[Long-term results after Spitzy's umbilical hernia repair]. / Langzeitergebnisse der Nabelhernienreparation nach Spitzy.

A total of 140 patients presenting with umbilical hernia underwent Spitzy's operation and were included in a retrospective study to analyse the recurrence rate. The patients received a questionnaire and were invited for a physical examination including ultrasound. Participation included 108 patients (follow-up 77%). A total of seven patients (6.5%) developed postoperative wound infections. Prolonged postoperative impairment was mentioned by nine patients (8.3%). After a mean period of 16 days, the patients were able to continue their occupation, and after 27 days, they could manage their usual physical activity. The recurrence rate was 13.0%. The risk for a recurrence correlated with the relative bodyweight. In the group with a body-mass-index (BMI) of less than 30, the recurrence rate was 8.1 %, whereas 31.8% of the patients with a BMI of more than 30 developed a recurrent hernia. The size of the hernial orifice also had an influence on the postoperative result. In patients with a hernial gap smaller than 1 cm the recurrence rate was 6.3%, with hernia orifices from 1 to 2 cm the rate was 4.1%, from 2 to 3 cm 14.3%, from 3 to 4 cm 25.0% and in patients with hernial gaps greater than 4 cm the rate of recurrences was 54.5%. Considering these results,we recommend the use of alloplastic material for umbilical hernia repair for patients with a BMI greater than 30.0 and hernia orifice larger than 3 cm. The decision for use of a mesh in hernial gaps from 2 to 3 cm should depend on individual factors.

[Effects of octreotide on serum and urine electrolytes in a patient with parathyroid carcinoma: clinical case]. / Efectos del octreotide sobre los electrolitos en suero y orina de un paciente con carcinoma de paratiroides: caso clínico.

Parathyroid carcinoma (PC) is a rare endocrine tumor whose management is difficult whenever surgery does not achieve complete en bloc resection or recurrence is detected. Medical options (mainly bisphosphonates) are scanty and often associated with toxic side-effects. We present a case report of a patient with recurrent PC after two surgical interventions who was treated with octreotide (SMS-201) taken into account the positive somatostatin staining of the specimen obtained during the last surgery. Short term effects (-2 weeks-) included a decrease in urinary calcium excretion paired with a simultaneous increase in urinary phosphorus excretion. Later on, continuous subcutaneous octreotide administration kept urinary calcium excretion at low levels and this effect was completely reversible/reinducible upon discontinuation/reintroduction of the drug. Neither iPTH nor total serum calcium were modified at short or long term basis. The lack of clear-cut therapeutic effects make this findings a pure clinical observation. Thus, octreotide cannot be recommended for the treatment of parathyroid carcinoma.

Poor permeability of morphine 3-glucuronide and morphine 6-glucuronide through the blood-brain barrier in the rat.

To better understand the in vivo pharmacological effects of morphine 3-glucuronide (M3G, a weak opioid antagonist) and morphine 6-glucuronide (M6G, a potent opioid agonist), the permeability of the blood-brain barrier (BBB) for these metabolites was compared with morphine. Tracers were prepared by enzymatic glucuronidation of [N-methyl-3H]morphine. Brain uptake in rats was measured by the internal carotid perfusion technique and after intravenous bolus injections. In the perfusion experiments morphine showed a permeability-surface area product (PS) of 3.52 +/- 0.61 microliter min-1 g-1. Uptake seemed to be mediated by passive diffusion and was not saturable by 100 microM morphine in the perfusate. The BBB permeability of [3H]M3G and [3H]M6G was too low to be quantified after 5 min of perfusion. Brain uptake of [3H]M3G and [3H]M6G 60 min after i.v. bolus injection reached 0.0060 +/- 0.0003% and 0.0030 +/- 0.0005% injected dose per g, respectively. From these brain concentrations and the corresponding plasma concentration-time curves, BBB PS values of 0.14 +/- 0.02 microliter min-1 g-1 and 0.11 +/- 0.01 microliter min-1 g-1, respectively, were calculated. The ratio of BBB PS values is complementary to the analgesic potencies of morphine and M6G after different routes of administration. The low PS of M6G explains why it is approximately equipotent to morphine after systemic injection, although it is about 2 orders of magnitude more potent than morphine after administration directly into the central nervous system.

Behavior of intracellular glutathione during platelet thromboxane synthesis in diabetes.

