Long-term lithium carbonate therapy causes hyperparathyroidism.

Twelve patients taking lithium carbonate for two to 13 years were compared with age- and sex-matched controls to determine whether long-term lithium carbonate therapy is associated with alterations in calcium metabolism. As a group and individually, patients had significantly higher levels of serum total calcium, ionized calcium, and parathyroid hormone. When compared with serum calcium levels, patients' parathyroid hormone levels were significantly more likely than those of controls to indicate hyperparathyroidism. Lithium carbonate-induced mild hyperparathyroidism appears to be more common than had previously been suspected.

Lack of effects of beta sympathetic blockade on the metabolic and respiratory responses to carbohydrate feeding.

Increases in metabolic rate, heart rate and ventilation occur following carbohydrate feeding or during beta sympathetic stimulation. Furthermore, insulin secretion and hypokalemia are features common to both which raises the question as to whether these effects of carbohydrate depend upon an intact sympathetic nervous system. Accordingly, in the present study, we measured the effects of carbohydrate feeding (250 gram meal) before and after chronic beta sympathetic blockade in sex normal men. Before blockade metabolic rate (O2 consumption) rose (P less than 0.05) from a fasting mean of 248 +/- 19.7 (SEM) ML O2/min to 292 +/- 15.2 at 1 hr. 269 +/- 13.7 at 2, and 262 +/- 18.0 at 3 hr following the meal. During blockade (oral propranolol 80 mg p.o. Q 6 h for 3 days) the post-prandial increase in O2 consumption was also significant (P less than 0.05) and almost identical to that found before blockade. A similar pattern was found for ventilation, heart rate, insulin secretion and hypokalemia, where the significant postprandial changes were not altered by blockade. A transient increase in serum triiodothyronine from a mean of 92 +/- 8.4 microgram/ML to 109 +/- 9.4 occurred at 1 hr (P less than 0.05) only during blockade. No other changes in thyroid hormonal concentrations occurred as a result of the meal. We conclude that although similarities exist between beta sympathetic stimulation and carbohydrate feeding, the post-prandial effects studied do not depend on intact beta sympathetic receptors.

Thoracic duct fistula and renal transplantation.

Thoracic duct drainage (TDD) was established for 21-115 days in 40 kidney recipients with an average removal per patient day of 4.7 1 lymph and 1.88 billion cells. Cellular and humoral immunity were depressed. TDD and immunosuppressive drugs were started at transplantation in 35 recipients of cross-match negative grafts. Although the results were better than in precedent non-TDD controls, eight patients rejected their grafts before a full TDD effect, and three of the eight developed predominantly anti-B lymphocyte cytotoxic antibodies which were probably responsible for positive cross-matches with their next donors. With continuing TDD, all eight patients had good initial function after early retransplantation. In five more "nontransplantable" patients with performed cytotoxic antibodies, TDD was started 30-56 days before transplantation. In these five pretreated patients, antibodies persisted with positive antidonor cross-matches. Hyperacute rejection occurred repeatedly in two patients with high anti-T (and anti-B) titers, but was surmounted in three patients with lower titers. From the clinical and immunologic data, we have concluded that TDD should be used for pretreatment of all cases with or without prior antibodies, and have suggested an adjustable management plan that takes into account new developments in antibody monitoring.

Hyperlipidemia following renal transplantation.

In a series of 175 adult renal transplant patients 59% of patients had hyperlipidemia. Hyperlipidemia in these patients was characterized by both hypercholesterolemia and hypertriglyceridemia and on lipoprotein electrophoresis was demonstrated to be a mixture of types IIa, IIb and IV hyperlipoproteinemia. Serum cholesterol and triglyceride levels could both be related to the dosage of prednisone these patients received. Serum triglyceride levels could further be correlated with obesity and negatively with the duration of graft function. The latter relationship was felt to reflect the lower dose of prednisone that was administered the longer the duration of graft function. Hypertriglyceridemia was more prevalent in the 47 transplant patients who received kidneys from cadaver donors than in the 128 patients who received kidneys from related-donors. The cadaver-donor renal transplant patients, however, were receiving a larger maintenance dose of corticosteroids and had had functioning transplants for a shorter period of time. In 17 patients followed for up to 20 wks immediately following transplantation both hypercholesterolemia and hypertriglyceridemia developed within 8 wks of transplantation and persisted for the remaining 12 wks. Both serum cholesterol and triglyceride levels in this early post-transplant phase could be related to the cumulative prednisone dosage.

