Effects of pyridostigmine on spontaneous and growth hormone-releasing hormone stimulated growth hormone secretion in children on daily glucocorticoid therapy after liver transplantation

OBJECTIVES: We aimed to investigate both nocturnal spontaneous and morning growth hormone (GH)-releasing hormone (GHRH)-induced GH secretion in children on daily glucocorticoid treatment after liver transplantation and to evaluate the effect of pyridostigmine (an acetylcholinesterase inhibitor thought to reduce hypothalamic somatostatin tone) on GH secretion in these patients. DESIGN: We performed a randomized, single-blind, cross-over study. PATIENTS: We studied three male and three female juvenile patients, within a year of orthotopic liver transplantation and under immunosuppressive glucocorticoid therapy (mean dose +/- SEM, 5.92 +/- 0.63 mg/day) and five normal children (four males, one female). MEASUREMENTS: Both nocturnal spontaneous and morning GHRH-induced GH secretion were evaluated after administration of placebo, 1 tablet p.o., or pyridostigmine, 2 mg/kg p.o. RESULTS: Spontaneous GH. Placebo: in liver transplanted children nocturnal GH secretion (mean GH level 10.8 +/- 2.0 mU/l) was not significantly different with respect to normal children (mean GH level 12.8 +/- 1.2 mU/l); pyridostigmine: nocturnal GH secretion was significantly increased as compared to placebo in subjects with liver transplantation but not in normal children. GHRH test. Placebo: liver transplanted patients showed a blunted GH response to GHRH with respect to normal children; pyridostigmine: the GH responses to GHRH (P less than 0.05) increased as compared to placebo and did not differ significantly in the two groups. CONCLUSIONS: Our data suggest a steroid-mediated increase in hypothalamic somatostatin tone in liver transplanted children.     

Functional meaning of tryptophan-induced increase of 5-HT metabolism as clarified by in vivo voltammetry

Differential pulse voltammetry with carbon fiber electrodes was used to study serotonin (5-HT) metabolism in freely moving rats. The electrodes implanted in the striatum recorded the extracellular 5-hydroxyindoleacetic acid (5-HIAA) oxidation peak after oral tryptophan (150 mg/kg). This 5-HT precursor did not modify the 5-HIAA peak in any rat tested, but it raised 5-HIAA levels determined in total tissue by a classical biochemical method (HPLC). The administration of 5-hydroxytryptophan (5-HTP) (25 mg/kg i.p.) induced an increase of 5-HIAA detectable both in the extracellular medium by voltammetry and in tissue samples. As previously shown, dorsal raphe electrical stimulation raises extracellular 5-HIAA in the striatum and this effect is enhanced by pretreatment with tryptophan. The results suggest that tryptophan in 'normal' conditions enhances 5-HT metabolism without affecting 5-HT release unless such release is stimulated. 5-HTP increases 5-HT metabolism and release.     

3-Carbonylacrylic derivatives as potential antimicrobial agents. Correlations between activity and reactivity toward cysteine

A number of 3-carbonylacrylic acid derivatives were prepared, with a view to varying systematically the stereoelectronic environment of the conjugated double bond. The rates of reaction with cysteine were measured spectrophotometrically when possible or by stopped flow when very fast. Some of the final reaction products were isolated. Other properties examined were partition substituent constants and antimicrobial activity. On the basis of published data and these studies, the activity appears to be the combined effect of at least two mechanisms, one probably related to the effect of these structures on surface tension, the other to the electrophilic properties of the unsaturated system.     

Paternal and Maternal Smoking Habits before Conception and During the First Trimester: Relation to Spontaneous Abortion

PURPOSE: This study examined the association between maternal smoking before and during the first trimester of pregnancy and spontaneous abortion.

METHODS: We have been conducting a hospital-based case-control study on risk factors for spontaneous abortion in the greater Milan area. We collected information from 782 cases of spontaneous abortions and 1543 controls (women who delivered at term healthy infants).