The time-dependent relationship between the levels of the reduced form of glutathione (GSH) and thromboxane A2 (TXA2) synthesis, as measured by the accumulation of TXB2, in platelets from human diabetic and control subjects was investigated during aggregation. In platelets from control subjects, the GSH level decreased to 21% of the initial level within 30 sec in response to arachidonic acid (1.65 mM) and rapidly recovered to 91% by 1 min. In platelets from diabetic subjects, the GSH level decreased to 3% of the initial level within 30 sec and recovered to only 41% by 1 min. During collagen (20 ug/ml) aggregation, platelets from control subjects had a 15 sec lag phase which was followed by a decrease in the GSH level to 21% of the initial level within 1 min and a recovery to 74% by 2 min. Platelets from diabetic subjects in response to collagen showed no lag phase and decreased to 10% of the initial level within 1 min which was followed by a recovery to 34% by 2 min. In all aggregations, the initial GSH level was significantly (p less than .001) lower in platelets from diabetic subjects and remained significantly (p less than .01) lower than GSH in platelets from control subjects throughout the aggregation. The amount of TXB2 formed by platelets from control subjects reached a maximum in response to arachidonic acid and collagen by 1 min and 2 min, respectively, whereas, the TXB2 continued to increase up to 4 min when platelets from diabetic subjects were aggregated. These data indicate that TXA2 synthesis occurs during the decrease in GSH and ceases when the GSH level recovers. The continued synthesis of TXA2 by platelets from diabetic subjects coincides with the gradual recovery of the GSH level.

Lack of demonstrable tumor growth in progressive hyperprolactinemia.

Prolactin has been regarded as an excellent tumor marker for patients harboring prolactinomas, and a significant rise in the basal prolactin level is generally regarded as being commensurate with tumor growth. This report describes a case in which the basal serum prolactin level rose from 250 ng/ml to 1,528 ng/ml over a 10-year follow-up period in the absence of definitive therapy. Three sequential contrast-enhanced direct coronal computed tomographic scans obtained over a four-year period failed to demonstrate any evidence of growth of the 5 mm microprolactinoma. Progressive hyperprolactinemia may not be synonymous with tumor growth in patients with microprolactinomas.

Autoimmune thyroiditis in manic-depressive patients treated with lithium.

To explore whether lithium-induced hypothyroidism is related to an exacerbation of underlying autoimmune processes such as thyroiditis, the authors comprehensively assessed thyroid function in 16 manic-depressive patients. Each of the three patients who showed detectable titers of thyroid microsomal antibodies before treatment manifested a marked increase in antibody titer from 4 to 12 months after lithium treatment was begun. Thus, lithium-induced thyroid dysfunction may not only involve direct effects on the thyroid itself but also involve exacerbation of an underlying indolent autoimmune thyroiditis, possibly by causing shifts in T lymphocyte subpopulations.

Platelet glutathione and thromboxane synthesis in diabetes.

The relationship of the reduced glutathione (GSH) content in unstimulated platelets and their capacity to synthesize thromboxane A2 (TXA2), measured by radioimmunoassay of TXB2, was investigated in diabetic and matched control subjects. The GSH content in platelets from diabetic subjects (6.52 +/- 0.73 microgram/10(9) platelets, mean +/- SD) was significantly (P less than 0.001) lower than in platelets from control subjects (10.10 +/- 1.58 microgram/10(9) platelets). When platelet-rich plasma (PRP) was stimulated with 1.65 mM arachidonic acid, significantly (P less than 0.001) more TXB2 was formed in PRP from diabetic subjects (344 +/- 87 ng/2.5 X 10(8) platelets) than in PRP from control subjects (132 +/- 35 ng/2.5 X 10(8) platelets). Furthermore, the plasma level of TXB2 was increased in diabetic subjects (522 +/- 117 pg/ml) in comparison with control subjects (187 +/- 63 pg/ml). An inverse correlation (r = 0.98) was observed between the GSH content in unstimulated platelets and their capacity to synthesize TXA2 when stimulated with 1.65 mM arachidonic acid. These data suggest that platelet GSH may have an important regulatory effect on platelet TXA2 synthesis and that increased TXA2 synthesis by platelets from diabetic subjects may be the result of low intracellular GSH levels.

Insulin-induced cardiac failure.

Self-limited edema is a well-recognized complication of insulin therapy. However, progression to overt cardiac failure has only recently been reported in one patient with pre-existing heart disease. This report describes the first case of insulin-induced cardiac failure in a patient without underlying heart disease. Current trends toward intensive insulin therapy for rapid near-normalization of blood glucose levels will increase the recognition of this entity. Careful follow-up of so-called "self-limited" insulin edema is encouraged, and the early institution of diuretic therapy is advocated in elderly patients to prevent the development of overt cardiac failure.

Adrenocortical carcinoma in children.

Adrenocortical carcinoma in childhood is a rare yet potentially fatal disease. We present 5 cases of adrenocortical carcinoma detected and managed in childhood. Of the 5 patients 4 presented with clinical signs of excess corticosteroid production and 1 presented suddenly with abdominal pain. All patients had palpable abdominal masses. All tumors were removed surgically and adjuvant therapy with mitotane was used in 4 children. Two patients are alive and 3 are dead. Our experience demonstrates that mitotane may be used safely in children, and that early diagnosis, aggressive surgical extirpation, and the use of mitotane and chemotherapy may lead to an increased survival of children with adrenocortical carcinoma.

