Transcranial Doppler in the management of extracranial cerebrovascular disease: implications in diagnosis and monitoring

Transcranial Doppler (TCD) insonation permits quantitative noninvasive evaluation of intracerebral arterial velocity. With the use of a 2 MHz Doppler through a transtemporal approach, middle cerebral artery blood velocity (MCA-V, centimeters per second) and major collaterals were measured in 96 patients, including 15 normal control subjects, 66 patients with extracranial cerebrovascular disease (ECCVD), and 15 patients with other medical problems without ECCVD. MCA-V was higher in control subjects (62.7 +/- 15.1) than in patients with ECCVD (45.0 +/- 16.3, p less than 0.05). There was a significant inverse correlation between MCA-V and the degree of internal carotid artery stenosis present by duplex examination. Twenty-three patients monitored during carotid endarterectomy had a mean MCA-V under anesthesia of 37.0 +/- 16.9, which decreased to 22.4 +/- 14.8 during cross-clamping (p less than 0.01). MCA-V during cross-clamping correlated directly with stump pressure (R = 0.87) and was higher when major collaterals were identified before operation by TCD than when none were seen (31.7 +/- 9.5 vs. 8.8 +/- 8.5, p less than 0.01). Shunt function was verified in all 11 patients shunted. Electroencephalographic changes occurred in four patients with an MCA-V of 14.7 +/- 8.5 compared with an average of 24.1 +/- 15.5 for patients with normal electroencephalograms. MCA-V increased from 46.6 +/- 21.2 before operation to 61.0 +/- 22.4 after carotid endarterectomy (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Dynamics of human chorionic gonadotropin, prolactin, and growth hormone in serum and amniotic fluid throughout normal human pregnancy

This study was performed to establish the dynamics of human chorionic gonadotropin, prolactin, and growth hormone throughout pregnancy in serum and amniotic fluid. Two hundred fifty healthy women at 8 to 42 weeks' gestation were studied. The highest serum human chorionic gonadotropin level was measured between weeks 8 to 12 (53,715 +/- 3574 mIU/ml, mean +/- SEM), with a decline to a mean plateau of 11,806 +/- 1250 mIU/ml from week 18. Amniotic fluid human chorionic gonadotropin had a similar pattern with a mean of 68,100 +/- 8422 mIU/ml at weeks 8 to 10, declining from week 18 to a plateau of 2005 +/- 260 mIU/ml. Human chorionic gonadotropin showed a significant correlation (r = 0.85, p less than 0.001) between levels of both compartments demonstrating an even distribution. Prolactin levels showed a dichotomy of patterns and levels. Serum prolactin showed a continuous rise from 45.3 +/- 14 ng/ml at week 8 to 224 +/- 20 ng/ml at week 36. In contrast, amniotic fluid prolactin remained low until week 14 (33.1 +/- 0.8 ng/ml), followed by a sharp and significant (p less than 0.001) increase to a plateau of 3750 +/- 200 ng/ml between weeks 18 to 26, declining to a second plateau of 500 +/- 50 ng/ml at week 36. Serum growth hormone increased from a mean of 3.5 +/- 1.4 ng/ml seen at weeks 8 to 10 to a mean of 14 +/- 2.0 ng/ml at weeks 28 to 30, followed by a plateau of similar levels. The pattern of growth hormone secretion in amniotic fluid demonstrated a sharp increase during the 14-16 interval with a maximum mean level of 15.5 +/- 1.5 ng/ml and a slow steady decline thereafter. In conclusion, the similar pattern and concentration of human chorionic gonadotropin throughout pregnancy in both maternal and amniotic fluid are probably the result of direct human chorionic gonadotropin diffusion from the placenta. The dissimilar pattern and concentration of prolactin are the result of two different sources of prolactin secretion during pregnancy. Serum prolactin originates from the pituitary and amniotic fluid prolactin from the decidua. Since the pattern of growth hormone secretion resembles that of prolactin, it is possible that growth hormone, like prolactin, is secreted by the same sources.     

Tarsal navicular stress fractures in runners

The number of participants in running programs at all levels has increased in recent years. As a consequence, practitioners are more frequently dealing with diagnoses in symptomatic runners. Detection of tarsal navicular stress fractures in long distance runners, including the diagnostic value of radionuclide bone scanning, is discussed.     

