugs and osteomalacia. This evidence is reviewed and it is concluded that in the presence of adequate sunlight exposure anticonvulsant therapy alone is most unlikely to lead to osteomalacia in adults.

Serum ionized calcium in acute pancreatitis.

Measurement of serum ionized calcium was performed daily for 7 days after admission in 8 consecutive patients with acute pancreatitis. The results support the findings of our previous study that the most common cause of the low serum calcium often found in patients with this disease is a low serum albumin; when correction of serum calcium is made for hypo-albuminanemia, most patients are found to be normocalcaemic. The occasional hypocalcaemia as shown by the 'corrected' serum calcium or by serum ionized calcium measurement is usually mild and transient, indicating that the normal homoeostatic mechanisms of the body can efficiently maintain the physiologically active fraction of the serum calcium within, or close to, the normal range. These findings explain the rarity of overt and subclinical tetany in acute pancreatitis. This study has shown that correction of serum calcium for albumin provides similar information to the direct measurement of serum ionized calcium. The value of 'apparent' hypocalcemia in assessing severity of acute pancreatitis requires reappraisal, while greater attention should be directed towards the investigation and management of hypoalbuminaemia in this disease.

Comparison of high-efficiency and standard haemodialysis providing equal urea clearances by partial and total dialysate quantification.

BACKGROUND: Short-duration high-efficiency haemodialysis has been utilized increasingly in recent years to deliver adequate blood urea clearances per dialysis session. However, high-efficiency and standard-duration haemodialysis schedules, which achieve equal patient urea clearances, may not represent equivalent dialytic therapy due to solute differences in intercompartmental dysequilibrium during dialysis and differences in dialysis mechanics. METHODS: To circumvent the effects of intercompartmental dysequilibrium and postdialysis rebound solute clearances were measured by direct dialysis quantification (total and partial dialysate collections) rather than blood clearances. High-efficiency haemodialysis (dialyser blood flow rate = 400 ml/min; dialysis time = 170.67 min) was compared with standard haemodialysis (dialyser blood flow rate = 200 ml/min; dialysis time = 240 min) performed in random order in six anuric patients using Fresenius F8 dialysers and the same haemodialysis machine. Such haemodialysis schedules were prescribed to provide equivalent urea clearances. RESULTS: Patient plasma water urea clearances measured by direct dialysis quantification were equivalent, whereas high efficiency haemodialysis achieved significantly lower phosphate clearances (P = 0.01), less net bicarbonate absorption (P = 0.01), and lower beta 2 microglobulin removal (P < 0.001) than standard haemodialysis. Estimated total dialysate effluent volumes with partial dialysate collection and total dialysate collection correlated closely (r = 0.95) and there were no differences between patient urea, creatinine and phosphate clearances measured by partial and total dialysate quantification. CONCLUSIONS: The data indicate that even if high-efficiency and standard haemodialysis provide equal whole-body urea clearances, delivered dialysis therapy is not equivalent. The partial dialysate collection method is as accurate as the cumbersome total dialysate collection approach and may be applied to assess delivered dialysis dose by minor modification of current haemodialysis machines.

Bone-resorbing activity in the sera of patients with rheumatoid arthritis.

1. Foetal rat hemi-calvaria were incubated in organ culture with sera from patients with active rheumatoid arthritis. 2. Increased 45Ca resorption was produced by sera from patients who were hypercalcaemic. 3. This bone-resorbing effect could be inhibited by calcitonin.

Recurrent aphthous ulceration: vitamin B1, B2 and B6 status and response to replacement therapy.

An evaluation of the thiamine, riboflavin and pyridoxine (vitamin B1, B2 and B6) status of 60 patients with recurrent mouth ulcers was performed. Seventeen patients (28.2%) were found to be deficient in one or more of these vitamins. Replacement therapy of these vitamins was given to a study group of deficient patients and a non-deficient group for one month. At the end of therapy and after a follow-up period of 3 months, only those patients who had a B complex deficiency had a significant sustained clinical improvement in their mouth ulcers. Vitamin B1, B2 and B6 deficiencies should, therefore, be considered as another possible precipitating factor in recurrent aphthous ulceration.

The significance of the incidental finding of basal ganglia calcification on computed tomography.