Hyperparathyroidism after radioactive iodine therapy for Graves disease.

The association of external ionizing radiation to the head and neck and the subsequent development of hyperfunctioning parathyroid glands has been documented in recent years. This also has been demonstrated experimentally in animals. Despite the numbers of patients with Graves disease who have been treated with radioactive iodine, there are no reports in the literature of parathyroid surgery for hyperparathyroidism secondary to earlier treatment with radioactive iodine for Graves disease. This report describes the operative and pathologic findings in four patients with hyperparathyroidism. These patients had previously been treated with radioactive iodine for Graves disease. The pathologic findings at surgery included in three cases a single enlarged hyperplastic gland consistent with a parathyroid adenoma. One patient had hyperplasia of all four glands. The two largest glands and halves of the two remaining glands were removed. In a long-term follow-up of children and adolescents treated with radioactive iodine for Graves disease, Levy and Schumacher found calcium elevations in 10 of 159 patients. The increased incidence of hyperparathyroidism following radioactive iodine treatment for Graves disease in children and adolescents would seem several times higher than normal. Whether adults who have radioactive iodine treatment for Graves disease have a similar increase incidence is not known. Meanwhile it would seem reasonable to suggest that patients whose hyperthyroidism is treated with radioactive iodine should have their serum calcium levels determined at 5-year intervals.

Prolactin-secreting pituitary adenoma: occurrence following prenatal exposure to diethylstilbestrol.

PIP: A case is reported of a prolactin-secreting pituitary adenoma in a young woman who had been referred for evaluation of amenorrhea with a history of in utero exposure to diethylstilbestrol. Following prolactin suppression ans stimulation tests bromocriptine (Parlodel), 2.5 mg orally, twice a day was prescribed. Followup at 1, 2, and 3 years after diagnosis with the use of sector scans of the sella turcica showed a decrease in size of the tumor from 12 x 12 mm in 1980 to 9 x 6 in 1982, over 50% reduction. Serum prolactin level measured 3 months after initiation of treatment was reduced by about 2/3 to 124 ng/ml. The direct role of estrogen in pituitary tumorigenesis in animals has been suggested both by the demonstration of estrogen receptors in the cytosol of estrogen-induced prolactinomas and growth inhibition of a transplantable estrogen-induced prolactin-secreting pituitary tumor by the administration of tamoxifen. In this case bromocriptine, a dopaminergic agonist, was successful in reducing both serum prolactin levels and tumor size.^ieng

Thromboxane biosynthesis in platelets of diabetic and coronary artery diseased patients.

We have shown that platelets of diabetic patients (D) with coronary artery disease (CAD) produce more thromboxane A2 (TXA2) compared to normal subjects (N), when induced to aggregate with arachidonic acid. The purpose of this investigation was to determine: 1) whether TXA2 biosynthesis in platelets of D without exogenous substrate is increased, 2) whether platelets of D without CAD produce more TXA2 than N and 3) to compare platelet TXA2 biosynthesis in D with those angiographically diagnosed as having CAD but without D. TXB2 (stable metabolite of TXA2) was measured by RIA in platelets of 100 volunteer subjects: 24 D without other clinical complications, 10 D with retinopathy or nephropathy, 7 D with CAD, 30 CAD without D and 11 had D and hypertension. Eighteen subjects had no D, CAD or hypertension. TXA2 synthesis in platelets, stimulated to aggregate with both endogenous and exogenous substrate was higher in all patient classes studied as compared to normal subjects. Plasma triglyceride concentration was higher in diabetics as compared to controls while total cholesterol as well as platelet phospholipid fatty acid distributions were similar in all groups of subjects indicating a similar substrate concentration for TXA2 biosynthesis. It is concluded that platelets of D and CAD with or without D have greater sensitivity to aggregation which might be due to the increased thromboxane synthetase system at one or more sites.

Diagnosis of self-induced hyperinsulinism in an insulin-dependent diabetic patient by radioimmunoassay of free C-peptide.

On the basis of results of simultaneous determinations of plasma free insulin and free c-peptide, episodes of hypoglycemia in an insulin-dependent diabetic were attributed to surreptitious self-administration of insulin. Immunoreactive c-peptide values were falsely increased and diagnostically misleading when measured in unextracted plasma. After preliminary removal of antigen/antibody complexes from the plasma by extraction with polyethylene glycol, the c-peptide values, referred to as "free c-peptide," were suppressed. We suggest that insulin antibodies formed complexes with proinsulin-like material in the plasma of this patient, which accounted for most of the c-peptide immunoreactivity in her unextracted plasma. These complexes must be removed if c-peptide measurements are to be accurate.