Arsenic-induced enhancement of ultraviolet radiation carcinogenesis in mouse skin: a dose-response study

The present study was designed to establish the form of the dose-response relationship for dietary sodium arsenite as a co-carcinogen with ultraviolet radiation (UVR) in a mouse skin model. Hairless mice (strain Skh1) were fed sodium arsenite continuously in drinking water starting at 21 days of age at concentrations of 0.0, 1.25, 2.5, 5.0, and 10 mg/L. At 42 days of age, solar spectrum UVR exposures were applied three times weekly to the dorsal skin at 1.0 kJ/m2 per exposure until the experiment ended at 182 days. Untreated mice and mice fed only arsenite developed no tumors. In the remaining groups a total of 322 locally invasive squamous carcinomas occurred. The carcinoma yield in mice exposed only to UVR was 2.4 +/- 0.5 cancers/mouse at 182 days. Dietary arsenite markedly enhanced the UVR-induced cancer yield in a pattern consistent with linearity up to a peak of 11.1 +/- 1.0 cancers/mouse at 5.0 mg/L arsenite, representing a peak enhancement ratio of 4.63 +/- 1.05. A decline occurred to 6.8 +/- 0.8 cancers/mouse at 10.0 mg/L arsenite. New cancer rates exhibited a consistent-with-linear dependence on time beginning after initial cancer-free intervals ranging between 88 and 95 days. Epidermal hyperplasia was elevated by arsenite alone and UVR alone and was greater than additive for the combined exposures as were growth rates of the cancers. These results demonstrate the usefulness of a new animal model for studying the carcinogenic action of dietary arsenite on skin exposed to UVR and should contribute to understanding how to make use of animal data for assessment of human cancer risks in tissues exposed to mixtures of carcinogens and cancer-enhancing agents.     

Evidence that arsenite acts as a cocarcinogen in skin cancer

Inorganic arsenic (arsenite and arsenate) in drinking water has been associated with skin cancers in several countries such as Taiwan, Chile, Argentina, Bangladesh, and Mexico. This association has not been established in the United States. In addition, inorganic arsenic alone in drinking water does not cause skin cancers in animals. We recently showed that concentrations as low as 1.25 mg/l sodium arsenite were able to enhance the tumorigenicity of solar UV irradiation in mice. The tumors were almost all squamous cell carcinomas (SCCs). These data suggest that arsenic in drinking water may need a carcinogenic partner, such as sunlight, in the induction of skin cancers. Arsenite may enhance tumorigenicity via effects on DNA repair and DNA damage-induced cell cycle effects, leading to genomic instability. Others have found that dimethlyarsinic acid (DMA), a metabolite of arsenite, can induce bladder cancers at high concentrations in drinking water. In those experiments, skin cancers were not produced. Taken together, these data suggest that arsenite (or possibly an earlier metabolite), and not DMA, is responsible for the skin cancers, but a second genotoxic agent may be a requirement. The differences between the US and the other arsenic-exposed populations with regard to skin cancers might be explained by the lower levels of arsenic in the US, less sun exposure, better nutrition, or perhaps genetic susceptibility differences.     

Is chronic beryllium disease sarcoidosis of known etiology?

Sarcoidosis is a granulomatosis that predominantly affects the lungs and is of unknown etiology. Chronic beryllium disease is a granulomatosis that predominantly affects the lungs and is due to a hypersensitivity response to beryllium. Similarities and differences between these two disorders are reviewed and lessons for both sarcoidosis and chronic beryllium disease are discussed.     

Two year prognosis of sarcoidosis: the ACCESS experience

A cohort of 215 sarcoidosis patients from the ACCESS study underwent a clinical evaluation at study enrollment and two years later. Approximately 80% of subjects had an improved or stable FVC, FEV1, chest radiograph determined by Scadding stage, and dyspnea scale. African-Americans had less improvement in FVC than Caucasians (p = 0.04). Patients with erythema nodosum at presentation were more likely to have improvement in the chest radiograph at two-year follow-up (p = 0.007). Patients with a lower annual family income were more likely to worsen with respect to dyspnea (p = 0.01) and more likely to have new organ involvement at two-year follow-up (p = 0.045). The development of new organ involvement over the two year follow-up period was more common in African-Americans compared to Caucasians (p = 0.002) and more likely in those with extrapulmonary involvement at study entry (p = 0.003). There was an excellent concordance between changes in FVC and FEV1 over the two-year period. However, changes in FVC alone were inadequate to describe the change in pulmonary status of the patients, as changes in chest radiographic findings or the level of dyspnea did often but not always move in the same direction as FVC. In conclusion, data from this heterogeneous United States sarcoidosis population indicate that sarcoidosis tends to improve or remain stable over two years in the majority of patients. Several factors associated with improved or worse outcome over two years were identified.