Future issues in children's health care: addressing psychosocial concerns.

A panel of experts, participating in a Delphi poll, identified significant issues facing psychosocial aspects of health care for children in the future. In three rounds of feedback and evaluation, ten top future issues were composited in rank order: chronic illness and complex health care needs; sociogenic problems; unequal access to health care; lack of financial resources for psychosocial services; increased focus on prevention; children without primary caregivers; complex ethical questions; family-centered care; training of health care professionals; and interdisciplinary integration. Implications of these issues are discussed.

Sleep apnea in active acromegaly.

Previous case reports have shown an association between acromegaly and the sleep apnea syndrome (SAS). Some of the patients described had central SAS, raising the possibility that an elevation of the growth hormone (GH) level may cause a defect in respiratory drive. We determined the prevalence of SAS in 21 patients with a history of acromegaly. We separated them into two groups based on serum GH concentrations. Ten patients had active acromegaly (mean GH concentration, 62.2 ng/mL; range, 12.6 to 148 ng/mL), while 11 patients had inactive acromegaly (mean GH, 3.2 ng/mL; range, 0.7 to 6.4 ng/mL). Four of the ten patients with active acromegaly had SAS; none of the 11 patients with inactive acromegaly had SAS. Three patients with SAS had the purely obstructive type, and one had the mixed central and obstructive type. The hypercapnic ventilatory response was normal in all patients tested and was not influenced by the GH level. We conclude that SAS is associated with active acromegaly and that the GH level does not affect the hypercapnic ventilatory response. The absence of SAS in successfully treated patients suggests that it may resolve after a normal GH level is restored.

Residual anterior pituitary function following transsphenoidal resection of pituitary macroadenomas.

A series of 84 patients with pituitary adenomas greater than 1 cm in diameter is presented. Full preoperative and postoperative endocrine evaluations were carried out, and the effects of transsphenoidal surgery on remaining anterior pituitary function were analyzed. Of the patients who had normal anterior pituitary function before surgery, 78% retained normal function after surgery. Thirty-three percent of those patients with pituitary deficits who did not have panhypopituitarism before surgery had improved function after surgery; 33% had worsened function after surgery. None of the patients with panhypopituitarism before surgery regained function after surgery. Transsphenoidal surgery carries an acceptable risk for sacrificing anterior pituitary function, but the risk is greater in patients with larger tumors and preoperatively compromised pituitary function.

Expression of murine leukemia viruses in RFM mice with host versus graft disease after perinatal inoculation of (T6 X RFM)F1 lymphohemopoietic cells.

Host versus graft disease is the fatal syndrome of altered immunity that follows the perinatal inoculation of related F1 hybrid spleen cells to susceptible strains of inbred mice. The allogenic reaction results in severe depletion of T-lymphocytes, but causes hyperplasia and hypersecretion of B-cells. Among the long-term survivors of acute host versus graft reactions, there is a high incidence of nonthymic lymphomas associated with ecotropic murine leukemia virus that may be of donor F1 origin. The present studies were done to determine whether ecotropic murine leukemia virus played any role in the pathogenesis of acute host versus graft disease in RFM mice perinatally inoculated with (T6 X RFM)F1 spleen cells. In RFM/(T6 X RFM)F1 chimeras, N-tropic murine leukemia virus can be detected as early as 3 days. The progression of the disease was accompanied by increasing viral expression. The inoculation of N-tropic virus of F1 donor origin into RFM neonates failed to induce disease, although the virus proliferated. Detection of progressively rising titers of antibody to murine leukemia virus linked the virus to the development of hyperimmunoglobulinemia by virtue of its ability to serve as a replicating source of antigens. These and other studies provided evidence that the seemingly paradoxical appearance of hyperimmunoglobulinemia in T-cell-deficient mice with the host versus graft syndrome is due, at least in part, to the stimulation of presensitized F1 donor B-cells, which are not destroyed in the allogenic reaction, as are the T-cells. Another unusual finding was the detection of polytropic murine leukemia virus in 25-day-old RFM/(T6 X RFM)F1 chimeras. It is suggested that the allogenic host versus graft reaction favored the formation of recombinants.

A cyproheptadine-reversible defect in ACTH control persisting after removal of the pituitary tumor in Cushing's disease.

We studied two phases of cortisol feedback suppression of ACTH in nine patients who had had adrenalectomy for Cushing's disease. Four had been treated by adrenalectomy alone and presumably had ACTH-secreting pituitary tumors. Five others were studied two or more years after transsphenoidal removal of an ACTH-secreting microadenoma. In both groups, cortisol-ACTH feedback during the first 30 minutes of cortisol infusion was abnormal; plasma ACTH fell only 2.7 +/- 2.6 per cent (mean +/- S.E.), as compared with 28.0 +/0 10.1 per cent in five hypoadrenal controls (p less than 0.01). The fall in ACTH during the second phase of cortisol infusion was similar in the patients and the controls. Cyproheptadine corrected the feedback abnormality occurring during the first phase in both groups of patients with Cushing's disease; ACTH fell by 24.4 +/- 4.8 per cent (P less than 0.005). Persistence of a cortisol-ACTH feedback abnormally after removal of the pituitary tumor in Cushing's disease, as well as the correction by cyproheptadine, suggests that higher centers have a role in the pathophysiology of Cushing's disease.

