Analyte flux through chronically implanted subcutaneous polyamide membranes differs in humans and rats.

The rat is commonly used to evaluate physiological responses of subcutaneous tissue to implanted devices. In vivo longevity of various devices and the biocompatibility of biomaterials depend on how adjacent tissue interacts. How closely the rat model predicts the human response has not been well characterized. The objective of this study was to compare rat and human subcutaneous foreign body responses by monitoring the biochemical environment at a polymer-tissue interface over 8 days using microdialysis. Polyamide microdialysis probes were implanted subcutaneously in humans and rats (n = 12). Daily microdialysis samples were analyzed for glucose, lactate, pyruvate, glycerol, and urea. Blood glucose was also monitored. Analyte concentrations differed significantly between rats and humans at the implant-tissue interface. There were also qualitative differences in the 8-day trends. For example, over 8 days, microdialysate glucose increased two- to fourfold in humans but decreased in rats (P < 0.001). This study reveals profound physiological differences at material-tissue interfaces in rats and humans and highlights the need for caution when extrapolating subcutaneous rat biocompatibility data to humans.

Increased lipolytic sensitivity to catecholamines in diabetic patients with severe autonomic neuropathy.

Lipolytic sensitivity to catecholamines was studied in gluteal adipocytes from diabetic subjects with severe (n = 3), mild (n = 6) or no autonomic neuropathy (n = 8). Two of the three patients with severe autonomic neuropathy had a completely abolished plasma epinephrine response to insulin-induced hypoglycaemia, whereas the third patient showed a reduced and delayed plasma epinephrine response. Lipolytic sensitivity to isoprenaline (P less than 0.05), and to epinephrine in the presence of yohimbine (P less than 0.0001), was significantly increased in the diabetic subjects with severe autonomic neuropathy, compared to the other study groups. Moreover, the specific binding of the beta-adrenoceptor antagonist (+-)-4-(3-butylamino-2-hydroxypropoxyl)-(5.7-3H)-benzimidazole- -2-one-hydrochloride (3H-CGP) was markedly exaggerated (P less than 0.05) in the patients with severe autonomic neuropathy. These findings demonstrate that the lipolytic sensitivity to catecholamines in adipose tissue was increased only in patients with severe autonomic neuropathy and impaired epinephrine response to insulin-induced hypoglycaemia. This increased beta-adrenergic sensitivity could, at least in part, be attributed to an increased density of beta-adrenergic receptors in the adipocytes.

Comparison of subcutaneous injection and high-dose inhalation of epinephrine--implications for self-treatment to prevent anaphylaxis.

The plasma concentrations of epinephrine were determined in healthy subjects administered epinephrine by subcutaneous injection of 0.5 mg or inhalation of 1.5 to 4.5 mg (10 to 30 inhalations from a metered-dose aerosol). The absorption of injected epinephrine was variable and in several cases very slow. The individual maximum values for epinephrine in plasma were 4.65 +/- 1.09 (range 0.74 to 8.31) nmol/L, and these maxima were attained 5 to 120 minutes after injection. Inhaled epinephrine was rapidly and dose dependently absorbed. Ten inhalations resulted in 2.72 +/- 0.84 (0.75 to 5.67) nmol/L within 5 minutes and 20 inhalations resulted in 7.19 +/- 1.78 (2.10 to 13.83) nmol/L with rapid increases and maxima within 20 minutes in seven of eight subjects. Gastrointestinal side effects were dose limiting when epinephrine was administered by inhalation. Our results indicate that inhalation of 2 to 3 mg of epinephrine produces rapid increases of epinephrine concentrations in plasma to levels that have previously been demonstrated to counteract bronchoconstriction induced by inhaled allergen in subjects with asthma. Inhalation has several advantages over injection for self-administration of epinephrine, e.g., in patients who are allergic to insect (Hymenoptera) stings. Apart from the absorption being more rapid, the locally high concentrations of epinephrine in the airways should be advantageous, since bronchoconstriction is one of the life-threatening phenomena of the anaphylactic reaction. This route of administration is also simple for the patient.

Surgical treatment of primary aldosteronism.

An aldosterone-producing adenoma is the cause of primary aldosteronism in about 85%. Unilateral adrenalectomy cures the potassium wasting and normalizes the blood-pressure in more than 70%, independently of the severity or duration of the hypertension. The location of an aldosteronoma is best obtained by computerized tomography and selective venous catheterization with determination of the aldosterone/cortisol ratio. When the biochemical studies suggest hyperplasia, medical treatment is recommended. It is, however, our policy to remove an adrenal gland with hyperplasia, when catheterization demonstrates unilateral hyperfunction. At operation a posterior or a flank approach is preferably used.

Interaction by cholestyramine on the uptake of hydrocortisone in the gastrointestinal tract.

An absolute reduction of the plasma cortisol levels and a delay of the peak concentrations were recorded in 10 healthy subjects, when a bile-sequestering anionic exchange resin, cholestyramine, was given prior to a single oral hydrocortisone dose, indicating that the resin interferes with the uptake of a neutral sterol in the human gastrointestinal tract. The possibility of a direct binding of drug to resin is supported by the affinity of hydrocortisone to cholestyramine in vitro, which was uninfluenced by the presence of sodium taurocholate. Cholestyramine significantly delayed the gastric emptying of a glucose solution, indicating that the resin not only decreases but also delays hydrocortisone absorption. Careful supervision is recommended when treatment with cholestyramine is given concomitant to neutral sterol drugs.