Prolactin and beta-endorphin responses to hypoglycemia are reduced in well-controlled insulin-dependent diabetes mellitus

Several pituitary hormones, including corticotropin (ACTH), growth hormone (GH), prolactin, and beta-endorphin (but not thyrotropin, follicle-stimulating hormone, or luteinizing hormone), are released in response to hypoglycemia in normal subjects. In patients with insulin-dependent diabetes mellitus (IDDM), the degree of glycemic control is known to alter ACTH and GH responses to hypoglycemia. The current study was performed to examine the effect of glycemic control on prolactin and beta-endorphin responses to hypoglycemia in subjects with IDDM. We performed 3-hour stopped hypoglycemic-hyperinsulinemic clamp studies (12 pmol/kg/min) during which plasma glucose was decreased from 5.0 mmol/L to 2.2 mmol/L in steps of 0.6 mmol/L every 30 minutes in 20 subjects with uncomplicated IDDM (12 males and eight females; age, 26 +/- 2 years; IDDM duration, 10 +/- 1 years; body mass index, 23.6 +/- 0.6 kg/m2) and 10 healthy subjects (five males and five females aged 30 +/- 1 years). The 10 diabetic subjects in good glycemic control (mean hemoglobin A1 [HbA1], 7.5% +/- 0.3%; normal range, 5.4% to 7.4%) were compared with the 10 poorly controlled patients (mean HbA1, 12.6% +/- 0.5%; P < .001 v well-controlled diabetic group). During hypoglycemia, prolactin levels in the well-controlled diabetic group did not change (7 +/- 1 microgram/L at plasma glucose 5.0 mmol/L to 9 +/- 2 micrograms/L at plasma glucose 2.2 mmol/L), whereas prolactin levels increased markedly in the poorly controlled diabetic group (7 +/- 2 micrograms/L to 44 +/- 17 micrograms/L) and healthy volunteers (12 +/- 2 micrograms/L to 60 +/- 19 micrograms/L, P < .05 between IDDM groups). The plasma glucose threshold required for stimulation of prolactin secretion was 2.2 +/- 0.1 mmol/L in well-controlled IDDM, 3.0 +/- 0.4 mmol/L in poorly controlled IDDM, and 2.4 +/- 0.1 mmol/L in healthy subjects (P < .05 between IDDM groups). Responses in males and females were similar. The increase in beta-endorphin levels was also attenuated in well-controlled IDDM patients (4 +/- 1 pmol/L at plasma glucose 5.0 mmol/L to 11 +/- 4 pmol/L at plasma glucose 2.2 mmol/L) versus poorly controlled IDDM patients (5 +/- 1 pmol/L to 26 +/- 7 pmol/L) and healthy subjects (8 +/- 1 pmol/L to 56 +/- 13 pmol/L). The plasma glucose threshold required for stimulation of beta-endorphin release was again lower in well-controlled IDDM versus poorly controlled IDDM patients (2.2 +/- 0.1 v 3.0 +/- 0.3 mmol/L) and healthy subjects (2.5 +/- 0.4 mmol/L, P < .05 between IDDM groups). In conclusion, prolactin and beta-endorphin responses to a standardized hypoglycemic stimulus (plasma glucose, 2.2 mmol/L) are reduced and plasma glucose levels required to stimulate release of prolactin and beta-endorphin are lower in well-controlled IDDM compared with poorly controlled IDDM and healthy subjects. Thus, stress hormones not previously considered to have a primary role in plasma glucose recovery from hypoglycemia are affected by glycemic control, suggesting a more generalized alteration of hypothalamic-pituitary responses to hypoglycemia in IDDM patients with strict glycemic control.     

False-positive hepatitis B surface antigen screening test results in patients receiving granulocyte-colony-stimulating factor

BACKGROUND: Granulocyte-colony-stimulating factor (G-CSF) is used for the mobilization of progenitor cells and granulocytes. False-positive hepatitis B surface antigen (HBsAg) enzyme-linked immunosorbent assays (ELISAs) (NML) from one manufacturer in individuals receiving G-CSF have been observed. STUDY DESIGN AND METHODS: Sixty-six autologous peripheral blood progenitor cell donors from 1994 were retrospectively reviewed. Donors typically received 5 to 10 micrograms of G-CSF per kg subcutaneously for 5 days before collection. Additional ELISA dilutional studies (1-in-10, 1-in-100, 1-in-1000) with known HBsAg-negative serum were made with G-CSF. Testing was performed by the University of North Carolina, the American Red Cross in Charlotte, NC, or the National American Red Cross, Washington, DC. RESULTS: Of the 66 patients, none reacted for antibody to hepatitis B core antigen, and 30 (45%) had a positive reaction in the ELISA. Surface antigen positivity was confirmed on 6 of the 30 patients by neutralizing ELISA reactivity with an antibody to HBsAg test from the same manufacturer. In all cases, the clinical presentation was not suggestive of hepatitis, and these individuals were not at high risk for hepatitis B. Twenty-seven of the 30 cases were tested with a monoclonal HBsAg ELISA (AUSZYME) from another manufacturer in the peridonation period and did not react. In 1994, 256 autologous whole-blood donors not receiving G-CSF were similarly tested and only 1 (0.4%) had a positive reaction with the second manufacturer's HBsAg ELISA (p < 0.001). Of this group, 41 patients with histories of malignancy were identified, which is comparable to the history of the peripheral blood progenitor cell donors in this study, and none of these blood donors tested positive for HBsAg (p < 0.001). Dilutional studies with G-CSF produced no reactions. CONCLUSION: The NML HBsAg ELISA studied has an unacceptably high false-positive rate in patients or donors receiving G-CSF. The false reactivity of this assay appears to be an indirect consequence of G-CSF administration, which can also lead to spurious confirmation by the HBsAg neutralization assay from the same manufacturer.     

