Lp(a) lipoprotein: relationship to cardiovascular disease risk factors, exercise, and estrogen.

OBJECTIVE: Lp(a) lipoprotein is a distinct lipoprotein particle that recently has been found to be associated with cardiovascular disease. A study was conducted to assess the influence of cardiovascular disease risk factors on levels of Lp(a) and to evaluate the effects of age, exercise, and estrogen on these levels. STUDY DESIGN: Two studies, a cross-sectional study of older men (n = 105) and women (n = 75) (mean age 76 years) and a prospective study of younger postmenopausal women (mean age 48 years), were carried out. Lp(a) and other lipoproteins were measured in the two studies and differences were sought by statistical analysis. RESULTS: In the cross-sectional study, serum Lp(a) was similar in men and women and was not influenced by age. Lp(a) levels in men and women were higher when there was more than one cardiovascular disease risk factor present (p less than 0.028). We could not demonstrate such a relationship with other lipid and lipoprotein measurements. In the prospective study exercise alone had no influence on Lp(a) levels. Oral estrogen decreased Lp(a) levels marginally (p = 0.08). The decrease in Lp(a) with oral estrogen was associated with increases in triglycerides (p less than 0.01) and very-low-density lipoprotein (p less than 0.06). CONCLUSIONS: These data confirm that elevated Lp(a) levels are an independent risk factor for cardiovascular disease. Lp(a) levels are primarily influenced by genetic factors and it appears estrogen may have a minor influence on its hepatic synthesis.     

Surgical management and prognostic factors in patients with subungual melanoma.

OBJECTIVE: Forty-six cases of subungual melanoma were reviewed to identify significant clinicopathologic prognostic factors, determine the role of DNA content analysis in the biologic assessment of these tumors, and evaluate the effectiveness of amputation level, lymph node dissection (LND), and regional limb perfusion on the survival of these patients. BACKGROUND: Subungual melanoma is a unique and rare subtype of melanoma, constituting only 1% to 3% of cases. Thus, little is known about prognostic factors and optimal management of patients with this disease. Moreover, the appropriate level of amputation and LND and limb perfusion in the management of subungual melanoma remain controversial. METHODS: Forty-six patients underwent amputation alone or in combination with LND and/or regional limb perfusion for primary subungual melanoma. The effects of these treatment modalities and the prognostic significance of patient and tumor-related variables, including DNA flow cytometric data, on overall survival were assessed. RESULTS: Univariate statistical analysis identified six factors that significantly affected patient survival. They were stage at diagnosis (p = 0.0001), percentage of aneuploid cells (p = 0.01), presence of ulceration (p = 0.02) or bone invasion (p = 0.02), thickness of the primary lesion (p = 0.03), and percentage of cells in S-phase (p = 0.03). Multivariate analyses identified tumor stage and S-phase fraction as independent prognostic factors in these patients. Survival did not differ among patients who received amputation alone or those who underwent amputation in combination with LND or perfusion (p = 0.90); however, the use of limb perfusion reduced the incidence of locally recurrent disease. The level of amputation did not affect patient survival (p = 0.74) or the incidence of local recurrence. CONCLUSIONS: The study identified several significant prognostic factors, including DNA flow cytometric parameters, in patients with subungual melanoma. In addition, it showed that conservative amputation of the affected digit at the level of the proximal interphalangeal or metacarpophalangeal/metatarsophalangeal joint appears to be safe, provided that clear margins are obtained. Although isolated limb perfusion may reduce the incidence of local recurrence, LND, or limb perfusion in the routine management of subungual melanoma remains controversial.     

Alterations in erythrocyte Na+,K+-cotransport in normal and hypertensive human pregnancy

Many physiological variables known or thought to affect erythrocyte Na+,K+-cotransport are altered in pregnancy. The interrelationships of Na+,K+-cotransport and pregnancy were therefore examined. Values were elevated by more than 30% in both second and third trimesters with a return towards non-pregnant levels in the postpartum period. Although pregnancy was also associated with elevated plasma cholesterol, renin activity and aldosterone, there was no significant relationship within the pregnant group between Na+,K+-cotransport and any of these factors. No change could be demonstrated in Na+,K+-cotransport values after 7 days of either high (greater than 250 mmol/day) or low (less than 50 mmol/day) sodium intake and values for those who developed pregnancy-associated hypertension (PAH, pre-eclampsia) were not significantly different from those in continuously normotensive women in either the second or the third trimesters of pregnancy.     

