Determination of N-nitrosodimethylamine at part-per-trillion levels in drinking waters and contaminated groundwaters

The carcinogen N-nitrosodimethylamine (NDMA) may be quantitated routinely at ultratrace (ng/L) levels in drinking water or contaminated groundwater. The aqueous sample is passed through a preconditioned Empore C18 filter disk to remove neutral nonpolar species and then extracted continuously overnight with highest purity dichloromethane. The latter is then concentrated to 1 mL, and a large aliquot (up to 200 microL) is loaded onto a dual-stage carbon sorbent trap, after which the solvent is removed with ultrapure helium. The concentrated residues are then injected onto a gas chromatographic column using a short-path thermal desorber. NDMA is selectively detected using a chemiluminescent nitrogen detector (CLND) operated in its nitrosamine-selective mode. The reporting limit for this procedure, evaluated using two independent statistically unbiased protocols, is 2 ng of NDMA/L. A related procedure, employing an automatic sampler instead of the short-path thermal desorber, provides convenient analysis of heavily contaminated samples and exhibits a reporting limit (same protocols cited previously) of 110 ng of NDMA/L. When the two methods are used together in a "two-tiered" protocol, NDMA concentrations spanning 4 orders of magnitude (ng/L to microgram/L levels) may be measured routinely. The low-level procedure employing only the short-path thermal desorber was applied successfully to three sources of drinking water, where NDMA concentrations ranged between 2 and 10 ng of NDMA/L. The two-tiered protocol was applied to a series of contaminated groundwaters whose NMDA concentrations ranged between approximately 10-7000 ng of NDMA/L. The results agreed with those obtained from an independent collaborating laboratory, which used a different analytical procedure.     

Effectiveness of slow release L-DOPA/benserazide in treatment of end-of-dose akinesia in Parkinson disease

In an open label study 63 patients with idiopathic Parkinson's disease suffering from end-of-dose akinesia were switched from a treatment with a L-DOPA standard formulation to a combined therapy of L-DOPA standard in the morning and L-DOPA slow release (levodopa, benserazide, Madopar Depot) at the remaining single doses. Substitution of L-DOPA standard by L-DOPA slow release took on average 2-4 weeks. Patients were subsequently treated for 6 months. Due to a lower bioavailability of the slow release formulation--the latter is based on the "hydrodynamically balanced system" (HBS)--, the patients remained initially on their time schedule of drug intake but received a higher dose of L-DOPA slow release compared to the preceding L-DOPA standard therapy. In 20 centers 37 men and 26 women were included into the study. 27 males and 20 females completed the 6 month treatment period. Before switching, the patients received 438 +/- 213 mg a day L-DOPA standard, after conversion, the average dose was 617 +/- 323 mg L-DOPA slow release and 107 +/- 95 mg L-DOPA standard a day. Fluctuations during the day and at night which were rated according to a newly developed clinical 5-point rating scale were significantly improved by the treatment regimen from 2.8 +/- 0.9 to 1.4 +/- 1.2. Additionally, parkinsonian symptoms were significantly reduced during the ON-phase as there was a significant decrease of the Webster rating score from 12.0 +/- 4.6 to 7.1 +/- 4.0. Quality of life as measured by subjective ratings of the patients improved. The tolerability of the new formulation of L-DOPA was rated to be good in 51.1% and very good in 48.9%. The results of this open label study suggest that the combination of L-DOPA standard in the morning and L-DOPA slow release formulation at the following time points can be an efficient therapy in parkinsonian patients who suffer form L-DOPA related end-of-dose motor akinesia.     

Stability and distribution of orally administered epidermal growth factor in neonatal pigs