Basal ganglia calcification was found as an incidental finding in 42 out of 7000 patients who underwent computed tomography. The calcification showed on plain skull radiography when the maximum density on computed tomography exceeded 100 Hounsfield units. The 26 patients with basal ganglia calcification detected on computed tomography who were available for follow-up, were investigated with matched controls. No clinical features of basal ganglia calcification were noted. Twenty-four patients had no significant metabolic abnormality and two patients had parathyroid disorder identified.

Parathyroid hormone and calcium homeostasis in acute pancreatitis.

Sequential daily measurements of plasma parathyroid hormone (PTH) have been performed in 89 patients with acute pancreatitis. A total of 439 PTH assays was obtained during 98 episodes of the disease. Three main patterns of PTH response were found. These responses were correlated with severity of disease graded by objective criteria and also to corrected serum calcium levels. The first type of PTH response was characterized by significantly elevated PTH levels soon after hospitalization with a subsequent decrease in levels to within the normal range by the third or fourth day of illness. This type of response was specifically associated with transient severe hypocalcaemia (corrected calcium less than 2.0 mmol/l). It was also associated with the most severe forms of disease and 6 of the 7 deaths. The second type of PTH response revealed initial PTH values in the upper level of the normal range (400--600 ng/l) while persistently low PTH levels were characteristic of the third type of response. Persistently low PTH levels were associated with normocalcaemia, and no patient in this group died. None of a group of 14 control patients exhibited the type 1 PTH response. An effective PTH response to an unidentified hypocalcaemic stimulus results in satisfactory calcium homeostasis in most patients with acute pancreatitis.

Skin pigmentation due to minocycline treatment of facial dermatoses.

Fifty-four patients taking minocycline for acne or rosacea were assessed for adverse effects. Their mean duration of treatment was 17 months, and their average cumulative dose was 47 g. No symptoms attributable to the therapy were reported. Biochemistry and haematology profiles were normal. There was no evidence of an adverse effect on thyroid function. Skin pigmentation was detected in eight patients (14.8%). Five patients had diffuse facial pigmentation, and three patients had localized pigmentation at the site of a scar or injury. Diffuse pigmentation occurred only in patients who had been on treatment for 3 years or more; 50% of such patients were affected. Age and solar damage may also have been factors in this type of pigmentation. Localized pigmentation occurred at sites of previous tissue damage, and was not directly related to the duration of therapy. Patients who receive long-term minocycline therapy should be regularly monitored for the development of pigmentation.

Effective intravenous cyclosporin therapy in a patient with severe Crohn's disease on parenteral nutrition.

We report a patient with severe Crohn's disease and the short bowel syndrome on parenteral feeding who was not responding to conventional therapy and underwent treatment with cyclosporin (CyA) given initially intravenously and subsequently orally in each of two courses. Plasma drug concentrations were largely kept within the therapeutic range but wide variability was observed on oral therapy. Improvement both clinically and by objective assessment, was observed on intravenous CyA therapy, but was not sustained when the drug was given orally for several months. None of the side effects observed resisted treatment or was severe enough to warrant discontinuation of therapy. These findings suggest that there may be a place for intravenous CyA therapy in patients with severe Crohn's disease who do not respond to conventional therapy or to oral treatment with CyA.

Immobilization-related hypercalcaemia--a possible novel mechanism and response to pamidronate.

Immobilization-related hypercalcaemia is an uncommon but important condition being associated not infrequently with both urolithiasis and osteoporosis. In this study 5 patients who had been immobilized for a mean of 3 months and had a mean adjusted serum calcium of 3.15 mmol/l were treated with doses of intravenous pamidronate ranging between 10 mg and 45 mg. All patients became normocalcaemic by day 3. Patients 1-3 mobilized shortly after treatment and remained normocalcaemic. In those patients who continued to be immobile hypercalcaemia recurred after an interval of several weeks. Retreatment with pamidronate again resulted in normocalcaemia. No side effects were noted with treatment. All of the patients studied had increased rates of bone resorption as shown by elevated urinary hydroxyproline/creatinine ratios (median:range) of 0.101:0.045-0.180 (normal less than 0.033) and elevated calcium/creatinine ratios of 2.50:0.69-3.63 (normal less than 0.50). None of the patients in this study had any of the usual risk factors for developing immobilization-related hypercalcaemia though all 5 patients had problems with significant sepsis which we postulate may have lead to cytokine release which in turn contributed to the development of hypercalcaemia. We conclude that pamidronate (at doses as low as 10 mg) is safe and effective in immobilization-related hypercalcaemia and suggest that sepsis should be added to the list of risk factors for development of this syndrome.