Gentamicin-induced increases in cytosolic calcium in pig kidney cells (LLC-PK1)

LLC-PK1 cells, an established epithelial cell line derived from pig kidney, were tested as a model system for assessing the role of calcium in gentamicin-induced nephrotoxicity. Cell viability was evaluated by a vital dye exclusion procedure, and intracellular free calcium [Ca2+]i was measured employing Fura-2 fluorescence. Exposing cell suspensions (10(6)/ml) to concentrations of the drug, which had no apparent effect on viability, produced a rapid and prolonged increase in intracellular [Ca2+]. The perturbation of calcium homeostasis could be blocked by the addition of mepiperphenidol, an inhibitor of the organic cation transport system. We propose that LLC-PK1 cells are an appropriate model to study drug-induced nephrotoxicity. Gentamicin disrupts calcium homeostasis and causes plasma membrane alterations. Since mepiperphenidol blocked the gentamicin-induced Ca2+ increases, the data suggest that aminoglycosides enter the cell via the organic cation transporter.     

Moderate head injury: a guide to initial management.

The purpose of this study is to determine the initial treatment of patients who appear to have sustained moderate head injuries when first evaluated. The authors reviewed the records of 341 patients whose initial Glasgow Coma Scale (GCS) scores ranged from 9 to 12, as well as another 106 patients with GCS scores of 13. All patients underwent cranial computerized tomography (CT) at the time of admission. In 40.3% of these patients the CT scans were abnormal (30.6% had intracranial lesions), and 8.1% required neurosurgical intervention (craniotomies for hematoma in 12, elevation of depressed fractures in five, and insertion of intracranial pressure monitors in 19). Four patients died of their intracranial injuries. A similar incidence of lesions found on CT and at surgery suggests that an initial GCS score of 13 be classified with the moderate head injury group. Skull fractures were found to be poor indicators of intracranial abnormalities. These results suggest that all patients with head injury thought to be moderate on initial examination be admitted to the hospital and undergo urgent CT scanning. Patients with intracranial lesions require immediate neurosurgical consultation, surgery as needed, and admission to a critical-care unit. Scans should be repeated in patients whose recovery is less rapid than expected and in all patients with evidence of clinical deterioration; this was necessary in almost half of the patients in this group, and 32% were found to have progression of radiological abnormalities on serial CT scans.     

Spinal MR findings in neurofibromatosis types 1 and 2.

PURPOSE: To evaluate the frequency and nature of spinal pathology, the frequency of clinically silent lesions, and the potential benefit of screening spinal MR in neurofibromatosis patients. PATIENTS AND METHODS: 28 neurofibromatosis type-1 (NF-1) patients and nine neurofibromatosis type-2 (NF-2) patients were studied with postcontrast spinal MR imaging. RESULTS: NF-1: One patient had a biopsy-proven low-grade glioma; five patients, intradural, extramedullary masses (N = 23); one patient, extradural masses (N = 2) (neurofibromas); 16 patients had bony abnormalities; and three patients thecal sac abnormalities. NF-2: Five patients demonstrated intramedullary masses (five/eight ependymomas); nine patients, intradural, extramedullary masses (meningiomas, schwannomas); and four patients, bony abnormalities. Eight/10 NF-1 and four/nine NF-2 patients had asymptomatic masses. CONCLUSION: Intradural disease is common, often asymptomatic, and often presents at a young age in NF-1 and NF-2 patients. Because of the propensity to develop significant asymptomatic as well as symptomatic intradural disease, screening of the entire spine with MR is recommended in both NF-1 and NF-2 patients.     

A model for estimating the potential costs and savings of osteoporosis prevention strategies

A model was developed which estimates the costs of osteoporosis risk evaluation and treatment, and the resulting savings in terms of reduced fracture frequency, for the adult female population of the United States. In the absence of treatment, the model predicts 1.44 million fractures will occur annually from non-violent causes. Treatment of all women beginning at age 50 with an agent that slows bone loss by 50% would reduce the number of these fractures by 0.59 million. Selective treatment of the 47% of women at the greatest fracture risk would reduce the number of fractures by 0.45 million, but would only cost 47% as much as treating all women. Additional data are required before the model can be used to evaluate specific treatment regimens. However, it appears that selective treatment of those at highest risk would yield the greatest benefit to cost ratio, if only benefits related to reduced fracture frequency are considered.