Citations

Healthy older men manifest concomitant hypoandrogenemia and attenuation of LH pulse size. Because exogenous GnRH remains effective, a plausible intuition is that aging reduces hypothalamic GnRH secretion, thus mediating relative hypogonadotropic hypogonadism. To assess the impact of age on central GnRH outflow indirectly, we quantitated graded suppression of pulsatile LH secretion by saline and escalating doses of a potent and selective GnRH-receptor antagonist, ganirelix, in 18 healthy men ages 23–72 yr. The rationale is that ganirelix should reduce the amplitude of LH pulses in proportion to both drug concentration and endogenous GnRH feedforward. To this end, blood was sampled every 10 min for 2 h before and 16 h after sc administration of saline or ganirelix and for 3 additional hours after iv injection of a fixed dose of GnRH (100 ng/kg); concentrations of LH and ganirelix were measured by immunochemiluminometry and RIA, respectively; and pulsatile LH secretion was quantitated by a deconvolution procedure. Log-linear regression analysis was used to estimate the sensitivity of pulsatile LH secretion to inhibition by a unit increase in serum ganirelix concentrations in each subject. Statistical analyses revealed that increasing age markedly attenuated the capability of ganirelix to decrease LH pulse size (viz., r = −0.648; P = 0.004). In contrast, age did not modify the competitive interaction between injected GnRH and ganirelix. These joint outcomes support the clinical hypothesis that age diminishes hypothalamic GnRH outflow without impairing GnRH action in healthy men.

The present study tests the clinical postulate that elevated testosterone (Te) and estradiol (E2) concentrations modulate the effects of constant iv infusion of saline vs. recombinant human IGF-I on free IGF-I, IGF binding protein (IGFBP)-1, and dimeric IGF-I/IGFBP-1 concentrations in healthy aging adults. To this end, comparisons were made after administration of placebo (Pl) vs. Te in eight older men (aged 61 ± 4 yr) and after Pl vs. E2 in eight postmenopausal women (62 ± 3 yr). In the saline session, E2 lowered and Te increased total IGF-I; E2 specifically elevated IGFBP-1 by 1.5-fold and suppressed free IGF-I by 34%; and E2 increased binary IGF-I/IGFBP-1 by 5-fold more than Te. During IGF-I infusion, the following were found: 1) total and free IGF-I rose 1.4- to 2.0-fold (Pl) and 2.1–2.5-fold (Te) more rapidly in men than women; 2) binary IGF-I/IGFBP-1 increased 3.4-fold more rapidly in men (Te) than women (E2); and 3) end-infusion free IGF-I was 1.6-fold higher in men than women. In summary, E2, compared with Te supplementation, lowers concentrations of total and ultrafiltratably free IGF-I and elevates those of IGFBP-1 and binary IGF-I/IGFBP-1, thus putatively limiting IGF-I bioavailability. If free IGF-I mediates certain biological actions, then exogenous Te and E2 may modulate the tissue effects of total IGF-I concentrations unequally.

SummarySmith–Lemli–Opitz syndrome is a rare autosomal recessive disorder characterized by multiple congenital anomalies and various degrees of cognitive deficits. This condition results from a deficiency of 7‐dehydrocholesterol reductase, a critical step in cholesterol biosynthesis. Children with Smith–Lemli–Opitz syndrome have frequent infections, particularly of the respiratory tract. Immunodeficiency, however, is not recognized as a part of this metabolic condition. Frequent infections are usually attributed to a decreased patient mobility and reduced respiratory effort secondary to muscular hypotonia and mental retardation, which are often present in affected individuals. We describe a patient with Smith–Lemli–Opitz syndrome and recurrent respiratory infections who was found to have a selective antibody deficiency. The immunological diagnosis was based on an absent immune response to Pneumovax. She also had no immunological response to hepatitis B vaccine and was unable to break down red cells with isoagglutinin B. Therapy with intravenous IgG (IVIG) was initiated. Infections were less severe, although they still occurred in a high frequency after initiation of the IVIG therapy. This finding prompts the need for a higher index of suspicion for an underlying immune deficiency in patients with Smith–Lemli–Opitz syndrome who present with recurrent and chronic infections. Early recognition and appropriate therapeutic interventions may decrease the severity of infections, prevent potentially fatal infections, and eventually improve the quality of life in these patients.

Among 2, 195 reference citations, published during 1975 in ten major US medical journals, 634 (29%) were found to be erroneous on direct checking of the original source. The percentage of error within individual journals ranged from 14 to 50 per cent. Such a high error rate would seem to seriously diminish the usefulness of published reference lists and, possibly, raise questions about the accuracy of other portions of the literature also.