Effects of thyrotropin-releasing hormone and metoclopramide in patients with phenothiazine-induced hyperprolactinemia.

TRH and metoclopramide tests were performed in 10 female patients with presumed phenothiazine-induced hyperprolactinemia to define the serum PRL response to these agents. Our results show that the serum PRL response to metoclopramide is blunted in most patients with phenothiazine-induced hyperprolactinemia, and the serum PRL response to TRH is exaggerated in most patients during and 3 weeks after stopping phenothiazines.

Galactorrhea-amenorrhea syndrome: follow-up of forty-five patients after pituitary tumor removal.

Forty-five patients with galactorrhea-amenorrhea were followed during a period of 1 to 8 years (mean 3.1) after transsphenoidal prolactinoma removal. The ratios of patients who appear to be cured to the total numbers treated were 20 patients of 27 with grade I tumors; six of 10 with grade II; two of five with grade III; and none with grade IV tumors. Six patients with normal prolactin levels one week postoperatively had relapse later, as did three with normal prolactin levels 2 months postoperatively. A normal prolactin level 6 months postoperatively predicted ultimate cure. The 19 pregnancies that occurred in 15 patients, four with high prolactin levels, were uneventful. Prolactin rose normally with pregnancy and returned to prepregnancy level in all but one patient. Prolactin responses to stimulation tests were blunted for 6 months after successful tumor removal. By 1 year, responses to thyrotropin releasing hormone and metoclopramide tests were returning to normal, although responses to chlorpromazine and hypoglycemia remained blunted. The postoperative inhibition of normal lactotropes for 6 months is suggested. Ultimate cure cannot be determined before 6 months and conception should be deferred until then.

Persistent defect in regulation of prolactin secretion after successful pituitary tumor removal in women with the galactorrhea-amenorrhea syndrome.

TRH, metoclopramide (MCP), chlorpromazine (CPZ), and insulin (ITT) stimulation tests of PRL secretion were carried out in age-matched controls and before and after successful removal of pituitary prolactinomas in women with the galactorrhea-amenorrhea syndrome. In preoperative patients there was a blunted or absent PRL response to TRH in 87%, to MCP in 100%, to CPZ in 100%, and to ITT in 93%. Two to 6 months after successful tumor removal, serum PRL rose 2-fold (the usual criterion for a normal response) in 73% after TRH, in 100% after MCP, but in only 13% after CPZ and in only 14% on ITT. However, the PRL increment with all four tests was significantly lower than that in normal controls. One to 8 yr after successful surgery, the PRL increments after TRH and MCP were returning to normal, but the PRL responses to CPZ and ITT remained blunted. GH, ACTH, and TSH reserves were intact in all patients. The diminished PRL response to all stimulation tests observed up to 6 months postoperatively might be explained by the persistence of a negative feedback effect from high PRL levels associated with the tumor. The more persistent impairment of the PRL response to CPZ and ITT is unexplained but suggests a hypothalamic defect.

The treatment of acromegaly by transsphenoidal surgery.

Pituitary tumors were removed transsphenoidally in 32 patients with acromegaly. Ten patients had high prolactin (PL) levels as well as elevated growth hormone (GH) levels. In 24 patients, GH levels were lowered to 5 ng/mL or less and remained low. The PL level was reduced to normal in eight patients. Of three patients with postoperative GH levels of 6 to 10 ng/mL, one patient remains in this range but two have relapsed. Five patients showed only a partial lowering in GH level. Pituitary irradiation lowered the level further. Hypopituitarism developed in four patients. Permanent diabetes insipidus occurred in one patient and meningitis developed in another. They subsequently recovered. There were no deaths. Abnormal GH responses to hyperglycemia, hypoglycemia, and levodopa returned to normal following surgery. Transsphenoidal tumor removal appears to be an effective treatment for acromegaly.

New trends in the management of diabetic ketoacidosis.

The diagnosis of ketoacidosis can be rapidly confirmed by simple determinations of blood glucose, serum ketones and arterial pH. The initial hydrating fluid is isotonic saline, followed by half-normal saline with buffered potassium phosphate. As soon as the blood glucose drops below 300 mg. percent, 5% glucose is added to the infusion. Following an initial regular insulin dose of 20 u. intramuscularly or 10 u. intravenously, subsequent doses of 10 u. every hour are given either by intravenous drip or by injection deep into the deltoid muscle.