RESULTS: With respect to never smokers, the odds ratio (OR) were 0.7 (95%, confidence interval (CI), 0.5–1.0) for women who quit smoking and 1.3 (95% CI, 1.0–1.6) for those who continued during pregnancy. Women who smoked more than 10 cigarettes/day in the first trimester were at increased risk of miscarriage, with an OR of 1.4 (95% CI, 1.0–2.1). No relationship was evident between the number of cigarettes smoked before conception and the risk of abortion. Likewise, no association emerged between paternal smoking and miscarriage. Moreover, no significant interaction or modification effect was obtained when strata of age and other major characteristics were investigated.

CONCLUSIONS: The risk of abortion associated with cigarette smoking during the first trimester of pregnancy was measurable and noticeable in this population, and accounted for 9% (95% CI, 6–13%) of all cases. The increased risk of spontaneous abortion in women smoking during pregnancy is a further reason to encourage pregnant women to quit.     

Computed tomography of renal metastases

Since the advent of CT, secondary neoplastic lesions of the kidneys have been detected with increasing frequency. After reviewing a large series of cases of renal metastases, we have been able to classify the CT findings into seven major categories that are discussed and illustrated in this article. The differential diagnoses between metastatic disease of the kidneys and other lesions such as renal infarctions, renal lymphoma, and primary malignancies are also considered.     

Influence of sensory inputs on standing balance in community-dwelling elders with a recent history of falling.

Vision and/or ankle somatosensory inputs often do not correlate with the position of the center of gravity. In this case, visual or somatosensory information may be in conflict with other sensory systems that convey a true sense of body orientation. The purpose of this study was to determine how conflicting visual and ankle somatosensory inputs influenced standing balance in elders with a history of falls. Forty-seven community-dwelling elders (8 male, 39 female), between 65 and 96 years of age (mean = 80.5, SD = 9.0), participated in this project. Subjects with two or more falls in the 6 months prior to study were assigned to a fall group (n = 16), whereas those with no history of falling during the same time interval were assigned to a no-fall group (n = 31). In order to remove any bias in the testing procedure, the tester was not aware of group assignments. Subjects were evaluated using a sensory organization test (SOT) for standing balance and a "Get Up and Go" test (GUGT) for general mobility. Analysis of covariance was used to evaluate the SOT scores (by group, vision, and surface condition) and the GUGT scores. Body sway is known to increase with the normal aging process, and for this reason, age was selected as a covariate. The association between the SOT total score and the GUGT score was evaluated using Spearman rank-order correlation coefficients. The results showed a significant interaction between group and surface conditions, which indicated a decreased stance duration for fallers on a compliant surface compared with the stance duration for nonfallers (adjusted mean faller stance duration = 53 seconds, SD = 42; mean nonfaller stance duration = 67 seconds, SD = 32). Subjects in the fall group also had significantly higher GUGT scores (which indicated poor mobility function) than did subjects in the nonfall group (adjusted mean faller GUGT score = 2.65, SD = 1.48; mean nonfaller GUGT score = 1.47, SD = 0.77). The Spearman correlation between total SOT scores and the GUGT scores was greater for fallers (r = -.67) than for nonfallers (r = -.44). Orientation input from the ankle appears to have greater importance for preventing falls compared with a visual reference. The SOT and GUGT may be useful in the field to establish criteria for screening elders in a fall-prevention program.     

The potential role of lonidamine (LND) in the treatment of malignant glioma

Summary Up-to-date unsatisfactory results obtained in multimodality treatments of malignant glioma have prompted the research of new therapeutic modalities with unconventional modes of action. Lonidamine (LND) is a drug which reduces aerobic glycolytic activity in both human and experimental tumors. This effect mainly depends on the inhibition of mitochondrially-bound hexokinase (HK) which is present in large amounts in malignant cells. A Phase II study was conducted on patients with recurrent glioma; 12 patients were admitted to the study. Clinical side effects were moderate, necessitating a reduction of the dosage in only 1 case. The objective results were evaluated according to the indications of Levin. 2 responders and 3 cases of stable disease were observed out of 10 evaluable patients. The potential value of this new drug is discussed.     