Stability and distribution of orally administered epidermal growth factor (EGF) were examined in newborn and 5-day-old pigs. Forty-five minutes after oral administration of iodine-125 labeled EGF, 60 and 50% of the radioactivity administered were recovered from the internal organs in newborn and 5-day-old pigs, respectively. In both age groups, over 95% of the recovered radioactivity was found in the gastrointestinal tract, of which 78-86% was found in the luminal contents with the remaining found in the gastrointestinal wall. Within the gastrointestinal tract, 65-71% of radioactivity was found in the stomach, 27-30% in the proximal and mid small intestine and 3-4% was found in the distal part of the small intestine. There were no significant differences in the overall distribution of orally administered radioactivity between two age groups. Based on liquid chromatography and trichloroacetic acid precipitation, a substantial amount of EGF recovered from the luminal contents (63-86%) and the gastrointestinal wall (42-81%) remained "intact". The receptor binding ability of the EGF recovered from the gastric contents was 96-102% comparable to the native EGF tracer. The receptor binding ability remained high (40-58%) in the proximal small intestinal lumen and it decreased to 15% in the distal small intestinal lumen in newborn pigs. In 5-day-old pigs, EGF recovered from the small intestinal contents had 5 to 24% receptor binding ability when compared with native EGF tracer. The receptor binding ability of the EGF recovered from all other organs was below 5% with an exception of the gastric wall, from which recovered EGF retained 9 to 26% receptor binding ability. These results indicate that most of orally ingested EGF remained in the gastrointestinal tract in neonatal pigs 45 min after oral ingestion, and significant amount of the ingested EGF remained biologically active. It suggests that milk-borne EGF can survive in the gastrointestinal tract and may play a role in regulating gut development in neonatal animals.     

Identification of volatile organic compounds emitted in the field by oilseed rape (Brassica napus ssp. oleifera) over the growing season

There is currently a trend gaining acceptance that explicitly recognizes the need to set priorities for making rational decisions in health policy, respecting at the same time the underlying purpose of health care - to improve people's health. This trend in health policy is referred to as "health targets" although definitions vary considerably. Having been initiated by the World Health Organization in the late 1970s, the international policy on health targets is in the process of renewal to become Health for All in the Twenty-First Century. The new program highlights 10 global targets, from the reduction of worldwide burden of diseases to improvement of access to comprehensive, essential quality care. Countries such as the United Kingdom and Australia have adopted and implemented such programs which basically include cardiovascular, cancer, accidents, and mental health targets. For many countries, however, there are several difficulties in establishing similar programs. One of them is the unavailability of reliable data, although political factors and structure of health systems also play a key role in the creation of health targets. Overall, health targets appear to be a key element in building a strong public health policy, taking into consideration not only the cost of healthcare, but also the outcomes in improving health which is the ultimate goal of health care systems.     

Acute vasoconstriction after subarachnoid hemorrhage

OBJECTIVE: Decreased cerebral blood flow (CBF) and cerebral ischemia occurring immediately after subarachnoid hemorrhage (SAH) may be caused by acute microvascular constriction. However, CBF can also be influenced by changes in intracranial pressure (ICP) and cerebral perfusion pressure (CPP). The goal of these experiments was to assess the significance of acute vasoconstriction after SAH and its relationship to changes in CBF, ICP, CPP, and extracellular glutamate concentrations. METHODS: Three experiments were performed using the endovascular filament technique to produce SAH. In the first experiment, CBF, ICP, and CPP were measured for 60 minutes after SAH (n = 21) and were correlated with the 24-hour mortality rate. In the second experiment, rats undergoing SAH (n = 23) or a sham procedure (n = 7) were perfused 60 minutes after SAH for measurement of the circumference and wall thickness of the internal carotid and anterior cerebral arteries and correlation with CBF, ICP, and CPP. In the third experiment (n = 11), extracellular glutamate concentrations determined by hippocampal and cortical microdialysis and high performance liquid chromatography were correlated with physiological changes. RESULTS: CBF reductions to less than 40% of baseline for 60 minutes after SAH predicted 24-hour mortality with 100% accuracy and were used to define "lethal" SAH. In contrast, ICP and CPP 60 minutes after SAH were not correlated with the mortality rate. The vascular circumference was significantly smaller in lethal than in sublethal SAH or sham-operated rats (P < 0.001). Vessel measurements were correlated with both CBF and hemorrhage size (P < 0.01). Extracellular glutamate concentration increased to 600% of baseline after lethal SAH in both hippocampus and cortex and was inversely correlated with CBF (r = 0.9, P < 0.001) but did not increase after sublethal SAH. CONCLUSION: Acute vasoconstriction after SAH occurs independently of changes in ICP and CPP and is associated with decreased CBF, larger hemorrhage size, persistent elevations of extracellular glutamate, and poor outcome. Acute vasoconstriction seems to contribute directly to ischemic brain injury after SAH. Further evaluations of pharmacological agents with the potential to reverse acute vasoconstriction may increase CBF and improve outcome.     

