Differential effects of maternal nutrient restriction through pregnancy on kidney development and later blood pressure control in the resulting offspring.

The mechanisms whereby maternal nutritional manipulation through pregnancy result in altered blood pressure in the offspring may include changes in fetal and newborn and adult renal prostaglandin (PG) synthesis, metabolism, and receptor expression. Since the postnatal effects of nutrient restriction on the renal PG synthesis and receptor system during nephrogenesis in conjunction with nephron numbers and blood pressure have not been evaluated in the rat, the present study examined the effect of reducing maternal food intake by 50% of ad libitum through pregnancy on young male rats. Six control-fed mothers and eight nutrient-restricted pregnant rats with single litter mates were used at each sampling time point, most of which occurred during nephrogenesis. Offspring of nutrient-restricted dams were lighter from birth to 3 days. This was accompanied by reduced PGE2, with smaller kidneys up to 14 days. Nutrient restriction also decreased mRNA expression of the PG synthesis enzyme, had little effect on the PG receptors, and increased mRNA expression of the degradation enzyme during nephrogenesis and the glucocorticoid receptor in the adult kidney. These mRNA changes were normally accompanied by similar changes in protein. Nephron number was also reduced from 7 days up to adulthood when blood pressure (measured by telemetry) did not increase as much as in control offspring during the dark, active period. In conclusion, maternal nutrient restriction suppressed renal PG concentrations in the offspring, and this was associated with suppressed kidney growth and development and decreased blood pressure.

Aerosol deposition of lipid complex amphotericin-B (Abelcet) in lung transplant recipients.

Lung transplant recipients exhibit a high incidence of invasive aspergillosis. The inhalation of lipid complex amphotericin-B (Abelcet; ABLC) offers a possible prophylactic strategy. The goals of this study were to select the optimal nebulizer delivery system for ABLC and to measure deposited aerosol dose in 12 lung transplant recipients. In vitro testing was performed to select a nebulizer delivery system, and an empirical model was used to estimate lung deposition. Estimated pulmonary doses varied by as much as 2-fold between different nebulizers. Aerosol deposition testing was performed in six single and six double lung recipients, each of whom received one 7 mL (35 mg) nebulized dose of Technetium-labeled ABLC using the selected nebulizer. In single lung recipients, the average deposited doses were 3.9 +/- 1.6 mg (mean +/- S.D.) in the allograft versus 2.1 +/- 1.1 mg in the native lung. Double lung recipients deposited on average 2.8 +/- 0.8 mg (left lung) and 4.0 +/- 1.3 mg (right lung). The drug was well distributed throughout the lungs, but delivery to the native lung was in some cases suboptimal. These studies provide an important precursor to studies of the efficacy of inhaled ABLC as a prophylaxis of invasive aspergillosis after lung transplant.

Efficacy and tolerability of policosanol in hypercholesterolemic postmenopausal women.

This randomized, double-blind, multicenter placebo-controlled study was conducted to investigate the efficacy and tolerability of policosanol, a cholesterol-lowering drug purified from sugar cane wax, in women who had experienced menopause and showed elevated serum total cholesterol and low density lipoprotein (LDL)-cholesterol levels despite a 6-week standard lipid-lowering diet. Thus, 56 eligible patients were randomized to receive placebo or policosanol 5 mg/day for 8 weeks and the dose was doubled to 10 mg/day during the next 8 weeks. Policosanol (5 and 10 mg/day) significantly decreased LDL-cholesterol (17.3% and 26.7%, respectively), total cholesterol (12.9% and 19.5%) as well as the ratios of LDL-cholesterol to high-density lipoprotein (HDL)-cholesterol (17.2% and 26.5%) and total cholesterol to HDL-cholesterol (16.3% and 21.0%) compared with baseline and placebo. HDL-cholesterol levels were significantly raised by 7.4% at study completion. No significant changes occurred in the lipid profile of the placebo group. The drug was safe and well tolerated. No drug-related adverse effects were observed. None of the patients administered policosanol but three of those administered placebo withdrew from the trial because of adverse effects: one due to a serious hypertensive status, one because of an allergic reaction (pruritus plus skin rash) and one due to gastrointestinal disturbances (nauseas plus vomiting). Eleven placebo patients reported 24 adverse effects compared with six policosanol patients who reported seven adverse effects (p < 0.05). In addition, five placebo (17.9%) and 13 policosanol patients (46.4%) (p < 0.05) reported improvements in habitual symptoms and health perception during the study. In conclusion, policosanol was effective and well tolerated in hypercholesterolemic postmenopausal women, showing additional benefits in the health perception of the study patients.

Staging lung carcinoma with a Tc-99m labeled monoclonal antibody.

Thirty-three patients with biopsy-proven lung cancer and a total of 150 lesions diagnosed by conventional staging procedures were imaged using a Tc-99m labeled monoclonal Fab fragment of an IgG2B murine monoclonal antibody (MoAb) (NR-LU-10, NeoRx Corporation). Immunoscintigraphy demonstrated 100% of primary and 78% of metastatic lesions. MoAb imaging detected 88% of lesions in 12 small cell lung cancer (SCLC) patients and 77% of lesions in 21 non-small cell lung cancer (NSCLC) patients. Based on initial evaluation by other methods, 29 sites of MoAb activity were not associated with evidence of disease. Eleven of these were subsequently shown to represent sites of metastases; 18 remain unconfirmed. Four of ten patients studied with limited NSCLC had eight unsuspected lesions on MoAb imaging. Confirmation of unsuspected lesions in two patients altered initial clinical staging, and surgical therapy was abandoned. This study demonstrates that Tc-99m labeled NR-LU-10 can accurately stage patients with lung cancer.

Multimodality imaging of the thyroid gland.

The continued development of high technology in the rapidly expanding field of computer-based imaging has had a significant impact on many areas of diagnostic imaging. The problem of rising medical costs emphasizes the importance of reaching a diagnosis by the most straightforward and cost-effective method while providing minimal patient discomfort. This responsibility to the patient and the medical care system rests with the physician. It is therefore essential that both imaging and referring physicians have a broad background of information regarding the potential limitations and relative merits of both old and new technologies available to patients with thyroid disorders. The appropriate utilization and relative roles of these imaging modalities have been discussed with respect to the individual clinical problem in this chapter.

Primary extraosseous osteogenic sarcoma of the mediastinum: clinical, pathologic, and radiologic correlation.

We have presented a rare case of primary involvement of the anterior mediastinum by osteogenic sarcoma in which CT was useful in demonstrating calcium within the mass, and in distinguishing the mass from surrounding bony structures. Although rare, extraosseous osteogenic sarcoma should be included in the differential diagnosis of a calcified anterior mediastinal mass.