Self-administration of GBR 12909 on a fixed ratio and progressive ratio schedule in rats

Intravenous self-administration of GBR 12909, an indirect dopamine agonist, was examined on a Fixed Ratio (FR 1) and a Progressive Ratio (PR) schedule of reinforcement in rats. Subjects were first trained to self-administer cocaine (1.5 mg/kg/inj) during daily 5 h sessions, after which GBR 12909 (0.187-1.5 mg/kg/inj) was substituted. On the FR 1 schedule, the inter-infusion interval for GBR 12909 self-administration was directly related to dose and was approximately three times longer than that established for equivalent doses of cocaine. Breaking points on the PR schedule were comparable for GBR 12909 and cocaine self-administration. The data indicate that, compared to cocaine, GBR 12909 has a longer duration of action and a similar reinforcing efficacy.     

Increased immunoglobulin binding to cerebral endothelium in patients with antiphospholipid antibodies

BACKGROUND AND PURPOSE: There is a strong link between antiphospholipid antibodies and stroke. The mechanism of action of antiphospholipid antibodies is unknown. Most theories of pathogenesis center around platelet or endothelial cell dysfunction. Our aim was to determine if there were immunoglobulins in the sera of patients with antiphospholipid antibodies that bind human brain microvascular endothelial cells. METHODS: We studied sera from three groups of subjects: patients with antiphospholipid antibodies and stroke (group 1), healthy control subjects (group 2), and patients with stroke but without antiphospholipid antibodies (group 3). We isolated human brain microvascular endothelial cells from temporal lobectomy specimens and used a cellular enzyme-linked immunosorbent assay (ELISA) to measure immunoglobulin binding to endothelial cells derived from human brain and from human umbilical vein. We used a chromium release assay to measure cytotoxicity. RESULTS: Patients with antiphospholipid antibodies and stroke had significantly higher immunoglobulin binding to human brain microvascular endothelial cells than subjects in the other groups ([ELISA index+standard deviation], 63 +/- 37 [group 1] versus 7 +/- 7 [group 2] versus 7 +/- 7 [group 3], P < .001). There was, however, poor correlation between binding to brain endothelial cells and binding to cardiolipin. The binding to brain microvascular cells was not specific to brain endothelium, as similar results were found in an ELISA using human umbilical vein cells. There was no evidence of complement-mediated brain endothelial cell cytotoxicity. CONCLUSIONS: Patients with stroke and antiphospholipid antibodies frequently have human brain microvascular endothelial-reactive antibodies in their serum. These antibodies are distinct from those to cardiolipin. We found no evidence that these antibodies are cytotoxic.     

Buttonhole ulceration and perforation of the rectum

Immune status was examined in 231 patients facing pneumoconiosis and coniotuberculosis so as to observe a dependence on pneumoconiosis type (silicosis, electric welder's pneumoconiosis), severity of the process, activity of tuberculosis. Markedly changed T and B immunity, having already appeared at initial stage of the disease, were revealed. Those changes due to the tuberculosis activity were characterized by lymphocytosis, marked functional immaturity of T lymphocytes, depressed B lymphocytes count, elevated serum Ig level.     

Proposed: an international code of ethics for medical genetics

Myeloid bodies (MBs) are distinct lamellar regions of the normally branched tubular smooth endoplasmic reticulum of retinal pigment epithelial (RPE) cells. These organelles are present in the retinas of many lower vertebrates. Previous investigations have reported a relationship between outer segment disk shedding and phagocytosis by the RPE, and the formation of MBs. The current morphometric study was undertaken to establish if a temporal relationship existed between MB occurrence and the phagocytosis of shed photoreceptor outer segment tips in the chick retina. We report on the occurrence of phagosomes, MBs, and for the first time, MB precursors (templates) in the RPE over a 24-hr diurnal cycle. Phagosome numbers were observed to be highest within 2 hr following lights on, and again following lights off, while MB precursors were most prevalent at two time points, immediately prior to the times for rod and cone outer segment shedding at lights on and lights off respectively. Traditional MBs of the small (0.06 to 0.239 microns2) and medium (0.24 to 0.99 microns2) variety increased both in size and number from 01:00 hr of a 24 hr time period, with smaller and fewer MBs being present late in the dark part of the diurnal cycle, and larger and more numerous MBs in the later part of the light portion and into the early part of the dark portion of the cycle.(ABSTRACT TRUNCATED AT 250 WORDS)     

Impact of federal regulations at a university

Last year the University of Iowa conducted an in-house study of how federal regulations, executive orders, and agency administrative policies affected the day-to-day operations of the university on all levels. This article is an analysis and reassessment of the federal impact issue based on the information uncovered in the University of Iowa survey.     

Proestrous gonadotropin levels in thyroparathyroidectomized female rats

Intact and TPTx animals showed the expected afternoon increase in serum LH,FSH and prolactin levels. But the afternoon increase in serum LH levels in TPTx rats was less than that observed for intact animals (p less than 0.001). Neither serum prolactin nor FSH levels were altered by TPTx.