Collection and transfusion of blood and blood components in the United States, 1989

A poor response to L-DOPA in addition to parkinsonian, cerebellar, and autonomic signs is commonly regarded as indicative of clinical multiple system atrophy (MSA). We compared the motor response to a single oral administration of 250 mg L-DOPA/25 mg carbidopa in eight MSA patients and eight Parkinson's disease (PD) patients with the "on-off" phenomenon, evaluating L-DOPA peripheral pharmacokinetics. Motor response was consistently good in all PD patients, but only four MSA patients had a (moderate) response. Pharmacokinetic parameters did not differ between the groups. The varying extent of putaminal damage could be responsible for the differing motor response to L-DOPA in MSA patients.     

Oestrogen therapy and endometrial cancer

The most controversial issue related to prolonged estrogen therapy is the possible relationship of this therapy to the etiology and pathogenesis of breast and uterine cancer. The imprecise nature of the relevant data does not allow full definition of the rish. To maintain proper perspective, smoking 20 cigarettes a day increases the risk of death from lung cancer 17 times; the risk from estrogens is less than that. There is no controversy over the use of estrogens for short-term relief of menopausal symptoms. The Mulley and Mitchell paper referred to was opinion based on no direct research and an inadequate knowledge of the literature. The early symptoms of estrogen dificiency, hot flushes and atrophic vaginitis, respond to short-term estrogen therapy, which in addition, provides a "mental tonic" effect. It is not justifiable to withhold such therapy from the normal informed patient requesting it, provided no contraindications exist. The patient should be reevaluated at frequent intervals, and the proper selection of drug, dosage, and therepeutic regimen administered. This can be accomplished, including research, through a menopause clinic.     

The clinical assessment of cancer tests: a statistical approach to the prediction of "false positive" rates from controls

As the sensitivity of the new in vitro cancer detection techniques increases, a larger number of "false positive" results can be expected from control populations apparently free from malignant disease at the time of the test. An attempt is made to predict the number of unexplained positives, together with the expected age and sex distribution, using published cancer registration statistics. The predicted numbers are compared with the observed numbers of unexplained positives in two clinical trials of the MEM test.     

H] Tryptamine and 3H-water as diffusible internal standards for measuring brain extraction of radio-labeled substances following carotid injection

Urinary amino acid excretion was determined in 31 leukemic patients and 29 normal individuals by rapid gas chromatographic analysis of 16 amino acids as their N-acetyl-n-propyl esters. The leukemic patients were concurrently undergoing, or had recently completed, chemotherapy. It was found that aspartic acid, threonine, and serine were of significance in distinguishing between patients "on" therapy and those "off" therapy. Patients with advanced disease have the greatest aminoaciduria, although both the normal and leukemic populations have wide individual ranges. Within both populations, men excrete a greater variety and quantity of amino acids than women. It is concluded that analysis of urinary amino acids represents a history of complex metabolic events, which is potentially useful for evaluating patient response to chemotherapy in leukemia.     

Family centered maternity care: its relationship to perinatal regionalization and neonatal intensive care

For several months prior to birth a major portion of a family's attention, conversation, thought, and often worry, is directed toward the idea of a new child. This prolonged attention and anticipation contribute to making childbirth an emotionally charged experience. In psychological terms, it is therefore a critical period of peak motivation for learning, and a time to peak susceptibility to reinforcement. Theory, reason, and scientific evidence indicate thng with childbirth and early postpartum experiences, can significantly affect subsequent parental behaviors, the child's central environment influence. Evidence strongly suggests that these parental attitudes and behaviors so crucial to the child's ultimate well-being are learned rather than derived instinctually, and therefore they are malleable and can be taught, directed, and corrected. Through education and reinforcement it is possible to encourage parental behaviors and child interactions which are products of feelings of control, competence, accomplishment, understanding, and caring. Similarly we can recognize and work toward replacing attitudes, feelings, and behaviors that express fear, worry, and insecurity about the child. Over the past 50 years major changes have occurred in the practice of obstetrics and newborn pediatrics. Other major changes will necessarily occur as we move toward perinatal regionalization. Changes instigated solely on physiologic data can have unrecognized collateral effects on the psychological component of the childbirth experience. All concerned health care personnel, especially obstetricians and pediatricians, can insist that the importance of desirable mother-father-child interactions be recognized and that practices fostering them be afforded a high priority. I would like to endorse a comment from a recent article by Richmond concerning the advent of behavioral pediatrics by adding that behavioral obstetrics is also "an idea whose time has arrived".