A dosimetric approach to patient-specific radioiodine treatment of Graves' disease with incorporation of treatment-induced changes in thyroid mass

The traditional algorithms (Marinelli-Quimby and MIRD) used for the absorbed dose calculation in radionuclide therapy generally assume that the mass of the target organs does not change with time. In radioiodine therapy for Graves' disease this approximation may not be valid. In this paper a mathematical model of thyroid mass reduction during the clearance phase (30-35 days) after 131I administration to patients with Graves' disease is presented. A new algorithm for the absorbed dose calculation is derived, taking into account the reduction of the mass of the gland resulting from the 131I therapy. It is demonstrated that thyroid mass reduction has a considerable effect on the calculated radiation dose. Either the model of the thyroid mass reduction or the new equation for the absorbed dose calculation depend on a parameter k for each patient. This parameter can be calculated after the administration of a diagnostic amount of radioiodine activity (0.37-1.85 MBq). Thus, thyroid absorbed dose and thyroid mass reduction during the first month after therapy can be predicted before therapy administration. The absorbed dose values calculated by the new algorithm are compared to those calculated by the traditional Marinelli-Quimby and MIRD algorithms.     

Attachment and spreading of fibroblasts on an RGD peptide-modified injectable hyaluronan hydrogel

Hyaluronan (HA) hydrogels resist attachment and spreading of fibroblasts and most other mammalian cell types. A thiol-modified HA (3,3'-dithiobis(propanoic dihydrazide) [HA-DTPH]) was modified with peptides containing the Arg-Gly-Asp (RGD) sequence and then crosslinked with polyethylene glycol (PEG) diacrylate (PEGDA) to create a biomaterial that supported cell attachment, spreading, and proliferation. The hydrogels were evaluated in vitro and in vivo in three assay systems. First, the behavior of human and murine fibroblasts on the surface of the hydrogels was evaluated. The concentration and structure of the RGD peptides and the length of the PEG spacer influenced cell attachment and spreading. Second, murine fibroblasts were seeded into HA-DTPH solutions and encapsulated via in situ crosslinking with or without bound RGD peptides. Cells remained viable and proliferated within the hydrogel for 15 days in vitro. Although the RGD peptides significantly enhanced cell proliferation on the hydrogel surface, the cell proliferation inside the hydrogel in vitro was increased only modestly. Third, HA-DTPH/PEGDA/peptide hydrogels were evaluated as injectable tissue engineering materials in vivo. A suspension of murine fibroblasts in HA-DTPH was crosslinked using PEGDA plus PEGDA peptide, and the viscous, gelling mixture was injected subcutaneously into the flanks of nude mice; gels formed in vivo following injection. After 4 weeks, growth of new fibrous tissue had been accelerated by the sense RGD peptides. Thus, attachment, spreading, and proliferation of cells is dramatically enhanced on RGD-modified surfaces but only modestly accelerated in vivo tissue formation.     

Search for poliovirus long-term excretors among patients affected by agammaglobulinemia

Patients with agammaglobulinemia may excrete enteroviruses, including vaccine-derived poliovirus, for prolonged periods of time. This poses a risk to the patients but it also may pose a risk to the population after eradication of poliovirus and the cessation of routine vaccination. To assess this risk, a pilot study was performed to identify potential poliovirus long-term excretors in a cohort of 38 patients with a definite/presumptive diagnosis of X-linked agammaglobulinemia (XLA). Stool samples were analyzed to detect any polio or other enteroviruses replicating in the gut and neutralizing antibodies against polioviruses were measured in the sera. No viruses were isolated from the stool samples and most sera had neutralizing antibody levels against all three poliovirus serotypes considered by the WHO to be protective in immunocompetent individuals. This suggests that long-term excretion of enteroviruses in patients with agammaglobulinemia is relatively uncommon.