A micromethod for the quantitative analysis of calcium, magnesium, and phosphorus in human skin.

An inexpensive and simple micromethod is described for determining calcium, magnesium, and phosphorus in a 4 mm. punch biopsy of human skin. This small biopsy requires no sutures, and can be repeated frequently with minimal trauma to patients in long-term studies. Normal ranges of calcium (125 to 300 mg. per kilogram of dry defatted weight (DDW), phosphates (450 to 980 mg. per kilogram of DDW), and magnesium (75 to 112 mg. per kilogram of DDW) are similar to reported results on much larger biopsies. Skin calcium but not skin magnesium or phosphate was significantly higher in 40- to 76-year-old subjects when compared to the 20- to 39-year-old individuals. Comparison of an acid extraction method with the standard ashing procedure showed no significant differences in calcium and magnesium content, but the acid extractable phosphate was significantly lower than the total phosphorus found in the ash.

In vitro uptake of calcium by dermis of patients with pseudoxanthoma elasticum.

The calcification of dermal elastic fibers is a characteristic feature of affected skin from patients with pseudoxanthoma elasticum (PXE). Punch biopsies of normal skin and of affected and unaffected skin from patients with PXE were obtained to study dermal calcification in vitro. Before incubation, the calcium, magnesium, and phosphorus content of normal and PXE unaffected dermis were similar and that of PXE affected dermis was significantly higher. Dermal samples were incubated for 2 and 4 days at 37 degrees C. in a calcium phosphate buffer and the Ca and P content were measured. After 4 days of incubation, both PXE affected and unaffected dermis took up significantly more Ca and PO4 than normal dermis. Thus in vitro uptake study could clearly distinguish between normal and PXE dermis. PXE is a disease of variable expression and mild or subclinical forms are difficult to diagnose. Dermal biopsies from clinicallu normal relatives of patients with PXE were obtained and the in vitro uptake of Ca and PO4 was measured. The results show that several of these individuals had elevated uptakes of Ca and PO4 similar to the unaffected dermis of the PXE patient. The results suggest that this test may be used as a diagnostic aid in the detection of individuals with mild forms of PXE and may be a genetic marker for PXE.

The acute effect of chlorothiazide on serum-ionized calcium. Evidence for a parathyroid hormone-dependent mechanism.

The acute effects of chlorothiazide (CTZ) on total (TSCA) and ionized (SCA-plus 2) serum calcium concentrations were studied in three groups of people: (a) eight subjects with normal parathyroid function; (b) six patients with hypoparathyroidism; and (c) two patients with hyperparathyroidism. Most subjects were studied on four occasions; at least 3 days intervened between studies on an individual subject. During each experiment the subject received an i.v. influsion of 5% dextrose in water at 1 ml/min from 8 a.m. to 4 p.m. Additions to the infusions were (a) none; (b) CTZ to deliver 3.33 mg/kg/h; (c) parathyroid extract to deliver 1 U/kg/h; or (d) both CTZ and parathyroid extract at the rates previously indicated. CTZ, when used, was added to the infusion at 10 a.m., parathyroid extract at 8 a.m. When CTZ was infused, the diuretic-induced losses of Na and water were replaced by i.v. infusion. In normal subjects 2 h after the start of CTZ infusion, there was a transient increase in SCA-plus 2 which coincided in time of day with a transient decrease in SCA-plus 2 in control experiments. At that time of day SCA-plus 2 was 4.18 plus or minus 0.12 mg/100 ml in control experiments and 4.56 plus or minus 0.08 in experiments with CTZ, P smaller than 0.025. The corresponding values for (TSCA) were 9.32 plus or minus 0.15 and 9.80 plus or minus 0.30, P smaller than 0.01. Such differences were not observed in the group with hypoparathyroidism. In the two patients with hyperparathyroidism, CTZ produced sustained increases in TSCA and SCA-plus 2. In normal subjects and those with hypoparathyroidism, CTZ plus parathyroid extract infusion resulted in sustained increases in both SCA-plus 2 and TSCA throughout the periods of observation when compared to experiments in which only parathyroid extract was infused, P smaller than 0.01 in all instances. The results suggest that the acute hypercalcemic action of CTZ requires the presence of circulating parathyroid hormone.